| 30/09/2022 |
£500,000 |
|
COUNCIL FOR AT-RISK ACADEMICS |
Cara was founded by academics and scientists in the UK to rescue their colleagues from Nazi Germany and other countries under fascism. Almost ninety years later, many academics and scientists around the world are still at grave risk because of what they say and write, because of violence and conflict, or for other reasons. We have a network of 129 UK university partners, and others abroad, who provide places and some funding for those who need to get away, with their families. But it is often our ability to contribute funds of our own too, for example to cover travel and up-front costs (visas, NHS surcharge) and the additional costs of family members (we try to limit the latter costs to £7,500 pa per case), that makes it possible to finalise the placement.
Recent events, in Afghanistan and Ukraine in particular, have led many more people to seek our help - some 750 from Afghanistan, and a growing number from Ukraine (though martial law currently prevents men aged 18-60 from leaving), on top of the continuing flow from other parts of the world, the Middle East in particular.
This funding would significantly increase our ability to help those in danger.
|
| 30/09/2022 |
£17,731 |
|
BABRAHAM INSTITUTE |
Not available |
| 30/09/2022 |
£42,889 |
|
MQ TRANSFORMING MENTAL HEALTH |
To have the greatest impact and be its most inclusive, the discipline of mental health science needs opportunity to convene, develop a common language and enable connection. Through discussions with Wellcome's Mental Health Team, we present this proposal to together convene the sector to achieve five outcomes:
To (a) catalyse new collaborations between diverse and often fragmented disciplines in mental health (b) with a particular highlight on combining or providing access to datasets and/or personalised and effective treatments
Engage 100 low-middle income country (LMICs) attendees and increase their representation amongst speakers whilst building their research capacity
To advance and promote the use of common metrics for mental health
Engage policy makers to ensure the relevance and importance of research is recognised, acted upon and invested in
To provide a meaningful and impactful opportunity for public and patient involvement and engagement to (a) influence the trajectory of mental health research and (b) be a showcase for government and NGOs
This desired progress can be accelerated through partnership within the mental health science family. We are delighted to be exploring how a partnership with Wellcome through an investment of expertise and £42,484, would allow us to convene the sector, increase impact.
|
| 30/09/2022 |
£1,009,420 |
|
UNIVERSITY OF OXFORD |
Taking the lessons learned from the international success of ISARIC’s COVID-19 data platform, we will expand the platform to answer new questions on COVID-19 and build data systems to respond to future outbreaks of infectious diseases. This collaboration brings together scientists who have developed world-leading data integration, processing and analytic technologies with health care workers and public health specialists who will use and tailor the technologies to deliver evidence that's relevant to patient care and public health policy decisions. Together we will expand the data platform to 1) integrate epidemiological and clinical data so that we can analyse research questions at an individual level and a population level; 2) integrate genomic data so that we can understand how different virus variants affect patient outcomes; and 3) provide the infrastructure to scale data processing and grow our international network to generate more evidence on emerging infectious diseases. We will analyse these integrated data sets to generate evidence on the impact of vaccination and new variants in COVID-19 infection and post-acute COVID-19 syndrome. We will also develop methods to accelerate science on the characterisation of future disease outbreaks.
|
| 30/09/2022 |
£107,641 |
|
GLOBAL HEALTHCARE INNOVATION ALLIANCE ACCELERATOR |
The GHIAA MAPGuide enables users to explore a range of approaches used to address key issues in global health agreements. As of 1 November 2021, the MAPGuide contained analysis of 387 provisions from 59 agreements, and our team is constantly working to expand on this. An important next step in widening the impact of the MAPGuide is to create educational resources that present key information and best practice recommendations in a format that can be easily understood by all stakeholders.
The objective of this application is to develop materials that provide guidance to global health funders, PDPs and government ministries as they work to develop equitable access policies and ensure that they are translated into actionable agreements. The materials will draw on the agreements and provisions in the MAPGuide to examine the key pillars of equitable access and how they can be achieved through meaningful and enforceable contract terms. This information will be presented on the MAPGuide website in an easy to use format using a combination of infographics and a series of ‘plain English’ articles that explore key topics in more detail.
|
| 30/09/2022 |
£18,096,927 |
|
COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS (CEPI) |
Funding will go toward critical R & D to meet the challenges of this rapidly evolving pandemic & facilitate equitable access to safe effective vaccines. Objectives are:
Enable equitable access to vaccines to reduce circulation of virus—thereby limiting opportunities for viral mutation—and reducing the disease burden on health systems.
Create conditions where vaccines can be rapidly adapted (within 100 days) to the new strains, and increase manufacturing capacity to make enough for global need
Optimise and deploy the existing suite of vaccines, including through the testing of ‘mix and match’ regimens and booster doses.
Support development of new strain-specific vaccines and second-generation vaccines that are more robust to viral evolution
Accelerating development of breakthrough vaccine candidates
Funding would support:
Next generation vaccine candidates with potentially significant health impacts, e.g. candidates that elicit mucosal immunity or single dose candidates. Scale-up development of promising candidates.
Expanding CEPI’s "Agility Programme" to understand the impact of variants on vaccine efficacy & support decision making on the need to adapt existing vaccines.
Building protection against variants to prepare for the emergence of potential new variants.
Developing a broadly protective coronavirus vaccine that could eliminate the risk of existing coronaviruses & new, unknown coronaviruses.
|
| 30/09/2022 |
£40,000 |
|
HARRIS ACCESS CONSULTING LTD |
In 2021, Harris Access Consulting and Charles River Associates were commissioned to provide an analysis of the vaccines regulatory ecosystem in low- and middle-income countries, especially on the African continent. The study was developed and delivered with a view to informing future investment decisions through a cost-benefit analysis on a range of selected, high-impact interventions by Wellcome and others that could accelerate systemic change. The next phase of the project will involve socialisation and dissemination of the results of the work, building on several opportunities and approaches to engage stakeholders and co-create solutions.
This will allow Wellcome to achieve the following objectives:
Engage with the stakeholder community and build trust
Validate findings, and listen to feedback and preferences
Demonstrate desire and capacity to engage in dialogue with funders and the wider set of partners in this space.
This work will involve professional and technical support for a five day digital event to deliver the fifth Scientific Conference on Medical Products Regulation in Africa and the African Medicines Regulators Conference (AMRC) in November 2021, using a professional company called Maximise Your Time (MYT) and their affiliate ManMade Productions to support AUDA-NEPAD and WHO, the agencies accountable for delivery of these events.
|
| 30/09/2022 |
£1,381,673 |
|
UNIVERSITY OF MINNESOTA |
Improved influenza vaccines are urgently needed to reduce the global burden of seasonal influenza and enable an effective public health response to the ongoing pandemic threat from emerging influenza viruses. The Influenza Vaccines R & D Roadmap (IVR), completed in September 2021 following an extensive global stakeholder engagement process, provides a framework for guiding R & D activities aimed at accelerating the development of improved seasonal influenza vaccines and broadly protective or universal influenza vaccines. To ensure successful implementation of the roadmap’s strategies, follow-up activities are needed to promote awareness, encourage stakeholder buy-in, and track outcomes. CIDRAP proposes to conduct a 3-year project to: (1) monitor and evaluate progress in achieving the IVR goals and milestones, including changes in the status of knowledge gaps and barriers to influenza vaccine R & D; (2) revise and update the roadmap to reflect R & D progress, changes in timelines, new knowledge gaps and barriers to influenza vaccine R & D, and learnings from the ongoing development of COVID-19 vaccines; and (3) maintain and update the IVR website as a communications hub for the influenza vaccine R & D community to strengthen engagement and share information and new developments.
|
| 30/09/2022 |
£35,547 |
|
ONWARD |
The ambition to become a science superpower present an opportunity to reconsider exactly what kind of science and technology system we are trying to build.
Should we be doubling down on basic science or investing more around translation and commercialisation?
Should government take more or less of a role in directing science investment, through strategic funds, pull-through procurement and new research institutions?
What role do we want privately funded R & D to play and how does it interact with publicly funded research and institutions? How do we define success, and how will we know if we have achieved it?
This paper will use both primary and secondary research to answer these questions and articulate a vision for what "becoming a science superpower" means in practice for a country like the UK. We will analyse how we spend existing science and technology funding – across the public, private and HE sectors – and the measurable outcomes that flow from that investment. We will compare this to the models and outcomes of other major developed economies. We will also explore the relationship between different kinds of research on total factor productivity and innovation, and what kinds of institutions generally return what results.
|
| 30/09/2022 |
£10,000 |
|
IMPERIAL COLLEGE LONDON |
Dr Philip Green agreed with Dame Bridget Ogilvie on 4 February 2020 to support the Sir Stanley Peart Memorial Symposium event with a grant of £10,000. The event was postponed due to the COVID-19 pandemic and been re-arranged for Friday 29 October 2021 at the Royal Society. We appreciate your support.
|
| 30/09/2022 |
£63,195 |
|
THE FRANCIS CRICK INSTITUTE |
Not available |
| 30/09/2022 |
£72,871 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2022 |
£46,394 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2022 |
£27,506 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2022 |
£107,587 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2022 |
£110,960 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2022 |
£152,585 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2022 |
£61,511 |
|
INSTITUTE OF CANCER RESEARCH |
Not available |
| 30/09/2022 |
£351,809 |
|
KING'S COLLEGE LONDON |
Not available |
| 30/09/2022 |
£200,577 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 30/09/2022 |
£13,151 |
|
THE PIRBRIGHT INSTITUTE |
Not available |
| 30/09/2022 |
£5,981 |
|
UNIVERSITY OF DURHAM |
Not available |
| 30/09/2022 |
£194,999 |
|
UNIVERSITY OF DUNDEE |
Not available |
| 30/09/2022 |
£806,724 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2022 |
£33,489 |
|
UNIVERSITY OF YORK |
Not available |
| 30/09/2022 |
£43,890 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/09/2022 |
£55,624 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 30/09/2022 |
£10,565 |
|
UNIVERSITY OF STRATHCLYDE |
Not available |
| 30/09/2022 |
£8,442 |
|
UNIVERSITY OF ST ANDREWS |
Not available |
| 30/09/2022 |
£29,272 |
|
UNIVERSITY OF SOUTHAMPTON |
Not available |
| 30/09/2022 |
£87,606 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2022 |
£26,404 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 30/09/2022 |
£57,332 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Not available |
| 30/09/2022 |
£963,442 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2022 |
£74,503 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2022 |
£37,488 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 30/09/2022 |
£108,308 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 30/09/2022 |
£180,418 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 30/09/2022 |
£22,233 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 30/09/2022 |
£54,831 |
|
UNIVERSITY OF LEEDS |
Not available |
| 30/09/2022 |
£13,780 |
|
KEELE UNIVERSITY |
Not available |
| 30/09/2022 |
£339,663 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2022 |
£141,242 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2022 |
£50,159 |
|
UNIVERSITY OF EXETER |
Not available |
| 30/09/2022 |
£391,412 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 30/09/2022 |
£14,755 |
|
UNIVERSITY OF EAST ANGLIA |
Not available |
| 30/09/2022 |
£68,275 |
|
CARDIFF UNIVERSITY |
Not available |
| 30/09/2022 |
£800,457 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2022 |
£179,295 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 30/09/2022 |
£88,741 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 30/09/2022 |
£27,104 |
|
BIRKBECK UNIVERSITY OF LONDON |
Not available |
| 30/09/2022 |
£17,347 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 30/09/2022 |
£522,860 |
|
PROTAS |
The Good Clinical Trials Collaborative (GCTC), currently hosted by Wellcome, is completing the first phase of the project during which it has developed new global guidance for the delivery of Randomised Controlled Trials. Phase 2 will focus on the uptake and application of the guidance by all groups of key stakeholders in the clinical trials sector, including major regulators, clinical researchers, funders of trials including industry and those supporting clinical research in LMICs such as Wellcome and BMGF.
Success for the GCTC project is wide adoption and utilisation of the guidance principles, both through established channels (e.g. updates to ICH or major Regulatory Authority guidance and practice that closely reflect the GCTC principles) and (where appropriate) through direct adoption and utilisation of GCTC guidance for relevant settings/jurisdictions. Successful delivery of this project will lead to better evidence of health interventions across all settings including challenging areas such as vaccines, mental health, common communicable diseases and particularly in LMICs.
Protas, a new, independent, not-for-profit company, created to design and deliver appropriately large randomized trials that address key patient care and public health needs, has offered to host the GCTC moving forward as Wellcome embarks upon its new organisational strategy.
|
| 30/09/2022 |
£1,189,735 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/09/2022 |
£292,811 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
As announced by the United Kingdom (UK) in its G7 Presidency, the World Health Organization (WHO) will lead an Implementation Consultation Group (ICG), supported by the Wellcome Trust and working with other governments’ centres of disease control, NGOs and research organizations, to launch the International Pathogen Surveillance Network – the ‘Global Pandemic Radar.’ The Secretariat for this global pathogen surveillance network will support the ICG in its work and will be provided by WHO, Wellcome, and the UK government and other interested parties. Resources for the Secretariat are requested from Wellcome.
|
| 30/09/2022 |
£1,549,553 |
|
KING ABDULLAH UNIVERSITY OF SCIENCE AND TECHNOLOGY |
We propose to form a consortium of researchers representing the MENA region (‘COVID-19 Genomics MENA’) with access to COVID-19 samples for setting up sequencing and analytical pipelines for large-scale sequencing-based genomic surveillance of the circulating lineages of the SARS-CoV-2 virus. The consortium will consist of investigators from four countries in the Middle East (Saudi Arabia, Qatar, Oman, and Kuwait) and three countries (Algeria, Morocco, and Egypt) in North Africa. The aim of this proposal is to sequence a large number of SARS-CoV-2 genomes for molecular tracking of the circulating lineages of the virus during the active vaccination period for the next 12 months. We pledge to sequence 12,000+ SARS-CoV-2 genomes and collect relevant clinical meta-datasets during the next 12 months in these seven countries in the MENA region. We shall be using a combination of next-generation sequencing technology platforms (Illumina, Oxford Nanopore, and Ion Torrent) and standard genome assembly, genomic-epidemiology analytical pipelines already available within the laboratories in the consortium. The resulting datasets will be made publicly available through the GISAID data portal for wider accessibility of the datasets. We also aim to integrate a ‘training component’ for local capacity building at the participating institutions in the MENA region.
|
| 30/09/2022 |
£745,891 |
|
BRITISH RED CROSS SOCIETY |
The Global Taskforce on Cholera Control (GTFCC) is a multi sectoral partnership of more than 50 institutions who support countries in the implementation of ENDING CHOLERA: A GLOBAL ROADMAP TO 2030. In October 2020, in response to countries' expressed needs, the GTFCC launched a Country Support Platform (CSP) that will support efforts - primarily at national level - to control and eliminate cholera. The International Federation of Red Cross and Red Crescent Societies (IFRC) has been selected to host the CSP on behalf of the GTFCC. This proposal outlines the establishment of a Senior Research Officer, Cholera Research to work with the GTFCC on research uptake at both global and country levels. The research focal point will support the GTFCC to strengthen and advocate for evidence-informed decision making whilst being embedded at the British Red Cross (BRC) on behalf of the IFRC as host of the CSP. The focus of the research focal point will be to act as Senior Research Officer (SRO), under the coordination of the GTFCC Secretariat to support and enable collaborative research uptake: the identification, generation, access and use of research evidence to inform policy and practice in cholera control.
|
| 30/09/2022 |
£500,001 |
|
HUMAN CELL ATLAS, INCORPORATED |
Funding is requested to support the 2022-23 operations of the Human Cell Atlas (HCA) Executive Office. HCA is an international scientific project whose mission is to create comprehensive reference maps of all human cells — the fundamental units of life — as a basis for both understanding human health and diagnosing, monitoring, and treating disease. The requested funds would support Phase 1 of the HCA initiative, which includes developing standardized experimental and computational methods to allow HCA scientists to compare diverse cell and tissue types and samples across human communities in consistent ways, ensuring that the resulting resource is comprehensive and global. The scientific and geographic scope and complexity of this project necessitate professional staff support to coordinate the activities of multiple governance and working groups and to create, collect, organize, and distribute a wide range of resources to the HCA community, as well as to support the scientific and legal processes that are required to build the Atlas. Support for these and other secretariat functions will be critical to ensure the continued smooth operation of the HCA consortium and the coherent assembly of the first draft of the Human Cell Atlas.
|
| 30/09/2022 |
£434,726 |
|
DATAKIND, INC |
In 2018, DataKind launched a new program to tackle common problems within the frontline health systems ecosystem through the creation of scalable data science tools. One high potential area of opportunity is to strengthen trust in frontline healthworker-generated data by identifying problematic data in leading mHealth platforms upstream.
Workstream 1 (WS1) is a continuation of this data integrity tooling. Due to the commonality of the problem the output of WS 1 – production-level data integrity assuring software – is both attainable and a realization of creating sector-impacting tools. In doing so, DataKind will also have developed a roadmap for integration of this tool with commercial, NGO, and individual health systems.
Workstream 2 is an extension of DataKind’s exploratory work, wherein we co-create a prototype tool with a local organization to provide meaningful learnings for a sector. Furthermore, as the Wellcome Trust embarks on scoping projects with the African Population Cohorts Consortium (APCC) we expect there to be pieces of digital infrastructure and software tools that are necessary to realize the underlying ambition of the APCC. Our expert data science teams would be glad to help shape a data science roadmap and complement the suggestions made by the APCC scoping team.
|
| 30/09/2022 |
£246,375 |
|
DUKE UNIVERSITY |
Successfully combating drug-resistant infections and antimicrobial resistance (AMR) requires innovative antibiotics to treat resistant infections and innovative bacterial diagnostics to enable improved prescribing and antibiotic stewardship. But despite the implementation of pre-market regulatory changes and progress toward post-market pull-incentives, antibiotic and bacterial diagnostic manufacturers continue to face uncertain markets and limited revenue. As a result, antibiotic and bacterial diagnostic development has slowed and many developers have abandoned the market or even gone bankrupt.
Duke-Margolis will conduct 18 months of focused policy research that informs efforts among policymakers and expert stakeholders as they design and implement pull-incentives to restore and sustain the market for critical novel antibiotics and bacterial diagnostics. As policymakers consider implementing substantial pull-incentives for novel antibiotics and bacterial diagnostics, focused policy research can inform feasible, effective designs and encourage stakeholder consensus.
The project will advance existing policy research and encourage stakeholder consensus on (a) next steps toward administrative and legislative pull-incentives for novel antibiotics, and (b) feasible reforms to advance bacterial diagnostic development, coverage, reimbursement, and utilization.
Duke-Margolis will advance policy research, disseminate strategic communications, and encourage stakeholder consensus through stakeholder convening, written deliverables including include white papers, issue briefs, or journal articles, and through conference presentations.
|
| 30/09/2022 |
£1,288,680 |
|
GRIFFITH UNIVERSITY |
Our world is heating up. WHO estimates that the number of persons exposed to extreme heat increased by around 125 million from 2000 to 2016. Climate change will increase the frequency, intensity, and duration of these extreme heat events globally. It is important to find ways to protect the most vulnerable from increasing heat-health risks. Older people are particularly vulnerable - exacerbated by reduced thermoregulatory function and high comorbidity. While existing heat warning systems target whole populations, response systems that consider individualised risk profiles for older citizens are largely missing. There is an urgent, unmet need for innovative solutions to enable older people, especially those who are isolated or socially disadvantaged, to effectively monitor and mitigate extreme heat effects.
This project will develop an individualised, early warning system to protect vulnerable older populations from increased heat risks. Our co-design approach combines best evidence in climate-heat-health impact research and advances in digital technologies. Key outputs will include a toolkit of research findings & code libraries, a community of practice, and a localised software application. Together, these outputs will enable older people to maintain healthy and safe home environments and provide a robust platform for expansion towards other sub-populations or countries.
|
| 30/09/2022 |
£799,862 |
|
BARCELONA SUPERCOMPUTING CENTER |
Extreme climatic events, environmental degradation and socio-economic inequalities exacerbate the risk of infectious disease epidemics. We lack the evidence-base to understand and predict the impacts of extreme events and landscape changes on disease risk, leaving communities in climate change hotspots vulnerable to increasing health threats. This is in part due to a lack of ‘ground truth’ data describing environmental change in remote and under-resourced areas, as well as a lack of trained research software engineers and data scientists. HARMONIZE will convene a transdisciplinary community of stakeholders, software engineers and data scientists to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots, including cities, small islands, highlands and the Amazon rainforest. We will strategically undertake one-off longitudinal ground truth data collection using drone technology and low-cost weather sensors, to improve classification algorithms and downscaling of coarser-resolution environmental datasets (e.g., satellite images, climate reanalysis and forecasts). We will then harmonize this post-processed data with socio-economic and health data in an automated workflow packaged for users in bespoke hotspot-specific toolkits. These sustainable tools will facilitate generation of actionable knowledge to inform local risk mapping and build robust early warning and response systems to build resilience in low-resource settings.
|
| 30/09/2022 |
£390,082 |
|
UNIVERSIDAD PERUANA CAYETANO HEREDIA |
Extreme climatic events, environmental degradation and socio-economic inequalities exacerbate the risk of infectious disease epidemics. We lack the evidence-base to understand and predict the impacts of extreme events and landscape changes on disease risk, leaving communities in climate change hotspots vulnerable to increasing health threats. This is in part due to a lack of ‘ground truth’ data describing environmental change in remote and under-resourced areas, as well as a lack of trained research software engineers and data scientists. HARMONIZE will convene a transdisciplinary community of stakeholders, software engineers and data scientists to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots, including cities, small islands, highlands and the Amazon rainforest. We will strategically undertake one-off longitudinal ground truth data collection using drone technology and low-cost weather sensors, to improve classification algorithms and downscaling of coarser-resolution environmental datasets (e.g., satellite images, climate reanalysis and forecasts). We will then harmonize this post-processed data with socio-economic and health data in an automated workflow packaged for users in bespoke hotspot-specific toolkits. These sustainable tools will facilitate generation of actionable knowledge to inform local risk mapping and build robust early warning and response systems to build resilience in low-resource settings.
|
| 30/09/2022 |
£577,375 |
|
UNIVERSIDAD DE LOS ANDES - BOGOTA |
Extreme climatic events, environmental degradation and socio-economic inequalities exacerbate the risk of infectious disease epidemics. We lack the evidence-base to understand and predict the impacts of extreme events and landscape changes on disease risk, leaving communities in climate change hotspots vulnerable to increasing health threats. This is in part due to a lack of ‘ground truth’ data describing environmental change in remote and under-resourced areas, as well as a lack of trained research software engineers and data scientists. HARMONIZE will convene a transdisciplinary community of stakeholders, software engineers and data scientists to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots, including cities, small islands, highlands and the Amazon rainforest. We will strategically undertake one-off longitudinal ground truth data collection using drone technology and low-cost weather sensors, to improve classification algorithms and downscaling of coarser-resolution environmental datasets (e.g., satellite images, climate reanalysis and forecasts). We will then harmonize this post-processed data with socio-economic and health data in an automated workflow packaged for users in bespoke hotspot-specific toolkits. These sustainable tools will facilitate generation of actionable knowledge to inform local risk mapping and build robust early warning and response systems to build resilience in low-resource settings.
|
| 30/09/2022 |
£710,042 |
|
THE FOUNDATION FOR SCIENTIFIC AND TECHNOLOGICAL DEVELOPMENT IN HEALTH |
Extreme climatic events, environmental degradation and socio-economic inequalities exacerbate the risk of infectious disease epidemics. We lack the evidence-base to understand and predict the impacts of extreme events and landscape changes on disease risk, leaving communities in climate change hotspots vulnerable to increasing health threats. This is in part due to a lack of ‘ground truth’ data describing environmental change in remote and under-resourced areas, as well as a lack of trained research software engineers and data scientists. HARMONIZE will convene a transdisciplinary community of stakeholders, software engineers and data scientists to develop cost-effective and reproducible digital infrastructure for stakeholders in climate change hotspots, including cities, small islands, highlands and the Amazon rainforest. We will strategically undertake one-off longitudinal ground truth data collection using drone technology and low-cost weather sensors, to improve classification algorithms and downscaling of coarser-resolution environmental datasets (e.g., satellite images, climate reanalysis and forecasts). We will then harmonize this post-processed data with socio-economic and health data in an automated workflow packaged for users in bespoke hotspot-specific toolkits. These sustainable tools will facilitate generation of actionable knowledge to inform local risk mapping and build robust early warning and response systems to build resilience in low-resource settings.
|
| 30/09/2022 |
£366,656 |
|
TASK FORCE FOR GLOBAL HEALTH |
Following a 2019 meeting of global health leaders with expertise in influenza, vaccinology and pandemic preparedness in London hosted at the Wellcome Trust, Ready2Respond was formed as a global collaboration of partners committed to enhancing low- and middle-income countries’ readiness to respond against influenza and respiratory pandemics. With a Secretariat hosted at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza, the organization's plan now includes COVID-19. Under the oversight of a Management Secretariat, Expert Working Groups design and execute cross-collaborative projects organized in 3 strategic pillars:
Burden of Disease
Risk Communication and Community Engagement
Vaccine Access
Ready2Respond seeks a grant from the Wellcome Trust of US$ 492,970. This grant will enable Ready2Respond to focus on two initial and critical projects identified in the Burden of Disease pillar. This grant will also allow for retention of paid Director, responsible for ensuring that identified projects represent discrete operational improvement activities for LMICs, and cover part-time staff. Finally, this grant will help secure communication activities aimed at raising awareness and funding from potential partners. This Phase 2 of funding will span September 2021 - February 2022.
|
| 30/09/2022 |
£4,955,809 |
|
OFFICE FOR NATIONAL STATISTICS |
This proposal is for a collaboration between the Office for National Statistics (with the UK Health Security Agency and the Cochrane Climate-Health Working Group) and two national statistical institutes in the African region, to develop a transparent and globally generalisable framework and technical platform for official statistics on climate change, environment and health, and a set of statistical methods to better estimate climate-related health risk using real world data sources, including modelling local-level impacts. By addressing the current lack of harmonised approaches, developing new methods in close partnership with LMICs and building capability, the project will advance global research on climate and health, help to address gaps in the knowledge base and support national monitoring and evidence-based policy. Users of the outputs will include government and NGO decision-makers who will be able to access information to guide interventions in clearer, more comprehensive and more actionable forms; producers of official statistics, especially in LMICs, whose ability to monitor effects of climate change will be increased by provision of practical, coherent standards and open source tools; and producers and consumers of climate change research who will benefit from faster study development based on shared approaches and more consistent ‘language’ for systematic communication.
|
| 30/09/2022 |
£976,251 |
|
CGD EUROPE |
Antimicrobial resistance (AMR) is a huge problem worldwide. Already thought to kill more than 700,000 people a year, some estimates suggest AMR could lead to 10 million deaths a year by 2050 if left unchecked. It is critical that we bolster funding for antibiotic research and development (R & D) and find ways to reduce unnecessary use. The Center for Global Development’s (CGD) goal under this proposal is to develop actionable global R & D policies that improve the landscape for antibiotics in LMICs, focusing on overcoming constraints on policy implementation at a national level within LMICs. We will explore how to improve incentives for pharmaceutical companies to sell their products in LMICs, specifically by improving access and supporting R & D. Policy recommendations will aim to improve both access to antibiotics, as well as reduce unnecessary use. We plan to develop these policy recommendations through a CGD working group made up of economists, epidemiologists, health practitioners, policy makers and representatives from the pharmaceutical industry. Recommendations will be informed by three extensive country case studies and CGD-commissioned research projects in participating LMIC countries and will be widely socialised through events and private meetings with key stakeholders.
|
| 30/09/2022 |
£1,226,240 |
|
HEPTARES THERAPEUTICS LTD |
Our company core values are to make a significant contribution to improving the quality of life and health of people around the world. We felt compelled to leverage our expertise in SBDD to discover an effective treatment for COVID-19. Our focused Not-for-Profit program, supported by our parent company Sosei, has employed SBDD to rapidly identify a potential clinical candidate to be used as an anti-viral treatment. This fulfilled our initial objectives, completing this stage of the program.
Having successfully identified compounds potentially suitable to be used as oral agents to treat COVID-19, we are well placed to progress compounds into preclinical development, after which we anticipate the program to be progressed by interested parties with expertise in antiviral clinical development. The UK Antiviral Task Force have confirmed a qualified candidate is required for further funding to be potentially be made available. Given the urgent clinical need for antiviral agents, we are seeking funding to progress our molecules up to the potential nomination of a pre-clinical candidate. We have designed a concise program of in vitro and in vivo profiling activities encompassing tolerability, safety, selectivity and efficacy to proceed rapidly, considering the likely desired dose regimen and route of administration. |
| 30/09/2022 |
£136,622,056 |
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THE FRANCIS CRICK INSTITUTE |
Not available |
| 30/09/2022 |
£2,762,200 |
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WORLD HEALTH ORGANIZATION, SWITZERLAND |
In 2020 The Pan American Health Organization (PAHO) established and now coordinates the COVID-19 Genomic Surveillance Regional Network. It includes 21 collaborating countries of which 10 do not have any appropriate in-country sequencing capacity and instead send their samples externally for sequencing to the network reference laboratories in Brazil and Chile. Here we propose to build direct sequencing and analytical capacity in all participating laboratories to generate relevant genomic data that can be used for public health decision making. Where batch sequencing capacity already exists we propose to use MinIon platforms to extend the within-country capacity to investigate changing patterns of disease. Combined, this will dramatically increase our understanding of the known and new SARS-CoV-2 variants circulating in this region. We will develop a hub-and-spoke organization with PAHO at the center forming the hub for coordination, training and data flow and the Network laboratories forming the spokes. Laboratories with existing genomics expertise will help build genomics surveillance capacity in those that don’t. Combining local and international expertise we aim to develop a regional network able to produce actionable SARS-CoV-2 data now with the potential to become a sustainable network able to track other diseases of regional importance in the future.
|
| 30/09/2022 |
£45,594 |
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UNIVERSITY OF CAMBRIDGE |
The introduction of SARS-CoV-2 sequencing to new settings during the COVID-19 pandemic can be hampered by a lack of understanding of the value of genomic surveillance and concerns which may be amplified by alarmist media messaging. Clear public engagement to accompany SARS-CoV-2 sequencing training is beneficial to ensure maximum public health benefit.
We will use the combined sequencing and communications expertise of COG-Train (University of Cambridge) with the public engagement, radio and co-production experience of the Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) to improve public and community engagement in Malawi.
We will deliver in-person and online training courses in the communication of SARS-CoV-2 variant information to scientists and public health officials in Malawi. The courses will be devised by communications specialists at the Malawi University of Business Studies using COG-Train material and include collaborative consultations via established radio listening clubs. A series of eight radio programmes will be aired and feedback collected from audiences. The training material and broadcasts will be repackaged to create online resources suitable for sharing with the Wellcome Africa and Asia Partnership (AAP) countries.
We hope that the proposal will contribute to an open environment where trustworthy genomics research can benefit all of society.
|
| 30/09/2022 |
£170,092 |
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UNIVERSITY OF OXFORD |
During the COVID-19 pandemic, genomic sequencing has provided valuable information on the spread of SARS-CoV-2 to ensure timely and targeted public health responses. Genomic surveillance programmes have been set up within Wellcome’s Africa/Asia Programmes (AAPs) and CIDRI in South Africa. However, there is suboptimal national-level resource allocation, insufficient strategy for sampling of specimens to optimize epidemiological and clinical inference, and gaps in meta-data needed to fully and quickly interpret genomic sequencing information. Policy makers presented with genomic data to support decision making must decide if a response is needed, how large the response should be, for whom, and when. To do this, a systematic approach to assessing genomic evidence is needed. It is also unclear what the public knows about SARS-COV-2 genomic sequencing, even though some media reports and anecdotal data from current policy and public engagement work being undertaken in the AAPs may suggest limited understanding of SARS-CoV-2 variants among this audience.
Through a suite of engagement activities at the AAPs, we will target both the public and policy makers to 1) increase the public's understanding of SARS-COV-2 genomic sequencing, and 2) support national level strategies by developing tools that guides the assessment of genomic evidence.
|
| 30/09/2022 |
£31,860 |
|
BIRAT NEPAL MEDICAL TRUST |
The Wellcome Trust funded Epidemic Intelligence project has implemented large scale genome sequencing for SARS CoV-2 at the only functioning sequencing laboratory in country, and stimulated discussion on the future role of pathogen sequencing and approaches to build capacity in Nepal.
COVID Kurakani (Covid Conversations) will engage stakeholders to stimulate increased understanding of the role of pathogen sequencing, allow researchers to listen to, be informed by and respond to community perceptions and concerns around sequencing, build trust between participating communities and the researchers and facilitate capacity building for genome sequencing in the country.
Our key goals are:
Build capacity among the epidemic intelligence team to develop and deliver high quality public engagement activities surrounding pathogen sequencing for epidemic response.
Conduct an EDGE analysis of public engagement status at BNMT.
Conduct an internal workshop to design the public engagement strategy, including the senior management team.
Utilise media expertise among the research team to develop and deliver a series of panel discussion programmes for national broadcast with three participatory target audiences.
Understand community and stakeholder perceptions of COVID-19 sequencing.
Address knowledge gaps and concerns among stakeholders to build trust and inform the dialogue surrounding pathogen sequencing.
|
| 30/09/2022 |
£250,000,000 |
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WELLCOME LEAP INC. |
Wellcome Leap Inc. has been established by Wellcome as a US, wholly owned not for profit entity with the aim of delivering breakthroughs in human health and demonstrate seemingly impossible results on seemingly impossible timescales. This will be achieved through the creation of a small portfolio of goal focused Programmes selected based upon their potential to improve health globally rather than by their potential financial or commercial return.
Wellcome provides initial funding of $306.9M to Leap to cover their first 10 years of operation (although further funding may be provided over this 10 years). This funding will support Leap’s operational costs and ‘Programmatic costs’ which will include (but not be limited to) the employment of Programme Directors to build and orchestrate large research programmes, subject matter advice and support to formulate a programme and the funding of sub-awardees to carry out research in pursuit of a programme goal.
Wellcome Leap’s strategic plan was approved by the BoG in August 2020. Since this time, Wellcome Leap have met or exceeded all Y0/Y1 goals, including launching 5 programmes with an average funding of $50M. Looking ahead, the Wellcome Leap BOD are recommending to the Wellcome BoG the commitment of an additional £250M to Wellcome Leap in FY 22/23 in order to launch ~5 programmes at the same pace as seen in Wellcome Leap’s first year of operation. Following approval of this request by BoG, the awarded amount was converted from GBP (£250,000,000) to USD ($337,087,500). |
| 30/09/2022 |
£71,618 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Across the world viral genomic surveillance has been key to understanding SARS-CoV-2 and how it spreads through populations. The AFRICO19 project aims to understand SARS-CoV-2 infection in three regions of Africa: Uganda, The Gambia and Kenya. This involves building capacity for rapid diagnosis and sequencing of SARS-CoV-2 to enhance genomic surveillance, inform contract tracing, variant detection and public health measures. However, through conversations with local colleagues and members of the public in Entebbe, Uganda and from an initial survey it has become apparent there is some misinformation and mistrust of the value of genomic surveillance within local communities. This has had potential knock-on effects for understanding the purpose of surveillance, vaccine uptake and acceptance of taking approved therapeutics.
Therefore during this project we aim to support researchers to engage with members of the public by building capacity and confidence through training opportunities, develop resources exploring viruses and their variants, the immune system and the importance of genomic surveillance, and build a platform to open dialogue between researchers and public groups. By doing this we aim to address misconceptions and mistrust associated with viral genomic sequencing therefore building public trust and awareness of the importance of this work.
|
| 30/09/2022 |
£100,000 |
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QUEEN'S UNIVERSITY BELFAST |
Background One of the hallmarks of cancer is evasion of cell death, which promotes tumourgrowth, metastasis and therapy resistance. FLIP regulates cell death by modulating theactivity of caspase-8 and is frequently overexpressed in cancer, including non-small cell lung cancer (NSCLC). NSCLC is a therapy-resistant disease with a dismal prognosis. When it occurs, therapyinduced cell death can lead to dramatic response rates in NSCLC, leading to disease control as evidenced by the effectiveness of targeted therapies against NSCLCs with mutated EGFR or EML4-ALK rearrangements. Our pre-clinical work suggests that activating core |
| 30/09/2022 |
£100,000 |
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CARDIFF UNIVERSITY |
Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications. However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problem-solving that result in a "brain fog". These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, "normal" life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion. Professor Simon Ward from the University of Sussex has received a Seeding Drug Discovery Award to identify and develop drug which is a selective modulator of the AMPA receptor which has the potential to provide an innovative new treatment for patients with schizophrenia. If successful the team expect to have a compound ready for clinical evaluation in just over three years time. Nerve cells (neurons) communicate with each other by releasing chemicals known as neurotransmitters that interact with proteins called receptors on adjacent neurons. Levels of the neurotransmitter glutamate, which is crucial for normal cognitive function, are altered in schizophrenia. A specific subtype of glutamate receptor, the AMPA receptor, is thought to be associated with cognition and therefore increasing AMPA receptor function should improve cognitive performance in schizophrenia and thereby addressing an unmet need and revolutionizing the functional outcome of this patient population. |
| 30/09/2022 |
£0 |
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UNIVERSITY OF LEICESTER |
It is now possible to purchase genetic tests online which claim to reveal whether an individual’s genetic profile might make it more likely that he will go on to develop certain diseases. These tests are not said to actually diagnose diseases, but the distinction can be confusing and those who use them may seek support in understanding and reacting to the information provided by accessing publicly funded healthcare under the NHS - particularly as the companies themselves do not provide such support. In order to understand how best to respond to the prevalence of this type of testing, I will evaluate the implications for the National Health Service in terms of resource allocation and potential liabilities for healthcare professionals. I will investigate the concept of ‘solidarity’, which encompasses a sense of community and assistance for the disadvantaged, in order to better understand the principles underpinning universal healthcare and explore whether this can accommodate individuals who pay for these supposedly recreational test results privately. This research will inform considerations as to the most appropriate management of this type of testing and the care of individuals who utilise such services.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF LEICESTER |
Many complex diseases such as coronary heart disease and Alzheimer's disease are often treated with drugs that target a certain protein, usually a biomarker of disease. Advances in technologies allow for the accurate measurements of protein levels at a large scale, together with the discovery of DNA variants influencing these.
A statistical principle known as Mendelian randomization (MR) uses the idea that different DNA variants can mimic actions of a drug by predisposing an individual to genetically higher/lower levels of a particular protein. This has been successfully used to anticipate the results of a drug trial before it had taken place, thus, is a promising key step in drug development, with potentially predicting the failure of multi-million pound drug trials before occurrence.
This project will focus upon key questions when assessing a potential drug: what is the magnitude of benefit, the added benefit over the standard care, and the potential benefit of combined therapy. Using current knowledge of MR, new statistical models will be developed and applied. With an initial focus on autoimmune diseases, particularly inflammatory bowel disease, I will work closely with the latest genetic and proteomic data developed in the SCALLOP consortium led by collaborators at Pfizer, Sweden.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF NOTTINGHAM |
Addiction is a severe, chronic disease that is currently lacking a wide enough range of efficacious, evidence-based pharmacological treatment options. In this study, I will aim to discover compounds capable of modulating the neurobiological mechanisms that drive drug and alcohol addiction, in the hope of aiding development of new pharmacological options.
DARPP-32, an acronym for Dopamine and cyclic AMP (cAMP) regulated phosphoprotein (a protein with a molecular weight of 32kDa) has been discovered to be critical in pathways leading to the neurochemical and molecular changes in the brain that are associated with addiction. I will determine compounds capable of modulating the phosphorylation status of this protein through high-throughput screening and subsequent proteomic and transcriptomic analysis of successful candidates.
The impact of this work would be the discovery of one or more novel compounds with the potential to progress to new, novel compounds capable of treating or reversing addiction.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF NOTTINGHAM |
Chronic pain associated with arthritis remains a leading cause of disability and poor quality of life among people affected. Different analgesic therapeutics such as non-steroidal anti-inflammatory drugs and opioids are used in the management of pain in arthritic conditions. However, the persistence of pain in these conditions requires the search for new targets. Vascular endothelial growth factor-A (VEGF-A) is an essential biochemical in the body that causes pain and
inflammation. Blocking VEGF-A has been suggested as a new treatment for arthritic pain. VEGF-A acts on multiple cell types in the body and exists in two forms made from the same gene called VEGF-Aa and VEGF-Ab through alternative splicing. The balance between VEGF-Aa and VEGF-Ab is very important in pain. A different protein called SRPK1 controls the splicing and balance between VEGF-Aa and VEGF-Ab. If SRPK1 is switched on, then VEGF-Aa is made; if SRPK1 is switched off, VEGF-Ab is made. When there is more VEGF-Aa it causes pain, but more VEGF-Ab can prevent or block the pain, acting through VEGF- receptors 1 and/or 2. This project will explore the mechanisms through which SRPK1 and alternative splicing controls chronic pain in experimental arthritis.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF NOTTINGHAM |
Opioids, like morphine, remain the most effective drugs to treat severe pain. Unfortunately, they also cause side effects such as addiction, constipation and suppression of breathing (the cause of fatality from overdose). This is because they act at the mu opioid receptors (MOR), proteins on the surface of cells that control both the therapeutic and the adverse side effects.
Another opioid receptor, the nociceptin receptor (NOR), has yet to be therapeutically exploited. Exciting preliminary research suggests that novel compounds with activity at both MOR and NOR are analgesic without the side effects induced by classical opioids.
Our understanding of the pharmacology and physiological effects of NOR is limited compared to other opioid receptors due to the lack of selective tool compounds to study it. This has hindered its development as a new drug target.
We will address this gap by developing new strategies to study this receptor including fluorescently-labelled compounds that will allow us to understand, and even visualise, NOR pharmacology in different cells in the body. We will perform a comprehensive comparison of the pharmacology of current NOR developmental compounds using these new tools, combined with measurements of antinociception and respiratory depression.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF LEICESTER |
Neisseria meningitidis (Nm), also known as meningococcus is a bacteria that causes meningitis and/or sepsis. It is an exclusive human pathogen that asymptomatically colonises the upper respiratory tract. However, it can invade and multiply systemically causing invasive meningococcal disease (IMD). IMD remains a major global health concern with high fatality rate and sequelae. Depending on propensity to cause disease, some lineages are designated as hypervirulent.
Meningococcal virulence is driven by phenotypic differences that might result from genetic variation between lineages, sub-clones or arises during IMD. This genetic variation can be classified as allelic: (e.g. single nucleotide polymorphisms in genes); accessory (e.g. presence or absence of genes); or phase variation (high frequency or reversible ON/OFF switching of gene expression). We will use a series of high-throughput multi-isolate assays to assess the extent of phenotypic variation between the disease and carriage isolates. We will then use genomic associations to test for associations of this phenotypic variation with the three types of genetic variation. We will also study the genetic and phenotypic determinants of invasiveness in the hypervirulent lineages.
Results from this study will help develop predictive sequence-based methods for assessing the disease/carriage potential of meningococcal lineages/clones.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF LEICESTER |
Telomere length (TL) is a biological marker that has previously been linked to biological age, shortening over time. One measure of TL, mean leucocyte TL (LTL) varies highly between individuals and LTL variation has been associated with a wide range of age-related diseases and their risk factors. Some of the LTL and age-related disease have been shown to have a causal relationship, with shorter or longer LTL being causally associated with an increase in disease risk. This has been shown using genetic information via Mendelian Randomisation (MR) and polygenic risk scores. However, it is not yet understood how this causal relationship works and what might be driving this link. I aim to extend the understanding of this causal relationship using UK Biobank data. Here I will extend the investigation by using more complex additional methods, including non-linear relationships. I will also look at multivariate MR, and interaction analyses to determine the direct causal pathways related to disease risk and the role that LTL takes in a wider disease context. This will increase the understanding of the relationship between TL and age-related diseases, which may help to identify new preventative and therapeutic targets.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF LEICESTER |
Asthma is a common lung condition affecting children and adults, with several symptoms including breathlessness, wheezing and cough. Most patients control asthma thanks to existing treatments, but 3-10% of them suffer from severe asthma, a worse type that does not respond well to current medications, has a large impact on health and life quality, and is a burden on the healthcare system.
Recently, our group published a genetic study showing 25 positions spanning the DNA with changes (variants) more common in people with asthma, including severe type1. However, the precise variants and genes causing increased risk of this worse condition are still unknown. My project aims at filling this gap in three main directions: 1) perform an updated genetic study of severe asthma to identify potentially causal variants and genes using individuals from the UK, with a possibility to expand this analysis to other world populations; 2) understand how these factors alter risk of asthma using human airway models in laboratory; 3) explore the potential of our findings for drug development during a placement at AstraZeneca.
This project will contribute to discover genetic risk factors and biological pathways involved in severe asthma and could inform the development of new treatments.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF OXFORD |
Characterising new and emerging life-threatening infectious diseases safely, and optimising clinical management strategies, are essential early activities in an epidemic/pandemic response. New technologies, wearable devices, cloud computing, and machine learning (ML), offer potentially transformative solutions. Vietnam has just experienced its first major COVID-19 wave. Cases are rising again. In wave one, a shortage of monitoring equipment caused serious delays in identifying and treating those with severe disease. Conventional remote-monitoring systems, needed for safe monitoring, cost upwards of £12,000 for a single patient which is unfeasible in Vietnam. Our objective therefore is to provide proof-of principle that a team within Vietnam can establish a low-cost remote monitoring platform during a pandemic that will aid clinical care and capture data for disease characterisation and research. Our multidisciplinary team in Ho Chi Minh city will develop the platform from a prototype implemented in 50 patients during wave one. The new platform will provide real-time continuous remote monitoring of oxygen saturations and heart rate in 150 patients. We will integrate device, clinical, and laboratory data, and develop a prototype ML-based clinical decision support system for COVID-19. The platform is designed to be rapidly deployable in other low-resource settings and for other emerging infectious diseases.
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| 30/09/2022 |
£0 |
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UNIVERSITY OF EDINBURGH |
Liver diseases are known to have high worldwide debilitating health and financial impacts. In a scenario of sustained liver injury, liver cells may lose the ability to repair and self-renew, risking progression into end-stage liver failure, for which liver transplantation remains the standard definitive therapy. However, donor organ demand outweighs availability, prompting an ongoing search for other treatment options. Bile duct cell injury and subsequent decreased bile flow, termed cholestasis, is frequently present in chronic liver diseases, either as their principal component, or combined with primary liver cell damage. A mechanism of irreversible arrest of cellular proliferation, called senescence, is a characteristic of chronic liver diseases, and is associated with production of molecules which are proposed to propagate cell injury. It is currently unknown if this mechanism could drive liver cells to reshape into bile duct cells when the latter are damaged enough to lose their self-regenerative capacity. My proposed research aims to understand if this cellular conversion process happens and which are the specific molecular substances and pathways behind it, as the identification of these mechanisms may contribute to future development of targeted bile duct regenerative therapies.
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| 30/09/2022 |
£0 |
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UNIVERSITY OF EDINBURGH |
Lung cancer is a major cause of death. When cancer spreads to another area of the body, this is called metastasis. Metastasis is accountable for approximately 90% of cancer deaths. The lung is surrounded by two membranes called pleura, which line the lungs and the inside of the chest cavity. Fluid between these two layers is called pleural fluid. Lung cancer cells can spread to the pleural fluid. Neutrophils are a type of white blood cell that defend the body against insults such as infection. However it is thought that this type of white blood cell may in some circumstances help cancer to grow and spread. In this project I will look at different types of neutrophils in the blood and pleural fluid of patients with lung cancer and also in patients with infection of the lung (pneumonia). In doing this I aim to better understand what proteins different neutrophils are trying to make and what proteins they contain (transcriptomics and proteomics) and how these differ from healthy controls and patients with pneumonia. I also aim to better understand the behaviour and function of different neutrophil populations and how this may influence tumour growth.
|
| 30/09/2022 |
£0 |
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UNIVERSITY OF SHEFFIELD |
Throat cancer, also known as oropharyngeal cancer, is a common type of cancer that has increased in prevalence over the last few decades. There are two forms of this type of cancer, one associated with a viral infection known as Human Papilloma Virus (shortened to HPV-positive) and one that shows no association with this virus (HPV-negative). HPV-negative cancer typically has a poorer response to treatment compared to HPV-positive cancer, however, there are also reports of patients with HPV-positive cancer whose cancer returns after treatment.
All cells contain DNA which provide the instructions for a cell to grow and divide by producing a messenger known as RNA. During production of this message the RNA can become incorrectly stuck on the DNA forming a structure known as a R-loop. R-loops can make the DNA more susceptible to damage and interfere with the instructions from the DNA.
The aim of this project is to investigate the role of R-loops in treatment resistance in oropharyngeal cancer. I will use cancer cells grown in the laboratory to investigate the role of R-loops in cells which develop resistance to treatment and investigate potential therapies that could be used in this situation in the future.
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| 30/09/2022 |
£0 |
|
NEWCASTLE UNIVERSITY |
Eczema and psoriasis are common inflammatory disorders of the skin that both carry a significant global disease burden. Novel insights have recently been gained into disease aetiopathogenesis from single cell RNA-sequencing of samples from healthy adult skin, eczema and psoriasis, which were generated within the context of the Skin Cell Atlas. These data were derived from ~500,000 cells from dissociated tissue, losing valuable information about spatial expression within their microenvironmental context. The aims of this project are to use spatial transcriptomics to comprehensively define the in situ transcriptome profile and molecular pathways present, and integrate these findings with our suspension single cell dataset. A larger patient cohort will subsequently be recruited to carry out focused validation studies at the protein level using imaging mass cytometry, allowing further investigation of cell-cell interactions present. The results of these studies will provide the microanatomical definition of pathological cellular and molecular interactions underpinning health and perturbations in disease to derive new potential therapeutic targets for eczema and psoriasis.
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| 30/09/2022 |
£0 |
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UNIVERSITY OF EDINBURGH |
Acute myeloid leukaemia (AML) is a malignancy arising within the haematopoietic system. Within the cancer cell population, there exists a subpopulation of leukaemic stem cells (LSCs). These LSCs display behaviours similar to normal haematopoietic stem cells (HSCs) such as self renewal, and are thought to underpin poor treatment response and recurrence in AML.
GPR56 is a protein which has been shown to be highly expressed on the surface of both malignant LSCs and normal HSCs. Previous studies have demonstrated high GPR56 expression to be associated with poorer clinical outcomes in AML, including lower remission rates following treatment and poorer long term survival.
Our hypothesis is that the action of GPR56 underlies some of the stem cell behaviours seen in both HSCs and LSCs. Through these behaviours, GPR56 may help the LSC population survive current chemotherapy regimens, exposing the patient to an increased risk of relapse.
The binding partner(s) of GPR56 and the intracellular consequences of receptor activation in LSCs remain unknown. By examining the mechanism and consequences of GPR56 activation, we hope to better understand this LSC population in AML and, in doing so, help identify new treatment strategies to target the LSC population and improve patient outcomes.
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| 30/09/2022 |
£0 |
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UNIVERSITY OF EDINBURGH |
Cancer is a disease of the genome caused by mutations - changes in the DNA sequence within cells. Ultraviolet radiation and a range of chemicals, such as those in tobacco smoke, readily damage DNA producing molecular lesions which result in mutations. While many of these lesions are perfectly repaired by cells, we have discovered that lesions which create mutations linger in the DNA causing new mutations to occur repeatedly. This leads to combinations of mutations previously thought impossible. The resulting genetic diversity provides opportunities for cancers to find the best set of mutations to grow, evade immune destruction and resist treatment. Furthermore, many drugs used in the treatment of cancer are themselves DNA. This project aims to understand how the processes of DNA damage, repair and mutation formation contribute to the cancer’s ability to diversify its genetic make-up. I aim to discover how common this mutational diversity is for clinically relevant drugs, DNA damaging chemicals and UV light; explore how important that diversity is for cancer development; and, by combining tumour pathology with DNA data, test the idea that the genetic diversity will be visible in the cellular structure of the tumour.
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| 30/09/2022 |
£0 |
|
UNIVERSITY OF EDINBURGH |
Many people ( > 95%) will be infected with Epstein Barr Virus (EBV) at some stage in their lives making it one of the most successful human-infecting viruses but accumulating evidence implicates EBV as a contributing cause of some common immune diseases. How EBV can be so successful (as a virus) but trigger immune damage in some people remains a stubborn mystery. Once EBV infects someone, it hides inside certain immune cells for the rest of that person’s life, and currently no drugs can combat the infection. In persisting, EBV needs to keep a low profile; it physically tethers itself to human-host DNA, whilst silencing most of its own genes. The virus then makes a lot of a substance called RNA, but it is not clear why. It has recently been discovered that RNA may act as a "glue" within the cells. We plan to investigate whether this viral "glue", an understudied aspect of the biology of EBV, helps it evade detection. EBV is an expert manipulator of human cells, understanding it may lead to better understanding of some fundamental aspects of how our genes are switched on and off, and also might generate new ideas for how to treat viral infections.
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| 30/09/2022 |
£0 |
|
UNIVERSITY COLLEGE CORK |
One quarter of babies in Ireland develops eczema in the first year of life and one in 30 babies develops severe eczema. Eczema can be extremely difficult to manage for children and families. Sleep is very important for brain development. Previous research has shown that babies who sleep poorly are at risk of future behavioural difficulties. For many reasons, babies with eczema have poor sleep compared to babies without eczema. They sleep less, and the quality of their sleep is worse.
We are performing research in the INFANT centre looking at the effects of eczema on sleep in young babies. We are inviting parents of babies with eczema to enroll their newborn babies in the SPINDLE study. Babies will have thorough assessments at six months, nine months, and 12 months, including a brain wave test, called an EEG, and expert assessment of eczema. We will also review the babies at 18 months for a developmental assessment. We are also interested in how inflammation in skin cells relates to their sleep and development. This will involve painlessly applying some tape to the skin.
The results will be used to develop better strategies for managing sleep disruption in eczema in future.
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| 30/09/2022 |
£0 |
|
ST GEORGE'S, UNIVERSITY OF LONDON |
Tuberculosis affecting the brain, called TB meningitis (TBM), is a lethal disease. Brain damage associated with TBM results from our own immune cells working in overdrive. Better understanding of this immune activation will help develop treatment to improve outcomes for patients.
There is evidence that aspirin (an anti-clotting drug) improves outcome in TBM patients. It is thought that aspirin reduces inflammation, but how it does this is not elucidated.
I will gather and analyze data from two clinical trials investigating the use of adding aspirin to standard treatment in TBM patients in South Africa, where rates of TBM are high. I will measure markers of inflammation in blood and spinal fluid before and during treatment. I will take patient blood cells and add them to a lab model of the blood brain barrier (an important line of defense in preventing disease) and examine how these cells affect barrier function. This will demonstrate how immune cells behave in TBM patients and the effect of aspirin. I will correlate immune responses with patient outcome i.e. whether patients get better or suffer disability.
Improved understanding of mechanisms of brain inflammation has the potential to lead to development of new treatments for TBM patients.
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| 30/09/2022 |
£0 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
The World Health Organisation is committed to help reduce malaria deaths by 90% by 2030. Although long-lasting insecticide treated bed nets (LLINs), rapid diagnostic tests (RDTs) and artemisinin-based medicines (ACT) are essential in reducing the death toll, they are insufficient. A cluster randomised trial will assess the impact of mass drug administration (MDA) of an ACT (dihydroartemisinin-piperaquine, DP) and the mosquito-killing drug ivermectin (IVM) to tackle both human and mosquito reservoirs of malaria infection in Guinea-Bissau. Nested within the trial, the proposed study aims to investigate (1) the origins, diversity, and drug resistance of P.falciparum, the malaria parasite, at the trial site before MDA is given, (2) the impact of MDA on parasite transmission and (3) characterisation and tracking of remaining parasites post-MDA. Whole genome sequencing and genotyping - methods to read parasite genes - will be used to characterise and track parasites after MDA. Antibodies to the parasite will also be investigated as a cost-effective alternative endpoint and sustainable surveillance tool. The study hypothesis is that MDA will decrease P.falciparum transmission to very low levels leading to a decrease in the diversity and numbers of different types of P.falciparum parasites at the trial site.
|
| 30/09/2022 |
£0 |
|
UNIVERSITY OF LEEDS |
Background
The microbiome is the collection of bacteria living in an environment. We know that the microbiome is important within the gut, as certain "good bacteria" have been shown to be related to good health, whereas other "bad bacteria" may result in disease. We know that people who have a certain infection called Helicobacter pylori have a higher risk of developing stomach cancer. However, there is still a lot to understand in the field of the stomach microbiome and cancer.
Approach
The aim of this research project is to investigate whether the different make-up of the stomach microbiome, or certain bacterial species of the stomach microbiome, lead to worse outcomes in patients who have stomach cancer. This investigation will use available databases to investigate the microbiome of patients with stomach cancer, as well as laboratory techniques to investigate the body’s immune response to different microbiome make-ups.
Expected Impact
We hope that this project will develop a greater understanding of how the microbiome may affect the outcome of people with stomach cancer. This could lead to future projects investigating manipulation of the microbiome to improve outcomes for patients with stomach cancer.
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| 30/09/2022 |
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TRINITY COLLEGE DUBLIN |
Tuberculosis is a bacterial infection that kills more people than any other infection. It spreads from one person to another through the air when they cough. Treating tuberculosis with antibiotics takes at least six months and sometimes two years. Treatment is becoming more difficult because the antibiotics have stopped working for resistant tuberculosis. The current vaccine does not work well at preventing tuberculosis. We need to find new ways to prevent and treat tuberculosis.
Our immune system kills tuberculosis most of the time. The most important part of our immune system for killing tuberculosis are macrophages. Macrophages are cells that live in our lungs. Macrophages ‘eat’ and try to ‘digest’ tuberculosis, which kills it. It might be possible to improve the macrophage's ability to kill tuberculosis. My project will try to improve the macrophage’s ability to kill tuberculosis by changing its energy system, or treating them with vitamin A. This might lead to better treatments. My project also will try to train the macrophages before they encounter tuberculosis. This might lead to a better vaccine.
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| 30/09/2022 |
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LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Background: Cryptococcal meningitis is a brain infection caused by a fungus. Approximately 250,000 cases occur every year and despite our best current treatments between a quarter and a half of all patients who develop cryptococcal meningitis will die.
Key goals: There is an urgent need to improve our understanding of why patients with cryptococcal meningitis die and to determine whether secondary infections including viral infections, bacterial bloodstream infections, and tuberculosis (TB) contribute to the extremely high mortality. We aim to determine whether early identification and treatment of secondary infections can improve survival.
Study plan: People with HIV and cryptococcal meningitis who agree to take part will be recruited into a hospital-based study in Uganda. In addition to routine meningitis treatment and care, they will have intensive investigations for secondary infections: bacterial bloodstream infections, herpes viruses and TB using innovative diagnostics. Secondary infections will be treated. We will determine the preferred treatment strategy for latent TB infection. With the agreement of the families, an autopsy will be performed for patients that die to understand the cause of death. Information from this study will be used to design an enhanced treatment package for patients with cryptococcal meningitis to try to improve outcomes.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Clinical depression often involves by a pessimistic view of things which have happened in the past and an impairment in the ability to experience pleasure or looking forward to things. A licensed drug called ketamine affects the levels of glutamate, a chemical messenger in the brain, and has been used as a treatment particularly for depression which hasn’t got better with other types of medication. Glutamate plays a role in learning and memory so we are interested in understanding how ketamine can affect how we remember our past negative and positive memories processes.
We are conducting a series of studies in both depressed participants and healthy volunteers to improve our understanding on how ketamine can influence memory and the way people learn from rewards and punishments. Study participants will undergo medical and psychiatric health screening, drug administration (ketamine or saline), questionnaires and computer tasks, and MRI scans before and after the administration of the study drug. MRI is a type of brain scan that allows us to see how the brain responds during for example memories of things which have happened in the past. This project will help us understand how ketamine may work in depression.
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| 30/09/2022 |
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ROYAL COLLEGE OF SURGEONS IN IRELAND |
Von Willebrand Factor (VWF) is a protein that blood needs to clot normally. VWF is made by cells that line our blood vessels called endothelial cells. About 1 in 100 people inherit low levels of Von Willebrand Factor. This means that they have a lifelong bleeding disorder known as Von Willebrand Disease (VWD). People with this disease bruise easily and suffer from nosebleeds. They also sometimes bleed after surgery or after having a tooth removed.
We do not fully understand why these patients have low levels of VWF. This is especially true for patients whose levels are only slightly less than usual. This group of patients is known as ‘Low VWF’. People with ‘Low VWF’ also often have bleeding that is more than would be expected.
To better understand this disorder, we will study why these patients have low VWF levels. We will study if they are making less VWF or clearing VWF from their circulation too quickly. Finally, we will study why these patients bleed by looking at other parts of the clotting system. This will help improve how we diagnose and treat these patients.
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| 30/09/2022 |
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KEELE UNIVERSITY |
Over 2 million Central and Eastern Europe (CEE) nationals live in the UK. They are at increased risk of poor mental health, stress, homelessness, alcohol overuse and suicide. It can be difficult for this community to use GP services, especially for mental health problems.
I will help GPs to provide better mental health care for the UK CEE community through describing what CEE nationals think about general practice and working with community members and GP staff to develop supportive resources and recommendations.
My research has four steps (WP1-4). WP1. Interviews with different CEE community members, WP2. Focus groups with GP practice healthcare, administration and reception staff. These will explore staff experiences of CEE community members using GP services, particularly for mental health problems. I will compare interview and focus group information to look for patterns. WP3. Working with community members I will develop a mental health resource package to help GPs to provide accessible care and treatments for CEE community members. WP4. I will test and improve this resource package in GP surgeries, getting feedback from community members and healthcare staff.
I will share the information and resources from my project with community members, other researchers and healthcare workers.
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| 30/09/2022 |
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UNIVERSITY OF LIVERPOOL |
Invasive non-typhoidal salmonella (iNTS) causes fever, septicaemia, meningitis and death in 15% of cases, mostly in sub-Saharan Africa. It affects adults with HIV and children under the age of 5; particularly with those with malaria, malnutrition, and anaemia. Currently no vaccine exists, however, several are in development. Immune markers that correlate with a reduced risk of disease can be used to determine vaccine efficacy and accelerate early vaccine licensure.
Blood samples for antibody levels and function against iNTS will be taken from 2000 children aged 0 to 5 years in a rural, high malaria region of Malawi. Malaria positivity, anaemia and malnutrition status will be determined. Additional samples collected from a peri-urban area of Malawi as part of another study (STRATAA), will also be available for analysis. Using the age-distribution of existing blood culture confirmed iNTS cases; the level of antibody that correlates with protection against invasive disease in 95% of children will be estimated using modelling techniques. Comparison of the immunological response between rural and peri-urban areas within Malawi will be made. Data from 1000 children 0 to 5 years will be available from three additional sub-Saharan African sites (within iNTS vaccine consortium) allowing comparison across different geographical settings.
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| 30/09/2022 |
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UNIVERSITY OF SHEFFIELD |
Pulmonary hypertension (PH) is a life-limiting condition with distinct sub-groups. Accurate diagnosis and identification of the underlying phenotype is an integral step in patient management as it informs treatment choice, response, and risk-stratification. Outcomes vary significantly between phenotypes. There exists diagnostic uncertainty between two groups - idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension secondary to lung disease (PH-CLD). Lung disease is believed to be of prognostic importance in IPAH, but the extent of its impact is unknown. The radiological patterns of lung disease in IPAH have not been characterised, their significance and prognostic impact unstudied. Our novel pilot data shows that even mild lung disease has a significantly adverse effect on survival and treatment response. Our study aims to quantify the impact of lung parenchymal disease, identify radiological findings of prognostic significance, and incorporate this into existing prognostic models to evaluate their added benefit. The study will also train a convolutional neural network (CNN) based artificial intelligence (AI) software to automatically quantify the CT changes observed. This will be the largest imaging study involving IPAH, the largest CT AI imaging study involving pulmonary hypertension, and one of the first thoracic AI studies in any context to use contrast-enhanced CT.
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| 30/09/2022 |
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LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Group A Streptococcus (GAS) is a bacteria which causes severe infections and leads to deadly diseases such as rheumatic heart disease which kills over 300,000 people a year globally, particularly in low-income countries. We do not know how GAS is spread between people, how often people carry GAS in their throat or on their skin without having symptoms, or what factors increase the chance of this occurring. It is important to understand these factors in order to know how to reduce GAS-related disease.
This study will follow 444 people in The Gambia, over 12 months, taking samples from the throats and skin of people living in the same households, and asking questions about themselves and their behaviour, at regular intervals. By taking samples over time, we can understand how common it is to carry GAS without having symptoms, how GAS is spread between people, and whether carrying GAS leads to more GAS infections in people or their household members.
We will use state-of-the-art techniques to look at the DNA of GAS bacteria that we find, and combine this with a mathematical model to investigate how different strains spread to people within and between households in the community.
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| 30/09/2022 |
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QUEEN'S UNIVERSITY BELFAST |
Research shows that stressful experiences even in childhood can impact your memory and brain function in later life. One possible explanation is that stressful experiences can cause "wear and tear" on the body systems and this built up damage increases the risk of problems later. Another possible explanation is that stressful experiences make small changes to your genes. If this happens a lot these changes can cause cells in your body to "age" more quickly making it more likely to experience problems earlier.
Northern Ireland experienced a lengthy period of civil unrest, known as "the Troubles" which had significant impact on people’s lives. This research will look at whether having more stressful experiences growing up during "the Troubles" made you more likely to do worse in memory tests when you are older.
Looking at small changes over time in response to something that happened can be done by following people up over time, known as longitudinal studies. This project will look at information in longitudinal studies in Northern Ireland and use statistics to compare the results with similar studies in the Republic of Ireland and North America to test the impact of stress on people’s memory.
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| 30/09/2022 |
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LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Adults in sub-Saharan Africa have a high burden of chronic respiratory symptoms such as breathlessness, wheeze or cough. Symptoms are caused by e.g. asthma, chronic obstructive lung disease (COPD) or post-TB lung disease. The availability of diagnostics is limited. Rather than using preventative medication continuously the chronic disease is often only treated when it flares up. We have little understanding of the barriers to preventative care for chronic lung disease and how to overcome them.
The aim of this study is to identify those who may benefit from a steroid inhaler out of those coming to hospital with a flare-up of chronic lung disease, using lung function, allergy tests and scans. Cape Town offers a unique opportunity to study those with the greatest need with diverse methods. Through interviews with people with chronic lung diseases and others immediately involved in their care (e.g. nurses, pharmacists, doctors) we will explore the lived experiences of chronic lung disease and identify barriers to care. A survey of the availability, accessibility and affordability of lung function, pharmacological and non-pharmacological treatments in sub-Saharan Africa, to allow comparison between Cape Town and the region, will also be conducted.
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| 30/09/2022 |
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UNIVERSITY OF LIVERPOOL |
Childhood malnutrition remains a widespread problem in low-income countries. Children with malnutrition are more likely to have severe infections and die in the short-term, but survivors also suffer from poor long-term growth and development.
We are following up 320 teenagers in Blantyre, Malawi who were previously treated for severe childhood malnutrition. We will compare them to their siblings and other children in the community who did not suffer from severe malnutrition.
We expect malnutrition to be associated with poorer body growth and a higher risk of heart disease and diabetes in later life which we will measure by assessing height & weight measurements, blood pressure and glucose tolerance.
We also expect malnutrition to be associated with changes in the way the brain functions. We will investigate this by measuring brain wave function (EEG), attention and problem solving using direct measures. We will also assess surviving adolescents’ mental health & behaviour using questionnaires and will measure cortisol in hair samples to assess chronic stress.
The results from this study will provide information on the long-term impacts of malnutrition and will inform treatment policies regarding the care of children with malnutrition in other settings.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Eosinophilic granulomatosis with polyangiitis (EGPA) is a condition affecting many different organs in the body, including the lungs, nose and sinuses. EGPA causes affected parts of the body to become inflamed and not work properly, for reasons which are unclear. There may also be different types of EGPA; some patients seem to have a blood marker called an ANCA, which we cannot detect in others.
Because we don’t know much about EGPA, we don’t have many effective treatments. Steroid treatment is effective in EGPA, but side effects are a problem. A treatment blocking a cell signal called IL-5 has recently been used to help to reduce the reliance of patients on steroid treatment. For reasons that we don’t understand, IL-5 blocking treatment doesn’t work for everyone with EGPA, and rarely works without steroid treatment alongside it.
My plan is to examine nose and blood samples from EGPA patients using a technique called single-cell RNA sequencing. This technique can examine the job of each cell in great detail. I aim to understand: the immune system changes driving EGPA and how this is different in patients who have an ANCA marker; and why IL-5 blocking treatment does not prevent active EGPA disease.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Non-alcoholic fatty liver disease (NAFLD) occurs when lipid (fat) accumulates in the liver in the absence of excess alcohol and is often found alongside being overweight. It is the commonest liver disease worldwide can increase the risk of developing more severe complications such as scarring of the liver (called cirrhosis), heart disease, and liver cancer. There is some evidence that the body’s internal 24-hour internal timer, called the ‘circadian clock’ may be involved in governing the processes that lead to fat accumulation in the liver.
The purpose of this study is to look for daily patterns in liver fat metabolism in overweight human participants with and without NAFLD. 17 participants with NAFLD and 14 participants without NAFLD will have detailed investigations performed during the daytime have the same investigations performed in the evening. Investigations will include state-of-the art techniques with infusions of ‘stable isotopes’ to look at how much lipid is produced, exported and broken down by the liver. In addition, as part of the same study we want to see whether a 12-week weight loss and lifestyle programme can affect these daily patterns and in return help reduce the amount of fat in the liver.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Preeclampsia, a condition unique to pregnancy, causes high blood pressure and multi-organ failure. In severe cases, mothers suffer seizures and babies die before birth. Worldwide, 76,000 mothers and 500,000 babies die every year from preeclampsia. I recently discovered tiny pieces of genetic code, called tRNA-halves, are released by the placenta in bubble-like structures called extracellular vesicles. It appears placental tRNA-halves provide a unique fingerprint, which is different in mothers with preeclampsia.
I aim to find if placental tRNA-halves can:
Be detected with a simple blood test
Be used to diagnose and predict preeclampsia
Contribute to organ failure in preeclampsia
I will develop a blood test for preeclampsia, measuring placental tRNA-halves. I will use this test on samples from women who presented with suspected preeclampsia, to see how well it diagnoses and predicts preeclampsia. I will grow blood vessel and liver cells in the laboratory, treat them with tRNA-halves and measure how those cells change.
This research seeks to uncover a new test for preeclampsia, allowing us to identify which mothers and babies will get sick, so we can intervene appropriately. I hope to better understand whether tRNA-halves cause damage in preeclampsia, which might direct us to new therapies.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
One in ten critically ill patients with sepsis develop a prolonged need for cardiovascular and respiratory organ support. This is termed ‘persistent critical illness’ and these patients have increased rates of mortality, subsequent infection, and sub-optimal functional recovery. Neutrophils are important white blood cells that are involved in defending against infection and have specialised functions for bacterial phagocytosis and killing. In persistent critical illness, these functions are reduced for prolonged periods of time compared to patients who recover more effectively.
Neutrophils are very short-lived cells, with a circulating half-life of a few hours. The circulating pool is constantly being replenished by cells derived from bone marrow stem cells, meaning that neutrophils that are dysfunctional weeks after an acute illness resolves may occur due to alterations in the bone marrow stem cells from which they are derived. This project aims to study how bone marrow stem cells may become injured, and thereby contribute to persistent critical illness and the increased risk of infection. Understanding this will be important in developing strategies to improve the outcomes of patients in intensive care.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Although we think of it as a muscle, the heart is comprised of highly distinct subunits, as diverse as valves and pacemaker tissue. All these tissues are made from only 11 types of cell. The effects of disease and ageing on the heart can be partly understood by assessing changes in these cell populations and the signature sets of genes they express, however it is vital to first characterise the healthy organ as a reference for what goes awry under different conditions.
Single-cell technologies allow us to dissociate tissues into their constituent cells and determine their type, expression profile (transcriptome), and protein levels (proteome). The Teichmann group have already produced a preliminary atlas of the cell types in the adult human heart. This initial data shows the variations in cell types between anatomic sites within the heart. However, this healthy heart atlas covers a limited subset of the tissues in the heart.
I will (a) expand the scope of the healthy heart atlas and (b) compare this with tissue from hearts affected by disease or put under stress. This will show the changes in cell populations and their function under these conditions – highlighting potential targets for therapies.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Research Question
Would a system for identifying undiagnosed high blood pressure in hospital patients improve patient health and NHS spending?
Background
When blood flows at high pressure around the body, this is known as hypertension. Hypertension can cause damage, including strokes, heart attacks, kidney failure and other serious illnesses. There are more than 5 million people currently living in England with undiagnosed hypertension.1 We need to improve how we identify people with undiagnosed hypertension.
My approach to this problem
One way to identify more people with hypertension could be using people's blood pressure measurements when they're admitted to hospital. This is now possible because most hospitals now use electronic systems to record blood pressure.2 I will design a calculation that predicts whether patents in hospital have undiagnosed hypertension. I will then look into whether these patients become diagnosed with hypertension by their GP, when they leave hospital and explore the impact on health for those patients who remain undiagnosed. Finally, I will estimate the health and cost benefit of using my calculation to identify and treat people with undiagnosed hypertension sooner.
Impact
Screening for hypertension using hospital blood pressure measurements could help diagnose an extra 1 million people each year.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Antimicrobial resistance (AMR) threatens the delivery of safe healthcare nationally and globally. However, different forms of AMR are not equal with respect to both causes and consequences. In particular, which patients are most at risk of poorer outcomes due to AMR is unclear, as are the future implications of changes in antibiotic usage on resistance. Using advanced statistical and artificial intelligence (machine learning) techniques to analyse regional and national electronic healthcare data, we will study the impact of different types of AMR on patient outcomes in those admitted to hospital with bloodstream infections and urosepsis. We will also use national data to study how historical antibiotic usage levels in the community and hospitals affect current and future resistance rates.
The DPhil will enable me to learn new data science and analytical skills which will become increasingly important as more routine electronic health record data becomes available over the next decade. It will also generate new insights into which patients are most at risk of adverse outcomes from AMR and provide decision aids to adjust their treatment accordingly. It will provide an evidence-based framework for making decisions about hospital antibiotic policies that balance the current patient needs with future AMR risks.
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| 30/09/2022 |
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UNIVERSITY OF OXFORD |
Building positive self-concept in patients with psychosis
Background to the research problem
Our self-concept is how we perceive ourselves. Lacking a positive self-concept is a putative contributory causal factor in mental health problems, including psychotic symptoms. Patients recognise its importance for recovery. Yet treatment is lacking.
Our approach
Our aim is to develop treatments that successfully target the key factors that underlie mental health problems. In this work, we will develop and test a treatment to build positive self-concept and hence reduce psychotic symptoms and improve wellbeing.
We will work with people with lived experience of psychosis to develop a brief, manualised intervention. Drawing on psychological theory the treatment will 1) identify positive cognitions and generate evidence through in-vivo learning and meaningful activity; 2) strengthen cognitions via imagery; and, 3) shift attentional focus through savouring. We will use an adaptive-design to test which techniques are most effective.
The 8-session intervention will be tested in a randomised trial with 80 patients. The comparator will be usual-care. Assessments will be conducted at baseline, mid-treatment, post-treatment, and follow-up.
Expected impact of our work
We will produce an effective treatment to increase positive self-concept. The intervention may be of benefit across mental health problems.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Trophoblast cells of the human placenta form the interface between the mother and fetus throughout pregnancy. Their role in oxygen and nutrient exchange and hormone regulation is well established. Trophoblast cells interface with the maternal immune system but express proteins of both maternal and paternal origin. How they maintain immunological tolerance across this barrier is not well understood. A failure to maintain this important fetal:maternal interface results in diseases of placental origin (pre-eclampsia, intrauterine growth restriction and recurrent miscarriage).
The unique immune molecule, HLA-G, is only expressed on extra-villous trophoblast (EVT) cells, a subset of trophoblast cells of the placenta. HLA-G plays a key role in switching off the mother’s immune cells. Pregnancy diseases such as pre-eclampsia are associated with a lack of HLA-G.
We do not know how the expression of HLA-G is regulated in EVT. My aims are to use CRISPR gene-editing technology to identify the genes that regulate HLA-G expression. I will then use specialised placental organoids to examine how the edited cells interact with the mother’s immune system. I aim to develop a new understanding of disease in pregnancy that will enable the development of novel treatments for these devastating disorders.
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| 30/09/2022 |
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UNIVERSITY COLLEGE LONDON |
In 2020, over one in four people who died from COVID-19 infection in England lived in a care-home . Reducing deaths in this vulnerable group by protecting them from infection using approaches like vaccination, is a priority. To understand if these work, and who has the biggest risk of getting infected, we need to know how many people have had the infection and how this affects their immune system. However, we cannot do this yet as collecting this information is difficult.
To answer these questions, researchers from UCL have set up the VIVALDI study, one of the biggest studies of COVID-19 in care-homes. Care-home staff and residents who take part have repeated swab testing to find out who is infected, and blood testing to see who had COVID-19 before. Information is collected about hospital admissions and deaths in these people, and about the care-homes themselves, like size. Using this information, I will find out which care-homes have had the most infections, who is most likely to get infected, and in people who have been infected or vaccinated, how long they are protected for. The results will help government officials understand which changes can prevent COVID-19 and other infections in care-homes.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Pathogen genetic sequencing is benefiting from improved laboratory workflows. COG-UK and the CARRIAGE study facilitate nation-wide acquisition and processing of SARS-CoV-2 and Staphylococcus aureus genomic data. I will utilise genomic and individual-level epidemiological data to understand the transmission and carriage dynamics.
SARS-CoV-2 and Staphylococcus aureus are major human pathogens with significant disease burden. Importations of SARS-CoV-2 into the UK and transmission within University settings are considered sources of sustained SARS-CoV-2 spread and subject to restrictive measures, though poorly understood. S. aureus is an established pathogen in human populations and results in persistent nasal colonisation of approximately 25% of healthy people. Understanding the factors that result in transmission and colonisation of both pathogens, respectively, is vital to reduce subsequent disease.
I will:
1) Characterise the contribution of imported SARS-CoV-2 to onwards transmission by coupling travel histories derived from Test and Trace to genetically linked clusters of infection.
2) Identify the transmission dynamics of SARS-CoV-2 by sequencing isolates derived through the University of Cambridge screening programme.
3) Characterise the microbial community structure that facilitates nasal Staphylococcus aureus carriage through microbiome analysis of 10,000 CARRIAGE study participants.
4) Experimentally validate genomic findings from microbiome data to identify pathways that facilitate S. aureus carriage
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Background:
Many types of joint disease are poorly understood, with little understanding of what is going wrong to make the healthy tissues stop working as they should.
One way to understand joint disease is growing cartilage in a laboratory, and seeing how it responds when we change its environment. Unfortunately, we cannot currently grow life-like cartilage in laboratories. This makes it difficult to design and test treatments. I will address this by increasing our understanding of how healthy joints develop, and using this knowledge to improve our ‘recipe’ for growing cartilage in the laboratory. My aims are:
understand how cartilage grown in the laboratory compares to 'real' cartilage that grows in the developing human. By using single-cell sequencing, we will investigate healthy cartilage development in more detail that ever before, gaining insights into the biological processes that make healthy tissue in the joints.
We will then look for key differences between the two. This will tell us what is missing in our laboratory process
Make appropriate changes to our laboratory ‘recipe’ to make our lab-grown cartilage more lifelike.
My broader goal is improving our ability to model bone and joint disease in order to bring us closer to effective therapies.
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| 30/09/2022 |
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UNIVERSITY OF CAMBRIDGE |
Cancer develops through cells acquiring multiple genetic mutations. "Driver mutations" actively contribute to cancer progression, whilst "passenger mutations" are random events.
Some passenger mutations actually worsen cell survival, but are compensated for; if a passenger mutation disrupts one gene, this may make the cancer cell dependent on another gene for survival. Inhibition of this other gene would cause cell death and is therefore a promising target for cancer drug treatment. This interaction between 2 genes, where loss of 1 gene does not cause cell death, but simultaneous loss does, is called synthetic lethality.
We will use CRISPR-based technology to disrupt the function of thousands of gene pairs (as well as each of the pair individually) in 30 different kinds of cancer cells, to determine those pairs that exhibit synthetic lethality.
To identify which gene pairs to test, we will analyse many previously sequenced cancer genomes. We will look for pairs of mutations which rarely/never occur together, as this suggests having both genes mutated simultaneously results in cell death.
From the CRISPR-based experiment, we will study those gene pairs which show significant synthetic lethality to determine which are promising drug targets, thus generating a novel resource for the drug discovery community.
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| 30/09/2022 |
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UNIVERSITY COLLEGE LONDON |
Background:
I am interested in a repetitive style of thinking called rumination and its association with adolescent depression. I aim to understand the neurocognitive underpinnings of rumination and its role as a potential risk factor leading to later depression.
Approach:
I will undertake two projects.
Using an established dataset of 2000 young people followed up between the ages of 10 to 24 years, I will explore the cross-sectional and longitudinal associations between aspects of how thinking is controlled, rumination and depression.
I will undertake an experimental study in a school-based sample of adolescents and measure trait levels of rumination in an 11-year-old and 15-year-old age group, reflecting a developmental period known to be important in the maturation of emotion regulation processes and is associated with an increased incidence of depression. This will also require the development of a computerized task that measures one specific aspect of thinking control (-the ability to disengage attention from no longer relevant information) which will be used to explore the nature of associated cognitive impairment.
Impact:
This project will support the future development of novel treatments for adolescent depression, including those that are aimed at the prevention of depression in this age group.
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| 30/09/2022 |
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UNIVERSITY OF BRISTOL |
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a devastating effect on adults living in long term care: it's estimated that this population accounted for at least 40% of COVID-19 related deaths in the UK during the first 3 months of the pandemic.
COVID-19, like many other infectious diseases, can spread silently - particularly among older people who are often infectious without displaying any symptoms. In care homes, this results in explosive outbreaks which are difficult to control.
In order to detect infectious organisms before they cause outbreaks, it's important to understand where the pathogens accumulate and how they are distributed. Since viruses and bacteria can be found on surfaces, in the air and in waste water, sampling the environment will provide clues about how they spread so effectively in care homes.
This study will investigate how the SARS-CoV-2 virus spreads around care homes during outbreaks. We will take regular environmental samples alongside diagnostic tests for staff and residents, and epidemiological information about the setting and its population. Using the findings from this study we will build a mathematical model to assess the best way to monitor care homes for the emergence of infectious diseases.
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| 30/09/2022 |
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UNIVERSITY OF BRISTOL |
Infection is very common, but rarely deadly. For my PhD I want to explore the balance between ‘resistance’ to infection - the ability to kill and destroy invading pathogens like bacteria, fungi and viruses, with ‘tolerance’ to infection - the ability to bear an infection without adverse effects when these pathogens attack. Both these strategies are governed by immune pathways and are critical to survival from infection.
I will focus on whether we can use large human studies, model or in vitro work about the activity of genes when we do get infected and attempt to identify specific pathways that are a ‘trade-off’ between these two evolutionary strategies - tolerance and resistance . I will target my investigation on the haem degradation pathway, which controls iron transport and storage. Iron is a critical nutrient for both hosts and pathogens, and has been shown to be important in determining infection outcomes. I will explore how this pathway is regulated in large datasets from sepsis and COVID-19 patients. I will also explore the balance between incidence and case fatality of infection using large genetic datasets, to explore whether genes that make you resist infection are more likely to make you die.
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| 30/09/2022 |
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INSTITUTE OF CANCER RESEARCH |
Metastatic prostate cancer is a leading cause of male cancer-related death. Recent advances in drugs that harness the patient’s own immune defenses to eradicate cancer cells have transformed the treatment of several cancer types but this approach remains largely ineffective in patients with prostate cancer. We have shown that a specific protein highly expressed by prostate cancer cells may be responsible for the prostate cancer cell’s capacity to evade eradication by the patient’s immune system. Emerging data from studies testing drugs targeting this protein in patients with various malignancies have shown that this approach can be safe; however, to date, little is known about the functions of this protein, how its expression evolves as tumours progress, and how it can be manipulated through novel prostate cancer drugs, to improve treatment outcomes in patients with these lethal diseases. The major objective of our research is to study how the expression of this protein varies over time and between individuals, how it is regulated, how it can be manipulated, the functions of this protein, and the antitumour effects of a new immunotherapy targeting this protein.
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| 30/09/2022 |
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UNIVERSITY COLLEGE LONDON |
Background
The aim of cancer screening is to detect cancers at an early, curable, stage before they have spread. In lung cancer screening, all who are eligible receive screening every year. However, there is a wide variation in cancers growth patterns. Some people will have aggressive, fast-growing, cancers that could appear and spread between the yearly screens. By contrast, others may be at lower risk of cancer or will have slower-growing tumours meaning they are exposed to tests unnecessarily if screening is not tailored to the individual.
Approach
First, I will study lung cancer growth patterns and factors - such as smoking intensity - associated with the likely aggressiveness of lung cancer. Using this information, I propose to develop a model to predict the likely growth pattern of a cancer that an individual undergoing screening for lung cancer may develop. Next, taking account of lung cancer growth patterns, I will study the benefits and risks of alternative lung cancer screening strategies.
Impact
By tailoring lung cancer screening to an individual’s likely cancer growth rate, more deaths from lung cancer could be prevented with fewer harms. This research will help to personalise lung cancer screening.
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| 30/09/2022 |
£0 |
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IMPERIAL COLLEGE LONDON |
COVID-19 is an infection caused by a virus that first emerged at the end of 2019 and has since been declared a global pandemic. Multiple vaccines have been in development globally including three vaccines that have now been approved for use in the UK. At Imperial College London a novel self-amplifying RNA (saRNA) vaccine has been developed and is being used as part of a clinical trial since June 2020 (COVAC1).
Those who have already had a natural SARS-CoV-2 infection are likely to have some protection against further infection, although reports of re-infection do exist. It is not clear how long such protection would last and so it is important to understand how a vaccine may boost the immune response in these individuals.
In order to explore this, I plan to look at immune responses up to one year post vaccination against SARS-CoV-2 using both the Imperial saRNA vaccine and the Pfizer/BioNTech mRNA vaccine in individuals who have recovered from natural infection compared to those who have never previously been infected. This will provide important information on how the immune system behaves after vaccination in those with pre-existing antibodies, and will help to inform further vaccination strategies and research.
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| 30/09/2022 |
£0 |
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UNIVERSITY COLLEGE DUBLIN |
Melanoma is an aggressive skin cancer, responsible for most skin cancer deaths. We still know very little about how melanoma spreads through the body. We need this knowledge to produce better treatments. Extracellular vesicles (EVs) are small packets that carry messages between cells, helping cancer cells grow and spread through the body. We will test the role of these EVs in melanoma, looking at messengers in them, known as chemokines. We will undertake this on cells in the laboratory, and blood samples from humans and our companion animal, the dog.
Dogs, like humans, can have melanoma and are treated with surgery and chemotherapy. Melanoma in dogs can also spread, and in general spreads faster than in humans. This quicker progression and survival time will allow us to find results in a shorter time.
The dogs in this project are pets, who develop melanoma naturally and are undergoing treatment with their Vet. We will only use blood samples from the dogs taken as part of their usual treatment, that would be thrown away otherwise. We will not be giving dogs melanoma.
We hope to find new ways to treat melanoma and pick it up earlier in both humans and dogs.
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| 30/09/2022 |
£0 |
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IMPERIAL COLLEGE LONDON |
Childhood cardiomyopathies are serious disorders that affect the heart muscle. They are the leading cause of heart transplant in children. Most cases develop from a genetic cause. Current genetic tests are limited and only reveal the diagnosis in approximately one third of patients. It remains unclear how certain genes play a role in the development and severity of disease in individual cases. Making a genetic diagnosis is important as it can help predict disease course, guide treatment and can impact family screening and reproductive choices.
It has been challenging to study the genetics of childhood cardiomyopathy because it is a rare condition with many different genes and genetic mutations (changes in the DNA sequence) involved.
Our purpose is to improve the understanding of the genetic cause of childhood cardiomyopathies. We plan to recruit children affected by severe cardiomyopathy and their parents. We will expand genetic testing to look at all genes, not just a select few. The genetic data will then be analysed using state-of-the-art software tools. We aim to identify new genes and genetic mutations that cause cardiomyopathy in children. These discoveries will provide diagnoses for patients and families and are the first step towards identifying new treatments.
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| 30/09/2022 |
£0 |
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IMPERIAL COLLEGE LONDON |
Sepsis is a life-threatening condition where an infection triggers an excessive response by the body, leading to severe organ problems. When sepsis worsens and strong drugs are needed to treat low blood pressure, this is called septic shock. Septic shock affects about 13000 people each year in the UK. More than half of them die in hospital.
Low blood pressure in septic shock can be caused by a failing heart, or by a weak (dilated) circulation. These need different treatments. Septic patients are different from one another in other ways too: their organ problems vary, and their immune systems behave differently. Given these differences, it may be that a more personalised and tailored approach to diagnosis and treatment is needed.
I want to help doctors decide on the right treatment for each patient, by applying artificial intelligence (AI) techniques to data from patient monitors. Previous AI algorithms tried to do this using just the data, but I want to add in knowledge of how the body works to make more powerful and reliable insights. My algorithm also aims to detect septic shock in its early stages, so that patients can get the treatment they need sooner.
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| 30/09/2022 |
£0 |
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INSTITUTE OF CANCER RESEARCH |
Multiple myeloma is a form of blood cancer that is currently incurable. However, it can be managed for several years with drug therapy. One of the most successful groups of medications are the immunomodulatory drugs. Most patients who take these medications initially respond to treatment and their myeloma is controlled. Unfortunately, over time, the myeloma cells become resistant to treatment and the disease returns. This project aims to look at pathways in myeloma cells that could be targeted to stop or reverse the occurrence of immunomodulatory drug resistance. By understanding this, we hope to treat patients more effectively and improve their outcomes.
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| 30/09/2022 |
£0 |
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IMPERIAL COLLEGE LONDON |
Injury to the endothelium, the layer of cells lining our blood vessels, is associated with diseases including diabetes, kidney disease, joint disease and inflammation of blood vessels (vasculitis). A poorly functioning endothelium increases the risk of atherosclerosis, the cause of heart attacks and strokes. Understanding how damage to the endothelium occurs will help us develop new preventative treatments. In 2014, the underlying cause of a rare disease of young people suffering from strokes & vasculitis (injury to blood vessels induced by white blood cells), was identified as an inherited deficiency of the protein adenosine deaminase 2 (ADA2). Analysis of skin samples from these patients suggested that ADA2 is important for maintaining healthy white blood cells, for regulating their activity and for protecting the endothelium. This discovery leads to three new and important research questions which we propose to answer: 1. How does ADA2 work to keep our white blood cells healthy and functioning normally? 2. How does loss of ADA2 disrupt white blood cells and allow them to damage the endothelium of blood vessels? 3. Does treatment with ADA2 itself or drugs including those already prescribed to patients with rheumatoid arthritis, help protect blood vessels against the impact of ADA2-deficiency?
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| 30/09/2022 |
£0 |
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UNIVERSITY OF EXETER |
Inflammatory bowel disease (IBD) is a life-long illness that affects over 300,000 people in the UK. It can cause abdominal pain, diarrhoea and weight loss, and causes significant disability and impact on daily life. There is currently no cure for IBD and without medical treatment, patients may require surgery.
Anti-TNF therapies are effective medications for patients with severe IBD, and often used when other treatments have failed. Unfortunately, many patients lose response to treatment over time. A major reason for this is when a patient’s immune system makes proteins (antibodies) that block the effect of the drug (immunogenicity) and reduce its effectiveness. These antibodies can also cause side effects such as skin rash, breathing difficulties and low blood pressure. Understanding why some patients develop antibodies will allow doctors to identify those at risk and prevent this.
Using the latest techniques, I will study the interactions between a patient’s genes, their environment, and the way the body reads the genes to identify unique immune system signals that are produced in patients who have developed immunogenicity. Together, this will build an understanding of the immune pathways causing immunogenicity, allowing doctors to target the most effective treatment for individual patients.
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| 30/09/2022 |
£0 |
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CARDIFF UNIVERSITY |
Autism Spectrum Disorder (autism) is a long-term condition which affects 1-2% of people [1]. People with autism can have difficulties with social skills and communicating with other people, repetitive behaviour and can have a small range of hobbies or interests. It can affect how people perceive the world. Some autistic people see, hear and feel the world differently. More autistic people are being identified, as people become more aware of the condition.
Mental health problems are common in autistic people, but we don’t understand why. This project will look at this, and what effects genetics or lifestyle have. We will study the rates of mental health problems in a group of people with autism taken from the National Centre for Mental Health (NCMH) Database, as well as people with autism from two large datasets of anonymised health records. A small number of autistic people with anxiety will then be seen and assessed more deeply. Through this we will assess the effects of genetic risk and life choices on mental health.
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| 18/01/2022 |
£190,773 |
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LANCASTER UNIVERSITY |
Despite being a central focus in research, policy, and practice in recent years, health inequalities have widened and are being further exacerbated by the Covid-19 pandemic. The reasons are multiple and complex, but there is increasing concern that the framing of health inequalities may be contributing to implementation challenges. This is important because while the health sector is not alone in grappling with socially-driven inequalities in outcomes, there is a persistent desire to embed a ‘health inequalities’ perspective across all sectors and policies. The aim of this research is to employ theoretical and methodological tools from framing analysis to explore, compare, and critically reflect upon different ways in which inequalities in outcomes are framed across multiple sectors beyond health. These sectors include early years education, youth justice, and housing, and, for each, data will be collected through documentary analysis of academic literature and policy reports; semi-structured interviews with actors working to reduce inequalities; and group 'framing reflection' exercises. The research will produce novel comparative analyses, and interdisciplinary reflections, on contrasting ways of framing inequalities. These findings will illuminate the potential for more cross-sectoral accounts of inequalities that would lead to greater collective understanding and action on the cross-cutting underlying causes.
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| 18/01/2022 |
£277,888 |
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UNIVERSITY OF DURHAM |
What is ‘normal’ health?
The way health scientists answered this question changed in the twentieth century, as they relied more heavily on social categories to measure health. These categories, sometimes termed reference-classes, rely on parameters such as age/weight/height/sex/gender/race/class. They still guide how providers distribute care and decide who deviates from ‘normal’ enough to count as disabled. Genetic research provides crucial theoretical scaffolding that legitimates their use. This project will demonstrate how proof of inheritance was established in genetic disability research and how proof of injury/illness was demonstrated in compensation cases. It investigates which categories were used to establish disability causation and interrogates biases inherent to the understanding of ‘biological’ versus ‘social’ determinants of health.
This project therefore moves beyond considering disability as normative, to question the extent to which the categories used to define it are normative. Considering disabled experiences and the use of categories in compensation moderation demonstrates the longer-term consequences of categorisation choices and shows how data has been used to obscure health inequalities related to society and the environment. My innovative interdisciplinary approach will reveal how both disability and eugenics relate to a history of categorizing inequality through obscuring the relationship between the environment and the individual.
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| 18/01/2022 |
£264,274 |
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UNIVERSITY OF STRATHCLYDE |
If mental illness is understood as a deviation from a norm, what prevents people who challenge social norms from being diagnosed with mental illnesses? In the 1960s, as mainstream psychiatric institutions, diagnoses and forms of treatment came under attack from antipsychiatrists across Western Europe and North America, evidence that dissidents were being sent to psychiatric hospitals for expressing views that challenged social norms in the USSR began to emerge.
This project will analyse international campaigns against the political abuse of psychiatry in the USSR, asking what they reveal about psychiatry across the iron curtain at a moment when its legitimacy was being questioned. It will explore politicised debates among psychiatrists about whether similar abuses of psychiatry was taking place elsewhere – in other state socialist contexts, in right-wing dictatorships in Latin America or in Apartheid South Africa – and examine antipsychiatric discussions that compared Soviet psychiatric practices to those in Western liberal democracies.
By probing unstable definitions of four pairs of concepts central to psychiatric and popular discourse on this issue - coercion/freedom, abnormality/normality, madness/sanity, dissent/conformity - this project will demonstrate how the issue of Soviet punitive psychiatry took on divergent, even contradictory, meanings across national borders and political affiliations.
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| 18/01/2022 |
£292,778 |
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UNIVERSITY OF OXFORD |
Parents often describe the enduring impact of their interactions with health care professionals (HCPs) following the diagnosis of a life-limiting fetal condition in pregnancy. These central relationships between parents and the HCPs caring for them in the antenatal period are crucial to how families tackle difficult decisions. Families in this situation are increasingly being offered antenatal palliative care to give them the support they need to plan the future care of their baby.
This research aims to provide a comprehensive analysis of the ethical considerations in providing antenatal palliative care with an eye to informing practice guidance. This will be achieved by using an ethics of care framework to understand the ethical dimensions of patient-caregiver relationships in antenatal palliative care encounters. This project will involve three work packages:
A comprehensive literature review
An empirical ethics study involving observations, audio recordings of antenatal consultations, interviews and focus groups with parents and HCPs
Ethical analysis using an ethics of care framework
This work will inform both clinical guidance and training for HCPs working at the frontiers of palliative care. Involving families and providers at the outset will ensure that the often hidden moral voices of parents and clinicians shape the way forward.
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| 18/01/2022 |
£247,837 |
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UNIVERSITY OF MANCHESTER |
During the current COVID-19 pandemic, the Chinese government celebrated face masks as symbols of modernity and national pride. This project hypothesizes that face mask’s authoritative position in China’s epidemic control today is rooted in Chinese history, specifically the semi-colonial period, when foreign powers and internal political forces were competing for control of China. This project argues that this narrative, of mask-wearing as an integral part of Chinese culture and politics today, is a modern myth. To unpack this myth, this study explores the parallel policies of the British and Japanese Empires, and China’s Nationalist and Communist Parties, in promoting mask-wearing as a form of epidemic control. This project will produce a comprehensive account of the social history of medicine on mask-wearing in the semi-colonial Republican period (1912-1949) in which it asks, ‘How did British and Japanese colonialism, and China’s domestic politics, contribute to masks’ authoritative position in semi-colonial China?’ To answer this central question, the project is structured chronologically around four themes: 1) Masks, race, and epidemics in the 1910s Shanghai International Settlement; 2) The national recommendation of mask-wearing in the 1929; 3) Japanese military promotion of masks in Manchuria (1930s-1940s); and 4) Chinese Communists’ wartime mask-wearing campaigns.
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| 18/01/2022 |
£197,028 |
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UNIVERSITY OF MANCHESTER |
This project offers new approaches to the history of 20th century medico-legal borders and puts migrants’ voices at its centre. Drawing on narratives of mental, emotional, and physical disorders as produced in accounts by arrivals to Britain, Egypt, and Palestine, the project will analyse the varied ways in which migrants understood and negotiated infirmities and border control. I will do this by bringing the conceptual framework of biocredibility together with a pathographical reading of precarious migrants’ historical sources. Focused on a period when imperial authorities accelerated the use of biopower as a tool to manage borders, the research will foreground the transnational circulation of knowledge among refugees, displaced persons, and low-waged labours labeled as ‘medically undesirable’. The empirical research investigates three linked questions: how did the medically undesirable justify their physical and mental illnesses and the suffering they experienced due to this label and to deportation? How does the focus on biocredibility and the reliance on subaltern voices alter or contextualise understandings of colonial borders and public health? How did migrants’ medical knowledge, or lack thereof, affect their relationship with states? The project will make a significant contribution toward understanding the responses to the medicalisation of imperial and colonial borders.
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| 18/01/2022 |
£176,342 |
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UNIVERSITY OF MANCHESTER |
This project focuses on the Soviet Red Cross to examine how Soviet society grappled with successive public health crises after 1953.
Its key goals are:
To understand the place and meaning of medical volunteerism within a socialist welfare state.
To examine how Red Cross volunteers conceptualised their work within the ideologically charged atmosphere of the Cold War.
To assess how practices of medical volunteerism varied across the multi-ethnic USSR.
To develop a model of ‘red humanitarianism’ that brings the USSR into global histories of medical humanitarianism.
The period 1953–1991 saw profound innovation in Soviet medical sciences, including mass production of antibiotics and widespread vaccination. However, severe population depletion, pervasive industrial pollution, and chronic underfunding of healthcare spurred increasing rates of infectious diseases, maternal and infant mortality, and declining life expectancy. In response, millions of Soviet citizens donated time and money to the Red Cross. The organisation tackled healthcare crises that were exacerbated by state policy, whilst remaining dependent on state approval and resources. Combining archival research and oral history, I will explore the meaning, scope, and motivations behind medical volunteerism in a society where compulsory citizen participation was vital to sustaining state healthcare services.
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| 18/01/2022 |
£331,217 |
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GOLDSMITHS, UNIVERSITY OF LONDON |
If we take death as the ultimate harm, the UK has never been a more harmful place for people who use substances. Death rates from both drug- and alcohol-specific reasons are at their highest ever level. Moreover, some areas are experiencing their worst HIV outbreaks among injecting drug users in 30 years, and alcohol-related liver disease is rising steeply. As Covid-19 works to ‘expose and amplify’ existing inequalities, the fear is that these deaths/harms will increase further. However, Covid-regulations have also brought drastic changes to the sector, including long-sought flexibilities in treatment options and regimes. Prominent practitioners refer to these as ‘ripping up the rulebook’ and a ‘natural experiment’ with ‘potential for a lot of learning’. This project studies these experimental practices and what they open-up for improving treatment attractiveness and responsiveness. It maps experiments in service provision through a UK-wide survey and carries out ethnographic inquiry to establish how these practices re-work treatment and the role of service users’ own experimentations in these processes. Extending this experimentality through its methodology, the project brings together key stakeholders in a theatre-informed workshop to quite literally ‘rip up the rulebook’ (clinical/policy guidelines) to provoke further thinking and action on treatment possibilities.
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| 02/12/2021 |
£33,988 |
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UNIVERSITY COLLEGE LONDON |
8,000+ Venezuelans living with HIV have fled their country and its crumbling health-system in search of life-saving medication. Yet, lived realities of pharmaceutical infrastructures and obstacles of access are scarcely known in host countries where they migrate, resulting in invisiblised migrant-experience and unaddressed HIV/refugee-related stigma.
How the project will look:
In collaboration with the Centre-for-Excellence-in-Chronic-Diseases(CRONICAS) at the Cayetano-Heredia-University(UPCH), Lima Museum-of-Memory,-Tolerance- & -Social-Inclusion(LUM), UCL-Culture, ONIGO-design-studios, and migrants living with HIV, we will place digitally-literate Peruvian & UK publics directly into migrants ‘shoes’ so that they can experience authentic pharmaceutical obstacles, develop deeper understandings of migrant experience, and engage meaningfully with the research. This will be achieved through developing a virtual ‘pharmacy escape-room’ (VER), designed collaboratively with HIV-positive Venezuelans, to tell real-world stories and involve the public in migrant worlds with the decisions/obstacles they face on a ‘lived’, experiential level. Post-initiative, collaborative discussions will be held between migrants and VER ‘players’, encouraging the public to greater value such people-centred health research, empower those with HIV to communicate their health-struggles, and address the HIV empathy gap through collaboratively brainstorming stigma reduction strategies.
What we will achieve for:
Research - This activity will enrich the research by feeding back collaboratively produced data surrounding HIV/migrant stigma reduction into the main project.
Collaborators- Migrants will be empowered through communicating lived experiences and pharmaceutical obstacles to the public and reflecting on changing perceptions in post-activity collaborative roundtables.
Public Participants – HIV empathy gap will be collaboratively addressed, incorporating pre- and post-gameplay public perspectives on stigma reduction and community integration.
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| 02/12/2021 |
£42,665 |
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KING'S COLLEGE LONDON |
The INDiGO trial will test the efficacy of micronutrient interventions on developmental outcomes in young infants. If our trial shows positive benefits the next step will be studies of effectiveness with a view to integrating targeted nutrition interventions in early infancy, beyond exclusive breastfeeding. As part of this vision, we recognise that other aspects of nurturing care, such as responsive caregiving, are also important determinants of neurodevelopmental outcomes, such as school readiness and mental health. Currently, most health messages delivered at antenatal and postnatal care clinics in The Gambia focus on more immediate health issues, with the aim of reducing morbidity and mortality in the short term. To ensure the outcomes of the INDiGO trial are fully impactful, we will work with the local community in The Gambia to determine how to most appropriately promote and enable nurturing care practices within routine health care.
In phase one, we will use qualitative research approaches, to obtain a better understanding around caregiver, community and stakeholder perceptions on nurturing care. This will include (i) what is perceived as adequate and optimal care, (ii) understanding of the five aspects of nurturing care, and (iii) the barriers to and facilitators of nurturing care practices. In the second phase, with continued involvement from community members and stakeholders, we will co-produce and pilot a communication tool for implementation across antenatal care (ANC) clinics in The Gambia, aimed at promoting the concept of nurturing care in infancy and early childhood having life-long and intergenerational benefits.
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| 02/12/2021 |
£49,350 |
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AMSTERDAM INSTITUTE FOR GLOBAL HEALTH AND DEVELOPMENT |
Antimicrobial resistance (AMR) disproportionately impacts low- and middle-income countries (LMIC) and overcoming AMR requires public understanding and engagement (1,2). The ROTA-biotic project evaluates the impact of vaccines on antibiotic usage in Zambia and Ghana. Caregivers in Zambia and other LMICs are often insufficiently informed about the hazards of inappropriate antibiotic use and AMR (2). This public engagement proposal aims to increase knowledge and awareness of AMR among caregivers of children under-5 using school-going children. To achieve this goal, we propose a youth-led intervention in Zambia where high-school children educate primary caregivers of under-5 children about AMR using narratives and performing arts. Our work will demonstrate implementation and outcomes of a process by which children will:
Be engaged in the co-creation of a knowledge-based intervention with social scientists, local actors and artists, teachers of basic science, and community-based safe motherhood action groups (SMAGs)
Be included in a research process, specifically recruitment, data collection and interpretation of findings, and
Lead the implementation of intervention activities created by them and informed by caregivers and other stakeholders
This will result in the production of visual materials and performing arts set/s aimed at educating caregivers on the concept of AMR and their role in controlling resistance in their children. Our work will facilitate broader dissemination of impactful AMR storylines within ROTA-biotic sites, schools, and ministries of health and education in both Zambia and Ghana.
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| 02/12/2021 |
£99,798 |
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KING'S COLLEGE LONDON |
This project will culminate in a series of co-produced immersive performances for the public which explore the idea of neurodiversity and the experiences of neurodivergent individuals. Musical compositions, which sonically and verbally depict neurodivergent experiences, will raise up neurodivergent voices and engage neurotypical audiences to reflect on what it means to be neurodivergent. Audiences will be encouraged to contemplate how we conceptualise individual differences in how our brains function, and to challenge negative stereotypes surrounding neurodevelopmental conditions (e.g., autism, ADHD).
The project will commence with a series of online interviews[1] with people who identify as neurodivergent to explore the concept of neurodiversity: how neurodivergent people experience the world differently, what may underpin these differences, and how does the neurodiversity approach differ from the traditional medical model. The project team will attend a co-production workshop to reach a consensus on themes that emerged in the interviews that should be showcased in the final performances. From this, musical interludes will be created based on the agreed themes. In parallel to the creation of interludes, a Neurodiversity Framework document will be created to summarise the neurodiversity approach, key themes from focus groups and lessons learnt from the project. This will serve as a guide to others interested in co-production projects with neurodivergent communities. A short film of the project will be disseminated through social media and public film festivals nationwide to ensure far-reaching impact.
[1] We will also offer alternative methods of engagement (e.g., written, voice notes) to ensure the project is inclusive
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| 02/12/2021 |
£83,519 |
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UNIVERSITY COLLEGE LONDON |
To date there is little accessible and relatable information about the neuroscience of OCD for those affected, especially for those who could benefit from this information the most: young people and their parents at early stages of the illness. This project, designed in collaborative working group sessions with lived experts and in partnership with OCD Action and the International OCD Foundation, will overcome the prevailing disconnect between neuroscience research and the OCD community through a co-productive and explorative practice.
By the end of this project we will have:
Built two engaging digital toolkits – one for young people (YP) with OCD, and one for their parents – that will bridge the gap between neuroscience and the personal experiences of those affected by OCD.
Tailored our toolkits to the needs of our target audience and shaped future research proposals in collaboration with patients/carers/charities through a series of ‘hypothesis exchange’ workshops.
Established a strong relationship between key community gatekeepers/lived experts and the research team.
Embedded resources developed into existing support networks in the UK and internationally through partnerships with OCD Action (UK’s largest OCD charity) and International OCD Foundation (largest international OCD organisation).
Our vision is that these toolkits will help establish an understanding that OCD is a brain illness that can be treated. By creating engaging, interactive toolkits for YP with OCD and parents, we will challenge misconceptions of OCD and provide vital resources identified (by both our working group and partner charities) as a gap in OCD support.
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| 02/12/2021 |
£43,097 |
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QUEEN MARY UNIVERSITY OF LONDON |
Research enrichment will have enhanced collaboration and co-creation processes with young autistic adults through a series of activities aimed to engage particular constituent groups.
A visual essay film narrated by autistic contributors conjuring the imagined experience of autistic children in clinical films of 1950s, will have reached film festival audiences. It will have engaged psychologists through a feature on the BMJ medical humanities site. The podcast, featuring a conversation between a neurodivergent team and a guest film professional discussing a film, will have connected an autistic perspective with cultural influencers. Instagram and QR code projects showcasing the method of film practice co-creation will have shared with industry professionals the work of autistic creatives, proposing a progressive and inclusive example of how films, and art can be made.
The shared co-creation methodology exists as a model that can be taken up by autism-focused charities and cultural organisations. The podcasts have profiled the professional work of early career autistic cultural commentators and the visual essay has enabled important debate to take place with psychologists and clinicians. Research discoveries will have reached an extensive general arts and film audience; our special events and workshops have offered a nuanced understanding of neurodivergence, benefiting constituencies who have limited narratives of autism, and research enhancement activities will have reached a large number of the neurodiverse community, including carers.
The visual essay, podcasts, publication, and co-creation methodology will have impacted the field of Film Studies, enabling neurodiverse perspectives to act as a prism for re-thinking film pedagogy.
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| 30/11/2021 |
£1,813,555 |
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UNIVERSITY OF BRISTOL |
Cell competition is a fundamental quality-control process that leads to elimination of less fit cells from tissues. The first competition type discovered was Minute cell competition, where cells heterozygous-mutant in ribosome protein genes (RPG) - known as Minute in Drosophila - are eliminated by wild-type cells. Minute cell competition may be frequent in diseases characterized by aneuploidy, like cancer, where deletions of large genomic regions often lead to RPG loss.
The work proposed will advance our knowledge of the mechanisms of Minute cell competition and unveil its possible role as a tumour vulnerability. I will:
a) Elucidate the mechanisms of Minute cell competition in mammals. We will establish mammalian Minute cell competition assays to study it mechanistically and elucidate if oxidative and proteotoxic stress, which cause Minute competition in flies, lead to cell competition in mammals.
b) Identify how Nrf2, master-regulator of the oxidative stress response, causes the Minute loser status. Recently we identified many novel Nrf2 target genes that cause competition, including importantly metabolic enzymes. Focusing on metabolism, we will identify small-molecule modulators of cell competition that could be used therapeutically.
c) Use human cancer bioinformatics and Drosophila genetics to elucidate how RPG-mutant human cancers overcome their loser status.
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| 30/11/2021 |
£3,491,551 |
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UNIVERSITY COLLEGE LONDON |
This proposal aims to understand how the neural circuits of the cerebellum implement computations that drive learning. The cerebellum has long been proposed to evaluate predictions about the consequences of actions using error signals delivered by the climbing fiber, a form of supervised learning. Our recent discovery that the cerebellum also exhibits signals associated with reward has transformed our view of cerebellar function and suggests that the cerebellum may also implement reinforcement learning. We will identify the sources of cerebellar reward and error signals and examine how they work together during learning in cerebellar and downstream circuits using an unprecedented combination of tools: circuit-wide and brain-wide recordings of activity using Neuropixels probes, anatomical tracing of input and target structures, and all-optical interrogation using 2-photon imaging and 2-photon optogenetics to provide causal links between activity in functionally defined cerebellar microzones and behaviour. These experiments will reveal how the cerebellar cortex interacts with other brain areas during learning; they will provide crucial constraints for constructing models of cerebellar cortex; and they will reveal clear targets for manipulation of an important neural circuit that may ultimately have translational relevance, particularly for treating the disorders of movement and cognition that may have cerebellar origins.
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| 30/11/2021 |
£1,863,430 |
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UNIVERSITY OF YORK |
The research will focus on understanding how dsDNA viruses fill their capsids with DNA. The main emphasis is on using structural approaches, mostly Cryo-EM, although we will also use complementary biophysical techniques including activity/binding assays, to define composition and stoichiometry of protein-nucleic acid complexes, in addition to the affinity of the interaction.
Key goals:
To understand the mechanism of DNA translocation by dsDNA viruses that fill their capsid with DNA using a terminase protein. This research will be based on in vitro packaging systems that we have established for bacteriophages HK97 and P23-45; and will also utilise crAssphages isolated from the human gut.
To understand the structure-function relationship in FtsK-like DNA packaging motors present in another large class of dsDNA viruses comprising bacterial tectiviruses, corticoviruses and eukaryotic poxviruses. This research will be performed using corticovirus RC12 and tectivirus PhiKo.
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| 30/11/2021 |
£3,500,000 |
|
UNIVERSITY OF EXETER |
This proposal builds on novel insights from our recent genetic discovery that a primate-specific KRAB Zinc Finger Protein (KZFP), ZNF808, is required for human pancreatic development. Our preliminary studies show that ZNF808 silences primate-specific MER11 transposons and that these need to be controlled for normal pancreas development, underscoring that this process differs between humans and rodents.
This project brings together an international and interdisciplinary group of experts to uncover the role and implications of human-specific regulation in pancreatic beta-cell development. We will:
1. Dissect the interplay between ZNF808 and other primate-specific KZFPs, MER11 elements, and transcription factors in pancreas development. This will use stem cell-derived models of beta-cell differentiation coupled with genome editing, functional genomics and computational approaches;
2. Sequence and analyse the genome of patients with diabetes to identify novel genes essential for beta-cell development and causal mutations in regulatory elements, focusing on transcription factor binding sites within primate-specific MER11 elements;
3. Assess the impact of disrupted human beta-cell development by examining the phenotype, post-natal growth and metabolism of patients with mutations disrupting beta-cell development and fetal insulin secretion.
These investigations will provide essential new knowledge to propel scientific efforts aimed at cell-based therapies for people with diabetes.
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| 30/11/2021 |
£1,092,568 |
|
UNIVERSITY COLLEGE LONDON |
This project has two main components, each exploring how the genome mediates our phenotypic responses to environmental pressures. The first component will develop new statistical methodology to pinpoint genetic sequence variants that have facilitated humans' ability to adapt over long-term time-scales to their environments, and hence are vital for influencing health. Specifically, this work will leverage large-scale cohorts (e.g. UK Biobank) containing people of mixed ancestry, whom typically are ignored in such analyses, to provide a substantial increase in the power to infer and characterise adaptation signatures. For the second project component, we will leverage available epigenetic data from hundreds of studies to identify loci that show high methylation variability across multiple tissues, ethnicities and ages, and for which methylation marks likely are established in the early embryo and stable throughout the life course. Cross-referencing such loci with published epigenome-wide association studies (EWAS) can indicate causal pathways whereby specific exposures modify methylation, which in turn influences health outcomes (e.g. disease susceptibility) throughout the life course. By combining both project components, we will test the hypothesis that these regions of variable methylation are conserved in human populations as a means to enable efficient adaptation to rapidly changing environments.
|
| 30/11/2021 |
£1,453,634 |
|
UNIVERSITY OF WARWICK |
Motorised intracellular transport allows cells to organise their contents, establish and maintain polarity and deliver building blocks to specific subcellular regions. It is achieved by kinesins and dynein that walk in a processive, unidirectional manner along microtubules. These transport motors also regulate the stability and arrangement of microtubule tracks. By sliding microtubules relative to each other, motors polarity-sort microtubules, generate pushing forces to induce morphogenesis events and advective flows for bulk cytoplasm transport. How motors switch between cargo transport and microtubule organising functions remains to be understood. We will dissect the mechanisms that activate the major transporters KIF1C and dynein for microtubule bundling and sliding in human cells. Because microtubule organisation requires motors to work in teams, we will aim to understand how these motors cooperate to generate large, collective forces and prevent a fruitless tug-of-war between opposite polarity motors. Finally, we will elucidate the prevalence and mechanisms of generating extensile forces in parallel microtubule arrays as these are the predominant arrangements in polarised cells, but only antiparallel sliding has been understood thus far. Success in this project will provide major insights into the mechanisms that establish and maintain cell polarity and why mutations in these motors cause disease.
|
| 30/11/2021 |
£3,309,491 |
|
UNIVERSITY COLLEGE LONDON |
My ambition is to generate a neurological model that incorporates the many different ways that the brain can support language functions. Recovery from aphasia will then be formulated in terms of: (A) the availability of brain structures that could learn to support a lost function; and (B) factors that determine whether of not patients engage these structures.
In three work-packages, I will study very large samples of patients recovering from aphasia in the first weeks and months post-stroke.
(1) Task-based fMRI will identify the neural systems supporting each of 13 language tasks in patients who have damage to different parts of the normal language system.
(2) Anatomical MRI, with biophysical modelling, will investigate changes in tissue microstructure (e.g. iron levels, free water and neuronal density) and ask whether these changes occur in peri-lesional tissue and/or the neural systems observed with fMRI.
(3) The multiple non-lesion factors affecting early recovery (e.g. co-occurring cognitive impairments, clinical interventions, physical and mental health) will be investigated, controlling for lesion-site.
The neural systems identified in Work-package 1 will be incorporated into neurological models of language. Work-packages 2 and 3 will identify the factors that influence whether or not these systems are engaged during recovery.
|
| 30/11/2021 |
£1,353,295 |
|
UNIVERSITY OF LEEDS |
We discovered a molecular mechanism that regulates virus assembly in different families of positive-sense, single-stranded RNA viruses and the para-retrovirus Hepatitis B Virus. These viruses encompass multiple dispersed sequences/secondary motifs termed Packaging Signals (PSs) in their genomes (gRNAs) that have distinct affinities for their cognate coat protein (CP). This hierarchy of CP affinities defines a preferred assembly pathway, simplifying assembly in complex molecular environments and ensuring genetic robustness to mutation. In this research programme we will investigate a further major gRNA-encoded principle of viral infectivity. Virions are transport vehicles between host cells, that cannot afford to become too stable, or they would lose the ability to deliver their cargoes. It appears that PS-gRNA contacts rearrange in the fully assembled virion, preparing it for gRNA release in response to defined cues from the host cell. We will explore the role(s) of this "molecular frustration" in clinically-important viral lifecycles using a unique interdisciplinary combination of tools we have created. As PSs motifs are evolutionarily conserved across viral families, their interactions with CP lend themselves as targets for broad-spectrum anti-viral therapy, including an emerging Virus X. Insights into cargo encapsidation and release can also be exploited in vaccination and gene therapy.
|
| 30/11/2021 |
£578,742 |
|
UNIVERSITY OF YORK |
We discovered a molecular mechanism that regulates virus assembly in different families of positive-sense, single-stranded RNA viruses and the para-retrovirus Hepatitis B Virus. These viruses encompass multiple dispersed sequences/secondary motifs termed Packaging Signals (PSs) in their genomes (gRNAs) that have distinct affinities for their cognate coat protein (CP). This hierarchy of CP affinities defines a preferred assembly pathway, simplifying assembly in complex molecular environments and ensuring genetic robustness to mutation. In this research programme we will investigate a further major gRNA-encoded principle of viral infectivity. Virions are transport vehicles between host cells, that cannot afford to become too stable, or they would lose the ability to deliver their cargoes. It appears that PS-gRNA contacts rearrange in the fully assembled virion, preparing it for gRNA release in response to defined cues from the host cell. We will explore the role(s) of this "molecular frustration" in clinically-important viral lifecycles using a unique interdisciplinary combination of tools we have created. As PSs motifs are evolutionarily conserved across viral families, their interactions with CP lend themselves as targets for broad-spectrum anti-viral therapy, including an emerging Virus X. Insights into cargo encapsidation and release can also be exploited in vaccination and gene therapy.
|
| 30/11/2021 |
£1,655,328 |
|
UNIVERSITY OF GLASGOW |
To ensure accurate genome transmission, eukaryotes employ regulated DNA replication programmes where DNA synthesis initiates in S-phase at multiple defined origins. Despite considerable understanding, many questions remain: what dictates origin location; how (in)flexible is a cell’s DNA replication programme; and when do cells employ origin-independent DNA replication? This application seeks to examine the DNA replication programme of two eukaryotic parasites, Trypanosoma brucei and Leishmania major, where DNA replication flexibility appears central to their biology:
1. T. brucei chromosomes are compartmentalised into a stable, highly transcribed core and unstable, transcriptionally silent subtelomeres, with dramatically differing levels of mapped origins. This application will ask how and why replication compartmentalisation occurs.
2. T. brucei survival relies on recombination of subtelomeric genes encoding Variant Surface Glycoproteins into telomere-adjacent transcription units, one of which is replicated uniquely early in S-phase. This application will ask how such targeted DNA replication occurs and if it drives recombination.
3. L. major appears to have evolved genome-wide DNA replication programme re-wiring: just one origin is activated in each chromosome during S-phase; and subtelomeric DNA replication occurs outside S-phase. This application will ask if L. major has de-emphasized conventional origin-derived replication, allowing more flexible DNA replication to promote genome plasticity.
|
| 30/11/2021 |
£3,624,260 |
|
UNIVERSITY COLLEGE LONDON |
Sensory perception, cognition and motor function all rely on neural processing that is distributed across brain regions. Much of this processing is carried out by the neocortex and cerebellar cortex, which anatomical studies show are highly interconnected, forming multiple closed loops. But the neocortex and cerebellum have traditionally been studied separately. To understand how they work together as a system to form associations, learn motor tasks, predict the sensory consequences of movement and make decisions, it is critical to study how information is represented and communicated between these structures – at the neural population level. We will record neural population dynamics in the neocortex and cerebellar cortex, simultaneously, during reward-based behavioural tasks. We will use widefield whole brain imaging, high resolution dual region 3D two-photon imaging and optogenetic approaches. These will enable us to record and play back specific patterns of neuronal activity thereby testing hypotheses on cortico-cerebellar communication and cerebellar function. This will be complemented with multiscale models that link cellular mechanisms to population level properties. Elucidating fundamental principles of communication, distributed processing and learning will reveal how neural populations in the neocortical and cerebellar circuits work together to learn sensorimotor associations and perform skilled motor tasks.
|
| 30/11/2021 |
£2,109,150 |
|
UNIVERSITY OF EDINBURGH |
Oligodendrocyte precursor cells (OPCs) have an established role in generating myelinating oligodendrocytes. However, many undifferentiated OPCs reside throughout the CNS lifelong suggesting additional, yet unclear roles of this cell population in regulating CNS form and function. Recently, my group has revealed that OPCs can sculpt neuronal connections, indicating that this cell type indeed has fundamental roles besides myelin generation. However, we do not know how OPCs exert these functions, nor do we know how resident OPCs integrate into neuronal networks, how they communicate with surrounding neurons, and how this communication shapes neural circuit assembly. Here, I propose a multiscale approach using zebrafish as model organism in which we use gene expression analysis, gene targetting and manipulation of neuronal activity, combined with structural in vivo imaging, physiological and behavioural analyses. Using these assays, we will determine how individual OPCs are integrated in a defined neural network and how they contribute to activity-dependent refinement of neuronal connectivity. Furthermore, we will elucidate the genetic code by which individual OPCs mediate connectivity between neurons and test how dysfunctional OPCs affect circuit assembly and animal behaviour. Together, this will reveal novel roles of OPCs for circuit formation, function and dysfunction.
|
| 30/11/2021 |
£3,500,000 |
|
INSTITUT DE RECHERCHE EN SCIENCES DE LA SANTé DIRECTION RéGIONALE DE L'OUEST |
Vector control is by far the most effective intervention for reducing malaria infection. It has contributed 78% of the total reduction of the disease burden from 2000-2015. Progress however has slowed since 2015 due to insecticide resistance, and there are calls for investments in new interventions. Gene drive is one of the most promising vector control approaches on the horizon. It requires the release of small numbers of modified mosquitoes with the aim of suppressing their populations or blocking the transmission of pathogens. Implementation of this strategy however requires that i) critical knowledge gaps in the ecology of gene drive be addressed, ii) an exhaustive landscaping of risks assessment and management plans be developed, and iii) technical capacity be built in Africa to take ownership of the technology. This project will, for the first time, connect and mobilize African scientists and their international partners to produce and gather key scientific information that will equip the public and policymakers with the requisite knowledge to take decision on whether or not to accept the technology. Four leading regional research institutes across Africa aided by two international world-class UK-based universities will join forces to run this interdisciplinary program.
|
| 30/11/2021 |
£2,094,546 |
|
IMPERIAL COLLEGE LONDON |
The prevalence of neurodegenerative disorders is increasing at an alarming rate, but our limited understanding of disease mechanisms has impeded the development of new treatments. The association between mitochondrial DNA (mtDNA) mutations, ageing and disease has been known for some time, but a causal link is mostly supported by extreme mouse-mutants or rare human genetic diseases. Our preliminary analysis has uncovered an unexpected, and enormous, diversity of hidden (or ‘cryptic’) mtDNA mutations at the single-cell level in aged humans. We have established new mathematical and experimental methods enabling us to show the functional consequences of these cryptic mutations, and have preliminary evidence they have aging-like effects on gene-expression which can be controlled by caloric-restriction. Here we will map the accumulation of cryptic-mtDNA-mutations in the human brain throughout the life-course, and then model this process in mice. We will determine whether three interventions can decelerate cryptic-mutation accumulation, and thereby slow progression in mouse models of Parkinson’s disease. Parkinson’s disease has been closely linked to age-related mtDNA mutations in humans. We anticipate this will show a direct link between the accumulation of cryptic-mtDNA-mutations in single-cells and age-related pathology at the single-cell level, and show that this is amenable to therapeutic manipulation.
|
| 30/11/2021 |
£1,380,654 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
The recent pandemic has highlighted the importance and great potential of electronic health record data for addressing urgent public health questions in a timely manner, while demonstrating key gaps in existing methodology for this setting.
The overall aim of this proposal is to develop statistical methodology to remove barriers that have hampered important public health issues in COVID-19 being fully addressed; and to apply the methods to answer the immediate and arising public health questions in COVID-19 and more broadly.
Key goals are to:
develop a suite of methodological tools to enable computationally-efficient self-recalibrating risk prediction in EHR databases;
develop a framework for assessing the worth of different treatments within EHR databases, accounting for potential high-dimensional confounding and implementing approaches to estimate individual treatment effects within this;
create analytic approaches to address causal questions requiring data from two separate sources in the absence of full individual linkage.
Data held within the OpenSAFELY platform and the UK Clinical Practice Research Database will be used to motivate the statistical methodological work. Optimal methodological approaches will be applied to address important questions arising in COVID-19 and more broadly, to key questions in chronic disease.
|
| 30/11/2021 |
£2,081,649 |
|
KING'S COLLEGE LONDON |
During division, eukaryotic cells perform a dramatic reorganisation of their cytoskeleton and their internal membranes. Whilst we know much about how the genome is separated, our understanding of how the cell reorganises, partitions and separates its organelles remains poorly understood. During division, the nuclear envelope (NE) is dismantled and regresses into the endoplasmic reticulum (ER), a major organelle occupying over a third of the cellular volume. This hybrid organelle is distributed as a continuous membrane system between daughter cells as cells leave division, but how this membrane is actually separated is unknown. This hybrid membrane also envelops the separating chromatin discs and a machinery called ESCRT-III assembles transiently at the reforming NE to seal gaps in this membrane.
We will use quantitative proteomics and structural mass spectrometry to identify control mechanisms allowing spatiotemporally controlled assembly of ESCRT-III at the reforming NE. We will use whole-cell volumetric EM correlated with live-cell imaging measurements of ER-connectivity to understand how the ER is physically separated during mitotic exit. We will use these approaches to examine how ER-separation and NE-reformation are coordinated and integrated with the inheritance of other major organelles, giving us new insight into the cellular reorganisation occurring as cells complete division.
|
| 30/11/2021 |
£2,151,007 |
|
UNIVERSITY OF MANCHESTER |
Immunological control at the gingiva, a key oral barrier, is poorly understood. This is an oversight as loss of gingiva immune homeostasis results in the development of periodontitis, the most prevalent chronic inflammatory condition of humans. Crucially, periodontitis is known to exacerbate many extra-oral diseases, including Alzheimer’s Disease, gastrointestinal cancer, COPD and rheumatoid arthritis. Thus, delineating immune mechanisms underpinning gingiva health would ensure development of better periodontitis therapies with implications for the treatment of other diseases.
This program will redefine our understanding of how effective gingival immunity is enforced. We recently revealed an unappreciated mechanism by which gingiva innate cells develop, identifying haematopoietic stem and progenitor cells (HSPC) resident in healthy gingiva that locally generate neutrophils and monocytes. Providing insights into the gingival haematopoietic niche we will outline how gingiva-resident HSPC support barrier integrity and impact periodontitis pathology, detailing functional consequences for neutrophils and monocytes of generation within gingival tissue. Moreover, we will ascertain whether gingiva-generated innate cells mediate inflammatory consequences in extra-oral tissues, providing unprecedented mechanistic insight into how periodontitis potentiates distal pathologies. Combined, this program will develop new concepts in mucosal immunology, substantially advancing the field of oral immunology, and identify novel strategies for therapeutic manipulation in periodontitis.
|
| 30/11/2021 |
£2,560,675 |
|
UNIVERSITY COLLEGE LONDON |
The existence of place, directional, boundary and grid cells in the rat hippocampal formation provides strong evidence that it functions as a cognitive map containing map-like representations of familiar environments which enable the animal to identify its current location together with desirable and undesirable locations, and to move towards or away from these. Using our newly developed honeycomb maze, we have shown that the CA1 place cells support flexible navigation by pointing the direction to the goal and, in addition, evaluating the suitability of all non-goalward directions as possible options if the goalward choice is not available. We plan to explore the properties of this representation, its environmental and path integation inputs and the way in which it underpins flexible navigation.
We have also shown that the CA1 place cells are sensitive to the size of the environment. Their firing rates are modulated by a range of environmental sizes with some cells preferring small environments, others intermediate sized ones, and yet others firing only to the largest environment. We will study exactly which aspect of environmental size and shape these cells are monitoring and how they are doing so.
|
| 30/11/2021 |
£2,593,547 |
|
UNIVERSITY OF CAMBRIDGE |
The overarching goal is to determine the functional heterogeneity within prefrontal cortex contributing to individual variation in the aetiology and treatment of key symptoms of major depressive disorder (MDD) including sadness, anhedonia (social and non-social), negatively biased decision making and lack of control/helplessness. Insights gained should facilitate refinement of individual diagnosis and treatment strategies. Key prefrontal regions in which altered activity is linked to MDD and its treatment will be targeted in a non-human primate, common marmosets. Specifically, acute chemogenetic activation/inactivation of these regions will determine (i) the relationship of the lateral orbitofrontal cortex to reward loss and disappointment/sadness, (ii) the contribution of the dorsolateral prefrontal cortex to conflict in decision making and negative bias, (iii) the involvement of the pregenual cingulate cortex in the ability to control environmental events. Behaviour and cardiovascular activity will be measured across multiple computerized cognitive tests and PET/functional MRI will assess distributed effects on circuit activity. With MDD onset associated with adolescence, acute regional interventions during adolescence will identify windows of perturbational vulnerability, whilst multi-parametric MRI will provide neurocircuit developmental insights. Foundational work on marmoset social development will establish novel toolsets for applying our approach in the social domain; highly relevant to MDD onset.
|
| 30/11/2021 |
£2,073,725 |
|
UNIVERSITY OF OXFORD |
I propose multi-modal, cross-species experiments to first determine the neurophysiological mechanisms underpinning motor plasticity, and then to develop approaches that drive plasticity to enhance behaviour. I will focus on the role of neural dynamics, particularly on phase-amplitude coupling of theta- and gamma-activity (theta-gamma PAC), in two key nodes of the motor network: the primary motor cortex (M1) and thalamus, to address these key aims:
Decoding the neurochemical and circuit underpinnings of M1 theta-gamma PAC and how it modulates network connectivity during motor plasticity
Driving motor network connectivity to optimise motor plasticity
Determining clinical relevance: the role of GABAergic signalling and theta-gamma PAC in stroke recovery
I will capitalise on the advantages of cross-species investigations to determine the causality and cell-type specificity of neural dynamics underpinning plasticity. I will drive plasticity using novel human neurophysiological tools to stimulate, and record from, deep brain structures to enhance behaviour. Finally, I will translate the physiologically defined stimulation approach developed in the fellowship to enhance behaviour in chronic stroke survivors. Taken together, this work will provide an essential understanding of the physiological changes underpinning motor skill acquisition, as well as resulting in putative therapeutic interventions to enhance stroke recovery: a substantial, under-met, clinical need.
|
| 30/11/2021 |
£3,426,793 |
|
UNIVERSITY OF CAMBRIDGE |
The unfolded protein response by which cells adapt their endoplasmic reticulum (ER) to changing levels of ER-stress, globally promotes fitness in eukaryotes. However, the outcome of specific pathological processes associated with ER stress may be improved by modulating the activity of specific strands of the UPR. Here we shall focus on three promising yet understudied aspects of the response, in hope of uncovering details that will enable us to exploit failures of homeostasis in the UPR. All three involve enzymes that we hope to attack with modern tools of Cryo-EM, CRISPR-based gene editing, somatic cell genetics, small-molecule (metabol)omics and structure-based tool-compound discovery.
The key ER chaperone BiP is regulated post-translationally by FICD-mediated AMPylation/deAMPylation. Understanding this bi-functional enzyme will provide a handle to manipulate conditions in the ER.
Stress-mediated attenuation of protein synthesis hinges on phosphorylated eIF2 attenuating the nucleotide exchange factor eIF2B via a recently discovered allosteric mechanism. We will search for endogenous metabolites and chemical ligands that exploit this path to allosterically regulate eIF2B bi-directionally.
The eIF2-directed holophosphatase that terminates signalling, has recently become accessible to structural studies; these we aim to deepen in hope of devising strategies to target this recalcitrant strand of the stress response pathway.
|
| 30/11/2021 |
£2,381,916 |
|
UNIVERSITY OF MANCHESTER |
Cell state transitions, whereby cells move from one state to another (i.e. from progenitor to differentiated cell), sometimes reversibly, are of key importance to most areas of biology, including development, regeneration and cancer. Our understanding of this inherently dynamic process is limited by the molecular approaches that are commonly used, such as "omic" approaches which are sophisticated and powerful, but essentially static, relying on "snapshot" data. My research vision is to pinpoint the mechanisms by which cell state transitions take place in real time by applying live molecular imaging, quantitative data and dynamical mathematical approaches.
We will study ultradian gene expression oscillations of key transcription factors (TFs) because recent data suggests that they represent a prevalent yet under-appreciated mode of regulation and are important in enabling cell state transitions. We will focus on how TF oscillations are decoded, the area that we know least about. We will study mammalian and zebrafish neurogenesis, ideal systems for capturing the impact of oscillations in a developmental context.
The proposal has three aims:
Aim 1. To visualise and characterise oscillatory dynamics during cell-state transitions.
Aim 2. To understand the function and decoding of oscillatory gene expression.
Aim 3. To uncover new oscillatory gene expression.
|
| 30/11/2021 |
£1,126,103 |
|
ST GEORGE'S, UNIVERSITY OF LONDON |
Early targeted intervention reduces risk of diabetic complications. We will compare the effectiveness of artificial intelligence (AI) based retinal image analysis, genotyping and linked health record data from people with diabetes mellitus to predict diabetes related complications - incident diabetic eye disease (particularly progression and sight-threatening retinopathy) and systemic (nephropathy, neuropathy, cardiovascular disease). We will apply novel end-to-end AI/machine learning approaches to retinal feature analysis and validated automated AI-enabled retinal vasculometry measurement to one of the largest and most ethnically diverse NHS Diabetic Eye Screening Programmes from North-East London (105,000 patients seen annually, 90,000 with 5 years follow-up, 40,000 with 10 years). We will develop new prognostic models, using retinal image analysis, genetics and health record data (alone and in combination) to predict diabetic complications (particularly retinopathy progression); model performance will be compared with published risk scores/algorithms. Models will be externally validated using the US Early Treatment Diabetic Retinopathy Study, cohort with gold standard retinopathy grading and high complication rates (20% mortality at 5 years). Findings will provide an early warning system of complications, which could be exploited within existing healthcare pathways to trigger early intervention.
|
| 30/11/2021 |
£1,829,135 |
|
UNIVERSITY OF OXFORD |
Vacuolar H+-ATPases (v-ATPases) are ATP-driven proton pumps that acidify intracellular compartments. Acidification is important for a plethora of cellular processes, ranging from neurotransmitter uptake to lysosomal degradation. The timing of acidification is essential for pathways where lowering of the luminal pH is vital, e.g. virus/protein activation, cargo-receptor separation. Despite decades of research, key open questions persist: How is v-ATPase regulated during a process that replenishes synaptic vesicles (SVs) and sustains neurotransmission? Is lysosomal pH dynamically regulated - if yes, how? What are the consequences of poorly regulated acidification for cellular homeostasis and health?
We will tackle these questions through Rabconnectin-3a, a conserved brain-enriched protein whose mutations cause mental retardation, neuropathy and/or hearing loss. Little is known about Rabconnectin-3a due to its large size, lack of tools and early embryonic lethality. We cloned Dmxl2 gene encoding Rabconnectin-3a, generated mouse models and a specific antibody, and detected Rabconnectin-3a on all organelles that acidify. I propose to examine a role of Rabconnectin-3a in the regulation of acidification, and to characterize its functions at the synapse and in two disorders. A multi-disciplinary approach will be employed, from studies of individual organelles to a characterization of neuronal networks by a combination of genetics and electrophysiology.
|
| 30/11/2021 |
£3,500,000 |
|
UNIVERSITY OF EDINBURGH |
Antifungal resistance is increasingly prevalent, raising fungal-borne disease frequencies in humans and crops important for human wellbeing. Conventional wisdom that resistance results solely from genetic mutations has been overturned by our landmark discovery that epigenetic gene repression can cause resistance via heterochromatin-island ‘epimutations’ that arise in fission yeast exposed to external insults. Transient ectopic methyl-H3K9-heterochromatin is normally rapidly erased by the counteracting Epe1-H3K9-demethylase. However, external insults/antifungals inactivate Epe1 via MAP Kinase-induced, proteasome-mediated cleavage, allowing heterochromatin-island formation. Epimutation-mediated repression of mitochondrial protein levels likely confers resistance through mitochondrial dysfunction. We propose that innate or imposed metabolic stress predisposes some cells in populations to form epimutations, and that heterochromatin islands increase mutation frequencies in underlying resistance genes. We will dedicate our expertise in chromatin-mediated epigenetic regulation to understanding how antifungals alter fungal epigenetic landscapes to promote resistance. We will determine how antifungals influence resistant epimutant emergence in human (Cryptococcus neoformans) and wheat (Zymoseptoria tritici) fungal pathogens. Using fission yeast as our workhorse alongside pathogenic fungi we will explore mechanistic conservation and divergence, and real-world impact. Evidence that heterochromatin-dependent epimutations provide a general pathway for initial antifungal evasion would dramatically alter understanding of resistance mechanisms in human and crop fungal pathogens, and beyond.
|
| 30/11/2021 |
£1,580,874 |
|
UNIVERSITY OF SHEFFIELD |
This proposal aims to generate a multi-scale understanding of the remodelling events (fusion and perforation) that change the topology of an epithelial sheet during organogenesis. Failure of these processes underlies common congenital anomalies, such as ocular coloboma, spina bifida and cleft palate.
We will study the developing zebrafish inner ear, which undergoes three rapid epithelial fusion and perforation events, each involving just a few cells. This model system is amenable to genetic, transgenic and pharmacological manipulation, and offers superb opportunities for live imaging.
Key goals are to:
Use live imaging to map patterns of mitosis and apoptosis across the developing ear
Identify genetic requirements for cytoskeletal, adhesion and cell shape changes during inversion of epithelial curvature
Image and manipulate cell behaviour during epithelial fusion and perforation, including live imaging of cytoskeletal changes
Test the role of selected signalling pathways (aGPCR, Wnt/Fzd1, Netrin) in the fusion/perforation event
Test the role of apoptosis in remodelling during and after epithelial fusion/perforation
The findings will improve our understanding of vertebrate otic organogenesis, with more general relevance to identify conserved modules of cell behaviour during epithelial morphogenesis. The project establishes new collaborations with experts on epithelial morphogenesis and cell signalling in other developing organ systems.
|
| 30/11/2021 |
£2,080,541 |
|
UNIVERSITY OF OXFORD |
The symptoms of malaria occur when Plasmodium parasites replicate within human blood cells. The largest parasite protein family displayed on Plasmodium falciparum-infected erythrocytes contains the RIFINs and STEVORs. Recently, applicants on this award discovered that RIFINs can suppress human immune cell function by mimicking the human ligand of inhibitory immune receptor LILRB1. We have also discovered RIFINs which bind four other human inhibitory immune receptors. We now aim to determine:
"How do RIFINs and STEVORs modulate human immunity during malaria?"
This requires a collaborative effort, bringing together the latest tools in transgenic parasite biology, structural biology, biophysics of cell interfaces and high-throughput technology.
Using these tools, we will determine how RIFINs which bind to five different inhibitory immune receptors affect survival of infected erythrocytes in the context of killing by four types of human immune cell, and will show how RIFIN-targeting antibodies modulate these effects. We will conduct high-throughput experiments to determine which RIFINs and STEVORs provide a survival advantage in the context of immune cell-mediated killing and will determine the ligand binding properties of all RIFINs and STEVORs from one parasite genome. These studies will show how RIFINs and STEVORs manipulate human immune cell function during malaria.
|
| 30/11/2021 |
£1,555,142 |
|
KING'S COLLEGE LONDON |
The complement membrane attack complex (MAC) is a human immune pore that directly kills Gram-negative bacteria. The bacterial envelope of these pathogens is composed of two lipid bilayers separated by a peptidoglycan layer. MAC pores must be locally assembled on the outer membrane by the C5 convertase to rupture both membranes and directly lyse cells. While structures of MAC show how the pore forms in a single lipid bilayer, the dimensions of the complex are incompatible with the depth of the bacterial cell envelope. Here we propose that the key for MAC’s bactericidal activity hinges on the local structure of the envelope and the clustering of pores. We will exploit a platform of novel artificial cell mimics to identify the fundamental determinants of bacterial killing. By integrating structural information from cryo electron microscopy with dynamic information from single molecule imaging we will address two central questions in innate immunity: 1) where is MAC located in the context of the cell envelope and 2) how does the C5 convertase control local clustering of MAC. In doing so, our results will provide a foundation for understanding why some bacteria are resistant to killing by MAC.
|
| 30/11/2021 |
£1,844,554 |
|
UNIVERSITY OF SHEFFIELD |
The processing of sensory information is a fundamental feature of human biology, yet we have limited understanding of how it occurs in vivo. The auditory system provides an ideal model to investigate sensory processing, as it incorporates arrays of cells with a precise organisation preserved from the periphery to the brain.
High-fidelity sound perception relies on cochlear hair cells and their nerve fibres to accurately encode acoustic information over broad frequency and intensity ranges. Our current knowledge of this complex process derives largely from ex vivo experiments, since in vivo recordings with subcellular resolution from the intact mammalian cochlea have long been considered unfeasible. This has created a substantial barrier towards our understanding of auditory function, since ex vivo work cannot replicate the sophisticated anatomy, innervation and physiology of the cochlea.
My laboratory has developed surgical and microscopy approaches that, combined with in vivo gene delivery and genetically modified mice, allow us to study the function of mammalian sensory hair cells and their synapses in vivo. We will use this pioneering approach to identify the mechanisms regulating cochlear function, how they change throughout life and, more broadly, to study how the ear and the brain communicate with each other.
|
| 30/11/2021 |
£1,659,685 |
|
UNIVERSITY OF EXETER |
We aim to resolve the chemical identity of molecular patterns that trigger antifungal immunity, and to exploit this information to understand immune evasion during disease progression and inform the future development of improved antifungal diagnostics. Our collaborative team will address this critical challenge through our complementary expertise in state-of-the-art high throughput approaches involving carbohydrate chemistry, antifungal immunobiology, genomics and precision reverse genetics.
Our immune defences provide protection against the constant threat of infection by opportunistic fungal pathogens, and pathogen recognition is a vital first step in these defences. We previously defined the relative contributions of major pathogen-associated molecular patterns (PAMPs) in the cell wall of Candida albicans that are recognised by pattern recognition receptors (PRRs) to illicit immune responses. We also discovered that this major fungal pathogen exploits host signals to activate PAMP masking strategies and evade immune recognition. Critical questions emerge from these studies. (1) What are the chemical identities of the actual PRR-ligands within PAMPs? (2) How does the fungus modulate PRR-ligand exposure as it adapts to host niches? (3) How does this modulation impact fungal virulence and anti-fungal immune responses? Answering these questions, which underlie fungal recognition phenomena, will provide invaluable opportunities for diagnostic and therapeutic developments.
|
| 30/11/2021 |
£2,450,016 |
|
UNIVERSITY OF YORK |
Leishmania donovani infection is characterised by widespread parasite dissemination within and between multiple tissues, a process intimately linked to the parasite’s intracellular lifestyle in myeloid cells. Yet despite dissemination underpinning the pathogenesis of visceral leishmaniasis (VL) and post kala azar dermal leishmaniasis (PKDL), little is known about this critical aspect of parasitism. To address this knowledge gap, we propose a program of research involving: i) comparative in situ analysis of infected human and rodent tissue at single cell resolution (including spatial proteomics / transcriptomics and mass spectroscopy imaging); ii) the application of sequence tag-based analysis of microbial populations to probe parasite within-host population dynamics, and iii) iterative rounds of modelling and experimentation to test hypotheses related to lateral parasite spread in the skin. By applying these orthogonal approaches at key inflection points in the natural history of disease, we will identify key changes in myeloid cell phenotype and function associated with dissemination, discover novel bottlenecks impacting parasite establishment and replication temporally and across different tissues, and gain new insights into the key transition from VL to PKDL. This research will increase our fundamental knowledge of L. donovani-host interactions and provide new targets for host-directed therapy aimed at minimising parasite dissemination.
|
| 30/11/2021 |
£1,858,706 |
|
IMPERIAL COLLEGE LONDON |
Gut mucosal surfaces are vulnerable to infection and diarrhoeal diseases remain a major public health concern worldwide. Many bacterial pathogens employ a T3SS to inject effectors that enable colonisation and evasion of immune responses. Thus far, most studies have concentrated on studying one effector at a time. However, in the majority of cases, single effector mutants do not present a disease phenotype in animal models. Using the mouse-adapted pathogen Citrobacter rodentium as a model, we have shown that the reason for the lack of phenotypes is due to the fact that, rather than operating individually, the effectors can form distinct intracellular subnetworks that can sustain significant perturbations while maintaining virulence. Moreover, we coined the term context-dependent essentiality to define how an effector/cytokine is essential for infection in a specific subnetwork but not another subnetwork. Our overarching aim is to explore the effector network paradigm and to address the following goals: (i) Explore context-dependent effector and cytokine essentialities; (ii) Investigate whether age and the host genetic background play a role in maintaining the expansive effector network; (iii) Build computational models to study and predict infection outcomes; iv) Study signal transduction from injection of effectors into intestinal epithelial cells to immune responses.
|
| 30/11/2021 |
£2,366,520 |
|
UNIVERSITY OF CAMBRIDGE |
Orientia tsutsugamushi (Ot) is an obligate intracellular Rickettsiales bacterium that causes the mite-borne human disease scrub typhus, a leading cause of severe febrile illness in Asia and an emerging public health challenge in other parts of the world. Scrub typhus is the most significant rickettsial disease in severity and prevalence. Its fundamental biology is not well understood, limiting advances in the development of urgently needed vaccines, diagnostics, and treatments. My lab has spent the past eight years working in the USA and Thailand to develop Ot into a robust and experimentally tractable system. We are now poised to gain a deep understanding of the cellular microbiology of this organism. We recently identified Ot subpopulations with distinct physical properties. This project will characterize the mechanism whereby these Ot forms enter cells and escape detection by the endolysosomal pathway. We will also investigate how Ot exploits the host cellular machinery to grow and develop; budding-off mechanisms preceding bacterial dissemination also will be explored. Our knowledge of Ot heterogeneity will provide essential insights for development of improved diagnostic tools. Our physical presence in Thailand and our local partners who can rapidly apply laboratory findings to the clinic will benefit at-risk populations the most.
|
| 30/11/2021 |
£570,748 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
The lack of reliable, timely data on deaths (who, when, what) and births in SSA continues to pose a considerable challenge to estimating intervention needs. Many events across Africa remain invisible to national and international health metrics and health system planners. Informed health policy requires reliable descriptions of births and the age, sex and causes of death for the entire population. New context-specific evidence is required to understand the challenges that plague CRVS systems in Africa. I will use a network of surveillance sites in Kenya to answer four related questions: a) What and where are the gaps and inefficiencies in the current civil registration processes? b) What is the true proportion of unregistered births and deaths in Kenya? c) do individuals have the same probability of being registered by CRVS when they are born or when they die? and d) Why are some births or deaths not registered and are these events systematically different, and what are the potential opportunities and strategies to strengthen registration of all children. This body of work will inform the design of an intervention package aimed at improved monitoring of changes in mortality and natality and demonstrate how to achieve comprehensive CRVS in Kenya
|
| 30/11/2021 |
£1,178,520 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
The lack of reliable, timely data on deaths (who, when, what) and births in SSA continues to pose a considerable challenge to estimating intervention needs. Many events across Africa remain invisible to national and international health metrics and health system planners. Informed health policy requires reliable descriptions of births and the age, sex and causes of death for the entire population. New context-specific evidence is required to understand the challenges that plague CRVS systems in Africa. I will use a network of surveillance sites in Kenya to answer four related questions: a) What and where are the gaps and inefficiencies in the current civil registration processes? b) What is the true proportion of unregistered births and deaths in Kenya? c) do individuals have the same probability of being registered by CRVS when they are born or when they die? and d) Why are some births or deaths not registered and are these events systematically different, and what are the potential opportunities and strategies to strengthen registration of all children. This body of work will inform the design of an intervention package aimed at improved monitoring of changes in mortality and natality and demonstrate how to achieve comprehensive CRVS in Kenya
|
| 30/11/2021 |
£1,828,847 |
|
CARDIFF UNIVERSITY |
Age-related arterial stiffening is a leading cause of neurological problems. The excessive cardiac pulsatile energy reaching the brain’s capillary bed damages the blood brain barrier. Loss of arterial elasticity with age is a natural process normally linked to primary hypertension and cardiovascular disease. However, mounting evidence suggests a strong causal link between reduced arterial elasticity in the body and brain disorders such as small vessel disease, stroke, and many forms of dementia.
We lack technology to image pulsatile flow in the cerebrovascular tree at multiple scales, from large arteries to capillaries. This has hampered our ability to understand the mechanisms by which arterial stiffness progresses in the brain and its contribution to blood brain barrier breakdown and consequent neural degeneration.
I will address this in three themes. The first will develop innovative MR imaging techniques, a Cerebrovascular Stiffness Toolbox, that can link vessel stiffness at all scales to capillary level damage. The second will characterise healthy and compromised buffering during ageing and hypertension. The third will compare acute interventions that change vascular stiffness in mechanistically differing ways (ACE inhibitor vs. calcium channel blocker anti-hypertensives and organic vs. inorganic dietary nitrate) to determine which might best prevent brain arterial stiffening.
|
| 30/11/2021 |
£1,880,390 |
|
UNIVERSITY OF EDINBURGH |
The correct regulation of the inflammatory response is critical to maintaining human health. Immune cells operate within a complex environment and are exposed to several different and often competing signals. They respond to damage signals produced at sites of tissue injury, ‘find me’ cues from apoptotic corpses, bacteria at sites of infection as well as attractive signals emanating from pre-malignant cancer cells. How exposure to one of these signals affects an immune cell’s ability to respond to subsequent cues is a largely understudied area of inflammatory cell biology but it is critical if we are to come up with novel therapeutic ways to manipulate inflammatory cell behaviour in the clinic. In this research proposal we will leverage the powerful genetics and live imaging potential of the fruitfly Drosophila to address this process of innate immune priming/memory. We will investigate how innate immune cells sense and respond to the earliest damage signals that trigger inflammation and uncover how exposure to these signals alters subsequent inflammatory behaviour. We will identify novel molecular controllers of the recognition, uptake and processing of apoptotic corpses as well as understand the inflammatory consequences of apoptotic cell uptake both in wounds and within the emerging tumour microenvironment.
|
| 30/11/2021 |
£3,902,813 |
|
KING'S COLLEGE LONDON |
Chronic pain is a frequent and disabling facet of many immune-mediated diseases, including inflammatory arthritis. A particularly puzzling phenomenon is that during disease-modifying treatments, pain can become uncoupled from inflammation. This results in minimal disease activity but persistent pain for the individuals affected.
Pain in the absence of overt inflammation is frequently ascribed to dysfunction of spinal cord and cortical pain circuits. Conversely, pain during inflammation is seen as a natural consequence of immune cells driving peripheral neuron hyperactivity. This perspective, however, neglects the potential of tissue-resident stromal cells, like fibroblasts, to drive pain in the absence of inflammation.
Our overarching hypothesis is that fibroblasts are key drivers of persistent pain in inflammatory disease. Using rheumatoid arthritis as a model, we will unite expertise across traditionally distinct disciplines to:
Demonstrate that human sub-lining synovial fibroblasts are a prominent source of pro-algesic mediators and can induce neurite outgrowth.
Demonstrate that sub-lining fibroblasts drive neuronal hyper-excitability and pain behaviours.
Find novel analgesic targets by blocking fibroblast-derived pro-algesic mediators or fibroblast sub-populations.
Our research will provide much-needed interdisciplinary insights into the basic principles of how peripheral nerves and fibroblasts interact in painful disease and accelerate the urgent search for more effective analgesics.
|
| 30/11/2021 |
£1,601,492 |
|
UNIVERSITY OF OXFORD |
Adaptive immunity provides essential protection from infectious diseases. This system depends on the ability of lymphocytes to reach distinct compartments within secondary lymphoid organs (SLOs), where specialized cells mediate controlled activation, and where homeostatic survival and peripheral tolerance-promoting cues are presented. Whilst much progress has been made towards defining the mechanisms that regulate these events in lymph-nodes, relatively little is known about how they are orchestrated in the largest SLO in our body, the spleen. Progress in this area lagged largely due to challenges in developing the necessary imaging technology to explore dynamic behaviour of cells within live intact spleens. Our group pioneered cutting-edge imaging approaches that allow us to perform this analysis with high resolution for the first time. Here, we will use a combination of advanced imaging approaches to define the microanatomical structures and molecular mechanisms that facilitate T cell 1) access into splenic T-zones, 2) acquisition of initial activation signals, and 3) egress before/after differentiation into effector cells. These studies will not only resolve fundamental open questions in the field, but also provide a solid foundation for future works aiming to understand how the spleen orchestrates immune responses and how it can be modulated for therapeutic interventions.
|
| 30/11/2021 |
£1,676,751 |
|
NEWCASTLE UNIVERSITY |
Staphylococcus aureus is a major antibiotic-resistant bacterial pathogen that colonises the nares of a large proportion of the human population. In common with several other bacterial pathogens, S. aureus encodes a Type VII protein secretion system (T7SS). While previous studies have implied a role for the T7SS in infection persistence, our work has shown that the S. aureus T7SS secretes large protein toxins whose primary targets are bacteria. We propose that S. aureus uses its T7SS to compete with components of the nasal microbiota during colonisation. Furthermore, in preliminary work we have identified a completely novel T7 substrate protein that may represent a new family of antibacterial toxins. Here we aim to characterise this novel substrate family, and address the role of the T7SS and its secreted toxins in colonisation. We will determine which bacterial species in nasal microbiomes are sensitive to T7SS-dependent antagonism by S. aureus. The antibacterial toxins we have identified must cross the envelope of competitor bacteria to access their cellular targets. We will define the pathway used by a large nuclease toxin to reach the bacterial cytoplasm. Collectively our work will significantly advance understanding of the role of the T7SS in bacterial antagonism.
|
| 24/11/2021 |
£1,268,533 |
|
IMPERIAL COLLEGE LONDON |
This project will identify the cis-regulatory networks that operate in non-alcoholic fatty liver disease (NAFLD) and characterise their role in hepatocyte lipidomic traits.
I will carry out single-cell multi-omics in a cohort of liver biopsies representing different stages of NAFLD progression to identify the active genes and corresponding cis-regulatory elements with unprecedented resolution. I will:
identify the hepatic cell populations that are mostly altered in different degrees of NAFLD and their corresponding marker genes;
identify the transcription factors that drive the transcriptional/phenotypical changes detected with NAFLD progression;
pinpoint the hepatic cell populations whose genetic disruption contributes the most to the heritability of NAFLD and/or NAFLD-associated traits.
To gain mechanistic insights into the contribution of specific genetic loci to NAFLD risk, I will:
carry out variant level in silico and experimental analyses to prioritise variants likely to be causal;
use the single-cell multi-omic maps to assign noncoding NAFLD risk variants to target genes in specific hepatic cell populations ('NAFLD genes');
perform an unbiased loss-of-function genetic screen to identify 'NAFLD genes' that affect intracellular lipid morphological features in human hepatocytes;
use gain/loss-of-function models (regulatory variant and gene levels) in human hepatocytes to validate findings and further characterise hits from the genetic screen.
|
| 24/11/2021 |
£654,442 |
|
UNIVERSITY OF MANCHESTER |
Children and young people’s (CYP’s) mental health is an urgent priority. Dramatic, socio-economic changes following the COVID-19 pandemic has already disproportionately affected families, and with economic uncertainty, further shocks are expected. This fellowship shall use epidemiology, biostatistics, causal inference and machine learning applied to high-quality psychiatric surveys to investigate how changes to the family ‘ecosystem’ affects CYP mental health.
The first goal is to describe typical family ecosystems and assess CYP mental health in each. The second goal will be to conduct first network analysis of mental health symptoms within families using graphical networks. The third goal will be to estimate the effect of acute changes from the pandemic (e.g. school closures) on CYP mental health. Finally, longer term changes to the family ecosystem will be determined, then analysed to assess their effect on CYP. For the latter two, I shall use causal mediation analysis to determine modifiable determinants of mental health and interaction analyses to determine which children are vulnerable, and what modifiable factors could create resilience. A website disseminating findings and provided a children’s mental health dashboard shall be co-created with a CYP advisory group.
|
| 24/11/2021 |
£1,201,313 |
|
UNIVERSITY OF BIRMINGHAM |
The human gut microbiota is a dense and interdependent community and has a mutualistic relationship with the human host. These microorganisms have significant but poorly-understood impacts on health, development, and disease. The major carbon source for these microbes are glycans and polysaccharides and a proportion of these are derived from the host, such as those from mucins and immunoglobulins. This research will focus on how the infant gut microbiota uses the N-glycans in breastmilk as a nutrient source. These N-glycans are an abundant nutrient source for the infant gut microbiota, but remarkably understudied in this context. The anticipated output of this research would be to highlight healthcare improvements, such as pre- and probiotics, that can be made for those infants that do not have access to breastmilk. This is significant as the UK has one of the lowest rate of breastfeeding in Europe, with only 34 % of mothers continuing to 6 months and 0.5 % to 12 months. This output will be achieved by producing a detailed molecular understanding of the enzymes used by Bifidobacterium spp. to access this nutrient source. This study will also characterise how these nutrients are cross-fed between different species and strains.
|
| 24/11/2021 |
£1,241,381 |
|
UNIVERSITY OF OXFORD |
Antibiotic tolerant bacteria transiently enter a non-growing ‘persister’ state in which they can survive exposure to bactericidal antibiotics despite not being resistant. After treatment finishes, persisters can resume growth leading to infection recurrence such as often seen in urinary tract infections (UTIs). Furthermore, typical once-daily antibiotic dosing can lead to rapid evolution of tolerance-conferring mutations. Despite their importance, we understand little about the physiology of persister cells or how they evolve in clinical settings. Here, I will take an interdisciplinary approach, using state-of-the-art single-cell fluorescence microscopy, high-throughput phenotyping, evolution experiments, and genomic analysis to link together our understanding of how genetic mechanisms triggering tolerance in E. coli lead to distinct cell physiological states and how physiology in turn affects antibiotic susceptibility. Importantly, I will test persister susceptibility to novel potential treatments, including bacteriocins and bacteriophages. To test these molecular-level concepts in a clinical scenario, I will analyse the genomes of a unique set of uropathogenic E. coli strains collected from patients who experienced treatment failure to determine how tolerance evolves during treatment of UTIs. Together, this data will be used to identify novel strategies to minimize the evolution of antibiotic tolerance during treatment of UTIs and bacterial infections more broadly.
|
| 24/11/2021 |
£1,282,199 |
|
UNIVERSITY OF OXFORD |
The basal ganglia are implicated in a wide range of behaviors and are particularly important for many types of learning. The diversity of basal ganglia function is tied to cortical diversity; indeed, the entire cortex outputs to the basal ganglia, which is routed in a loop via the thalamus back to the cortex. These three components of the cortex, basal ganglia, and thalamus likely form an archetypal circuit which carries out similar computations in the perceptual, cognitive, and motor domains. The way in which activity propagates across these structures, and how this propagation changes to support learning, are largely unknown. I propose to investigate the interdependence within this circuit by building on my prior work on communication between the cortex and striatum. In those experiments, I developed methodology towards defining the functional relationship between structures, and identified specific learning-induced changes. Here, I will trace those changes across structures throughout learning, I will determine how these changes affect the little-studied output arm of the basal ganglia, and I will causally determine which connections within this circuit drive specific components of both activity and learned behavior. These experiments will contribute toward a holistic understanding of a major neural circuit.
|
| 24/11/2021 |
£986,766 |
|
UNIVERSITY OF BIRMINGHAM |
This fellowship focusses on the growth hormone secretagogue receptor-1a (GHSR1a), a G protein-coupled receptor (GPCR) that binds the orexigenic hormone ghrelin, and is an attractive pharmacological target to regulate appetite. I hypothesise that efforts to target GHSR1a have poor outcomes as GHSR1a signalling is complex, involving GPCR heterodimerisation, interacting proteins and dynamic spatiotemporal signalling. I postulate these mechanisms exist to facilitate GHSR1a’s role as a ‘hub’ at arcuate neurons, where physiological signals are integrated to regulate appetite. Understanding these mechanisms could define new therapeutic targets for obesity and undernutrition.
My fellowship will explore GHSR1a signalling in detail. Aim 1 and 2 will address: how GHSR1a interacts with other GPCRs at membranes; how this modulates signalling; if heterodimers form in hypothalamic brain tissue; and whether this affects ghrelin-mediated physiological functions. Aim 3, will identify proteins that interact with GHSR1a and how they affect GHSR1a signalling. Aim 4 will determine how interacting proteins affect GHSR1a trafficking, and whether GHSR1a can continue to signal from intracellular sites once internalised. State-of-the-art kinetic signalling assays (cAMP Glosensor, calflux, NanoBiT-BRET, HTRF); advanced microscopy (TIRF microscopy with single-particle tracking, HILO, single-molecule pull-down); quantitative proteomics (peroxidase-catalysed proximity labelling); and animal models will be utilised to achieve these aims.
|
| 24/11/2021 |
£1,260,735 |
|
UNIVERSITY OF OXFORD |
More than 100 chromatin proteins have been identified as causative genes in human genetic disease. Most of these genes are broadly expressed and have fundamental roles in transcriptional regulation, yet their disruption causes tissue-specific effects. We do not understand the molecular basis of this tissue-specificity, as it has been challenging to identify the specific cell types affected and to study the consequences of these mutations in the proper tissue context.
I will focus on Cornelia de Lange Syndrome (CdLS), a genetic disorder of cohesin function. Cohesin is a ring-shaped protein complex that encircles DNA and stabilises the 3D folding of chromatin. Mutations in cohesin complex members are thought to disrupt chromatin folding and impair cells’ ability to properly regulate gene expression. This project will determine which genes are particularly cohesin-sensitive and lead to the tissue-specific pathologies of CdLS. I will identify dysregulated genes by applying single-cell and spatial transcriptomics to CdLS mouse models. I will find common chromatin folding features of these genes using genome architecture mapping and look for similar patterns of disruption in banked CdLS patient samples. This project will lay the foundations for a broad research programme exploring chromatin disruption in other developmental diseases.
|
| 24/11/2021 |
£537,211 |
|
UNIVERSITY OF CAMBRIDGE |
Monoclonal antibodies have revolutionised medicine, yet the majority of the proteome remains off limits owing to its intracellular localisation. We identified a receptor for antibody inside cells with E3 ubiquitin ligase activity called TRIM21, which represents a powerful tool by which antibodies can degrade intracellular targets. During the SHDF, we found that delivery of antibodies to a mouse model of pathological tau, a protein that becomes aggregated inside neurons in several neurodegenerative diseases, resulted in protection against aggregated tau in a TRIM21-dependent manner. In this extension, we aim to investigate how different epitopes of tau result in differing mechanisms of protection. Specifically, we will test whether TRIM21-dependent mechanisms and blocking of entry of tau to the cytosol can be achieved by binding alternative epitopes. We will use the results to compare immunotherapies that rely and different mechanisms in vivo. Secondly, we aim to determine the ability of antibodies to gain access to the cytosol of neurons in a quantitative manner. We will examine the properties of cells and antibodies that enable this transfer and whether TRIM21-mediated protein knockdown can be elicited and further improved. Together the results will extend immunotherapy to the intracellular environment for future therapy against neurodegenerative diseases.
|
| 24/11/2021 |
£559,842 |
|
UNIVERSITY OF DUNDEE |
Intestinal intraepithelial T lymphocytes (IEL) reside at the forefront of mucosal immunity, located as they are between nutrient-absorptive intestinal epithelial cells, close to the anaerobic microbes in the intestinal lumen. This specialized environment dictates the fuels and oxygen available to IEL and metabolites that influence their function. I aim to understand how mitochondria and cellular metabolism regulate cellular bioenergetics, macromolecule biosynthesis, redox balance, and metabolite waste management in IEL, thus driving appropriate responses to intestinal metabolic perturbations, including diet and microbial challenges. In this project, I will investigate how metabolic adaptation of IEL to the nutrient-limiting, hypoxic intestinal environment enables their homeostasis and response to infection. We will use cutting-edge techniques including:- stable isotope tracing of glucose utilisation in vivo and mitochondrial metabolomics to elucidate sources of energy fuelling IEL responses; high-resolution respirometry to obtain detailed insights into mitochondrial regulation; genetic models and super-resolution microscopy to study mitochondrial dynamics; and signalling studies to understand how IEL are metabolically activated. This work will provide fundamental insights into the unique metabolic wiring of IEL and illuminate links between diet, intestinal metabolism and intestinal immune responses, findings that can be leveraged therapeutically to tune IEL activity in infectious, autoimmune and/or metabolic diseases.
|
| 24/11/2021 |
£813,463 |
|
IMPERIAL COLLEGE LONDON |
I propose a new and significant departure from our current studies of mTORC1 signalling. The majority of the complexes involved in integrating signals affecting cell-growth have now been understood at a basic molecular level; our understanding of how all of the signalling components fit together at the lysosome, however, remains compromised and incomplete. In particular the TSC and GATOR2 complexes have been implied to modify membranes and to have homology to COPII membrane trafficking components respectively. My intention is to bind our purified TSC and GATOR complexes to lysosomal vesicles to interogate them biochemically, and tailor our on-grid purification techniques to purify and enrich lysosomal signalling complexes for cryo-EM tomography. I expect to learn key details of the mechanisms underpinning signal integration at the lysosome in the mTORC1 signaling pathway, and more generally of the (dys)regulation of cell-growth.
Goals:
- To understand the effects of lysosomal membrane binding on TSC and GATOR protein complex signalling; does lysosomal recruitment affect signal integration and GAP function in each case?
- To understand the effects of binding of the TSC and GATOR complexes on the lysosomal membrane; does membrane remodelling take place in either case, and what is its likely function if so?
|
| 24/11/2021 |
£1,100,243 |
|
UNIVERSITY OF OXFORD |
The primate brain’s reward and decision systems are shaped by biological needs to fine-tune nutrient balance under ecological constraints. Here, we investigate how neurons in these brain systems evaluate specific macronutrients (fat, sugar, protein) and sensory food qualities (taste, flavour, texture) to implement human-typical value-based food choice. We record single-neuron activity from amygdala, orbitofrontal cortex, and anterior cingulate cortex while macaques perform an ecologically inspired food-choice task to obtain nutrient rewards and track visual-nutrient associations. We determine how neurons encode valuation and decision processes for specific nutrients to regulate nutrient balance. Building on our recent work, we apply the Geometric Framework for Nutrition to link monkeys’ nutrient choices and neuronal signals to ecological reference points and foraging strategies. In a parallel neuroimaging study, we translate the same nutrient-choice task and rewards to human functional brain networks. Using transcranial focused ultrasound stimulation in macaques, we test which brain areas contribute critically to nutrient-balancing food choices. Computational modelling determines how neurons interact mechanistically to generate identified neural and behavioural patterns. By challenging neurons with an ecologically relevant food-choice problem for nutrient rewards, we aim to discover functional principles governing the primate brain’s reward systems and identify vulnerabilities for their dysfunction in diseases.
|
| 24/11/2021 |
£653,924 |
|
UNIVERSITY OF YORK |
The bio-activity of cell surface membrane proteins, which perform diverse and critical functions, is governed by membrane trafficking decisions. Internalised surface proteins rely on different endosomal recycling pathways that return them to the surface. My lab has used yeast as a discovery system to identify critical machinery that regulates the trafficking of surface proteins, and we have started to mechanistically dissect their function. We hypothesise critical regulators of yeast recycling, which have obvious human orthologues, function through novel modes of action (Aim 1). As our yeast papers have generated testable hypotheses in mammalian cells, we have optimised assays to measure endocytosis and recycling in cultured human cells, which will be used to understand how surface protein recycling is coordinated through specific lipid regulators (Aim 2). This aim will also be the basis for an exciting complementary research direction in collaboration with Chris Stefan, LMCB, UCL. Finally, we plan to understand how surface proteins are regulated at the surface membrane itself, as we recently revealed this regulation integrates with endocytosis/recycling (Aim 3). In combination, this research programme is aimed at discovering and defining fundamental trafficking mechanisms that control surface protein bio-activity across eukaryotic systems.
|
| 24/11/2021 |
£668,564 |
|
UNIVERSITY OF SHEFFIELD |
Epithelial-to-mesenchymal transitions (EMTs) and mesenchymal-to-epithelial transitions (METs) allow cells to shift reversibly between adherent, static states and more detached, migratory states. Crucial for the formation of many tissues and organs, they are also key drivers of cancer metastasis. METs are often described as the reverse of EMT, driven by the downregulation of EMT-inducing factors. Accordingly, in the Drosophila midgut, we have shown that the EMT transcription factor Serpent needs to be downregulated for MET to successfully proceed, suggesting that there are common mechanisms underlying both processes. However, we recently showed that downregulation of Serpent is not sufficient for MET, and that specific extrinsic cues are also required. These cues appear to drive MET through pathways that are distinct from those affecting EMT. I propose to identify the common and distinct molecular mechanisms underlying EMT/MET. I will do this by interrogating our recently generated single-cell datasets, which chart gene expression changes in midgut cells as they transition from epithelial to mesenchymal states and back again, with our analytical and experimental toolkits. Given the role of EMTs and METs in cancer metastasis, this will likely lead to the identification of therapeutic targets for blocking one process without inadvertently promoting the other.
|
| 24/11/2021 |
£848,519 |
|
UNIVERSITY OF CAMBRIDGE |
All human tissues contain specialised macrophages, that have specific functional properties key to function of the organ where they reside. The human placenta has specialised fetal macrophages termed Hofbauer cells (HBC) located within human placental villi from 18 days post conception to term. They are extra-embryonic immune cells because they are present before any vascular connection to the embryo. Importantly, they are the only placental immune cell throughout gestation. Although, the early appearance of these cells is indicative of an origin from primitive haematopoietic stem cells, this remains to be formally investigated.
During my current fellowship, using state-of-the art technologies, I have demonstrated that first trimester HBC have unique phenotypic and functional properties, in comparison with adult macrophages. I will now: i) characterise the putative HBC progenitors identified in pilot studies, ii) determine the ontogeny of two HBC subsets that I found at term, HLA-DRpos and HLA-DRneg HBC iii) analyse how HBC respond to a common pathogen capable of vertical transmission, Listeria monocytogenes.
These experiments will determine the origin, differentiation, phenotype and function of HBC throughout gestation. The findings will provided a much-needed experimental framework to further study their role in normal and pathological pregnancies.
|
| 24/11/2021 |
£535,361 |
|
UNIVERSITY OF GLASGOW |
New malaria control measures are urgently needed and their development requires a better understanding of the complex life cycle of the disease agent - a protozoan parasite from Plasmodium genus. The biggest bottleneck of this cycle takes place during the initial stages of obligatory mosquito transmission when Plasmodium gametocytes fertilise and create motile ookinete forms, able to penetrate the insect midgut. This transition requires major modification of the parasite's transcriptome but the molecular mechanisms regulating this process are still very poorly understood. Their investigation is further complicated by the fact that Plasmodium zygote contains two parental genomes and both mono- and bi-allelic expression has been observed during the ookinete development.
During my fellowship, I have been investigating the parasite's transcriptome during the ookinete formation and the role of key transcription factors and chromatin accessibility in this process. Now I propose to analyse the sex-specific allele expression at this stage, using both rodent and human malaria models, and the combination of genetic crosses, single-cell sequencing and conditional mutagenesis. This will add an additional dimension to the datasets I have already produced and consolidate my research programme by generating a comprehensive model of the gene expression changes at the ookinete stage
|
| 24/11/2021 |
£774,372 |
|
IMPERIAL COLLEGE LONDON |
Apicomplexan pathogens such as Toxoplasma gondii are obligate intracellular parasites. These parasites are dependent upon the secretion of a highly conserved group of apical organelles for host cell invasion. In T. gondii a lipid post-translational modification (PTM) called palmitoylation is known to regulate apical organelle secretion. Perturbation of palmitoylation disrupts apical organelle secretion, impacting motility and invasion, highlighting its critical regulatory role in this fundamentally important process. While individual palmitoylated protein species have been studied, the wider molecular basis for the regulation of apical organelle secretion by this cysteine-targeted PTM is not known.
This PTM been identified throughout the T. gondii proteome, but it remains to be determined: (1) which specific palmitoylated cysteines on proteins regulate apical organelle secretion? (2) how does this PTM influence the molecular function of these proteins? Studying PTMs one-by-one is challenging. Addressing our questions and overcoming this challenge, we will take advantage of a new CRISPR-based proteome engineering method we have pioneered. This will be complemented with focused cell and biochemical analyses to define how palmitoylation regulates the fundamental process of apical organelle secretion. This will be the first functional analysis of how palmitoylation regulates a specific cellular process in T. gondii.
|
| 24/11/2021 |
£671,399 |
|
UNIVERSITY OF CAMBRIDGE |
Mitochondrial mutations are associated with a spectrum of incurable diseases and ageing. They often arise as unique variants among thousands of wild-type genomes. Their subsequent prevalence, which shapes disease progression and mitochondrial DNA (mtDNA) evolution, depends on how they compete with the pre-existing genomes for transmission. The nuclear genome, which encodes most mitochondrial proteins and functions, can modulate aspects of mtDNA competition. How it works, however, remains unclear as few tools exist to experimentally dissect the nuclear inputs. We have established powerful in vivo and cell-culture based heteroplasmic systems in Drosophila to identify and study the nuclear inputs. Through a genome-wide in vivo screen using deficiencies, we identified multiple nuclear regions containing genes that influenced mtDNA competition (Chiang et al., 2019). We have also identified multiple nuclear genes and compounds that influence mtDNA transmission through the RNAi and compound screening of immortalised cell lines. To fully benefit from these new discovery platforms, we will complete the RNAi and compound screens and characterise some already identified candidates in detail. This will put us in a unique position to reveal molecular rules governing mtDNA transmission and uncover targets for interventions that reduce the propagation of pathogenic mitochondrial mutations.
|
| 18/11/2021 |
£120,000 |
|
BOTSWANA HARVARD AIDS INSTITUTE PARTNERSHIP |
Perinatal transmission is a major route of hepatitis B virus (HBV) transmission in countries with high prevalence rates. 80-90% of HBV infections acquired in the first year of life result in a chronic infection. HBV e antigen positivity and/or HBV viral loads, increases risk of perinatal transmission. HBV vaccination has reduced HBV incidence in infants in some parts of the world. However, the African region has the highest HBV incidence of 2.34% in children under 5 years of age. The World Health Organization plans to eliminate HBV by 2030, by decreasing the HBV prevalence to less than 0.1% in children who are 5 years of age. This project aims to investigate viral transmission dynamics and intra-host evolution of HBV in mother-infant pairs in Botswana. We will screen for HBV infections in 450 mother-infant pairs from a previous study conducted in 2016–2021. We will further determine HBV diversity in the HBV positive mother-infant pairs using next generation sequencing and novel bioinformatics pipelines. This study will enhance understanding of HBV evolution and inform development of vaccines which are effective against vaccine escape mutations and including routine HBV screening as part of antenatal care. Understanding HBV evolution gives insights in virus-host interactions.
|
| 18/11/2021 |
£310,290 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Chronic hepatitis B (CHB) infection affects 257 million individuals and accounts for 900,000 deaths annually. The World Health Organisation has set targets to eliminate hepatitis B virus (HBV) by 2030. However, there are significant gaps in our understanding of the mechanisms underlying HBV disease evolution in Africans. As a result, current guidelines have poor performance to correctly identify Africans in need of CHB treatment, and available antiviral treatment does not clear CHB infection or eliminate risk of cancer.
Recent advancements in metabolomics provide a unique opportunity to identify metabolites and mechanisms involved in HBV persistence and spontaneous hepatitis B surface antigen (HBsAg) loss (functional cure).
In this project, I will use serial plasma/serum samples collected between 2011-2020 during annual follow-up of a well characterised cohort of African adults with CHB infection in The Gambia to identify metabolic fingerprints of HBV-disease progression and HBsAg loss. I will then directly measure the in vitro influence of candidate metabolites on HBV replication and clearance (macrophage response) using a liver-on-chip microphysiological system. Finally I will propose cellular pathways of HBV-disease progression and potential targets for cure.
Study findings will support the development of adapted HBV guidelines for Africans and drive further research towards cure.
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| 18/11/2021 |
£849,898 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Despite the implementation of pneumococcal conjugate vaccines (PCVs) in infant immunisation programmes across Africa, residual carriage of pneumococcal vaccine serotypes (VTs) amongst under-fives in the household poses substantial risk to infants too young to be vaccine protected.
Using a vaccine probe approach, I will determine if under-fives are the primary source of VT transmission to PCV-age-ineligible infants living within the same household in Malawi. I will enrol 784 mother-infant pairs and their PCV-immunised household contacts 12-59 months old (HHC) into a two-arm randomised controlled trial. The HCC will receive either a single booster of the 13-valent PCV (PCV13) in the intervention arm or a comparator vaccine in the control arm. With regular sampling of households, I will determine the extent to which the PCV13 booster for HHCs indirectly protects (cocoons) PCV-age-ineligible infants from VT carriage. Transmission within the household will be examined by sampling pneumococcal carriage and shedding using bacteriologic and cutting-edge genomic sequencing methods.
Combining epidemiological and genomic investigations, I will determine the proportion of VT carriage among PCV-age-ineligible infants attributed to under-fives living within the same household. I will also generate evidence to inform policymaking considerations of the benefits of a targeted PCV booster dose in low-resource settings.
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| 18/11/2021 |
£56,000 |
|
WELLCOME SANGER INSTITUTE |
Despite the implementation of pneumococcal conjugate vaccines (PCVs) in infant immunisation programmes across Africa, residual carriage of pneumococcal vaccine serotypes (VTs) amongst under-fives in the household poses substantial risk to infants too young to be vaccine protected.
Using a vaccine probe approach, I will determine if under-fives are the primary source of VT transmission to PCV-age-ineligible infants living within the same household in Malawi. I will enrol 784 mother-infant pairs and their PCV-immunised household contacts 12-59 months old (HHC) into a two-arm randomised controlled trial. The HCC will receive either a single booster of the 13-valent PCV (PCV13) in the intervention arm or a comparator vaccine in the control arm. With regular sampling of households, I will determine the extent to which the PCV13 booster for HHCs indirectly protects (cocoons) PCV-age-ineligible infants from VT carriage. Transmission within the household will be examined by sampling pneumococcal carriage and shedding using bacteriologic and cutting-edge genomic sequencing methods.
Combining epidemiological and genomic investigations, I will determine the proportion of VT carriage among PCV-age-ineligible infants attributed to under-fives living within the same household. I will also generate evidence to inform policymaking considerations of the benefits of a targeted PCV booster dose in low-resource settings.
|
| 18/11/2021 |
£300,867 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Despite high prevalence of iron deficiency and anaemia in Africa, there are longstanding concerns regarding whether treatment of iron deficiency by giving iron supplements increases the risk of infections, hospitalisation, and deaths. Previous studies have not conclusively addressed this dilemma due to study design limitations such as confounding bias, reverse causality and a requirement of large sample sizes and long follow-up times to investigate rare outcomes in clinical trials. During my post-doctoral studies, I conducted a GWAS and identified novel genetic variants that are unique to African populations that can be used to proxy iron status and anaemia. This now affords me the unique and exciting opportunity to test how these variants influence severe infections and mortality using a Mendelian randomisation approach that overcomes many of the limitations of previous study designs. I propose to identify likely causal genetic variants through fine-mapping, comprehensive functional annotation, and integration of my findings with transcriptomic and epigenomic data. I will then determine whether the prioritised causal variants influence risk of severe malaria, bacteraemia, tuberculosis, and mortality using already available data/samples from large case-control studies in Africa. This novel approach has not previously been applied to iron status and infections/deaths in Africa.
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| 18/11/2021 |
£123,536 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Severe anaemia and bacteraemia are strongly associated in African children, although the precise mechanisms underlying this association remain unknown. I found that this association is observed with specific organisms (e.g. Escherichia.coli, non-typhoidal Salmonella) but not others (e.g. Staphylococcus aureus). Given the multiple putative aetiologies of severe anaemia and increase in antimicrobial resistance, developing a full understanding of the mechanisms that predispose to these bacterial infections will enable the development of better interventions. I propose to test the hypothesis that disruption of iron metabolism and/or immune pathways contributes to increased risk of bacterial infections among severely anaemic children. I will utilise clinical and laboratory data and samples collected over the last 21 years to examine the associations between severe anaemia, immune responses, bacterial iron acquisition and genetic signatures of bacteria during severe anaemia. I will also evaluate the effects of anaemia on bacterial vaccine responses using data and samples from vaccine trials conducted in Kilifi. Findings from this project will elucidate key iron and immune pathways that can be targeted to develop interventions for severe anaemia and prevention of bacteraemia.
|
| 18/11/2021 |
£133,014 |
|
SOUTH AFRICAN MEDICAL RESEARCH COUNCIL |
Forced migrants’ health is a global concern, especially because forced migration is expected to increase substantially driven by war and human caused climate change [1]. In South Africa, there are approximately 2.1 million forced migrants (refugees). This population experiences poor health, driven by exposure to violence, and xenophobia, which further limits access to health care. High rates of intimate partner violence (IPV) have been found among these population [2]. However, little is known about how gender inequalities, xenophobia, and experiences of forced migration, intertwine to shape IPV among forced migrants. This innovative study uses a mixed methods approach and co-development process with young (18-30) forced migrants to understand and then address IPV in forced migrant communities in Durban, South Africa. I will first, using qualitative and quantitative data describe these issues, then co-develop with Youth Peer Research Associates (YPRAs), who are forced migrants themselves, an intervention to address IPV. Finally, I will assess the intervention’s feasibility and acceptability with young (18-30) forced migrants. I will also, together with YPRAs, engage extensively with forced migrant communities, advocacy groups, and government, ensuring research translates to policy change. Study results will inform the co-design of a pilot RCT with this population.
|
| 18/11/2021 |
£269,339 |
|
UNIVERSITY OF CAPE TOWN |
Despite the recognition of anaemia as a global health priority of particular relevance to low- and middle-income countries, little is known about its impact on the developing brain. The aim of this neuroimaging research is to investigate the impact of antenatal maternal anaemia on brain structure and neurodevelopment in children from two high-risk South African birth cohorts. Both a traditional, high-field MRI and the newly introduced Hyperfine low-field MRI will be used to answer this research question, and to explore whether the findings can be replicated across systems. The high-field MRI will be used to determine whether the association between antenatal maternal anaemia and lower corpus callosum and basal ganglia volumes in 2-3 year-olds from a preliminary birth cohort study persists in the same children at age 6. This relationship will also be investigated in 2-3 year-old children from a second birth cohort to confirm whether findings can be replicated, and to assess the role of iron-deficiency. The low-field MRI system’s ability to detect brain alterations associated with antenatal maternal anaemia will be assessed by comparing replicated neuroimaging finds across MRI systems in the second birth cohort. Structural brain changes will be correlated with neurodevelopmental outcomes in both birth cohorts.
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| 18/11/2021 |
£296,299 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Drivers of population differences in vaccine-specific immune responses and vaccine efficacy are not completely understood. This project will address the hypothesis that pre-vaccination immunological and metabolic profiles are key determinants of vaccine response, and parasite exposure a key driver of these profiles.
Three interrelated Ugandan trials have been designed to investigate the impact of helminth and malaria exposure and treatment on immune responses to a panel of live (BCG, Yellow Fever, oral Typhoid), virus-like particle (HPV) and toxoid (Tetanus/Diphtheria) vaccines among adolescents. The current project will exploit the unique opportunity provided by samples from these trials, to investigate
1. pre-vaccination immunological parameters underpinning high and low vaccine responses, using multiplex Luminex® immunoassays and high-dimensional multi-parameter (≥30) spectral flow cytometry
2. cellular and circulating metabolic profiles and their association with magnitude of vaccine response, using flow cytometry and plasma metabolome measurement by high-throughput mass spectrometry
3. relationships between parasite exposure, immunological and metabolic profile, and vaccine responses, using regression, causal mediation and multi-omics approaches
The rich collection of distinct datasets generated will provide a unique opportunity to employ integrative computational analyses for a comprehensive view of biological predictors of vaccine response.
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| 18/11/2021 |
£140,959 |
|
INSTITUT DE RECHERCHE EN SCIENCES DE LA SANTé DIRECTION RéGIONALE DE L'OUEST |
Genetic control approaches through application of CRISPR/Cas9-based gene drives represent a promising strategy to control vector borne diseases such as malaria. While the technology is still being optimized, there is urgent need to address several knowledge gaps crucial for safe and effective field implementation. One of the most important need is to elucidate ecological processes that will influence spread and persistence of transgenes in wild mosquito populations; such as mosquito migration and aestivation. This research project aims to understand these phenomena with the objective of developing a reliable field data-based predictive model of transgene diffusion in the field.
Short and long-range migration, aestivation and spatial population dynamics of An. gambiae (s.l.) will be explored in a group of village clusters in Burkina Faso, to understand their relative contribution to the sustainability and spread of malaria mosquitoes across different ecological settings. Activities will include sequential mark-release-recapture experiments to quantify and characterize dispersal and survival using long-term marking approaches and entomological surveillance to measure spatial population dynamics and highlight the role of aestivation. All these data will be used to inform and build accurate modelling tools for vector control.
Keywords: Genetic control, Gene drive, Mosquito migration, Mosquito aestivation, Mark-Release-Recapture, predictive model.
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| 18/11/2021 |
£674,526 |
|
UNIVERSITY OF CAPE TOWN |
TBM is associated with high rates of mortality and morbidity in children. A delay in diagnosis and brain injury (manifest by infarcts) are important drivers of poor outcome. TBM is a challenge to diagnose due to its non-specific presentation and brain injury is often permanent at hospital admission. Highly sensitive blood-based biomarkers of brain injury could aid in earlier clinical suspicion of meningitis, prompter treatment, and improved patient outcome. Although promising in cerebrospinal fluid, biomarker kits have lacked sensitivity in blood. In this study we will test a new blood-based kit with 1000-fold greater sensitivity for biomarkers ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), which predicts injury severity and outcome in patients with traumatic brain injury. Further, we will examine advanced brain imaging (magnetic resonance and diffusion tensor imaging) over the first 6 months of treatment to identify structural and microstructural biomarkers of outcome. Previous research suggests that neuroexcitotoxicity and cytokine profiles associated with diffuse cellular inflammation may be mechanisms driving TBM brain injury. Therefore, we will also examine the association of metabolomic and genetic markers of neuroexcitotoxicity and differential inflammatory profiles with outcome to identify novel potential treatment targets to mitigate brain injury and improve outcome.
|
| 16/11/2021 |
£820,936 |
|
UNIVERSITY COLLEGE LONDON |
Hemianopia is common following acquired brain injury, and is estimated to affect over 230,000 people living in the UK. Despite its high prevalence and well-described impact on society, it is a neglected clinical problem with no treatments to recover vision. My research shows that patients with hemianopia can show residual vision in their blind field, a phenomenon called 'blindsight'. Patterns of blindsight and one's capacity for visual retraining appear to vary according to the presence of preserved 'secondary' visual pathways. Where pathways remain intact, they represent an important potential target for rehabilitation. I will use cutting-edge neuroimaging techniques in patients and healthy controls to build a normative connectivity atlas of the central visual pathways. I will quantify the relationship between secondary visual pathway integrity and function in patients and controls, to learn how to optimally drive their response. I will use results to develop a novel visual-training protocol targeting the ventral visual stream, and test whether the integrity of ventral and dorsal visual pathways can predict improvement with visual training protocols targeting those two domains in patients with hemianopia. Understanding the secondary visual pathways will expand neural targets and enhance precision through a customised approach to treat hemianopia.
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| 16/11/2021 |
£685,229 |
|
UNIVERSITY OF MANCHESTER |
The fovea is the small depression at the neurosensory retina that underlies high-resolution central vision. It is particularly vulnerable to disease and disruption of its normal architecture causes visual disability. Notably, foveal morphology varies significantly across individuals and this is thought to be linked to variations in foveal development. The molecular causes and functional consequences of this anatomical diversity are incompletely understood. Addressing this knowledge gap is this proposal’s main objective.
My central hypothesis is that variation in foveal morphology is caused by variation in the pigmentation of the retinal pigment epithelium (RPE), the monolayer supporting retinal neurons. To test this, I will analyse retinal scans available through the UK Biobank and perform a genome-wide association study of image-derived foveal phenotypes. Preliminary analyses have highlighted a number of variants including a common missense change in tyrosinase, the rate-limiting enzyme of melanogenesis. I will use high-resolution imaging to study how foveal morphology is altered in people carrying this tyrosinase variant. I will also generate iPSC from these individuals and use CRISPR-Cas9 editing to study/rescue melanin defects in iPSC-RPE.
This work will elucidate the molecular factors that underlie variability in foveal morphology and will advance understanding of both fundamental and clinically-relevant neurobiology.
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| 16/11/2021 |
£932,288 |
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UNIVERSITY OF EDINBURGH |
Neutrophil driven tissue injury is a common feature of inflammatory lung disease. I have shown that tissue neutrophils are biosynthetically active and utilise extracellular proteins to fuel de novo protein synthesis. The neutrophil proteome is highly dynamic, with protein turnover regulating key process and defining effector functions at sites of injury. The mechanisms which determine the repertoire of neutrophil protein synthesis are unknown. The requirement for ATP and amino acids suggests a role for the nutrient-sensing kinases, AMPK and mTORC1 and the related proteolytic organelle, the lysosome. mTORC1 and AMPK respond to environmental signals in a cell-specific manner to permit or restrain growth. Neutrophils are non-proliferative but synthetically active cells and, as such, are subject to unique growth pressures. The role of the mTORC1/AMPK/lysosome axis in responding to these pressures and the factors downstream of them which drive protein synthesis in the neutrophil are unknown. I hypothesise that delineating these pathways will identify novel therapeutic targets in neutrophilic inflammation.
My key aims are therefore to:
1. Determine the factors which regulate neutrophil protein synthesis
2. Investigate the relationship between protein synthesis and inflammation in the neutrophil
3. Target protein synthesis in tissue neutrophils to alter outcomes in inflammatory lung disease
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| 16/11/2021 |
£644,817 |
|
UNIVERSITY COLLEGE LONDON |
I previously showed that in Alzheimer's disease (AD) amyloid beta constricts brain capillaries via signalling to pericytes.
I now wish to investigate:
(1) Parkinson's disease (PD) / Lewy Body Dementia (DLB), where alpha-synuclein evokes ROS production and hypothesise that endothelin will be released (as observed in AD) and evoke pericyte-mediated capillary constriction to decrease cerebral blood flow.
(2) The role of APOE receptor LRP-1 in regulating increased tau phosphorylation in AD. LRP-1 is a master regulator of tau uptake/spread and highly expressed on pericytes. In AD model mice, pericyte deficiency leads to tau pathology and early neuronal loss. Thus, pericyte LRP-1 may play an important role in clearing/processing tau in the setting of amyloid pathology. I will examine whether AD-like tau pathology develops in an APP knock-in AD/pericyte-LRP-1 deficient mouse model.
(3) The effect of Covid-19 on live human pericytes and capillaries.
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| 16/11/2021 |
£843,855 |
|
KING'S COLLEGE LONDON |
Cognitive symptoms of schizophrenia account for a significant proportion of the disease’s morbidity but have no effective pharmacological treatments. Cognition involves coordinated patterns of activity in functional brain networks, which in turn depend on interactions between excitatory glutamatergic pyramidal cells and inhibitory GABAergic interneurons. Perturbation of the excitatory and inhibitory (E/I) balance may underlie disruption of the functional networks in schizophrenia, and therefore result in cognitive impairments. Normalisation of this putative E/I imbalance represents a promising therapeutic target for novel treatments of schizophrenia, particularly those intended to improve cognition. A major obstacle to investigating these hypotheses is the lack of methods to derive mesoscale measures of E/I imbalance from observable macroscale measures of functional networks in patients.
I will develop a novel cross-species biomarker of E/I balance, derived from computational modelling of functional MRI and EEG. I will validate the approach using a mouse model in which the true microcircuit nature of E/I dysfunction is known. I will then use this method to characterise E/I balance in individuals with schizophrenia and determine possible connections with cognitive impairments. Finally, I will use the approach to elucidate whether memantine, a potential treatment for cognitive deficits in schizophrenia, acts by restoring E/I balance.
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| 16/11/2021 |
£1,130,275 |
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UNIVERSITY OF OXFORD |
Oesophageal adenocarcinoma (OAC), a disease of unmet need, demonstrates high rates of chromosomal instability (CIN).
CIN constitutively activates the cGAS-STING pathway, producing extracellular 2’3’cGAMP which should stimulate host immune cells. Recently, we identified upregulation of ENPP1 as a key mechanism of immunosuppression in CIN-high cancers, hydrolysing 2’3’cGAMP and increasing adenosine in the tumour microenvironment (TME).
My data support that:
- Fibroblast-ENPP1 expression is a mechanism of immune exclusion, upregulated by extracellular vesicles (EVs) from CIN-high cells
- ENPP1 correlates with a protumourigenic extracellular matrix (ECM) promoting immunosuppression.
This fellowship will identify novel targets mediating immunosuppression in CIN-high OAC.
AIMS
(1) How do constitutively cGAS-STING-active CIN-high tumours signal to stromal cells, resulting in ENPP1 upregulation?
EVs from CIN-high and CIN-low cells will be profiled (proteome, miRNA, genome).
(2) What influence does CIN-associated fibroblast ENPP1 expression exert on the ECM?
Organoid-fibroblast co-cultures will delineate how fibroblast-ENPP1 influences tissue stiffness, using biomechanical characterisation.
(3) Is T-cell exclusion from the TME ENPP1-dependent and fibroblast-specific, and what are the underlying mechanisms?
OAC samples will be characterised (using flow cytometry and digital spatial profiling) identifying fibroblast-ENPP1-regulated immune populations. Tri-culture models (matched organoid-fibroblast-immune cells) will analyse T-cell reactivity and cytotoxicity regulated by fibroblast-ENPP1 and novel targets.
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| 16/11/2021 |
£666,043 |
|
KING'S COLLEGE LONDON |
Cerebellar anomalies represent the most consistent defect in many prevalent neuropsychiatric disorders such as autism. Imbalance in excitatory: inhibitory (E:I) neurons has been implicated in the pathogenesis of these disorders in the cerebral cortex yet the precise role of E:I imbalance in cerebellar associated disease has been largely overlooked. We recently identified a novel human genetic disorder associated with cerebellar hypoplasia and autistic features caused by mutation in PRDM13 and subsequently discovered a novel function for Prdm13 in cerebellar GABAergic interneuron fate specification. Little is currently known about what regulates GABAergic interneuron specification or how these neurons function to influence behaviour. I will identify central regulators of inhibitory cell specification in the cerebellum, and the underlying molecular mechanisms and consequences of altered specification on circuit function. I will combine mouse genetics, single cell transcriptomics and state-of-the-art in vivo functional imaging and electrophysiology to address the following goals:
(1) Characterise molecular mechanisms driving specification and diversification of cerebellar inhibitory interneurons.
(2) Identify how Prdm13 regulates inhibitory fate specification.
(3) Determine consequences of Prdm13 disruption on the functional properties of cerebellar interneurons.
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| 16/11/2021 |
£472,823 |
|
UNIVERSITY OF CAMBRIDGE |
My overarching research goal is to understand the mechanisms by which body weight and hypothalamic-pituitary-gonadal axis function are coupled, and how this becomes disrupted in obesity.
We have identified three girls with severe obesity harbouring duplications at chromosome Xp11.22-p11.23. Duplications at this locus are associated with obesity and precocious puberty in other patients. The minimal critical region encompasses PCSK1N, a gene that encodes ProSAAS, a propeptide highly expressed in the hypothalamus and neuroendocrine tissues.
Very little is known about the function of ProSAAS in humans. In cells, ProSAAS-derived peptides inhibit prohormone convertase 1/3 (PC1/3), an enzyme that cleaves and activates hormones and neuropeptides including those regulating food intake. In the hypothalamus, Pro-opiomelanocortin (POMC) is cleaved into alpha melanocyte stimulating hormone (alphaMSH) which activates melanocortin-4 receptor (MC4R) to suppress food intake. Our team has previously shown that genetic loss of function of PC1/3, POMC or MC4R causes obesity in humans.
In this fellowship, I will test the hypothesis that excess ProSAAS causes obesity in patients with Xp11.22-p11.23 duplication. Combining mass spectrometric peptide analysis, advanced microscopy and metabolic phenotyping in patients, I will evaluate ProSAAS’s role in regulating the intracellular processing, trafficking, secretion and function of key neuropeptides involved in energy homeostasis.
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| 16/11/2021 |
£1,218,129 |
|
UNIVERSITY COLLEGE LONDON |
The immune system is central to almost every aspect of human health and disease, with tissues accepted as the determinative site of immune cell function. Biopsies have provided valuable insight but remain static snapshots that miss the critical temporal dynamics of immune responses. The ultimate aspiration would be to observe real-time, unperturbed, immune cell behaviour deep within the tissues of patients. The eye can realise this goal, as the transparent ocular tissues are inherently suited for repeated in vivo imaging across time.
I discovered offset-aperture adaptive optics scanning laser ophthalmoscopy (AOSLO) allowed label-free, non-invasive imaging of individual immune cells within the mouse retina. This project will apply the approach to man for the first time, pioneered in patients with retinal inflammation (Uveitis). Achieving this would transform patient care through improved diagnosis and monitoring, alongside unprecedented opportunities to study fundamental human immunobiology.
To interpret the offset-aperture characteristics of recorded immune cell subsets, I will establish the first mouse AOSLO platform in the UK. These intravital recordings will be directly correlated to ex vivo immunohistochemistry using a highly multiplexed technique I recently developed (3D-IBEX). This technique will be further employed to construct the first 3D human retina atlas of health and disease.
|
| 13/11/2021 |
£0 |
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UNIVERSITY COLLEGE LONDON |
To successfully navigate through their environment, animals must constantly compare sensory information about the world around them with their own ideas about current location, heading direction and motion status. Precisely which areas of the mammalian brain contribute to this comparison process is unknown, but recent work has shown that information regarding head movements provided by the vestibular system is present in the earliest stage of visual processing in mouse neocortex, specifically, in a group of excitatory neurons residing in its deepest layer.
I aim to understand the cellular basis of how vestibular signals, alongside other internally generated inputs, modulate the responses of these neurons to visual input, and how these neurons modulate the response profiles of other neurons in their cortical column.
I will design and build a microscope capable of simultaneous volumetric three-photon calcium imaging and two-photon optogenetic stimulation in headfixed mice. I will also implement a modification to the conventional headpost setup which allows mice to make self-generated movements that can be reversibly coupled to visual and vestibular input.
These experiments will contribute to our understanding of context-dependent processing in an understudied class of pyramidal neuron.
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| 13/11/2021 |
£0 |
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UNIVERSITY COLLEGE LONDON |
Epithelial tissues line most of our organs. They have two distinct surfaces with the apical surface facing the inside of the organ and the basal surface facing the outside environment, including the extracellular matrix. While we understand how cells interact to organise the apical surface of tissues, we know very little about the pathways that organise the basal surface, and how morphogenesis is coordinated between the apical and basal surfaces to shape a tissue in 3D. The objective of my PhD research is to establish the pathways that induce basal surface organisation and reveal those that mediate coordinated movement and cell shape changes along the apical-basal axis to shape tissue in 3D. For my research, I will use Drosophila and take advantage of its genetic tools and imaging capabilities to manipulate and image cells in living tissues. Generating functionally distinct surfaces underpins epithelial shape and function. It is essential for nutrient absorption (intestine) and gas exchange (lungs) for example. Therefore, I expect my work to be broadly applicable to epithelial tissues, to both their formation and how this can go wrong in disease.
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| 13/11/2021 |
£0 |
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UNIVERSITY COLLEGE LONDON |
Epithelial tissues form boundaries between external and internal environments in organisms. When epithelia are injured, they must repair quickly and accurately to minimise damage and preserve organ function. Two possible mechanisms of wound repair are cell shape changes and rearrangements. Both mechanisms are linked to the basement membrane (BM), a layer of extracellular matrix (ECM) underlying epithelial cells, through cell-ECM adhesions. The BM has a key role in controlling the physical properties of tissues, but how the BM modulates its mechanical properties to control wound healing remains unknown.
We will use Drosophila wing discs as a model system because they robustly repair wounds, are easy to genetically manipulate and have a simple 3D geometry. After wounding discs, we will visualise epithelia and BM and measure their mechanical interactions using quantitative live and fixed super-resolution microscopy, electron microscopy and biophysical methods. Machine-learning-based image analysis pipelines will be used to accurately quantify 3D cell shapes in dense live tissues. These experiments will inform parameters in 3D computational models, allowing us to further understand the forces between cells and BM components. This research will identify novel methods to edit the physical properties of cells or BM and design scaffolds for tissue repair treatments.
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| 13/11/2021 |
£0 |
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UNIVERSITY COLLEGE LONDON |
Despite over 70 years of research on the neural basis of working memory (WM), it is still not understood how information is maintained in the brain over short periods of time (seconds to minutes). Classical neurophysiological studies since the 1970s have posited that the sustained firing of neurons in the cortex could explain how information is held in WM. There have been alternative theories for maintenance of information via synaptic changes. However, because electrophysiology dominated most of neuroscience research in the 20th century and made it relatively easy to record the firing rate of neurons, the study of these alternative mechanisms has remained somewhat unexplored. With the advent of new techniques such as two-photon calcium imaging, optogenetics and computer generated holography, it is now possible to record and manipulate the activity of single neurons in awake behaving rodents. Using an auditory parametric WM (PWM) task in head-fixed mice, we aim to implement a closed-loop ‘all-optical’ setup to probe whether the maintenance of cues in WM is accompanied by changes in the functional connectivity between neurons in the cortex. This research will provide fundamental insights into the neural mechanisms underlying PWM and the nature of the neural code.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Fatness is linked to increased risk of diseases including type 2 diabetes, cardiovascular disease, cancer and some infectious diseases. However, the reasons for these links are not fully understood. Metabolites are small molecules in the blood that can be measured and potentially help to explain links between differences in body composition and disease outcomes. I will use metabolite data from blood samples from patients who have undergone a weight loss intervention (bariatric surgery or a lifestyle intervention) to try to unpick the relationship between fatness and disease. Metabolites are linked to a person’s genes, so I will also use genetic data from population-based studies to support my findings using alternative methods. This study will increase understanding of the pathways between fatness and disease at a molecular level. In addition, findings from this study may help to identify who will benefit most from different weight loss interventions, or even identify potential pathways that can be targeted to help patients with obesity improve their health.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF EAST ANGLIA |
Healthy ageing poses a constant challenge we are facing globally. We strive for feasible and affordable solutions to combat age-related chronic diseases. Evidence is accumulating of the health-promoting properties of plant-rich diets. Characteristically, anthocyanins are red, purple or blue, and water-soluble pigments, commonly found in many fruits and vegetables. Anthocyanins have drawn considerable interest due to their biological importance and versatile applications in many fields. Notably, dietary anthocyanin intake has been associated with a low risk of human chronic disorders (e.g., cardiovascular disease, type 2 diabetes mellitus and neurological diseases), and consumption mediates inflammatory markers, weight control, memory and is associated positively with mood enhancement.
I aim to investigate how the consumption of coloured potatoes containing anthocyanins might contribute to gut and brain health. Overall, the primary objective is to identify varieties of common foods that differ in their anthocyanin content, and the approach is to undertake compositional analysis prior to comparing their efficacy in protecting against chronic disease and/or in enhancing mood and memory. Finally, this study will enable me to gain insights into the mechanisms by which how anthocyanin-enriched foods benefit health, and provide evidence-based recommendations for diets to relieve the socioeconomic burdens of unhealthy ageing.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Microtubules and actin are core components of the cell cytoskeleton and critical for many cell processes from ranging from intracellular transport, to cell migration and division. Microtubules are helical polymers of tubulin monomers that form a hollow cylinder. Actin monomers assemble to form a helical filament. They have been understood as distinct structures but recently, actin filaments have been found in the microtubule lumen (microtubule lumenal (ML-)actin), revealing an unexpected versatility in cytoskeletal form. These ML-actin filaments were found to exist in two conformational classes, both of which have a higher degree of helical twist than canonical actin filaments.
It is unclear how these structures form and how they influence microtubule properties. I will address this question using cryo-EM techniques in model HAP1 cells where ML-actin was first discovered. I will integrate these findings with biochemical experiments to reveal its regulation. I will also be relating my findings to a physiological system, platelets, where lumenal filaments have been previously observed.
Understanding microtubule lumenal actin will uncover new aspects and functions of the cell cytoskeleton and reveal how they could be targeted in disease states.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF SHEFFIELD |
The making of economic and policy decisions about public health is widely acknowledged to be a 'messy' or 'wicked' problem. As such, it should be an ideal candidate for the use of complex systems modelling. However, these techniques have been slow to gain acceptance in the public health arena.
The SIPHER Consortium (sipher.ac.uk) brings together several universities and policy organisations with the aim of maximising health and wellbeing through the application of systems science. One of its key objectives is the transfer of systems modelling and analysis skills into the partner organisations themselves.
My research will focus on how the SIPHER modelling approach can be made as accessible as possible to in-house analysts and as meaningful as possible to decision-makers. This is expected to involve the development of an open-source 'framework tool', designed to guide users through the modelling workflow step by step. By standardising and streamlining the process, it is hoped to bring complex systems modelling into the mainstream, so that the health and wellbeing benefits of its contribution to intelligence-led policymaking can be realised.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Cancer is one of the major causes of illness and death in the world1. Its burden is expected to increase due to population ageing and growth, and because people are leading increasingly unhealthy lifestyles by smoking, drinking alcohol, gaining excess weight, eating unhealthy diets and being physically inactive2. Although evidence regarding the aetiology of cancer is growing and several causes of cancer have already been identified, evidence for some risk factors is still weak and the underlying biological mechanisms driving many of the observed associations remain unclear2,3. I will explore associations between several lifestyle/biological risk factors and cancer, as well as potential metabolic pathways mediating these associations using novel causal inference methods, such as Mendelian randomization. A better understanding of the causes of cancer and the mechanisms involved in cancer development could contribute to the targeted prevention and treatment of the disease.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Depression is a common mental health problem and the use of drugs, known as antidepressants, are being prescribed more and more to help people with depression. Pregnant women also suffer from depression and may need antidepressants, however we don't know enough about their potential harms to give good advice to women about whether these drugs are safe in pregnancy. In this PhD, I will use GP data to try and understand the effects of antidepressant use and untreated depression during pregnancy on the baby. I will look at three groups of outcomes: pregnancy (including miscarriage and stillbirth), birth (including whether the baby is born early or is small when it is born) and childhood (including autism) outcomes. I will use a range of methods that use statistics to tackle the different sources of bias that pose a problem to this kind of research; in doing so, the overall conclusion of whether antidepressant use during pregnancy negatively impacts on these outcomes or not will be more accurate than previous studies that only use one or two methods. In order to properly communicate risk, I will work with patient groups to ensure that the findings best explain the findings without placing blame.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Double-stranded DNA, the genetic material in most organisms, carries all the information required for fundamental life processes. Damages to DNA molecules in the form of breaks occur due to factors like irradiation, mechanical stress and reactive oxygen species. Cells have evolved mechanisms to repair breaks in their DNA which are otherwise lethal. The first step of the repair pathway involves recognition and resection of the DNA end. Resection inhibits error-prone repair by classical end joining and is mediated by nucleases and helicases (MRN, Exo1, Dna2). CtIP, a DNA binding protein and cofactor for the MRN complex, is critical for DNA end resection which promotes DNA break repair by homologous recombination (HR). Here we are seeking to understand how cells repair breaks and the role of CtIP using biochemical and biophysical approaches including HDX-MS and X-ray crystallography. CtIP interacts with other protein partners and we will also aim to elucidate the roles of these interactions in the repair pathway. Mutations in CtIP are associated with cancer and neurological diseases like Seckel and Jawad syndromes. This work will provide new insights into the repair mechanisms and the possible role of CtIP in these disease states.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Vegetarian diets are defined as diets without the intake of meat, fish, or seafood. Vegetarianism is socially and culturally patterned, and nutrient intakes also differ between vegetarians and non-vegetarians. While previous studies have found that vegetarian diets are associated with a range of health outcomes in the general population, evidence on the relationship between maternal vegetarian diets during pregnancy and offspring health remains scarce. Using the data from several European birth cohorts, we will first profile and compare the nutrient intakes and nutritional profile between vegetarian and non-vegetarian pregnant women and then apply a series of causal inference methods (e.g. observational association analysis, Mendelian randomisation, paternal negative control, within-sibling comparisons, and cross-context comparisons) and multi-omic approaches (e.g. epigenomic and metabolomic analyses) to find out whether following a vegetarian diet during pregnancy causally affects the health of offspring and whether any of these effects are mediated by early-life epigenetic and metabolic alterations. Given the increasing popularity of vegetarianism and the importance of optimal nutrition during pregnancy for maternal and child health, our findings will help comprehensively evaluate the pros and cons of the increasingly popular vegetarianism and have implications for dietary counselling and guidelines for pregnant women.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Rapamycin is a drug currently used to treat some cancers and to prevent organ rejection. In yeast, flies, fish and mice, rapamycin improves both healthspan and lifespan, and therefore makes it a promising anti-ageing treatment. However, long-term treatment with rapamycin is associated with numerous side-effects such as decreased wound healing, making it unsuitable for an anti-ageing treatment in humans.
The "mechanistic target of rapamycin" (mTOR) pathway is a vital cellular pathway. It is involved in the regulation of cellular growth and protein synthesis. Rapamycin is an inhibitor of the mTOR pathway and rapamycin or inhibition of mTOR has been shown to decrease cell movement. We have recently described a distinct pool of mTORC1 activity at the edge of the cell, in an area important for movement. We hypothesise that inhibition of mTORC1 by rapamycin prevents the formation of proteins required for cell movement leading to reduced wound healing. My project aims to investigate the role of mTORC1 in cell movement, to see if we would ever be able to use rapamycin as a human anti-ageing treatment.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Alzheimer’s disease (AD) arises through the aggregation of amyloid-beta (a cleavage product of APP) and tau protein throughout the brain. The build-up of these proteins can result in harmful changes to neuronal functioning and health, including dysfunction of mitochondria, which are responsible for energy production within the cell, and changes to the way neurons communicate with each other at synapses. My project aims to express AD-causing mutant forms of APP and tau proteins in primary neuronal cultures to generate a sped-up model for neurodegeneration in AD. Upon validating these models with regards to neuronal health and production of neurotoxic proteins, the models will then be used to investigate the changes to mitochondria morphology and proteins controlling this. Using a mixture of protein biochemistry, immunofluorescence imaging and potentially electrophysiology, I will detect changes that occur when either or both of these neurotoxic proteins are expressed to dissect each proteins’ role in mitochondrial dysfunction. Further to this, the cellular localization, surface expression and activity of synaptic proteins including AMPA receptors and CB1 receptors will be investigated following expression of these neurotoxic proteins. This work could help to find new points of intervention to slow dementia in AD.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Pregnant women are heavily underrepresented in clinical trials as it would be unethical to conduct a human trial with a potential outcome of neonatal birth defects. Thus, prescribing medication to pregnant patients provides a challenge for physicians as the beneficial effect of the drug must be balanced against possible maternal and neonatal adverse effects. This presents a significant problem as there are a range of chronic conditions requiring ongoing treatment that precede or develop during pregnancy. I aim to evaluate the potential risks and benefits currently associated with continuing medications through triangulation of evidence from pharmacoepidemiological and genetic studies to inform clinicians and patients. I will use electronic healthcare record data to investigate the beneficial and detrimental effects of maternal prescriptive drug use for diabetes, hypertension, and thyroid disorders for both mother and neonate. I will also proxy maternal prescriptive drug use through analysis of genetic drug exposures on neonatal outcomes to determine whether genetic proxies can indicate adverse neonatal drug reactions. This PhD will establish reliable evidence for the intrauterine exposure of prescription drugs on the mother and neonate to provide evidence to guide clinical decisions under circumstances where we are unable to perform a randomised controlled trial.
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| 13/11/2021 |
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UNIVERSITY OF BRISTOL |
Background: Colorectal cancer (CRC) patients often present at clinic with advanced disease (where the tumour has spread) making it more difficult to treat. Rectal cancer patients are treated with chemotherapy and radiotherapy (CRT) prior to surgery, although response is variable and patients who do not respond have a worse prognosis. The aim of this work is to improve the response of CRC patients to therapy. Previous work from our laboratory suggests tumours with high levels of the BCL-3 protein are less responsive to CRT because BCL-3 promotes DNA damage repair, allowing the cancer cells to become resistant to DNA damaging therapy.
Approach: I aim to investigate how targeting BCL-3 levels inhibits DNA repair, leading to sensitization of cancer cells to therapy. We will study the effect of BCL-3 on the density of DNA (which can modify repair processes), and identify which proteins interact with BCL-3 when DNA is damaged to understand the mechanism. We will test the suitability of BCL-3 as a therapeutic target, using a small molecule BCL-3 inhibitor to treat colorectal cancer models.
Impact: This work will help us understand the link between BCL-3 and therapeutic resistance, and the validity of BCL-3 as a therapeutic target for CRC.
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| 13/11/2021 |
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UNIVERSITY OF CAMBRIDGE |
Oligodendrocyte progenitor cells (OPCs) must maintain myelin in the central nervous system (CNS), a lipid layer that supports neuronal function. Damaged or lost myelin therefore must be replaced by OPCs to preserve optimal CNS function through a complex process called remyelination. However, remyelination efficiency gradually declines with age until it fails completely, with recent work showing that aged OPCs are unable to activate and initiate remyelination. Intriguingly, if OPCs are pushed into an active state, the entire process of remyelination can be restored in aged animals. While this highlights the importance of OPC activation, its precise mechanisms are not well understood.
In this project, I aim to characterise the changes in gene expression and chromatin accessibility in OPCs with activation and age through multi-omic analyses. This may identify novel genes that drive OPC activation and explain its impairment during ageing. I will then demonstrate the involvement of these candidate genes using in vitro assays with primary OPC cultures, and finally assess the ability of these candidates to bolster remyelination in aged mice. Such findings could reveal the key regulatory mechanisms of remyelination, and initiate the development of new therapeutic strategies for demyelinating diseases such as multiple sclerosis.
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| 13/11/2021 |
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UNIVERSITY OF CAMBRIDGE |
After implantation in the uterus, embryonic cells diverge into a multitude of cell types during a process called gastrulation, which lays the foundation for later organogenesis. During this process, the three main lineages of the mammalian body, ectoderm, mesoderm and endoderm, are specified. Neuromesodermal progenitors arise early in gastrulation and retain their unique potential to generate both mesodermal and ectodermal tissues until late organogenesis.
Genetic expression, termed transcription, in eukaryotes is discontinuous, and regulated by variable molecular processes ranging from milliseconds to days, whilst transcription itself occurs on a scale of minutes. How various transcriptional regulatory elements dynamically interact to direct cell fate decisions at the single cell level remains an open question.
I therefore aim to establish a live single-cell approach to address how key transcriptional regulators dynamically modulate gene expression programs in neuromesodermal progenitors. I will use single cell super resolution live-imaging techniques and multiomic datasets to study live transcriptional dynamics, and model the relative contribution of the multi-layered regulatory components to transcriptional output and cellular identity. These studies will provide single-cell level information about transcriptional control in NMPs, providing a major advance on prevailing studies emphasising population-level dynamics, and contribute to the nascent field of transcriptional dynamics.
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| 13/11/2021 |
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UNIVERSITY OF CAMBRIDGE |
During development, the cells of an embryo divide and gradually specify towards mature cell-types. This process of cell-type specification is incredibly complex and is regulated via a multitude of underlying layers. Ultimately, the identity of a cell is determined by which genes are actively expressed in that cell. Some genes, termed transcription factors (TFs), are important regulators of the expression of other genes. Understanding the precise role of TFs and how networks of TFs change during cell-type specification is important to understand how similar cells can give rise to vastly different mature cell-types. In this project, I will investigate the role of important TFs on the format of embryonic blood, one of the first cell-types to be specified. To do this, I will knock-out (KO) specific TFs using genetic perturbations, and measure the effect on blood formation in the developing embryo at a single-cell resolution. Additionally, I will aim to determine where on the DNA these TFs bind when there is no KO, as this is another important indicator of their function. Together, this will give insight into the role of important TFs and how changes to TF networks underlie cell-type specification during early embryonic blood formation.
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| 13/11/2021 |
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UNIVERSITY OF CAMBRIDGE |
In order to perform their function (differentiation or self-renewal), stem cells need to receive a signal. Historically, the focus was put on the importance of soluble factor signals, but it is nowadays widely appreciated that the mechanical environment of stem cells plays a role in their function and affects soluble factor signalling. This is for example illustrated in oligodendrocyte progenitor cells (OPCs). With ageing, due to alterations in stiffness of the extracellular matrix (ECM) in the brain, OPCs lose their function, becoming unable to give rise to oligodendrocytes, a cell type which supports neurons. Using human pluripotent stem cells (hPSCs) and OPCs as systems, I will investigate the mechanism which underlies the effect that various properties of the mechanical environment (stiffness, stability) have on interpretation of soluble factor signalling (intracellular signalling) in stem cells and on their function. In response to different properties of the mechanical environment, I will monitor changes in membrane tension, receptors binding ECM and signalling platforms clustering soluble factor receptors. Understanding of how cell surface mechanics gates intracellular signalling in a basic model such as the hPSCs can further be applied to OPCs to shed light on how and why OPCs lose function as they age.
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| 13/11/2021 |
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UNIVERSITY OF CAMBRIDGE |
The liver is responsible for a plethora of vital functions within the body. Despite the importance of this organ, the mechanisms controlling liver development are poorly understood especially in humans. This knowledge gap not only represents a challenge for the development of new therapies against liver diseases but also a key limitation to establish protocols for producing liver cells in vitro. Therefore, new systems to model and understand human liver development are urgently needed. My project aims to understand the mechanisms which drive specification of the liver bud which represents the first stage of liver development. Specifically, I aim to define the function of key signalling pathways controlling human liver bud induction and develop a new platform to model human foregut development. By performing various high-throughput analyses, I will also investigate the regulatory mechanisms with which Activin/Nodal promotes commitment to liver fate whilst concomitantly preventing specification towards pancreatic fate. Finally, I plan to use newly-derived liver bud progenitors to generate hepatoblast organoids which closely resemble their in vivo counterpart. If successful, this work would not only enhance our understanding of liver development, but could also contribute to the development of novel regenerative approaches for the treatment of liver disease.
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| 13/11/2021 |
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UNIVERSITY COLLEGE LONDON |
As we begin to see greater acceptance of psychedelics as legitimate psychiatric medications, as well as a continued (if not increased) interest in psychedelic retreat participation, it is of fundamental importance to elucidate which preparatory practices have a substantial impact on the drug-induced experience, and subsequent mental health outcomes.
The aim of this project is to develop and pilot a ‘psychedelic preparation intervention’, based on MRC guidelines for developing a complex intervention. I will develop the intervention systematically, by first identifying and synthesising/reviewing the evidence. I will also use qualitative methods to identify practises that aid participants in their preparation for retreats, from both the participant and facilitator perspectives. I will subsequently develop a preparation intervention to be piloted within collaborating psilocybin retreat centres. A mixture of qualitative and quantitative methods is likely to be needed, for example, to understand barriers to participation and to estimate response rates. These initial studies will be used to assess feasibility, acceptability, compliance, recruitment/retention and delivery of the intervention. (The study is not going to be conducted on participants receiving/seeking treatments for diagnosed psychological disorders).
This project will help mental health professionals understand how best to prepare individuals for safe psychedelic therapies/trials.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
It has been observed that critically ill COVID-19 patients exhibit a wide range of clinical phenotypes which also affect the patients’ response to treatment. The group I am joining has shown that 25 genes are significantly associated with individual risk of developing serious illness following infection with SARS-CoV-2. Understanding the genetic background of COVID-19 patients may improve current treatment of the disease by identifying therapeutic targets.
I aim to divide a set of 8788 critically ill COVID-19 patients into different groups based on clinical information available at the time of hospitalization. By comparing the effect sizes for known genetic associations across clinical subgroups, I aim to identify genetic markers for differential therapeutic effect.
My project will deepen understanding of the genetic mechanisms underlying critical illness in COVID-19 and may discover genetic predictions of differential therapeutic effect that could, in future, direct the design of stratified clinical trials.
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| 13/11/2021 |
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UNIVERSITY COLLEGE LONDON |
People who migrate during childhood and adolescence face multiple adversities that impact on their mental health and wellbeing. It has been suggested that immigration at younger ages increases psychosis risk more than migration in adulthood however we are unsure why. This study will use existing large-scale data to explore childhood and adolescence migration and what factors may explain the association between psychosis and migration in ethnic minority populations. In addition, I will collect primary data for two qualitative studies. First, I will explore the views and experiences of barriers and facilitators to migration that play a role in psychotic disorder risk in minoritised young adults and compare these with quantitative findings. I will also do a case-study of young Pakistani migrants with experience of psychotic disorders to provide an insight into specific migration routes and circumstances. This work will provide a more in-depth analysis of increased psychotic disorder risk in young migrants from ethnic minority communities. This study will help us identify factors and events that could potentially be addressed for interventions in preventing psychotic disorder in young migrants. The study will be informed by lived experience and provide an insight into both participants experiences alongside epidemiological findings.
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| 13/11/2021 |
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UNIVERSITY COLLEGE LONDON |
Depression is the leading cause of disability worldwide. Effective treatments are available, but it is difficult to predict which treatment will be effective for which patient. To better target the available effective treatments, and develop new ones, we need to understand the underlying neurobiological mechanisms of depression. This is complicated by its considerable neurobiological heterogeneity. In this project, I will focus on cases where depression develops secondarily to other medical conditions (such as stroke, inflammatory or endocrine disorders) because the pathophysiological mechanisms by which symptoms of depression develop in these cases should be neurobiologically less heterogeneous and there can be better hypotheses based on the knowledge of the biology of the underlying conditions. Specifically, I aim to identify the neural circuits which drive some of the symptoms of depression in these cases, and test whether these neural circuits are involved also in cases where depression develops without any underlying medical condition. To achieve this, I will mainly use neuroimaging techniques in combination with behavioural testing of the relevant patient populations. Identification of the neural circuits driving the symptoms of depression could help target the available effective treatments and stimulate development of novel treatments, ultimately reducing the burden of depression.
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| 13/11/2021 |
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UNIVERSITY COLLEGE LONDON |
Millions of children and adolescents live in persistent poverty worldwide, and therefore are at a high risk of future mental health problems. How poverty leads to the development of adolescent mental health problems is likely to vary between different countries and cultures. Further action is needed to understand how poverty in adolescence and childhood leads to mental health problems so that effective interventions and policies can be put in place to prevent mental health problems developing.
I will analyse data from existing longitudinal studies to investigate if poverty impacts adolescent mental health differently across different high- and low-income countries. I will also investigate how the social consequences following mental health problems varies across countries, and what factors predict better social outcomes such as future educational attainment, employment and income following mental health problems and poverty.
Findings from the research could increase understanding of how mental health problems develop across different cultures and could help identify appropriate actions and interventions to mitigate the negative impact of poverty and mental health problems.
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| 13/11/2021 |
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UNIVERSITY COLLEGE LONDON |
Depression is mental disease with a complex and heterogeneous presentation. We can conceptualise it as a network of symptoms that can cluster together, reciprocally cause each other and interact in intricate ways, rather than one mental disorder with a common cause. We aim to use network analysis to reveal new information about the genetic risk of developing depression, as well as the progression of pharmacological treatment with common antidepressants. Using large existing datasets, we will build networks of polygenic risk scores for depression and symptoms of childhood internalising disorders to observe the developmental trajectory of the association between genetic risk and symptomatology. We will incorporate brain imaging measures to investigate their role as intermediate phenotypes between genes and behaviour. In addition, we will study the network dynamics of antidepressant treatment. Analysing previously collected data, we will test how changes in low-level affective processing interact with higher-order symptoms. We will collect new neuroimaging data to observe changes in brain activity during antidepressant treatment and their relation to individual symptoms. Through this work, we aim to better understand how the genetic liability to depression is related to its phenotype, as well as how pharmacological treatment brings about an amelioration of depressive symptoms.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Individuals vary widely in their ability to acquire and transmit pathogens, making it challenging to predict and manage the spread of infection. It is therefore key to understand the drivers of variation in the behavioural, physiological, and immune traits that contribute to pathogen transmission. The fruit fly, Drosophila melanogaster is a genetically tractable model system for infection, immunity and behaviour and is therefore ideal to investigate how individual host heterogeneity scales up to population disease dynamics. My first aim will ask how the innate immune system regulates avoidance behaviours and pathogen shedding, using existing loss-of-function mutants to investigate the crosstalk between immunity, behaviour and pathogen shedding. My second aim will be to measure the broad sense heritability in these traits. This will quantify the genetic contribution to each phase of pathogen acquisition and spread. Finally, I will investigate evolutionary trade-offs underlying super-spreading hosts. Using a large outbred fly population, I will continuously select on standing genetic variation to create fly populations with extreme shedding phenotypes. I will then test how experimental evolution for these extremes has affected the correlated evolution of other behavioural and immune traits. Altogether, this project will aim to answer the question: "what makes a super-spreader?"
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Despite the great efforts of international vaccination campaigns, the COVID-19 pandemic remains a major global health threat, as no antiviral drugs are available for severe COVID-19 patients, and the emergence of mutant viral strains risks to nullify vaccinations’ efforts.
SARS-CoV-2’s genome has been found to encode for several strain-specific, non-essential accessory proteins with diverse functions. Some of these are known to be expressed from overlapping sequences within structural genes (e.g. 9b/9c within the Nucleocapsid (N) gene), but other overlapping sequences’ potential for protein production remain unascertained.
To identify new targets for drug development and help assess the threat variants pose to public health, it is crucial to identify these protein-coding sequences, study their products’ functions and understand their origins.
Our goals are to:
Identify additional potential accessory genes encoded within SARS-CoV-2 N gene through in vitro translations and cell viability assays.
Assess their role in in vitro infection models through generation of mutant SARS-CoV-2 strains.
Dissect the dynamics of accessory gene birth/death in SARS-CoV-2 and related coronaviruses through phylogenetic analyses and dN/dS calculations.
Test the hypothesis that coronaviruses adapt to changing host environments by acquiring/losing accessory genes by expressing a functional library of coronaviruses’ accessory genes in multiple cell systems.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
SARS-CoV-2 is the virus that causes COVID-19 in humans and has resulted in a global pandemic since March 2020. Viruses are small pathogens that need to find, bind and enter host cells to replicate and assemble new virus particles that are then released to infect neighbouring cells or other hosts. This project aims to find parts of the human cell (known as host factors) that are involved in SARS-CoV-2 infection. I will continue research from a large experiment which will identify host factors that either help or hinder the virus. We can then use drugs to either inhibit that which helps the virus (pro-viral factors), or promote that which fights the virus (anti-viral factors) to develop antiviral therapies for the treatment of COVID-19. Drugs with potential antiviral activity in cell models may then be moved to preclinical mouse models to test if they work against SARS-CoV-2 infection and are safe. I will also assess if any drug targets are translatable to other coronavirus infections. Finding drugs that act against a broad range of coronaviruses may be important in the event of a new, infectious coronavirus outbreak in future.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Tuberculosis is a bacterial disease that affects 10 million people per year globally, with an associated 1.4 million deaths (2019). Current tuberculosis treatment plans are lengthy (minimum of six months) and have extensive side effects, resulting in patients not taking drug doses.
The impact of missing doses on success of a patient’s treatment are poorly known. This is dependent on a treatment drug’s ability to ‘forgive’ (i.e. be robust to) missed doses, which is a function of how long a drug is in the body for and stays at a level where it is working.
Recently, new digital technologies that monitor patients have started to give us detailed information about how precisely patients take, or miss, doses of their treatment. This allows us to investigate how these drug taking patterns are affecting patient outcomes. I aim to explore how real-world dose-taking affects the performance of rifampicin, an anti-tuberculosis drug. I will do this by adapting an existing mathematical model, including improving its ability to model how missing doses affects how the bacteria grows through laboratory experiments. I will use the model to assess the impact of missing doses on the performance of rifampicin and whether this could be improved.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Small vessel disease (SVD) is a chronic brain disease that causes vascular cognitive impairment (VCI). Insufficient oxygen delivery to the brain occurs in SVD and causes damage to parts of the brain containing bundles of nerve fibres, termed the white matter, as well as activation of the immune cells of the brain, microglia. We think that microglia act to reduce the white matter damage, thus slowing the disease progression. We also think that this protective immune response relies on energy provided through adjustments in microglial cellular metabolism, however this has never been investigated.
Therefore, in my PhD I aim to characterise how microglial metabolism changes when oxygen levels are low, to understand how these changes relate to white matter health and to investigate whether they are controlled by the microglial receptor TREM2. I will also look for molecular signatures of metabolically altered microglia in brain tissue from people with SVD and from rodent models of SVD/VCI. Finally, I will try to manipulate microglial metabolism in an effort to improve white matter health and cognition in a rodent model of SVD/VCI.
These studies will increase our understanding of immune responses in SVD/VCI and will contribute to identification of potential therapeutic targets.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Disordered sleep is commonly reported in autism from a young age, as are symptoms of mental illness. Mental health and sleep are known to influence each other in a bidirectional manner in the general population, but the nature of the association between sleep and mental health problems in autism is poorly understood. Moreover, the underlying causes of sleep problems in autism are unknown. Thus, current treatments for sleep problems are largely ineffective in autistic people, and they also face severe consequences of mental ill health, such as high rates of suicidality and in-patient care. I aim to characterise the relationship between sleep problems and mental ill health, and identify factors underpinning the sleep problems in autistic children and adolescents. I will answer these questions firstly more generally using a "big data" approach, and subsequently in more detail by conducting a small-scale observational study. These studies will help to:
characterise the contribution of sleep to mental health in autism
increase understanding of the underlying mechanisms of sleep problems in autism
inform current treatment, and the development of novel interventions.
Ultimately, this research could help improve sleep, mental health and quality of life for autistic people.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Small vessel disease is a very common neurodegenerative disease that starts in the blood vessels in the brain and causes brain cell death; it accounts for a quarter of all strokes and contributes to over half of dementia cases. Despite its importance in public health, the underlying pathological mechanisms are not entirely understood and there are currently no effective therapeutic interventions. Blood vessel cell dysfunction and the degeneration of specific blood vessel-related cells called pericytes are key catalysts in a series of changes evident in small vessel disease pathology. Using novel cell-specific mouse models, imaging techniques and transcriptomics, we aim to examine the molecular pathways behind blood vessel and pericyte dysfunction, with a particular focus on the mechanisms influencing an impaired communication between the two. We also seek to examine whether there is a relationship between blood markers of pericyte dysfunction in patients and several markers of small vessel disease burden using patient data on neuroimaging and cognition. These studies will help uncover some of the causes and consequences of the neurovascular breakdown observed in small vessel disease and other neurodegenerative disorders and help identify potential targets for therapeutic avenues.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Although more people now survive following a heart attack, the heart often sustains damage that increases the risk of developing debilitating loss of heart function in the longer term. It has been shown that in mice the prevention of steroid hormone formation within cells prevents the loss of heart function after heart attack by increasing blood supply to the damaged area during repair. In this project we will test the ability of a medicine that blocks steroid hormone regeneration to prevent loss of heart function in a more clinically relevant model of heart attack in the pig. Tissues from the pigs will also be analysed for indicators of increasing blood supply. Finally, we will be looking in more detail at what our drug does within the heart muscle using the new technique of mass spectrometery imaging.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
The maintenance of tissue homeostasis is dependent on the function of stem cells (SCs) and tissue-resident immune cells. How tissue-resident immune cells influence SCs is poorly understood. Regulatory T cells (Tregs) are a specialised T cell subset that plays a significant role in regulating inflammatory responses. Emerging evidence suggests that subsets of Tregs stably residing in barrier tissue sites (e.g. skin) are highly implicated in tissue regeneration and cancer. Our group has demonstrated that a subset of skin-resident Tregs localise to SCs, and are functionally required for skin regeneration. Skin-resident Tregs express the Notch ligand, Jagged-1 (Jag1), as a critical receptor that augments SC function. Additionally, several studies have functionally linked Jag1 to the maintenance of cancer stem cells (CSCs).
This research aims to understand how Treg-specific expression of Jag1 regulates the tumour associated Treg niche and affects skin tumour progression. We will primarily utilise in vivo model systems, but also cell culture, multi-colour flow cytometry and advanced molecular profiling, including RNA-sequencing, qPCR analysis, and tissue histopathology techniques. Upon completing this PhD project, we hope to better understand the underlying Treg-mediated regulatory mechanism of CSCs in skin cancers.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Inflammation of the CNS and the consequential neuronal responses play pivotal roles in Amyotrophic Lateral Sclerosis (ALS). Gliosis, the accumulation of functionally altered glial-cells, is frequently observed in ALS brain however, its role in disease pathogenesis remains elusive. Microglia in particular, the immune cells of the brain, are key regulators of neuronal function that maintain homeostasis and orchestrate the innate immune response. Microglia-neuronal interactions may be central to triggering pathology at the earliest phase of the disease, amplifying existing damage and spreading it to neighbouring neurons. Crucial gaps in the study of ALS aetiology remain: What is the specific microglia state induced by pathological TAR-DNA-Binding-Protein (TARDBP) mislocalisation? What is the effect of this molecular switch on neighbouring cells? How do TARDBP mutations in microglia affect their inflammatory state and their homeostatic functions? Our approach to study the effects of mutant TARDBP protein on microglia physiology using patient stem cells will be critical for aiming at disease-specific molecular targets that could regulate the pro-inflammatory response as well as pathological protein accumulation. We expect to gain important insight at microglia subtypes and states unique in ALS, leading to a refined disease model and uncovering novel drug targets for the treatment of ALS.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Humans generate new neurons from stem cells throughout life in the hippocampus; a process called adult hippocampal neurogenesis which is important for learning, memory, and mood regulation. Pro-inflammatory molecules which are produced in response to an activated immune system have a negative effect on adult neurogenesis. However, many open questions remain about how inflammation affects human brain stem cells. We hypothesize that chronic pro-inflammatory stimulation of human brain stem cells can cause them to undergo a switch from neuron-generating to immune-like cells. By stimulating human brain stem cells with pro-inflammatory molecules we will model how adult hippocampal neurogenesis is affected by inflammation. Using this model, we will identify critical molecular mechanisms involved in the stem cell switch from neurogenesis to immune function. Additionally, we will characterize the molecules stem cells produce in a pro-inflammatory environment to communicate back to the immune system and map the effect on their cell fate. Findings from this project can have implications for research into depression, ageing, and Alzheimer’s as these conditions are associated with elevated inflammation and decreased adult neurogenesis.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
About 1:100 people in the UK live with rheumatoid arthritis (RA), an autoimmune disease that causes swollen and painful joints. We now have drugs that treat joint swelling effectively, but they are not great at reducing pain. As a result, pain is rated as one of the top concerns by individuals who suffer from RA.
Scientists studying the disease are often divided into two camps: immunologists who study inflammation and neuroscientists who study pain. Our team aspires to bridge the gap between the two disciplines and improve pain research in RA. We will re-examine current literature to find out which cell types are most likely to sensitise nerves and cause pain in RA. We will study their interactions using human cells in a dish. Human nerves will be made from stem cells originating from people’s skin. Other cells which interact with them, such as immune and connective tissue cells, will be taken from the joints of RA patients.
Together, our team hopes to identify how the many different cell types in the joint may talk to nerves and cause pain in RA. Our findings have the potential to speed up the development of better painkillers for this agonising disease.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Complement cascade is an important part of the immune system that also plays a role in development and brain function. We are interested in a specific complement protein that is increased in emotionality disorders such as depression and autism-spectrum disorders. One way of studying a molecule's function is to see what happens in the absence of it. Indeed, mice lacking this molecule have profound innate anxiety and a memory deficit. Preliminary work in our laboratory has shown that these mice also have reduced synapse density in an area related to both anxiety and memory—the hippocampus. However, the exact role of this molecule in regulating emotionality and cognition is not known. I will use longitudinal structural and functional resting state magnetic resonance imaging and behavioural testing to understand the role of this part of the complement cascade in the maturation of anxiety and memory networks. I will then use single cell gene expression analysis to see which cell types are responsible for the changes observed in brain imaging. Understanding immune signalling in pathological memory and anxiety is clinically relevant because the studied molecule is a pharmacologically accessible receptor, making it a potentially useful target in treating psychiatric disease.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Tissue-resident macrophages (TRM) have crucial roles in development and tissue functions, many of which are not well defined. Interestingly, certain genetic defects and pathogens demonstrate selective affinity for specific human TRMs. For instance, mycobacterium tuberculosis preferably affects and survives better in TRMs residing in the lungs, but not those in other organs. To shed light on their organ-specific functions and unique disease biology, we wanted to unravel the molecular mechanisms underlying human TRM identity. However, the current understanding of human TRMs is based on monocyte-derived macrophages, which constitute only a subpopulation of TRM in tissues, and mice TRMs, which introduces significant inter-species differences in our knowledge. We aim to derive TRMs from human induced pluripotent stem cells through 3 complementary approaches: 1) adding defined growth factors in culture medium, 2) genetic engineering to induce TRM fate programme, and 3) co-culturing with 3D organoids. Then, we examine whether epigenetics and metabolic landscapes form the determinants of TRM cell fate using ATAC-seq, NMR and gene editing techniques. Based on the understanding, we will genetically engineer macrophages with enhanced functions, and assess their engraftment and safety in preclinical disease models to pave the way for their clinical use as advanced therapy.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease is an incurable illness. Cells in the brain and spinal cord called motor neurons (MNs) control muscle movements, for example, walking, swallowing and breathing. Over the course of ALS, many MNs die leading to progressive muscle loss. For unknown reasons, certain MNs do not die as ALS progresses.
Perineuronal nets (PNNs) are mesh like structures that wrap around many MNs. Loss of PNNs has been associated with worsening ALS disease progression. The status of PNNs in areas where cells do not die is unknown.
· We aim to understand if PNNs influence the ability of certain MNs to evade cell death. To achieve this, we will assess the integrity, composition and stiffness of PNNs from areas where cells did not die in human post-mortem samples
· We aim to create a 3D model of these PNNs in a dish to try and understand the impact of changes to the integrity, composition and stiffness on MNs viability
We hope that this research will clarify what role, if any, is played by PNNs in the selective resistance of MNs to cell death in ALS.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
The ability to form long-term memories is a fundamental property of the brain. Age-associated memory impairment negatively impacts quality of life, with approximately 40% of people aged 65 or older experiencing significant memory impairment. Both ageing of the hippocampus and the immune system appear to contribute to age-associated memory decline and interventions targeting the immune system can at least partially rescue age-related memory decline. We and others have identified transcriptional changes in hippocampus-resident immune cells, which may trigger abnormal neuroimmune interactions in the aged hippocampus. We hypothesise that changes to cell's transcriptional control mechanism's, known as epigenetics, which are known to accumulate over time, are responsible for these transcriptional changes. The primary aim of this project is to use 10x Genomics Single-Cell Multiome-sequencing to identify epigenetic and transcriptional changes that occur in individual nervous and immune system cells of the hippocampus during ageing. This data will be used to identify potential transcription factors that drive these epigenetic changes. We will target these factors to test if we can restore cognitive function in aged mice. This work will identify neuroimmune mechanisms underlying age-related cognitive decline and suggest novel therapies for cognitive impairment.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Parkinson’s Disease (PD) is generally known as a neurodegenerative disease that affects motor function; but it is also frequently associated with abnormalities in the gut. Indeed, many scientists believe that PD might start in the gut. This is because a key biological sign of PD, a mis-folded protein called alpha-synuclein (alpha-Syn), can first be found in the nerves and brain regions that connect to our intestines. However, evidence for this theory comes largely from animal studies. In humans, we only have "correlational evidence". For example, if you have inflammatory bowel disease, you are more likely to develop PD.
With my PhD, I aim to develop a human cell culture model to help study whether PD starts in the gut. I will grow human intestinal organoids with different types of gut neurons made from human pluripotent stem cells. I will then investigate how inflammation of this system affects the communication between different cell types and whether it will make it more likely for misfolded alpha-Syn to "cross-over" from the gut organoids into nerves. My system will help better understand what initially causes PD, with the hope of identifying new ways to prevent or treat it early, before it reaches the brain.
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| 13/11/2021 |
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KING'S COLLEGE LONDON |
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a severe skin disease with no cure. Normally, two layer of the skin are held together by rope like structures called anchoring fibrils, which are made of Type VII Collagen (C7). However, in patients with RDEB the anchoring fibrils don’t work and the layers of the skin are fragile, resulting in blistering, chronic wounds, and cancer. RDEB is caused by mutations in the gene COL7A1, which makes C7. I aim to correct those COL7A1 mutations with new gene editing tools called base editor and prime editor, to fix the anchoring fibrils in patient cells. After editing COL7A1, I will use molecular techniques including Sanger sequencing, qPCR, western blot and immunofluorescent microscopy to confirm if the edit worked and if it fixed C7 function. It’s also important to know whether the gene editors have affected areas of the DNA which I don't want to edit, so I will do "off-target analysis" to test the safety of these tools. Additionally, I aim to make 3D models of RDEB skin in a dish to aid future research. By the end of my PhD I aim to have aided the development of potential cures for RDEB.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Memory consolidation, the process by which novel experiences are gradually transformed into stable memories, is a fundamental neurobiological phenomenon. Current models suggest that interactions between where the memories are initially encoded (hippocampus) and subsequently stored for long-term (neocortex) are crucial. During an experience, inputs from the hippocampal region are thought to "tag" groups of neurons in the neocortex, which allows their reactivation during sleep or rest subsequently changing the neocortical circuit architecture. We hypothesize that this initial tagging of neocortical neurons is a result of structural changes in the very connection points, synapses, between the hippocampus and its target neurons in the neocortex.
To test our hypothesis, we will implement state-of-the-art molecular-genetic methods to mark synapses of hippocampal neurons in the neocortex and investigate whether these have undergone learning associated structural changes and whether these are dependent on hippocampal output. A further angle of our study will be to test if the changes in synapse structure we discovered are affected by disturbances in circadian rhythms which is highly influential on effective learning and remembering. These studies will help to identify the neural substrates for long-term memories and to explain how disparate cortical areas generate coherent cognitive states.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Malaria is initiated by infected mosquitos that bite mammals and deposit Plasmodium parasites in their skin. The parasites then reach their livers via the bloodstream and invade liver cells. Inside these hepatocytes, the parasites differentiate and become capable of infecting red blood cells, which causes typical symptoms of malaria. Previous research have implicated the role of multiple host surface proteins for liver invasion as well as parasite proteins that interact with the mammalian receptors.
My research aims to determine which proteins are necessary for liver invasion at a molecular level. I will produce mammalian and parasite proteins and confirm interactions between them. For that purpose, I will use techniques that either detect the binding of proteins or a change in molecular weight upon protein binding. Next, I will employ methods that elucidate structures of host and Plasmodium proteins. To accomplish that, I will subject protein complexes to X-ray and electron beams and analyse the resulting data. Finally, I will use cellular assays to demonstrate the necessity of confirmed protein-protein interactions for the liver invasion. My research will help explaining the molecular basis of liver invasion by Plasmodium parasites potentially paving the way for a novel strategy of malaria vaccine development.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
One of the primary barriers to successful antibiotics is the bacterial cell envelope, a dense and impenetrable coat structure which protects bacteria from environmental toxins. In bacteria such as Escherichia coli, membrane-bound proteins such as Tol and Pal crosslink and stabilise the cell envelope. However, certain predatory bacterial proteins (bacteriocins) exploit these Tol-Pal proteins to bypass the cell envelope. Here we will examine:
The role of Tol-Pal proteins in stabilising the E. coli cell envelope
How bacteriocins exploit Tol-Pal to enter target cells
We will investigate these questions with electron cryotomography (cryo-ET), a specialised form of electron microscopy used to image protein complexes within their native environment. We will apply this technique to bacteriocins trapped in E. coli cells, to physically observe the process of bacteriocin uptake. We will combine these data with supplementary approaches including protein mass-spectrometry, folding prediction software, and computational modelling to identify the molecular mechanisms of bacteriocin uptake. This will further our fundamental understanding of both symbiotic and pathogenic bacteria, and the mechanisms by which foreign proteins bypass the bacterial cell envelope. This may be applied to either creating synthetic bacteriocins, or fusing bacteriocins to existing antibiotics to assist cell entry.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Over recent years there has been an enormous number of developments in the ways we obtain molecular information from patients with disease. This has resulted in the ability to generate multiple measurements per patient for large cohorts, including levels of various proteins in their blood stream, gene activity across multiple different cell types at the resolution of single cell as well as precise methods of counting the numbers of different cells present in the system of interest. At the same time, there is an acute need to integrate this information and enable using all the data at once and not one at a time. Multilayer networks which at each layer summarize information available from a single experiment and then connect these layers allow us to integrate molecular information across various molecular measurements. We aim to develop statistically robust network methods and apply them to a dataset of more than 100 hospitalized COVID-19 patients of different severities. We also aim to compare them with sepsis, hospitalized flu patients and COVID-19 non-hospitalized patients and healthy volunteers to discover better ways to stratify patients and understand the underlying biological mechanisms driving their disease.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Translocations of the MLL gene lead to acute leukaemias with poor prognosis. Recently, small molecule compounds that disrupt the protein-protein interaction (PPI) between MLL and its binding partner Menin (MEN1) have shown efficacy against a subset of leukaemias. However, beyond changes in the expression of a few genes regulated by MLL, the consequences of inhibiting Menin’s protein-protein interactions on leukaemia cells remain poorly understood. We will use proximity labelling followed by quantitative mass spectrometry to identify proteins interacting with Menin in leukaemia cells, and identify changes in interactions after treatment with the Menin PPI inhibitor. In addition, we will characterise Menin's role in transcriptional regulation through its activity at enhancers by integrating multiple methods for profiling chromatin, including ChIP-seq, ATAC-seq and Capture-C. Understanding Menin's role in transcriptional regulation and its proximal protein environment can reveal vulnerabilities in cancers that depend on pathways regulated by Menin PPIs. This can offer insights into which patients are most likely to benefit from emerging treatments targeting Menin PPIs.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
B cells are key players of the immune system through the secretion of antibodies, antigen presentation and through cell-cell signalling. The fine balance of B cell activation and regulation is key to both protecting us from infection, whilst staying tolerant to our own self. Different tolerance mechanisms are essential in shaping the human B cell repertoire by elimination of autoreactive B cells at different stages of B cell development. Dysregulation in the tolerant B cell compartment is characteristic of many autoimmune diseases, but in Psoriatic Arthritis (PsA), the role of B cells remains unknown. I will firstly investigate mechanisms of B cell tolerance in health and infection, and then apply this knowledge to PsA to determine if tolerance is broken in this context and the functional implications of this in disease pathogenesis. I will determine if auto-reactivity is a feature of PsA and role of synovial B cells. Understanding underlying mechanisms that contribute to fine balance of B cell activation and regulation could allow us to better understand processes involved in autoimmune diseases. These studies will hopefully decipher new layers of PsA pathology, that could translate into novel therapeutics.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Fat distribution has been closely linked with a variety of metabolic complications, cardiovascular disease and obesity. Thus, studying genes linked to fat distribution, could lead to important insights that would benefit our understanding of multiple diseases. I am interested in combining genetic studies and proteomic experiments to explore the role of protein-protein interactions in the context of this trait. I will use large-scale genetic studies to nominate genes/proteins involved in fat distribution and subsequently temporally characterize their protein-protein interaction partners throughout fat cell differentiation. Tracking the expression of risk genes and their interaction partners will allow us to build protein-protein interaction networks that represent biological circuits that are functionally important for disease etiology. To understand the consequences of perturbing these networks, I will then use UK-Biobank’s electronic health records to link mutations of individuals within networks to phenotypes. Finally, we will develop a model that incorporates network and individual-level genetic information to predict disease liability. Together, this work will link statistical genetics and proteomic analysis to enable a deeper understanding of the genetic architecture of complex diseases that is driven by fat cell biology.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Malaria is a deadly infectious disease caused by a parasite called Plasmodium. It has a complex life cycle that involves sexual and asexual stages and can live in both the human host and the mosquito vector. It is challenging to search for effective malarial vaccines as the Plasmodium surface proteins can adapt rapidly and hide from the host’s immune system. Hence, an effective vaccine will require multiple antigens that present on the surface of the parasites at different stages. Transmission-blocking vaccines aim to reduce the infectivity of parasites and prevent the spreading of the disease. The potential candidates for transmission-blocking vaccines are proteins located on the surface of Plasmodium gametocytes, the specialised sexual cells that can be transmitted from human host to the mosquito. We aim to see what candidates for transmission-blocking vaccines look like, using X-ray crystallography and cryo-EM. Together with biochemical and biophysical methods, we are able to investigate their interactions with monoclonal antibodies and understand how these proteins regulate the fertility of the parasites. These studies will provide structural information for developing transmission-blocking vaccines.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Malaria is a substantial public health problem responsible for approximately 409,000 deaths every year according to the World Health Organisation. Despite decades of research and significant financial investment an effective malaria vaccine is yet to be developed. Malaria parasites continually evolve to counteract human resistance traits and understanding how malaria parasites are changing could lead to the development of more effective vaccines and antimalarial drugs. I aim to use a combination of human and malaria genome sequencing to dissect host-parasite genetic interactions. I plan to expand existing datasets by sequencing ancient parasite DNA samples and to use the modern technique of single cell sequencing to enable in depth, highly powered analysis of malaria parasite genome evolution and function.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
The electrical pulses our nervous system uses for signal transmission are generated by a controlled flow of metal ions into and out of neurons. One important class of proteins involved in the regulation of this flow are the voltage-gated sodium channels (Navs). Members of this class sit on neurons involved in important physiological processes, such as pain-sensing (Nav1.7) or heart muscle contraction (Nav1.5), but many questions regarding their mechanism of function remain. We don't know, for example, precisely what makes these different channels behave distinctly, or how interaction with auxiliary beta-subunits influences their opening behaviour. In this project, I will use state-of-the-art computational methods, including molecular dynamics simulations, to build on recent structural and electrophysiological data of these channels. My goal is to bridge the gap between these experimental results and arrive at a hypothesis for the full mechanism of function of these channels, including their regulation and the role of interactions with their associated beta-subunits. These results will provide a deeper understanding of neuronal signalling and regulation of a variety of physiological processes, and have the potential to be highly useful in drug-discovery projects.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Genetics underpins variability in observed traits. While many people study the genetic effects driving phenotypic variation for the general population, I am interested in using data from the UK Biobank1 to study the genetic effects responsible for the rare individuals with outlier phenotype measurements. I will consider two types of phenotypic outliers:
1. An individual whose measured trait is at an extreme end of the cohort-wide distribution.
2. An individual whose measured trait differs significantly from the trait expected based on their genetic predisposition. To identify this type of outlier we start by predicting the expected phenotypes. We will use both existing methods for phenotype prediction using genetics or family history of disease, and develop a novel method trained on data from the ALSPAC dataset7.
Using these definitions, we will determine outliers for all heritable and commonly measured phenotypes across ancestry groups. We will seek to discover associations between outlier status and genetic variation, outlier status for other phenotypes, sex, age, and ancestry.
I expect this work to improve our understanding of the genetic basis for outliers, lead to an understanding of ancestry-dependent diagnosis patterns, explain why some existing phenotype prediction methods perform poorly, and inform future phenotype prediction methods.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Salmonella is a bacterial pathogen of global importance. Some types of Salmonella are specific to humans and cause typhoid, a severe systemic disease (e.g. S. Typhi). A capsule comprised of sugars on the surface of S. Typhi is believed to help it evade the immune system, but this is challenging to study in people. The same capsule (called the Vi antigen encoded by via genes) is present in some strains of Salmonella Dublin, which cause typhoid-like disease in cattle. This offers a tractable model to understand the role it plays during infection.
My research will involve creating mutations within the via genes of S. Dublin and testing how these affect interactions with immune system components in the laboratory (e.g. blood cells and serum components that kill bacteria). I will then use surgical models to study how Vi helps S. Dublin to spread from the gut to other organs and produce disease in cattle.
The role of Vi has mostly been researched using mouse models and strains that naturally lack via genes but have been engineered to express them. The presence of Vi in S. Dublin offers a rare opportunity to study the role of Vi in a natural microbe-host combination.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Respiratory disease is one of the most common causes of morbidity and mortality in cattle, representing not only a serious threat to animal welfare but also an important loss from an economical point of view in the livestock industry. The entry mechanisms of most of the pathogens involved together with immune response of the lungs, especially in young animals, are not clearly understood. The major method of investigation of the pathogens' interaction with the lungs is the in vivo approach as, to date, there is no suitable lung model able to mimic both the epithelial and immune system functions at the same time. The aim of this project is evaluation of the models that are currently available, in particular regarding their similarity with ex-vivo lung tissues, and to improve these models to include immune cells. Additionally, the detailed study of ex-vivo tissues will allow a better understanding of the basic physiological and immunological composition of the bovine lungs which is currently not exhaustive. The knowledge gained from both ex-vivo and currently used in vitro studies will lead to the development of appropriate, complex, 3D models such as organoids that can replace animal use in bovine respiratory system research.
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| 13/11/2021 |
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UNIVERSITY OF EAST ANGLIA |
My project explores the molecular biology of pod shape and colour in pea, as a model legume crop, for human nutrition. Legumes are an enormous family of flowering plants. These plants are united by their unicarpellate (single-chambered) fruits known as pods, which contain their offspring in the form of seeds. Among legume species are several protein-rich vegetable and dry pulse crops, including peas, chickpeas, lentils, beans, and others. Legumes are unusually rich in protein, and also contain abundant starch, fibre, and micronutrients. We intend to use pea as a model legume for crop alteration (metabolically, developmentally) for human health and nutrition; we will achieve this using both genetic approaches (to identify genes controlling pod shape and colour) and molecular biology to dissect gene function. The rationale for this research is that alteration in pea pod shape, size, thickness, colour etc. will alter pod photosynthetic dynamics. As pods heavily contribute photosynthate to developing seeds, we hypothesise that altered pod developmental biology will alter seed nutritional profile, which may be useful to develop a health-promoting pod ideotype in this and other legumes. We also maintain an interest in the health-promoting potential of certain legume metabolites, such as anthocyanins and resistant starches.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
1.5 million people contracted a Human Immunodeficiency Virus (HIV) infection in 2020. Due to advancements in antiretroviral therapy, this diagnosis is no longer life-limiting, but continues to be life-changing. People living with HIV are still at a significantly higher risk for depression than HIV– individuals, but the reason for this high prevalence of depression is unclear. Inflammation (that is, activation of the body’s innate immune system) has been linked to depression in the general population, and HIV infection in the brain elicits a sustained neuroinflammatory response. Could this neuroinflammation be responsible for the high rates of depression amongst people living with HIV? This project aims to determine whether neuroinflammation, measured using brain imaging and blood assays, contributes to the association between HIV infection status and depression. Two independent groups of HIV+ and HIV– participants with varying levels of depression, one in the UK and one in South Africa, will be assessed for neuroinflammation and depression severity. Using this data, this project will seek to investigate links between HIV and depression in two distinct populations. In doing so, this research may guide clinical practice and alleviate the burden of depression amongst people living with HIV.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Every year, the malaria-causing agent Plasmodium falciparum results in over 400,000 deaths and 200 million clinical cases in humans. These outcomes have negative socio-economic implications in malaria-endemic regions of the world and thus require urgent interventions such as vaccines. During infection, P. falciparum attacks and multiplies in human red blood cells. Of importance, the parasite alters the infected red blood cell surface by expressing its own proteins. These P. falciparum derived proteins mediate binding to various tissues, uninfected red blood cells and serum proteins – leading to severe disease outcomes. Interestingly, preliminary evidence suggests that P. falciparum derived proteins (known as DBLepsilon and DBLzeta) that bind to serum proteins are conserved across the global P. falciparum population. This offers the possibility of developing a vaccine against severe malaria. In this study, I will be exploring these serum-binding P. falciparum proteins by examining their conservation and function. I will also produce antibodies from these proteins and test for activity against diverse P. falciparum samples. This study will provide insight into the viability of the serum-binding P. falciparum derived proteins as potential vaccine candidates for protection against severe malaria.
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| 13/11/2021 |
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UNIVERSITY OF EAST ANGLIA |
The gut microbiota has a profound impact on host physiology affecting overall health through the fermentation of carbohydrates such as plant polysaccharides (Thursby and Juge, 2017 474:1823). However, little is known about the impact of pulses on the gut microbial metabolism. Previous work at JIC showed that pea mutations in the gene encoding for galactinol—sucrose galactosyltransferase resulted in changes in myoinositol, galactinol and raffinose metabolites in the seeds. This may influence gut microbiota structure and function, where major gut symbionts such as Ruminococcus gnavus can metabolize raffinose family oligosaccharides (RFO) as shown at QIB (Cervera-Tison et al, 2012 78:7720, Lafond et al. 2020 11:579521).
Nonetheless, RFO have been associated with discomfort when intestinal fermentation occurs. We want to understand whether the changes in RFO content in the seeds of pea mutants beneficially affect human gut barrier function and immunity. For this, pea mutants will be characterised and metabolic effects of these mutants will be determined on the faecal microbiota. Finally, functional assays using human-based organoids will be used to assess gut barrier function and immune response.
The expected impact of this multidisciplinary work is to select a pea candidate mutant line that could be used for future human intervention studies.
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| 13/11/2021 |
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UNIVERSITY OF EAST ANGLIA |
The gut microbiome holds the largest number of microorganisms in the body, responsible for producing a wide array of metabolites and modulating numerous physiological functions. Not only has the gut microbiome been studied to adapt responses in distant organs, but gut microbial perturbations may also be associated with breast cancer risk and progression. We therefore propose that dietary supplementation to improve the gut microbiome could slow tumour initiation and progression. I aim to utilise probiotic combined with prebiotic supplementation in breast cancer mouse models to define a cancer-protective microbiota. To evaluate any anti-cancer mechanisms of probiotics and plant-derived prebiotics, I will use techniques, such as flow cytometry, immunohistochemistry and immunoassays, to assess immune function systemically and in tumour microenvironments. By monitoring any alterations in metabolic output of the microbiota, using NMR and mass spectrometry, I aim to identify if the mechanisms are metabolite driven. It is also vital to profile microbial populations by whole genome sequencing and link back to metabolite profiles. These studies will help to understand how the gut microbiota links to breast cancer initiation and progression and aim to develop dietary interventions which could be used as part of preventative and therapeutic strategies.
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| 13/11/2021 |
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QUEEN MARY UNIVERSITY OF LONDON |
Our goal is to use Artificial Intelligence (AI) to better understand the biology of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, psoriasis, lupus, and Sjögren’s syndrome. Despite being common conditions, the mechanisms which explain how IMIDs work are poorly understood. We consider there must be key cellular mechanisms underlying IMIDs and that studying the differences between them will provide clues as to their origin and development. This project will focus on studying interferon signalling, a central mechanism for control of inflammation, known to influence IMID development and drug response. Using genomic data from a range of IMIDs, we will build networks explaining the relation between the different components of interferon signalling. We will also integrate patient clinical information, genomic and imaging data to find sub-groups of patients whose disease and response to treatment progresses in a similar manner. Finally, we will use this research to identify pharmaceutical drugs, already on the market and in use for different conditions, which might be effective in the treatment of IMIDs because their mechanism of action indicates they would affect important areas of IMID biology. This could also lead to identifying areas of interest for future IMID drug development research.
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| 13/11/2021 |
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QUEEN MARY UNIVERSITY OF LONDON |
The early detection of mental health disorders is vital to prevent severe cases and hospitalisations. Therefore, identifying risk factors is important.
Abnormal eye gaze (a measure of what one is paying attention to) is linked to traits like social anxiety and depression. However, research tends to focus on one specific disorder. There is a need to examine the relationship between eye-tracking measures and general psychopathology. This will help accelerate research that can identify predictors of psychopathology.
We will collect participants’ eye-gaze while viewing different types of visual stimuli and measure their self-referential bias (SRB) using an gaze perception task. This is the phenomenon where a person thinks others are looking at them or talking about them (1), which is linked to various conditions (e.g. psychosis).
The first question is whether visual eye-tracking data (and SRB) can predict mental wellbeing and mental health symptomology. Secondly, we will develop a visual training programme designed to reduce problematic SRB and conduct a small study to see whether it shows promise for future research (2).
We want eye-tracking data to be used in psychopathology risk detection and create training programme designed to reduce SRB which can be tested in a future clinical trial.
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| 13/11/2021 |
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QUEEN MARY UNIVERSITY OF LONDON |
Research on the communication of genetic risk information for common conditions like type 2 diabetes (T2D) has largely focused on disease identification, prevention and management in older, White European populations. Much remains unknown about the use of genetic risk prediction tools in diverse ethnic and/or age groups—however, emerging work in South Asian populations suggest that such tools may have added benefits for the identification of younger people at risk of developing T2D. We are interested in applying a life course perspective to this research area to examine potential age differences in perceptions and beliefs surrounding T2D—including whether young people perceive unique benefits from acting on their genetic risk status. We will first synthesise currently available evidence on genetic risk communication and illness perceptions. Then, we will provide genetic risk information about T2D to a community-based cohort of British Bangladeshis and British Pakistanis in the UK—integrating the findings from our synthesis—to investigate any age differences in how people evaluate information and formulate ideas about their risk; and compare different formats of risk communication. This research will inform efforts addressing the potential of genetic risk communication for a population disproportionately affected by T2D—yet underrepresented in genetics research.
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| 13/11/2021 |
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QUEEN MARY UNIVERSITY OF LONDON |
Stratified medicine, in which information from a patient’s genome is used to help direct their treatment, has revolutionised some areas of clinical practice. However, most diseases do not involve changes in an individual’s genome, so the power of insights derived from genotyping and whole genome sequencing is limited.
Interrogation of a patient’s proteome (the collection of 20,000+ unique proteins that can be extracted from human tissue and body fluids) promises much more fine-grained insight into the state of a patient, because proteins are the key functional molecules of biology. The abundance, location, physical structure and activity of each protein can vary substantially during disease progression, providing a wealth of information for assessing a patient’s state and forming a treatment plan. But how to reliably turn proteomic data into clinical insights remains an open question.
This project will investigate the extent to which artificial intelligence (AI) can be used to leverage proteomics data for stratified medicine. This will be achieved by applying cutting edge data science and AI techniques with the aim of producing reliable and explainable readouts of disease state from clinical proteomics data, overcoming inherent challenges in these data such as heterogeneity, missingness and lack of statistical power.
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| 13/11/2021 |
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QUEEN MARY UNIVERSITY OF LONDON |
Trials that assess methods to help implement health interventions of proven effectiveness are known as implementation trials. However, randomised trials tend to be expensive and take many years to conduct. The use of patient health data collected from routine practice, such as GPs, hospitals, and secondary care services, may make these types of trials more efficient. However, there are many challenges such as gaining access to such data and the data might be inaccurate.
In this PhD I will explore how patient health data are used in implementation trials.
I plan to start by reviewing reports of these types of trials and consulting the experts in the field. I will survey and interview those who have conducted or have been involved in such trials (e.g., trialists, IT staff, statisticians, researchers, patient participants etc.) and carry out some in-depth case studies. The involvement of patients and public representatives in all stages of the study will be vital.
The key outcome will be a set of recommendations on the use of routine health data in studies implementing health interventions into practice. I hope the outputs of this PhD will increase the speed of adopting health interventions of proven effectiveness into real-world.
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| 13/11/2021 |
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UNIVERSITY OF SHEFFIELD |
Background:
Mathematical models are often used to inform decisions on how best to spend finite public health resources. These models combine relevant information (in the form of model parameters) about disease processes and relevant interventions to estimate the long-term consequences of the interventions. Unfortunately, some disease processes can not be directly observed but could be estimated through calibration. Model calibration identifies the values of input parameters for which the resulting model outputs are consistent with the observed data. Calibration methods are either Bayesian or non-Bayesian. While Bayesian methods identify the posterior distribution of the parameters, it is easier and quicker to perform non-Bayesian methods. Nonetheless, these methods agree on some occasions.
The questions posed by this study are, first, what is the error associated with using non-Bayesian calibration approaches, when are such methods suitable, and what is the value of employing Bayesian methods? Second, what is the error in the net benefits associated with employing imperfect calibration target data, and what is the value of collecting better data?
Approach:
We will survey relevant literature to identify calibration methods, develop (adopt) methods to answer posed questions, utilise simulations to test developed methods and apply developed methods in a real case study.
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| 13/11/2021 |
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UNIVERSITY OF SHEFFIELD |
Background:
Ill-health has a multitude of causes; one being commercial products (West & Marteau, 2013). Some industries, including tobacco and alcohol, sell products that are harmful to public health, contributing significantly to the rise in non-communicable diseases (Kickbusch et al., 2016). An area much less researched, but no less important, is the gambling industry. In recent years, there has been an explosion of gambling marketing and advertising; particularly in the context of sport (Ireland et al. 2019). Public health experts are becoming concerned about the level of exposure to gambling advertising, particularly as there is inequity in the distribution of gambling-related harm (Goyder et al., 2020).
Approach and Impact:
My research will investigate the mechanisms of a policy that restricts gambling advertising in sport. I will do this firstly by studying the literature on gambling advertising and sport, and assessing the impact of current voluntary policies on exposure to advertising. I will then undertake two studies that seek to understand the relationship between gambling advertising and individual gambling behaviour, and how this may differ by gambling severity. My research will encourage a public health approach to gambling and will contribute to the small amount of literature in this area.
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| 13/11/2021 |
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UNIVERSITY OF SHEFFIELD |
South Africa, like most developing countries, has a burden of breast cancer characterised by late presentation and high mortality rates. It has the highest level of wealth inequality in the world, which is accompanied by inequalities in health, including cancer inequalities. These inequalities need to be addressed to achieve the goal of reducing within country health inequalities associated with the Sustainable Development Goal 10 (SDG 10) for which South Africa is a signatory. We will construct a mathematical model which illustrates the impact of various interventions that can be implemented in improving breast cancer outcomes. The proposed interventions will only utilize available resources in the country. We will use information obtained from the literature, a local dataset and informal stakeholder consultation to inform and populate the model. We expect to produce a model that can be used in decision making to predict the impact of interventions in reducing breast cancer inequalities in South Africa and possibly in sub-Saharan Africa. The research will contribute to the body of knowledge on the modelling of breast cancer inequalities in a resource constrained setting.
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| 13/11/2021 |
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UNIVERSITY OF SHEFFIELD |
Drinking behaviour of one’s friends is found to be a strong predictor of one’s alcohol use, especially among adolescents. Two mechanisms have been extensively explored to explain drinking similarity among friendship groups: 1) selection, i.e. adolescents choosing to become friends with those who have similar drinking behaviours, and 2) influence, i.e. adolescents changing their drinking behaviours to match with their friends. The main aim of this study is to develop or adapt an agent-based model (ABM) to examine how social network formation processes shape drinking behaviour and alcohol-related harm. We will focus on exploring the bidirectional relationship between drinking behaviours and friendship groups among first year university students, and its health economic consequences. This study will build on the social contagion theory ABM developed by the CASCADE (Calibrated Agent Simulations for Combined Analysis of Drinking Etiologies) project, which will be calibrated by evidence found in literatures and collected from first-year undergraduate students at the University of Sheffield via web-based questionnaires. We aim to provide insights on the how social network formation processes shape drinking behaviour and alcohol-related harm among young British adult drinkers, when they drink within a newly formed friendship group, and inform individual-level or group-level intervention policies accordingly.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
The World Health Organization (WHO) defines neglected tropical diseases (NTDs) as those which are neglected by research and funding, and disproportionately infect poor and marginalised communities. One such NTD is schistosomiasis, a waterborne parasitic disease which infects over 250 million people worldwide, and is second only to malaria in terms of socioeconomic burden. In the new NTD roadmap 2020-2030, the WHO aims to eliminate schistosomiasis as a public health problem by 2030. Preventive chemotherapy has been a pillar of intervention strategy for many years in endemic countries of Africa, but some regions do not respond as expected, with persistent high prevalence of schistosomiasis. In this PHD I aim to investigate factors which could be maintaining these persistent hotspots, and therefore hindering the goal of elimination. I will investigate whether using preventive chemotherapy at a defined time in the transmission pattern of S.haematobium would reduce prevalence and reinfection. I will also carry out a survey of attitudes and practices involving WASH in Zimbabwe with a focus on COVID-19 and its effects on endemic schistosomiasis. Finally, I will explore genetic differences in parasite populations, post treatment in persistent and non-persistent regions, allowing an investigation into parasite susceptibility to treatment.
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| 13/11/2021 |
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HEALTH DATA RESEARCH UK |
Deep learning is a way to train computers to do complex tasks by learning from large amounts of data. Developing rapidly over the last decade, it has been particularly successful in the understanding of images and natural language. However, deep learning has not had a large impact in important tasks of medical science and healthcare. Traditional statistical techniques are favoured due to their advantages in terms of interpreting their results and understanding the decision-making process. However, such techniques are often difficult to scale up to larger patient populations or to the large amounts of data produced by new technologies like smartphones and fitness trackers.
This PhD project aims at combining statistical concepts with recent deep learning technology. In particular, I am interested in developing these methods for estimating the effect of a treatment on a patient’s outcome. I intend to extend existing technology to provide a tool to assess when such an estimation is feasible. Further, I am interested in the stability of such methods when data is corrupted by some controlled mechanism trying to trick the algorithm. I aim at enabling novel data science methods that help health data scientists, health practitioners and ultimately patients to make better decisions.
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| 13/11/2021 |
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HEALTH DATA RESEARCH UK |
The combination of different drugs for treatment of illnesses such as cancers holds great potential for advances in healthcare due to its ability to achieve more effect with less toxicity. However, the interaction between drugs is highly complex due to combinatorial explosion in possible associations, diverse drug-to-drug interactions and differences in drug metabolism that impinges on the drug dose regime. In this project, we aim to leverage advances in statistical learning and data science to optimise drug-to-drug interactions and learn from a large and complex data space of novel and potentially synergistic drug interactions. To achieve this with high accuracy, we will use both monotherapy and drug combination data to design and model the effect of drug interactions. We aim to combine the approach with active learning strategies to provide information about the most informative drug combinations given the landscape of interaction. Furthermore, this statistical model will enable us to optimise the dose-response problem, providing novel insights on tasks such as how to minimise dose while retaining effective outcome.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
RNA are widely modified and the modifications have a range of effects. One such modification found in animals is the m6A modification. It is found in wide variety of different types of RNA & is the most common modification in messenger RNA. While the modification has been known about for 30 years, modern methods have only just identified the enzymes that create it. I aim to study a couple of these newly discovered enzymes. We will look into their enzymology making use of the existing x-ray structures. We hope to develop small molecule inhibitors for the enzymes. I hope to apply these inhibitors & the enzymology to cell assays. We might then better understand why the m6A modification is made and what effect it has.
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| 13/11/2021 |
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UNIVERSITY OF GLASGOW |
Colorectal cancer is the third most common cause of tumours worldwide. Evidence suggests that bacteria residing in the gut play a role in the onset of this disease, with research showing links between diet, the bacteria living in our gut and the overall health of the individual. Patients suffering from disorders of the gut are routinely given probiotics, cultures of health-promoting bacteria that colonise the host’s gut, outcompeting harmful bacteria and restoring a healthy microbial population within the intestine. One probiotic bacteria, Escherichia coli, has been shown to have antibiotic and anti-inflammatory properties, but research also suggests that these bacteria can release harmful toxins that damage intestinal cells, initiating the development of colorectal cancer. I aim to investigate how specific dietary components affect the expression of probiotic toxins in a way that reduces tumour development. I will use molecular biology techniques to work out how components of the diet affect gene expression of the toxin in probiotic strains, and I will use mouse models to study tumour development in living organisms. In the future, I hope that coupling administration of probiotics with specific dietary components could reduce the risks of developing colorectal cancer and become an effective therapeutic approach.
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| 13/11/2021 |
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UNIVERSITY OF GLASGOW |
The COVID-19 pandemic has shown us the consequences of coronaviruses jumping from an animal into humans. Coronaviruses originate in bats and rodents but can also jump into humans via an intermediate species such as camels or cows. Immune defences that we inherit, such as interferon-stimulated genes (ISGs), are important in determining whether we can be successfully infected by animal viruses. However, very few ISGs that specifically inhibit coronaviruses have been identified. Our lab has built a large library of ISGs from many species including humans, monkeys and cows and we will use this to test their antiviral activity against coronaviruses found in bats as well as coronaviruses that already infect humans. Since SARS-CoV-2 is unlikely to be the last animal coronavirus to transmit to humans, learning how these ISGs protect us from coronavirus infection will strengthen our understanding of the immune barriers that hinder the cross-species transmission of coronaviruses, and help determine the risk posed by animal coronaviruses to human health.
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| 13/11/2021 |
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UNIVERSITY OF GLASGOW |
Influenza viruses cause hundreds of thousands of deaths each year. Despite a long-standing awareness of 'flu' in the research community, leading to the availability of vaccines for almost 70 years, it still presents a very real concern for public health. This is largely due to the fact that influenza viruses undergo a process known as antigenic drift. This allows the virus to sidestep immune responses that have been formed in individuals who have been exposed to the virus in the past or who have been vaccinated against influenza, by acquiring mutations in the surface protein haemagglutinin. By using electron microscopy to solve the structure of many haemagglutinin molecules from diverse strains of influenza and leveraging protein structure data from previous studies, we plan to construct computer models of the changes in this key protein which allow it to evade immune responses. These models will help vaccine designers and public health officials to anticipate trends in the spread of different flu strains and prevent deaths from flu by designing more effective vaccines faster.
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| 13/11/2021 |
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UNIVERSITY OF GLASGOW |
Virus genome sequencing is increasingly used in outbreak control. By combining the evolutionary insights gained from sequence analyses with case data and geographic information, current transmission patterns can be mapped, and risk factors identified to model future scenarios. Vampire bat rabies (VBR) is a deadly zoonotic disease which continues to threaten human health and exerts a major economic burden via livestock mortality. Persistence of the virus is spatially dependent, dying out if unable to regularly infect new colonies. In Central America, the narrow landscape intersected by mountain ranges likely restricts the spread of the virus to specific ‘transmission corridors’, where strategic deployment of vaccination could therefore protect wider areas ahead by blocking transmission. In collaboration with the International Agricultural Health Organisation (OIRSA), we will develop sustainable regional sequencing of livestock VBR in Central America to complement national case surveillance and identify transmission corridors. Predicted transmission corridors will be verified in wild bat populations in Costa Rica with seroprevalence studies. Meanwhile, the grooming interactions of co-roosting bats will be studied using an ingestible fluorescent biomarker to explore the feasibility of using transferable wildlife vaccines in this setting. Overall, this work will deepen our understanding of VBR transmission and support preventative management.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Ubiquitin is a regulatory protein whose addition to substrates can signal for a protein to be degraded and is also involved in other processes such as trafficking. PROTACs (proteolysis targeting chimeras) have recently been developed, which act to recruit the cellular machinery to attach ubiquitin to a protein of interest and tag it for degradation by the proteasome.
Our approach is analogous but opposite to this; we aim to develop DUBTACs (deubiquitinase targeting chimeras) to remove ubiquitin from our target protein and prevent degradation, and therefore prolong the duration of cellular activity or potentially turn off ubiquitin dependent signalling in the cell.
This has a broad scope of impact; many disease states are caused by proteins that are degraded too readily and so could be targeted by this approach such as such as Cystic Fibrosis (CFTR protein), Long QT syndrome (KCNQ1) as well as tumour suppressor proteins in Cancer [4,5].
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Organisms respond to environmental changes by adjusting their physiological state, for example switching to oxygen-independent metabolism if oxygen provision is limited. Such coping mechanisms are encoded within the genetic information which provides the template for a cellular response. This is the reason why geneexpression and metabolism are highly interconnected via crosstalk between nutrient availability and the accessability of genetic information, the chromatin state. This interdependence has been shown to affect and contribute to many human disorders such as cancer and inflammatory diseases. Not surprisingly, alterations in metabolite pools can also have a significant impact on the therapeutic efficacy of drugs. With this project I’m aiming to develop methods and tools to monitor cellular responsiveness to drugs in the context of metabolic perturbations in cells to identify and define sensitivity patterns as well as factors that may provide novel therapeutic opportunities.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
The human proton-coupled oligopeptide transporters PepT1 and PepT2 play a crucial role not only in the absorption of dietary nitrogen in the form of di- and tri-peptides, but also in absorption and retention of structurally similar drugs, such as beta-lactam antibiotics.
Recent structural studies on bacterial homologues have highlighted the roles for key protein residues involved in transport, and molecular dynamics (MD) simulations have been used to gain insight into the free energy landscape of the alternating access mechanism of conformational changes during transport. The molecular basis of the transporter’s substrate promiscuity, that is why some molecules are transported but not others, remains poorly understood, however.
In this project, we aim in the first instance to use MD to probe how binding of transported drugs affects the transporter on a molecular level. This will enable us to construct a pharmacophore model for transport to cover the wider chemical space of drugs, by helping us understand key substrate–transporter interactions which initiate transport. We will test these computational predictions in transport assays, and collaborate with synthetic chemists to design better substrates for transport. These studies will help the design of drugs and prodrugs with better pharmacokinetic properties.
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| 13/11/2021 |
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UNIVERSITY OF OXFORD |
Chagas disease (caused by the parasite Trypanosoma cruzi) and cutaneous and visceral leishmaniasis (caused by Leishmania spp.) are neglected tropical diseases that affect tens of millions of people worldwide. These diseases are often fatal, and treatments are limited in efficacy, exhibiting severe side-effects. A family of natural products extracted from the Brazilian plant Nectandra leucantha has been shown to have good activity against these parasites. In this project I will combine synthetic organic chemistry with cell biology to explore these synthetically accessible natural products as a potential source of new therapeutic leads, focussing on improving their pharmacological profile. I will also identify molecular targets and mechanism of action of promising compounds, using various techniques including tracking fluorescently labelled analogues and photolabile crosslinking. I will carry out genome mutation of Leishmania and selection for compound resistance, followed by genome sequencing to identify genes likely to be involved in the mechanism of action of these compounds. These studies will help to discover novel therapeutics with improved anti-parasitic activity, and their potential cellular targets.
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| 13/11/2021 |
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HEALTH DATA RESEARCH UK |
Computers can now create algorithms to give personalised predictions about an individual’s risk of developing diseases. These can be used to help make decisions about medical treatments and screening before the person gets sick. They could have a big impact on healthcare, because they can prevent illness and save healthcare systems money. It is also very important that these algorithms are fair. This means that they must be able to make equally good predictions for all races, ethnicities, genders, ages, and backgrounds. But this is not easy, and many give worse predictions for some groups of people. It is important to improve fairness in these algorithms as they are starting to be used to make real-world decisions.
I will study definitions of fairness, and use these to look at how fair algorithms are, and how to improve their fairness. Then, I will create new algorithms which use medical and personal information and genetic data, with fairness as a focus. I will create multiple algorithms to make sure that each group of people have good predictions for their disease risk.
The more fairness is studied and improved, the more sure we can be that these algorithms will benefit everyone in society.
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| 13/11/2021 |
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UNIVERSITY OF MANCHESTER |
Psoriasis is a skin disease associated with painful itchy lesions caused by immune cells entering the skin from the blood. Reoccurring flares of psoriasis often occur in the exact same patches of skin, suggesting these areas are primed for inflammation and never fully resolve. The components of the blood vessel wall regulate the migration of immune cells into skin and can be split into different layers. The glycocalyx is a layer of sugars and proteins lining the internal surface of the blood vessel wall, whilst the basement membrane is a layer of proteins covering the outside of blood vessels. Both layers can limit immune cell migration and are altered in inflammatory conditions. Despite the importance of immune cell migration to psoriasis, the role of these blood vessel components has not been fully investigated. We hypothesize that in psoriasis, blood vessel layers are changed to allow immune cell migration, but these changes are not fully reversed in resolved skin, allowing psoriasis to reoccur in the same location. This project will examine the make-up of these blood vessel layers in healthy, psoriasis and resolved psoriasis skin and will determine the significance of these changes to immune cell recruitment and inflammation in psoriasis.
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| 13/11/2021 |
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UNIVERSITY OF MANCHESTER |
Asthma is a chronic inflammatory disorder of the lungs which causes the airways to temporarily narrow in response to specific triggers. Narrowing can usually be relieved using an inhaler but there are multiple long-term impacts of asthma. Alongside chronic inflammation, asthma is also characterised by airway remodelling. Airway remodelling is a process whereby structural tissue cells make excessive matrix proteins (e.g. collagen) leaving the lung stiff, less elastic and with reduced function. Current treatments fail to reverse/prevent these structural lung changes from occurring in asthma. I aim to learn more about lung remodelling in asthma and how it is regulated. Initially, I will investigate the different types of matrix changes in the lungs tissue from people with asthma and see whether any changes are associated with any specific types of inflammation. I will also use a mouse model of airway remodelling to examine how remodelling is initiated and whether inhibiting inflammation or specific molecules that are increased in asthma, prevents remodelling from developing. Overall, this project will help us understand how the matrix changes in the lungs during remodelling and will help identify the cells or molecules that could be targeted therapeutically to prevent or reverse lung remodelling in asthma.
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| 13/11/2021 |
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UNIVERSITY OF MANCHESTER |
Dysregulation of the extracellular matrix (ECM) drives chronic diseases including osteoarthritis, fibrosis and cancer. Processes leading to dysregulation remain to be fully elucidated, though evidence shows that both the circadian clock and immune cells are involved in ECM deposition and turnover. My PhD will focus on collagen, the predominant component of the ECM. As an overproduction of collagen fibrils is the hallmark of conditions such as fibrosis, we will investigate how immune cells and the circadian clock influence collagen secretory pathways. Fibroblasts are the predominant ECM-producing cell type and their dysregulation is involved with driving progressive fibrosis. We will study the circadian clock in fibroblasts, with a particular focus on determining how clock-altering cross talk between immune cells and tissue-resident fibroblasts alters collagen synthesis and deposition. We will culture immune cells with fibroblasts expressing bioluminescently-tagged pro-collagen in order to quantitatively assess collagen fibril assembly. We will identify circadian clock-controlled proteins (CCCPs) using mass spectrometry tools. We will then use light microscopy to image matrix assembly in edited cells that are deficient in or constitutively expressing the identified CCCPs. This work will provide insight into collagen regulation and how the collagen secretory pathways can be subverted for therapeutic benefit.
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| 13/11/2021 |
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UNIVERSITY OF MANCHESTER |
Innate lymphoid cells (ILC) are rare immune cells enriched in barrier tissues such as the gut or lung, and within lymph nodes, that are important regulators of tissue immunity and wound healing. Whilst some of the interactions that occur between ILC and other cells are understood, many are poorly defined, especially within the context of inflammation and tissue remodelling. A better understanding of the interactions between ILC and stromal cells may reveal therapeutic targets and therefore enable the design of better therapeutics that can be used in cases of chronic disease that ILC mediate. Therefore, to better define how ILC communicate with other cells and what signals are involved in regulating their localisation both in health and disease I will firstly use bioinformatic tools to assess whether there are novel cell-cell interactions between ILC and other cells. I will then image ILC over the time-course of an infection using imaging mass cytometry. This work will help us understand how ILC communicate with other cells and give new insights into cues that regulate ILC localisation in both health, and throughout infection, and in turn, how ILC modulate the adaptive and innate immune response.
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| 13/11/2021 |
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UNIVERSITY OF MANCHESTER |
Natural killer (NK) cells play a key role in our first line of defence against cancer and infectious diseases. NK cells achieve this through activating and inhibitory receptors that survey proteins on nearby cells through the formation of an immune synapse. Healthy cells express surface proteins that bind to inhibitory receptors and dampen the activating signals, whereas abnormal cells have either too many activating signals or too few inhibitory signals, which results in their killing by NK cells. Adhesion receptors, known as integrins, harmonise with NK cell receptors and cytoskeletal proteins to form the immune synapse and subsequent NK cell killing. I aim to gain a greater insight into the activating receptor, NKG2D. I will do this using an approach known as proximity labelling (PL). I will add labels onto proteins of interest (baits) and in specific conditions, these baits will label nearby proteins (prey). Using mass spectrometry, the prey will then be identified and validated for function. The application of PL on NKG2D can help uncover new protein associations (both signalling proteins and receptors) and provide insight into its link with adhesion signalling. This can inform future therapeutic targeting strategies or even discover novel targets for future cancer treatments.
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| 13/11/2021 |
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HEALTH DATA RESEARCH UK |
The epithelial to mesenchymal transition (EMT) is a key process in cancer that leads to tumours spreading from their original site and resisting various treatments. Tumours can be classified into three states within this process based on their genetic data. Identifying these states in tumour tissue that is routinely collected during surgery would enable us to predict whether a cancer patient is at high risk for developing metastases and responses to therapies. While artificial intelligence approaches have revolutionised our ability to detect patterns of interest in cancer tissue images in recent years, it has not yet been shown whether EMT states can be identified in tumour images. Furthermore, how cells in different EMT states organise spatially and interact with other non-cancer cells in their environment is not known. We will predict EMT states from pathology images by developing deep learning based methods. We will also analyse the spatial arrangement of the tissue in these different states from the tumour images. This will be carried out using graph-based methods and will enable us to further characterise EMT. Overall, this project will provide a greater understanding of how cancer cells transform and progress towards more advanced stages by interacting with their environment.
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| 13/11/2021 |
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HEALTH DATA RESEARCH UK |
My project will support efforts to improve the quality and safety of medical diagnosis. I will focus on exemplar conditions known for their diagnostic difficulty - resulting in long periods between patients first complaining to their GP about symptoms relating to their condition and them receiving the correct diagnosis. It may be possible that some pathways to diagnosis can be improved by better decision-making by doctors, empowered by new knowledge that will arise from my research.
I plan to focus on certain exemplar diseases (e.g., endometriosis, ankylosing spondylitis and chronic obstructive pulmonary disorder), known for their long diagnostic intervals. A patient’s electronic health record (EHR) contains lots of information about their medical history – for example, when, and how often, they visited the doctor and what symptoms they had. Using large collections of anonymous EHRs, I will identify different presenting features that patients shared before they were diagnosed and related healthcare utilisation events – so called ‘pathways’ to diagnosis. Having done that, I can examine patients who take similar pathways, and analyse whether different pathways have different diagnostic intervals. Associations between different presenting features and risk of as-yet-undiagnosed illness will also be examined in the latter part of the project.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
The Nrd1-Nab3-Sen1 (NNS) complex terminates transcription of approximately 12,000 RNAs in Saccharomyces cerevisiae. During the stress response, the NNS complex changes its occupancy to reprogram gene expression. Some of the transcripts that are only targeted by the NNS complex during the adaptive response are specifically upregulated during glucose starvation. PIC2, which encodes for a mitochondrial copper importer, is one of these NNS stress-specific targets. Whereas lack of PIC2 expression leads to defective mitochondrial respiration in yeast and humans, overexpression of copper transporters makes standard copper levels toxic for cells. Accordingly, we hypothesise that PIC2 expression is tightly regulated by the NNS complex, which suppresses transcriptional noise during glucose depletion. We will compare the phenotype of strains encoding for wild-type and deleted PIC2 NNS RNA-binding sites in varying concentrations of glucose and copper, and determine whether the variability of PIC2 expression during glucose deprivation is higher when NNS regulation is impeded. Our results could validate the NNS complex as one of the first stress-specific suppressors of stochastic expression, outline a methodology to test this role in similar NNS targets, provide a synthetic biology tool to repress gene expression in yeast and shed light on how transcriptional noise elicits human disease.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
Recent research showed that the emergence of resistance in fungi can be linked to epigenetic mutations. Those are not changes in the DNA sequence, but rather in the chromatin environment. Some parts of the genome are packaged in heterochromatin: in those areas, the DNA is bunched up much more tightly and thus not easily accessible, so genes are repressed. We want to investigate how specific heterochromatin regions are formed and removed. I am especially interested to find out why two seemingly identical cells can acquire differences in their epigenetic landscape and thus develop different phenotypes. To visualise cell-to-cell variations, I plan on using real-time fluorescent imaging, to track different proteins that are known to regulate heterochromatin. From the amount of protein and the movement of the fluorescent molecules, we can better understand how the heterochromatin distribution in individual cells changes in response to stress. Additionally, I am developing a probe, which can differentiate between different chromatin environments at specific locations.
Understanding the development of these epigenetic differences is important, as they are likely involved in the development of antifungal resistance in pathogenic fungi.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
The highly specialized neurons that make up the nervous system of an organism develop from a small number of precursor neural cells. This development is driven by a remodelling of the neuronal proteome. Many neurological disorders have been attributed to the dysregulation of genes that are important for the development of neurons. However, a systematic understanding of which genes or proteins control the complex process of neurodevelopment is so far missing. Therefore, we aim to create a precise temporal map of proteome expression changes that occur during neurodevelopment, and systematically identify proteins that regulate this process. We will take advantage of recent advances in proteomics techniques, such as metabolite and proximity labelling mass spectrometry, which enable the study of tissue-specific protein expression in model organisms. We will use this map to identify proteome changes associated with the assembly and maintenance of neural circuits in Caenorhabditis elegans, with focus on microtubule-related proteins. We expect that this will help to understand how the temporal expression of microtubule-related proteins in neurons affect the development and maintenance of neural circuits and facilitate the development of therapies against neurological disorders.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
MeCP2 is a protein found in the brain which prefers binding to methylated DNA. It can then help to block gene expression through the recruitment of other factors. MeCP2 is essential for proper neurodevelopment and mutations in the protein often cause the autism-spectrum disorder Rett syndrome, which is characterised by a lack of speech and loss of motor skills. In Rett syndrome-like mutated mice these developmental problems can be reversed, suggesting that a future treatment for Rett syndrome may be possible.
While a lot is known about how MeCP2 binds linear methylated DNA, this is not the natural state of DNA in cells. Instead DNA is often found wrapped around proteins called histones which package and compact it into chromatin. Initial evidence has suggested that MeCP2 can not only bind methylated DNA, but also to the histone proteins that the DNA wraps around. This project aims to investigate how exactly MeCP2 interacts with chromatin, understand the relevance of MeCP2’s proposed interaction with histone proteins, and discover if mutations that cause Rett syndrome also disrupt this interaction.
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| 13/11/2021 |
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UNIVERSITY OF EDINBURGH |
At different stages in life some cells acquire the ability to wander from one site to another through a process called epithelial-mesenchymal transition (EMT). This process is essential during development because it ensures that specialised cells form tissues in the right place at the right time. EMT remains important later in life, too, for mechanisms such as wound healing and tissue remodelling. However, EMT is also linked to pathologies including fibrosis and cancer metastasis. Here, we seek to distinguish epithelial cells from wandering mesenchymal cells and then investigate how the decision to undergo EMT is triggered. We hypothesise that EMT can be spread to the cell’s neighbourhood and that this spread depends on a critical starting number of EMT inducing cells, which helps maintain conformity in the community. Understanding how cells decide to migrate and how their neighbours respond to this change will give us an insight in normal developmental processes and has potential to reveal markers for metastatic cancer types and molecular targets to prevent metastasis.
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| 13/11/2021 |
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UNIVERSITY OF DUNDEE |
Parasitic worms can infect people for many years, despite the efforts of the immune system to eject them. They achieve this through the release of molecules which suppress parts of the immune response designed to kill them. In this project, we will investigate how a parasite can suppress mast cells - an important component of the anti-parasite immune response. We hypothesise that parasitic worms may produce proteins which prevent mast cell responses - in this project we will identify and characterise these immunosuppressive proteins.
We will also investigate how the immune system combats parasite infections through mast cell responses. Many parasitic worms infect by burrowing through our skin, and travelling through the blood to the gut, where they live for the rest of their lives. Recent evidence suggests that damage to the skin can be interpreted by the immune system as a parasitic infection, and leads to the accumulation of mast cells in the gut. We will investigate how this skin-to-gut communication is mediated, and how it can prevent parasite infection. We will also investigate the signals that travel from the skin to the gut, and how these act on mast cells to prepare the gut to eject parasitic worms.
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| 13/11/2021 |
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UNIVERSITY OF DUNDEE |
Much of our understanding of bacteria, and the biological processes which sustain them, comes from the study of rapidly growing populations in nutrient-rich conditions. However, in natural environments and during infections, bacteria are often stressed and starved of key nutrients. Upon starvation, many bacteria dramatically reduce biological processes and effectively enter a hibernating state where they become highly tolerant of antibiotics. I’m interested in how bacteria regulate this state of dormancy, both at the single-cell level and across populations of cells. Specifically, since data suggest that rates may fluctuate between cells, I’m interested in how protein synthesis is coordinated in time and space during starvation and how these dynamics relate to antibiotic susceptibility. Using the opportunistic pathogen Pseudomonas aeruginosa, I will label and analyse protein synthesised during starvation via fluorescence microscopy and FACS. By employing a FACS-based Tn-Seq screen and mass-spectrometry to find proteomic changes, I will identify, validate and characterise regulators of protein synthesis during starvation. This study will provide both a descriptive and a mechanistic understanding of protein synthesis during bacterial starvation, giving insights into how this activity coordinates with cellular physiology and contributes to antibiotic tolerance.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF DUNDEE |
Many tissues of our bodies are made of sheets of polarised epithelial cells. During development, these features allow tissues to fulfil their physiological function and, during morphogenesis, to fold when individual groups of cells contract. How exactly does the machinery that polarises cells intersect with actomyosin and how does contractility impinge on tissue and cellular behaviour? In the nervous system of flies, cell polarity and actomyosin regulation intersect driving cell fate decisions. During human corticogenesis, forces and actomyosin control cell behaviour and fate. The signals regulating actomyosin and contractility in these contexts are unclear.
aPKC, a key effector kinase of the polarisation machinery can negatively affect contractility by regulating Rho kinase. Our preliminary data suggest, however, that aPKC regulates actomyosin also through other pathways. We have developed a strategy to screen for genes regulating contractility in Drosophila epithelia, based on a contractility assay induced by acute and specific aPKC inhibition. We will further study the relationship between the cell polarity machinery and actomyosin regulation during human corticogenesis using iPS cell-derived neural rosettes. This work could help understand corticogenesis’ regulation by mechanochemical signalling which, in the long term, could help find strategies against developmental disorders or neuronal degenerative diseases.
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| 13/11/2021 |
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UNIVERSITY OF DUNDEE |
Bacteria typically exist in mixed communities with other microorganisms and therefore, need to compete with rival microorganisms for resources and space. The Type VI secretion system (T6SS) is a protein nanomachine that many bacteria use to fire toxic ‘effector’ proteins directly into neighbouring cells. Usually, the T6SS is used against rival bacteria, making it an important weapon by which bacteria compete with and kill each other.
I aim to identify new genes which are involved in T6SS-mediated anti-bacterial activity and to determine how some of them work. The experiments will be carried out using a representative bacterial pathogen called Serratia marcescens and results should also tell us more about many other pathogens. In addition to studying the ‘attacker’ cells bearing the T6SS, we will also be investigating what happens in the ‘target’ cells on the receiving end of the toxic effectors. We will try to understand if target cells can become resistant to particular effectors, and if so, how this happens. Overall, this project will lead to a better understanding of how bacteria survive in communities, infect host organisms, and kill each other and thus, may help develop new anti-bacterial drugs and strategies in the future.
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| 13/11/2021 |
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UNIVERSITY OF DUNDEE |
Ubiquitin is a small protein, its addition to other proteins regulates many cellular processes such as protein homeostasis and cell signalling. The addition of ubiquitin to protein substrates is catalysed by an enzymatic cascade. Ubiquitin is transferred from a ubiquitin-activating enzyme (E1) to a ubiquitin conjugating enzyme (E2). The ubiquitin bound E2 interacts with an E3 ligase which catalyses the transfer of ubiquitin to the substrate. Methods to identify interactions between ubiquitin bound E2s and E3 ligases in cells are limited. To try to capture these interactions I will develop a ubiquitin directed photoreactive probe. The probe will consist of a photoreactive diazirine group chemically conjugated to recombinant ubiquitin bound to the E2, Ube2W. The ability of this probe to form covalent attachments with E3 ligases will be validated in vitro using the SUMO-targeted ubiquitin ligase RNF4. Following validation, multiple probes will be made using different E2s. These will be incubated with cell lysates and irradiated to form photo cross-linked products that will be identified using mass spectrometry. This approach could potentially identify physiologically relevant E2-E3 pairs and novel E3 ligases which would be beneficial for the development of targeted protein degradation strategies.
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| 13/11/2021 |
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UNIVERSITY OF NOTTINGHAM |
Angiogenesis is the growth of new blood vessels from pre-exisiting vessels. Tumours require angiogenesis to occur in order to access nutrients and oxygen, but angiogenic vessels also provide a route for tumour cells to escape and migrate to distant sites within the body. Endothelial Cells (ECs) line all blood vessels. When ECs are activated by tumour growth they begin to divide and migrate, leading to angiogenesis. ECs exist in various sub-types (i.e. active and inactive) and respond in different ways to stimulation. Transcription Factors (TFs) are proteins that turn genes on/off and are a contributing factor to the existence of EC sub-types. There is evidence to suggest that one TF, Zeb1, is present in inactive ECs and that removing Zeb1 from mice spontaneously causes angiogenesis. This leads us to the hypothesis that Zeb1 plays a role in controlling EC sub-types and leads to activated ECs. To investigate this, we will compare mice with Zeb1 and mice without Zeb1 and examine the effects on individual ECs, exploring how the EC sub-types change. This work will lead to an understanding of how Zeb1 leads to spontaneous angiogenesis and may highlight potential targets for new therapies to tackle tumour angiogenesis in cancer treatment.
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| 13/11/2021 |
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UNIVERSITY OF NOTTINGHAM |
Vascular endothelial growth factor receptor 3 (VEGFR3) is a transmembrane protein found on the surface of cells that line the lymphatic vessels of the body. Its primary role is regulating the growth of new lymph vessels by interacting with its ligands, vascular endothelial growth factor (VEGF) C and D. Recently, VEGFR3 was reported to function in blood vessel development, particularly in cancer (cancer angiogenesis), supporting tumour growth and metastasis. However, our coverage of VEGFR3 pharmacology and signalling in living cells, is poor. Although typically assembled in homodimers, VEGFR3 can also form heterodimers with a different VEGFR isoform, VEGFR2. Comparative analyses of homodimer versus heterodimer configuration, relating to protein signalling and pharmacology is limited due to the difficulty in defining specific complexes. This project will combine the use of two powerful analytical tools, bioluminescence resonance energy transfer (BRET) and BioID to further understanding of the molecular pharmacology of the VEGFRs including Neuropilin receptors. These complementary approaches will allow the interaction of fluorescently labelled VEGF with VEGFR3 to be characterised in real time in living cells with the VEGFR3 ‘interactome’ to mapped, in vivo. Split tags of BioID and NanoBRET will also be used to define the molecular pharmacology of VEGFR2/3 heterodimers.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF NOTTINGHAM |
Tumour cells requires oxygen and nutrient to grow. As tumours outgrow their existing blood supply they develop regions that have low oxygen (hypoxia) and nutrient levels. These regions are often found in breast cancer and they are associated with resistance to chemotherapy and radiotherapy. Cancer cells exposed to low oxygen release chemical signals that stimulate the growth of new blood vessels which can then deliver the required oxygen and nutrients. There are four Bromodomain and extra terminal (BET) proteins that bind to sections of the DNA that has been chemically modified to indicate if a gene should be active or inactive. The BET proteins then recruit other proteins which are important for transcribing genes. It has been shown that drugs that inhibit the BET proteins change how the cells respond to hypoxia and reduce the growth of new blood vessels.
I will investigate how the BET proteins regulate the growth of new blood vessels and identify which of the four BET proteins is the best target for new therapies. Regulating blood vessel growth can lead to the reperfusion of tumours and allow radiotherapy and chemotherapy to effectively treat patients with solid tumours.
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| 13/11/2021 |
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UNIVERSITY OF LEICESTER |
In the UK, men aged 65 are invited to screening to check for an Abdominal Aortic Aneurysm (AAA). Untreated aneurysms may rupture, which is usually fatal, although many aneurysms do not progress to this stage. There are known risk factors for AAA such as smoking and family history. Evidence of genetic association with AAA has been found which means that some people are more at risk from birth of having an aneurysm.
I plan to investigate the role of genetics in both the presence and progression of disease, utilising data from UKBiobank, the UK Aneurysm Growth Study and AAA-Express. These findings will be adopted into a hypothetical computer model. I will investigate the possibility of targeted screening for AAA. This involves identification of risk factors that will also consider the benefit of genetic data to identify individuals at high risk of AAA for screening invitation. I will then investigate an adapted clinical pathway after detection of aneurysm based on the risk of rupture. Incorporating genetic information may improve patient outcomes and the cost-effectiveness of the screening program by limiting screening to those most at risk and by ensuring that those diagnosed with an aneurysm have the most appropriate clinical intervention.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF LEICESTER |
Idiopathic Pulmonary Fibrosis (IPF) affects around five people in every 100,000 in the UK and is amongst the most devastating of lung diseases, with a median survival time of 3 years and variable progression. Comparable disease prevalence (6.8 per 100,000 persons) has also been reported in other countries such as the USA, Italy, and Canada. About 5000 cases are detected annually in the UK, and there is rising disease prevalence globally. Despite the substantial disease burden, there is little understanding of the disease etiology, and it has a poor prognosis. Other than a lung transplant, the available drugs are not curative. The majority of cases are diagnosed in patients > 50 years and males are disproportionately affected than females. Both genetic and environmental factors have been associated with IPF. The genetic mutations described so far only account for about 19% of genetic risk associated with IPF. Therefore, the analysis of other types of genetic variations is pertinent. In particular, our study will use whole-genome sequences in case-control cohorts to identify other genetic mutations associated with IPF susceptibility. Identifying risky mutations can help understand disease etiology and develop more targeted therapies.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF LEICESTER |
Patients differ in the way they respond to radiation treatment. Approximately 5% of patients are sensitive to radiotherapy and at risk of suffering long-term side-effects (1). However, there is no effective way to identify these patients. The REQUITE trial was established with the aim of reducing long-term side-effects from radiation (2). A total of 4438 cancer patients were enrolled in the study. Before receiving radiotherapy, patients completed a questionnaire and provided a blood sample which was analysed for genetic variants.
The researchers tested for other biomarkers that might predict sensitivity to radiation. One example includes the radiation-induced cell death assay called RILA. This is a measure of the percentage of white blood cells that are killed by radiation (3). The researchers found that a low RILA score is associated with long-term side-effects.
My research aims include finding possible genetic associations with the RILA assay. In addition to finding possible genetic associations to predict late side-effects in breast cancer patients and a genetic study on patient reported outcome measures such as quality of life scores. The overall long-term goal of this project is to integrate biomarkers, genetic and clinical data to help predict which patients will suffer from worse side-effects.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF LEICESTER |
Idiopathic Lung Fibrosis (IPF) is a disease which leads to death three years after diagnosis in half of cases. IPF is a complex genetic disease - variants of DNA that contribute to disease risk have been identified, though we have yet to fully understand how these risk factors lead to lung scarring.
A Genome-Wide Association Study (GWAS) can be used to determine which regions of DNA are associated with disease. GWAS can be used to look at individual variant sites in the DNA called Single Nucleotide Polymorphisms (SNPs). By comparing the entire DNAs (Genomes) of people with and without IPF, we can narrow down the suspected sequences that may contribute to the development of the disease to very fine resolution.
Once SNPs associated with IPF are identified, we then need to understand why they are associated. Determining which SNP leads to IPF requires 1) Linking SNPs to genes, 2) finding biochemical pathways associated with these genes, and 3) finding drugs that can be used to target the biochemical pathways. These steps enable us to understand the pathology of IPF and could lead to the identification of potential drug treatments for this currently incurable disease.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF LEICESTER |
Genetic information is becoming increasingly utilised by healthcare professionals in order to provide patients with more precise diagnosis and treatments. An individual's genetic information may show their risk of inheriting a genetic disorder, and although most individuals would consent to healthcare professionals sharing their genetic information with relatives who may also be at risk, some individuals refuse. It can be argued that a failure to disclose the risks of inheriting genetic disorders to relatives is ethically wrong, because it restricts the autonomy of individuals to make life choices. Alternatively, it can be contended that it is legally wrong for a healthcare professional to not adhere to the duty of confidentiality that they owe to patients.
This debate demonstrates the conflict of duties that healthcare professionals face as the use of genetic information in medicine develops, and highlights the need to develop a new legal framework which takes into account the needs of patients, relatives, and healthcare professionals. In order to create an appropriate legal framework, I aim to assess academic commentary, examine case law, and conduct qualitative interviews with healthcare professionals in order to assess scientific opinion, and potentially inform new policy guidance.
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| 13/11/2021 |
£0 |
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UNIVERSITY OF NOTTINGHAM |
The human P2Y2 receptor is one of a large and diverse family of disease-relevant drug targets called G protein-coupled receptors. The P2Y2 receptor is a promising therapeutic target for important conditions, including metastatic cancer. However, no drugs which block the P2Y2 receptor have ever entered clinical trials.
The research group recently published an initial study where novel P2Y2 receptor inhibitors, that prevent the action of the receptor, with good biological activity were produced. The project will build on this previous work to design, synthesise and evaluate further inhibitors with improved biological activity and drug-like properties to make them more clinically viable. The design of these inhibitors will be driven by visualisation of key interactions with the P2Y2 receptor in computational models. Another subsequent part of the project will involve equipping these novel inhibitors with a light emitting fluorescent dye that can be used to investigate their interaction with the P2Y2 receptor in cell and tissue-based experiments with state of the art imaging equipment.
Novel, high affinity and drug-like P2Y2 receptor inhibitors and their fluorescently-labelled counterparts would provide a vital tool to further validate the role of P2Y2 in disease and aid in the development of clinically viable drugs.
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| 09/11/2021 |
£300,000 |
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IMPERIAL COLLEGE LONDON |
Emergence of SARS-CoV-2 variants has underscored the importance of genomic surveillance in enabling timely identification of new viral threats, and the role of transmission modelling in characterising the public-health risk they pose. These analyses have largely been considered independently of each other during the pandemic however, despite evidence that genomic and epidemiological data can provide complementary insights into virus dynamics. I will develop a Bayesian transmission-modelling framework reconciling both data-sources and use this framework to systematically compare the epidemiological properties (e.g. transmissibility, disease-severity and immune-evasion potential) of key variants (including but not limited to Alpha, Beta, Gamma and Delta), across settings including Brazil, Colombia, India, Panama, South Africa and the UK. I will explore how the dynamics of variant establishment and spread are shaped by intrinsic variant properties and their modification by epidemiological context (e.g. control measures or levels of population-immunity), and examine whether there is evidence for different contexts influencing the establishment of variants with particular properties. This work will improve our understanding of the types of SARS-CoV-2 variants likely to establish and spread in the future; inform decisions aimed at mitigating their potential public-health impact; and provide insight into the ways epidemiological pressures influence viral evolution.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Despite significant increases in our understanding of brain functioning over the last decades, the translation of this knowledge into novel therapeutic approaches had lagged behind. Here, I propose a network dynamics approach to alter brain circuits and cognition in a cross-species, closed-loop manner, employing both rodent as well as human experiments.
First, I will perform exploratory experiments to probe frontal cortex neural dynamics during flexible decision making, concomitantly in rodents using high-density local field potential (LFP) recordings and in human subjects using magnetoencephalography/electroencephalography (MEG/EEG). I will employ a singular analysis pipeline with a particular interest in interactions between theta and gamma oscillations. Following this, I will perform open-loop non-invasive transcranial alternating current manipulations of neural circuits and cognition restricted to a rodent model to explore and optimize stimulation parameters. Finally, I will perform phase-dependent, ultra-fast closed-loop stimulation in both rodent and human subjects to dynamically modulate network oscillations and cognitive functioning in a non-invasive manner.
Successful completion of this ambitious project could have important translational implications for a wide range of disorders of the brain, from neurology to psychiatry.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY COLLEGE LONDON |
Quick and effective decision-making in a rich sensory world requires animals to use prior knowledge and internal goals to prioritise relevant sensory evidence to guide their actions. Spatial attention is the cognitive ability to constrain the processing of sensory evidence to particular spatial locations while ignoring presumed irrelevant sensory evidence from other locations. The mechanisms by which spatial attention is realized in neural circuits are poorly understood.
I will use a combination of Neuropixels recordings, circuit tools, and computational analyses and modelling in a novel attentional change detection task wherein mice continuously track attended content without responding. This will allow neural investigation of attentional mechanisms and attended sensory content in the absence of motor confounds.
Firstly, I aim to determine how neural representations of sensory evidence are modulated by spatial attention in brain areas representing task-relevant sensory evidence. Secondly, I aim to understand how interactions between brain areas causally shape attended task-relevant sensory representations and dynamics.
The outcome of this work is a better understanding of how attentional processes mechanistically influence task-relevant sensory processing at a single-cell, neural population, and circuits levels. This will help us develop a model of how internal cognitive processes integrate with the external sensory world.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Arthritogenic alphaviruses are re-emerging mosquito-borne viruses that cause severe arthritis. Chikungunya virus (CHIKV), the most prominent arthritogenic alphavirus, has caused explosive outbreaks affecting millions of people world-wide. Currently, there are currently no available vaccines or specific drugs against the virus. Global spread of Aedes mosquito vectors underscores the potential emergence and threat of arthritogenic alphaviruses.
The humoral response to CHIKV infection is key in controlling infection. However, currently there are few studies that have characterised human CHIKV mAbs from vaccinated volunteers, so our understanding of the underlying cellular and molecular mechanisms induced by CHIKV vaccines is limited. The first-in-human trial of ChAdOx1 Chik in Oxford elicited outstanding immunogenicity. It induced neutralising antibodies against 4 distinctive CHIKV lineages and 100% seroconversion by PRNT50. The same vaccine also conferred some cross-protective efficacy against MAYV in mice.
I will characterise the nature of the immune responses arising from CHIKV vaccines by achieving following aims:(1)Isolate human mAbs from volunteers in the ChAdOx1 Chik trial; (2)Functionally characterise a panel of neutralising mAb (3)Characterise the structural basis for how CHIKV-specific mAbs and broadly reactive mAbs target alphaviruses. This project will provide valuable insights into human antibody response to vaccination and identify candidate mAbs for therapeutic intervention.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF BRISTOL |
Daily partitioning of feeding is crucial for well-being and survival, but neuronal mechanisms underlying this process remain poorly understood. The dysregulation of circadian rhythmicity seen in the modern 24/7 society leads to obesity, cardio-vascular problems, metabolic syndrome and some kinds of cancer, constituting a major public health burden. Recently, we found that a brainstem satiety centre – the dorsal vagal complex (DVC) harvests exceptionally robust timekeeping properties, which are additionally sensitive to diet. This projects aims at understanding the neurochemical identity of the DVC clock, its possible ways of entrainment and role in physiology and obesity. These goals will be achieved with the use of a unique combination of tools, including cutting-edge molecular techniques (single-cell RNAseq and RNAscope) and real time monitoring of bioluminescence reporters. Additionally, we will combine optogenetic tools to stimulate vagal afferents, with multi-channel electrophysiology ex vivo and behavioural monitoring of food and water intake. Moreover, the output of the brainstem clock will be measured with the working brainstem-gut model. Results of this project have a potential to elucidate neural mechanisms of daily rhythms in satiety, but also possess clear translational clinical values for a restoration of circadian rhythmicity in obese patients by timed vagus nerve stimulations.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF BRISTOL |
Social transitions during emerging adulthood (starting further education/training/employment, leaving the family home, cohabitation, marriage, parenthood), have been shown to influence health and related behaviours in subsequent years. However, there is a lack of evidence on adult social transition patterns among today’s young people, or the likely complex mechanistic pathways to later health outcomes.
Using rich clinical, questionnaire, genetic, and linked administrative health data from three contemporary European cohorts, and advanced longitudinal epidemiological methods, this project will address the following objectives:
Determine the most common adult social transition patterns in terms of timing, quantity, and unique combinations.
Identify causal determinants of adult social transition patterns.
Determine the causal relationship between different adult social transition patterns and adult health outcomes.
Estimate the contribution of psycho-social factors as moderators/mediators of the relationship between different adult social transition patterns and health outcomes.
Estimate bi-directional associations between different adult social transitions, and psychological and socio-economic (psycho-social) factors.
Where possible, I will explore these objectives separately for different important subgroups, e.g. by sex, to establish who might need targeting/supporting differently. The research project's overall aim is to provide evidence that can better inform support of young people and prevent downstream adverse health outcomes.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY COLLEGE LONDON |
How are signals conveying sensory information and internal physiology combined to produce adaptive behaviour? The strategic location, connectivity and diverse neuronal composition of the habenular nuclei suggest that they may act as a hub where multimodal information converges to facilitate selection of appropriate actions. These nuclei also display conspicuous left-right asymmetries in terms of neurochemistry, neuronal activity and connectivity. I propose to investigate the role of the habenulae and their neuronal asymmetries in selection of behavioural responses, and how these responses are modulated dependent on internal states. Specifically, I will implement a behavioural assay based on phototaxis in larval zebrafish and compare responses between wildtype fish and genetic mutants with disrupted habenular asymmetry, following different sensory contexts (luminance history) and internal states (feeding states). By bridging physiology and spatial transcriptomics, I will then aim to identify the habenular neuronal sub-types and their functional features that impact the encoding of relevant behavioural parameters, as well as their state-dependent modulation. Through this project, I will gain a better understanding of the neural and molecular basis of adaptive behaviour, as well as advance the research field in fundamental aspects of habenular physiology and functional roles of circuit asymmetries.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Over 60% of Parkinson’s disease (PD) patients will experience visual hallucinations (VH) as their disease progresses. The mechanisms underpinning VH are not well understood, hindering development of treatments. VH in PD likely relate to the inability to resolve ambiguous visual information; a process shaped by inhibitory neurotransmitter GABA in the healthy brain. Here, I will investigate the role of pathological GABAergic inhibition in visual processing that may result in VH.
My proposal has two aims. First, to identify the subtype of GABAergic signalling (tonic vs. phasic) that predominantly affects ambiguous visual processing, thus introducing new pharmacological targets for reducing misperceptions. Second, to identify connections between brain regions that relate to pathological GABAergic signalling during VH in PD. Using non-invasive non-invasive ultrasound neuromodulation, I will target these connections to reduce VH in PD.
My work will use complementary methods in healthy adults and PD patients with VH, overcoming limitations that testing either population would incur. I will provide a mechanistic understanding of VH, proposing putative targets for therapeutic interventions to alleviate VH symptoms in PD patients.
Key words: Parkinson’s disease, visual hallucinations, GABA
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Anorexia nervosa (AN) is a serious psychiatric condition characterised by restricted food intake that leads to life-threatening weight loss. AN patients suffer with disruptions in the metabolic and neurocognitive processes that guide eating behaviour. However, it remains unclear how these processes interact to drive a core AN feature: maladaptive choice behaviour, where patients prefer low-calorie foods despite starvation. This fellowship will examine how interactions between metabolic markers and neural mechanisms involved in value-based choice shape eating behaviour in AN. To achieve this, I will combine computational modelling, high-field (7-Tesla) neuroimaging and metabolic profiling to comprehensively characterise, for the first time, how AN patients estimate reward value and use it during decision-making, by addressing three primary aims:
Develop behaviour assays to examine value-guided decision-making in AN for food and non-food reward and apply computational modelling techniques to generate estimates of reward value.
Optimise 7-Tesla functional neuroimaging of dopaminergic midbrain activation during decision-making.
Apply these tools in a high-field, case-control neuroimaging study of AN to investigate group differences in the neuro-computational mechanisms of value estimation, examine how these are modulated by gut hormones, and test whether they predict real-world eating behaviour and symptom trajectories.
Keywords: Anorexia, decision-making, 7-Tesla MRI, midbrain nuclei
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Post-translational modifications (PTMs) greatly diversify the properties and functions of proteins. ADP-ribosylation (ADPr) catalysed by the family of PARP enzymes is a therapeutically-relevant reversible nucleotide-sugar PTM with roles in pathogen infections, immune signalling, and the DNA damage response.
Recently, advances in proteomic techniques enabled the identification of non-canonical cysteine (Cys) ADPr modification sites in human cells. PARP7 has been proposed as a Cys-ADPr-transferase while PARP8 is auto-modified exclusively on Cys, strongly suggesting inherent Cys-ADPr activity. Human Cys-ADPr hydrolases are currently unknown. Multiple known Cys-ADPr substrates and phenotypes from mouse PARP7 knockout suggest roles in cancer and important physiological roles in the regulation of the immune system and development. Despite recent findings, very little is known about the molecular mechanisms of Cys-ADPr signalling and its roles in human cell signalling.
I will perform systems-wide profiling of Cys-ADPr sites in human cells using a novel enrichment technology and mass spectrometry-based proteomics. Using CRISPR-Cas9 genome editing as well as biochemical approaches, I will develop a toolkit to study this PTM site-specifically to ultimately characterise its roles in cellular signalling. This will inform future drug discovery efforts that exploit site-specific targeting of cysteine PTM sites.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY COLLEGE LONDON |
Mental health problems have a significant impact on society. Health-related behaviours such as sleep, exercise, dietary habits, alcohol use and smoking are modifiable and may be important risk-increasing or protective behaviours associated with depression, anxiety and psychosis. The biological and causal mechanisms underlying these associations are, however, poorly understood. Additionally, both children’s and their parent’s health-related behaviours are associated with childhood mental health symptoms, suggesting that intergenerational mechanisms may be important.
During this fellowship, I will use advanced genetically informed designs to investigate whether shared biological pathways and causal relationships may explain associations between health-related behaviours and mental health. I will identify genes involved in these associations and investigate their biological implications. Causal relationships will be investigated using new methods that mitigate bias due to unmeasured confounders, and whilst accounting for intergenerational transmission of risk. I will investigate whether genetic or environmental mechanisms can account for intergenerational associations.
Findings will advance aetiological models and inform causal inference. Confirming causality will be essential knowledge to help prioritise targets for intervention. Findings can inform whether interventions will be most promising when aimed at parents, in the case of environmentally mediated routes of transmission, or individuals, in cases of genetic transmission risk.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF OXFORD |
Sleep is a vital physiological process. However, we still lack a molecular interpretation of sleep pressure and a detailed map of the neural circuits underlying sleep regulation in the mammalian brain. Drosophila research informs us that oxidative stress build up, and sensing by beta-subunits of voltage gated potassium channels could reflect an evolutionarily conserved principle which underlies accumulating sleep need, a process termed sleep homeostasis. I recently demonstrated that mammalian cortex plays a role in vigilance state control and sleep homeostasis. My project merges these two lines of research and tests if pyramidal neurons in the cortex sense sleep need via redox-sensitive KVbeta subunits and subsequently initiate sleep through projections to the centromedial thalamus and lateral hypothalamus. I will perform in vivo electrophysiological sleep recordings in Kcnab1-3 mutant mice and chemogenetically stimulate cortical pyramidal neurons to assess whether sensing of oxidative biproducts of neuronal activity underlies sleep homeostasis. I will further perform optogenetic stimulation of pyramidal neuron terminals in centromedial thalamus and lateral hypothalamus and use retrograde tracing to map out the pathways through which cortex interacts with subcortical sleep-control areas. This project could reveal key principles of sleep physiology and advance sleep science and sleep medicine alike.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY OF CAMBRIDGE |
During early embryonic development, pluripotent cells differentiate, change shapes, and rearrange spatially to form the blueprint of the adult body. Classically, the orchestration of cell fate commitment in the developing embryo has been attributed to the activity of biochemical signalling pathways. More recently, biophysical factors have emerged as important players in this process.
The aim of my research project is to explore how cell fate is influenced by cell surface mechanics in gastruloids, a multicellular model system mimicking a gastrulating embryo. I will first trace changes in cell shape and mechanics concomitant with cell differentiation towards mesendoderm and neurectoderm in the multicellular context of the gastruloid. To achieve this, I will implement advanced microscopy techniques and state-of-the-art methods for in situ mechanical characterisation. In the final stages of the projects, I will perturb cell mechanics during gastruloid growth using (opto)genetic tools, and monitor the impact of these perturbations on cell fate and spatial patterning.
My project will generate a single-cell-level understanding of the interplay between cell surface mechanics, cell shape, and cell fate in developing gastruloids, and thus contribute to answering the long-standing question in developmental biology of how physical determinants coalesce with biochemical signalling to drive embryogenesis.
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| 09/11/2021 |
£300,000 |
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UNIVERSITY COLLEGE LONDON |
My research aims to develop a new generation of sensitive, low-cost, nanoparticle-based diagnostic platform technologies by exploiting the quantum properties of nitrogen-vacancy centres in fluorescent nanodiamonds. My previous proof-of-concept work showed that selectively manipulating their fluorescence with microwaves gave a fundamental detection limit of just 0.5 particles/µL in lateral flow assays, a 105-fold improvement over commonly used gold nanoparticles. Their brightness and electromagnetic field manipulation enable biosensing modalities that are not possible with existing technologies. In this fellowship I will:
Develop proximity-based assays using nanodiamonds with magnetic nanoparticles, addressing the limitations of FRET-based approaches. Preliminary feasibility modelling suggests possible separation distances up to 930 nm, allowing a range of diagnostic assays using larger biomolecules. This could also allow the separation of specific and nonspecific signals using optically detected magnetic resonance.
Combine CRISPR-based diagnostics with nanodiamonds, removing the amplification step currently required to reach clinical sensitivities. I will develop a tri-functional probe with a low-cost nanodiamond lateral flow readout, giving a projected 7,500-fold improvement over gold nanoparticles.
Investigate time-gated fluorescence imaging – exploiting nanodiamonds' relatively long fluorescence lifetimes – in combination with previously demonstrated microwave modulation, to further reduce background in lateral flow, improving nanodiamond detection limits towards the single-particle regime.
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| 09/11/2021 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
My main objective is to address outstanding questions of how inductive cues direct cell-fate specification in the early mouse embryo, focussing on the second fate decision, where FGF4 signalling mediates asynchronous segregation of the inner cell mass into epiblast and primitive endoderm (PrE). Current understanding of this developmental step is limited to cell-intrinsic properties, like intracellular signalling and transcription factor networks, whereas the mechanisms of ligand delivery remain unknown. I hypothesize that local variations in the FGF4 morphogen gradient are driving the asynchronous allocation of epiblast and PrE. Here I propose to determine (1) how FGF4 is communicated from cell-to-cell and (2) how this signal is differentially integrated to produce cell-fate decisions. To accomplish this challenging task, I will employ the tools of live-cell single-molecule localisation microscopy (SMLM) to image the FGF4 morphogen gradient and transcriptional outputs, in vitro and in vivo. This work will result in the creation of machine learning platforms for the analysis of SMLM data and a quantitative spatiotemporal model for the formation of the FGF4 morphogen gradient. This interdisciplinary project will allow me to directly measure previously inaccessible parameters about the FGF4 morphogen gradient that have long been sought.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY OF YORK |
Horizontal gene transfer (HGT) enables microbes to rapidly acquire novel genes such as those conferring antibiotic resistance. Virus-like particles called gene transfer agents (GTAs) mediate high-frequency HGT but remain largely unstudied.
Understanding how GTAs recognise their hosts will allow us to assess their impact on environmental HGT and will inform biomedical applications such as gene delivery to the microbiome. To achieve this, I aim to characterise molecular mechanisms of receptor recognition by GTA proteins. Putative receptor-binding proteins will be produced, and their carbohydrate ligands identified by glycan arrays and mass spectrometry. The importance of individual protein regions will be assessed by structural analysis of protein-ligand complexes and domain exchange between two related GTA producer species.
Knowledge of how GTA particles package bacterial genes during assembly is important for understanding GTA evolution and for informing strategies to interfere with GTA-mediated HGT. I aim to describe DNA packaging in genetically distinct GTAs. Cells in an intermediate state of GTA production will be produced by chemical induction and reporter-based cell sorting. Wild-type and DNA packaging gene knock-out strains will be analysed by mass spectrometry and whole cells by cryo-electron tomography to achieve a holistic overview of the DNA packaging process in situ.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Macropinocytosis is an evolutionarily conserved yet ill-studied endocytic process. It is characterised by the formation of Rac1-actin-dependent membrane ruffles and shares the same core machinery with the process of cell migration. Macropinocytosis can be utilised by professional antigen-presenting cells like macrophages to sample their surrounding environments for signs of infection or by cancer cells to fuel their proliferation. Despite its important roles in many pathophysiological conditions, factors that regulate macropinocytosis remain largely unclear.
Traditionally, it is believed that growth factors play a central role in triggering macropinocytosis. However, recent in vitro evidence suggests physical cues such as hydraulic pressure and membrane tension also significantly impact this process. Nevertheless, an in vivo model that intercalates physical factors in the regulation of macropinocytosis is still lacking.
This proposal looks at the highly macropinocytic macrophages and aims to combine the advantage of the mechanically tunable Xenopus embryos with the high-resolution imaging capability of zebrafish embryos and larvae to address three key questions:
Can tissue mechanical properties affect the migration and macropinocytosis of macrophages?
Establishing a Xenopus ex vivo primitive myeloid-derived macrophage model for macropinocytosis study.
Can substrate stiffness affect bacterial clearance by macrophages during wounding and inflammation?
Keywords: Macropinocytosis, mechanosensing, macrophages, Xenopus, zebrafish.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Infectious disease remains a global health burden. Blood and immune cells play a central role in underlying pathology, however long-term consequences of infection on these cells in otherwise healthy people are unknown. This project aims to understand whether infection modifies cellular programmes, leaving scars on the haematopoietic system, even after recovery, that compromise health in later life. Using a murine influenza model, non-infected, infected and recovered groups (where subjects are administered antiviral treatment post-infection and are analysed after a period of time) will be investigated. By combining a DNA barcoding tool with single cell Multiome analysis of bone marrow cells from these groups, a high dimensional comparison of the transcriptome and epigenome of sister cells will be generated. These data will address fundamental questions including whether cell fate potential is and remains perturbed by infection. Next, following bioinformatic stratification of the data and employing in vitro functional experiments to screen candidate genes using CRISPR-Cas9, molecular targets to be manipulated in vivo will be identified. These experiments will address whether it is possible to mitigate effects of infectious perturbations on the haematopoietic system. Overall, this work will begin to elucidate mechanisms driving the response to infection and highlight potential therapeutic interventions.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Obsessive-compulsive disorder (OCD) is a common and debilitating mental health condition with limited treatment success. The first-line psychotherapeutic treatment, Exposure and Response Prevention (ERP), is only effective for ~50% of patients. My goal is to understand this failure and to improve OCD treatment success.
ERP aims to suppress compulsions using precepts from learning theory, but computational mechanisms underlying its success/failure have never been studied. Using a novel task that mimics ERP and applying computational modelling, I will quantitatively characterise clinical predictors of ERP failure in OCD patients undergoing therapy. This will allow me to understand why ERP fails, and how we can improve it to prevent failure.
In a second workstream, I will examine the other major symptom of OCD, obsessions, that psychotherapy currently does not adequately target. Little is understood about how obsessions arise or become distressing in OCD. Using cutting-edge MEG machine-learning decoding techniques, I will examine how mental representations and thought processes are distorted in OCD, which could quantify why obsessions are so distressing and how we can target this core process in future treatments.
Using a computational psychotherapy approach, this research promises to revolutionise how we understand, improve, and construct effective, individualised treatments for OCD.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Diabetic neuropathy is the most common complication of diabetes, yet the underlying aetiology of this disorder remains poorly understood. A growing body of evidence suggests that diabetic neuropathy involves nerve injury downstream of reduced local blood flow due to capillary dysfunction. Pericytes are key regulators of capillary blood flow in other tissues, and are central to the pathophysiology of other diabetic disorders including diabetic retinopathy. Pericyte loss has been reported in patients with diabetic neuropathy, but the consequences are unexplored. We hypothesise that pericyte pathology drives reduced blood flow in diabetic neuropathy, thereby contributing to nerve injury. To test this hypothesis we will:
1) Characterise the progression and distribution of lower limb pericyte, capillary and neuronal dysfunction
2) Elucidate changes in pericyte function and how pericytes contribute to vascular dysfunction
3) Resolve whether pericyte and sensory neuron dysfunction in diabetes occur secondary to hyperglycaemia or ischaemia
4) Translate observed results to the Db/Db type 2 diabetes model and human tissue
To this end, this project will use a combination of ex vivo and in vivo functional study to evaluate the time-course, mechanisms and implications of pericyte dysfunction/loss during diabetes, and how this contributes to diabetic neuropathy.
|
| 09/11/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
T cells use small and dynamic microvilli to efficiently scan cells for abnormalities. Recognition induces synapse formation; a large polarised interface that drives effector functions e.g. cytotoxic granule release. The importance of the actin cytoskeleton in microvilli and synapse formation is well established. However, it remains unclear how actin remodeling is spatiotemporally coordinated to drive these structures and whether they are impacted by metabolic state. This proposal aims to (1) identify the drivers of microvilli formation and dynamics, (2) explain how the cytoskeleton is coordinated from microvillar scanning to synapse formation, and (3) explore the link between cytoskeletal remodeling and metabolism. Aims 1 and 2 will focus on Rho GTPases; the ‘master regulators’ of the actin cytoskeleton. I will use biosensors, optogenetic manipulators, light-sheet microscopy, and computer vision analyses to quantify and manipulate GTPase signaling networks in relation to microvilli and synapse formation in 4D. Aim 3 will use biosensors, pharmacological manipulation, and metabolic readouts to examine the impact of metabolic state on microvillar scanning and synapse formation. All aims will use tuneable reconstituted systems to capture and manipulate these key behaviours. Complete understanding of cytoskeletal remodeling may uncover novel ways to control T-cell function for therapeutic benefit.
|
| 30/09/2021 |
£20,000 |
|
UNIVERSITY OF AUCKLAND |
This proposal repurposes funding that Wellcome had intended for use to support LMIC delegate travel to the INGSA biennial conference. It would now enable acceleration of our Online Outreach and Training Strategy. Our current funding envelope pre-dates the pandemic, and did not anticipated the extent of online delivery now required. We have tried hard to transform programming with existing resources, but gaps remain. Will now focus on delivery of accessible, inclusive and interactive capacity-building online. We have content that can be turned into pedagogically-robust modules and made available via a reputable learning platform. Deliverables include:
"INGSA Shorts" series of 2-3 minute videos which condense learning/wisdom from the 2021 conference (estimated cost: $12,000 NZD)
Minimum three MOOC-style courses, framed around the conference's themes: Science Advice in Crisis (i.e. lessons learned from the pandemic); Science advice for complex/long-term issues (i.e. foresight/resilience; Evidence/democracy. Content drawn from 2021 conference and other Wellcome/IDRC funded programming including past LMIC workshops, the Covid-19 comparisons, Knowledge Associates projects. This approach leverages the full complement of INGSA programming (estimated cost: $28,000 NZD)
We will work with new INGSA Board and LMIC partners to co-design, contextualise and field-test material, ensuring that content and format is robust and appropriate to context.
|
| 30/09/2021 |
£49,243,757 |
|
BOSTON UNIVERSITY |
The overall objective of this proposal is to build and accelerate the early development of a globally relevant, scientifically diverse portfolio of antibacterial projects (treatments, preventatives and diagnostics) with scientific/drug development and portfolio management rigor ensuring the most efficient and effective use of funding to deliver clinically valuable projects that, upon graduation from CARB-X, increase the likelihood of securing follow-on funding from private or public funders for advanced-development activities.
The strategy, scope and budget to guide investment priorities will be set by the JOC but is expected to continue to include the most important bacterial pathogens highlighted on the CDC Threat/WHO Priority Pathogen Lists and include projects from early- to clinical-stages of development and will be refined from time-to-time based on strategic review update processes.
The antibacterial preclinical pipeline is in the hands of less than 400 small enterprises. With 5 years of unprecedented success, CARB-X is uniquely poised to identify the most promising programs, provide what these teams lack (funding and gaps in their expertise), and to manage the resulting portfolio to protect us all from drug-resistant infections. We look forward to working with you in the years to come to bring products to patients.
|
| 30/09/2021 |
£89,870 |
|
UNIVERSITY OF THE WEST OF ENGLAND |
Our goal is to collaborate with the SL+ teams to galvanise innovation in research and practice in ISL, and to enable multiple stakeholders to locate themselves within, access and contribute to the ISL landscape.
We are proposing a three-phase programme of work (each is explained in more detail later):
Explore and map phase: we will develop a ‘landscape view’ of the field. The SL+ projects will be key ‘landmarks’ in this map, and we will contextualise their work in a broader context, and to identify where gaps and opportunities remain.
Connect and develop phase: we will run a series of virtual workshops and events to share and test the emerging findings from the SL+ programme with key stakeholder groups. This phase will focus on three areas: the relevance of the research for current policy and practice; how it can be mobilised; and gaps and opportunities for further research
Mobilise and sustain phase: we will act on the findings of the first two phases to finalise and share useful tools and resources, and we will support network(s) to access and use these. We will support the programme teams and other stakeholders to take forward new research, building on prior learning
|
| 30/09/2021 |
£20,000 |
|
WORLD OBESITY FEDERATION |
Leveraging our existing projects and partnerships with young people, World Obesity has a unique opportunity to help the HCN expand its audiences, as we mobilise youth organisations from food, health and climate spaces to help disseminate the messages produced and take forward the HCN’s work in 2022. By focusing on youth rather than driving a specific issue ourselves, we open the door to mobilise and create momentum across a wide range of areas relevant to HCN. In the lead up to COP26, World Obesity will work with youth leaders to produce advocacy videos for social media based on the HCN core messages. The short videos will be montaged into a digital youth HCN manifesto, which will be launched at The UN Climate Change Conference of Youth (COY). Following COP26, we will continue to develop the youth arm of HCN, convening a workshop for young people already engaged, as well as other youth leaders who emerged at COP26. The virtual convening will aim to reflect on COP26, refine the HCN’s existing messages and co-create new strategies to progress the HCN’s work in 2022. In Q1 2022 we will also produce three podcast episodes, hosted on our youth facing platform Healthy Voices.
|
| 30/09/2021 |
£49,999 |
|
UNIVERSITY OF LEEDS |
This award will fund preparatory work for a project exploring "genetic imaginaries" and their cultural and biomedical genealogies in African literatures and creative cultures. The main aim of this preparatory work is to provide proof of concept for an innovative literary medical humanities methodology: creative writing workshops designed to explore, examine, and observe the creative processes involved in conceptualising and (re)imagining the genetic as it relates to embodied conditions and differences, genetic "categories," lived experience, and public health. Through this award, I will prepare for and run two pilot workshops in Cameroon and Nigeria to establish protocols and good practice for creative writing workshops as part of an interdisciplinary medical humanities methodology. I will also develop my theoretical and practical understanding of co-production through research and mentorship, undertake field trips to make connections with medical humanities researchers and publishers, and extend my conceptual thinking on genetics. I have arrived at these plans following careful reflection in response to the constructive feedback of the Wellcome interview panel for my prior application to the Wellcome Research Fellowship in Humanities and Social Sciences Award scheme. Through these activities, I hope to lay the groundwork for an application to the Wellcome Career Development Award.
|
| 30/09/2021 |
£19,667 |
|
PUBLIC HEALTH ASSOCIATION OF SOUTH AFRICA |
We aim to primarily disseminate HCN’s messages on Energy Systems That Protect Climate and Health to government and civil society so as to promote health- centred climate policy and advocacy in South Africa.
Expected outcomes:
A database of audiences for a targeted dissemination campaign;
a social media campaign about the key HCN messages;
press releases with AMREF and the SA Medical Association;
monthly webinars about climate and health at COP26;
regular engagement with HCN global partners in the run up to COP26;
a published journal paper about the campaign;
an online resource for public health educators and professionals about protecting public health from climate change, and educating for sustainable healthcare, which incorporate key HCN policy messages.
These will support HCN’s intended short-term outcomes by enhancing collaboration between health and non-health advocacy organisations in SA; disseminating key messages of HCN briefs to key target audiences; and strengthening the capacity of PHASA as a champion for health- centred climate policy and advocacy in SA, especially with respect to energy policy.
|
| 30/09/2021 |
£99,600 |
|
UNIVERSITY OF CAMBRIDGE |
The proposed economic analysis aims to estimate the extent to which a carbon price on energy could transform road transport, increasing active travel including the use of public transport, bringing benefits to both the climate and health. This extends an analysis underway (Phase 1) assessing the impacts of carbon pricing on the land-use sector on agricultural production, food prices, diets, and health outcomes.
The work will comprise modelling the consequences of carbon pricing at two levels: (i) keeping global temperature rise below 2oC above pre-industrial levels; (ii) achieving a rise of less than 1.5oC. The analysis will also consider potential differential effects of carbon pricing across socio-economic groups and between high, medium and low-income countries, as a basis for identifying policy interventions to equitably mitigate harmful outcomes.
This analysis will contribute to the goal of The Lancet-Chatham House Commission which is to identify actions that can impact positively across the shared drivers of threats to human and planetary health. Importantly it will provide novel evidence for the ways in which co-benefits and co-costs of interventions might form a significant part of the political and economic cases for intervening at national and international levels and optimising policy design.
|
| 30/09/2021 |
£262,700 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2021 |
£76,300 |
|
UNIVERSITY OF LEIDEN |
Not available |
| 30/09/2021 |
£20,000 |
|
RESEARCH AND TRAINING CENTER FOR COMMUNITY DEVELOPMENT |
NCDs-VN (hosted by RTCCD), together with other national partner NGOs, is poised to establish a CSOs-One Health and Climate Change Partnership (CSO-OHCCP) to increase government action and coordination on health and climate change. The CSO-OHCCP will use the HCN policy briefs and recommendations as a basis for engagement with Vietnamese government ministries to influence key policies relating to health and climate change, and will work closely with national government delegates attending COP26 to encourage incorporation of HCN policy priorities into national negotiating positions. This will be achieved through the translation of materials, organisation of meetings and events for both civil society and government, policy submissions to government, and accompanying communications campaigns, as well as direct participation in the Vietnamese COP26 delegation. Through this work, civil society organisations working across health and environmental issues in Vietnam will become united and better coordinated and will continue to advocate on health and climate change in months and years to come. RTCCD/ NCDs-VN will be responsible for overall management and delivery of the project, and makes this proposal for activities with a budget of 20,000 GBP.
|
| 30/09/2021 |
£20,000 |
|
BRAZILIAN INSTITUTE FOR CONSUMERS DEFENCE |
Considering the current discussions on the urgency for food systems transformation and climate change mitigation, in view of the UN global events Food Systems Summit and COP26 and their outcomes, Idec proposes to articulate partners and deepen discussions at national and regional levels, influencing the political agenda. The proposal's objectives are: 1) To translate and disseminate the four Health and Climate Network (HCN) briefings in order to expand dialogue with strategic partners in Latin America involved in COP26; 2) To promote discussions to deepen connections on current food systems and their outcomes on the people's and planetary health in Brazil and Latin America.
Proposed activities are: a) To translate to Portuguese and Spanish and disseminate the four briefings in Idec's own media and explore other media and share them among strategic partners in Latin America; b) To present the HCN Briefing 1 on Food Systems in strategic meetings, to discuss its recommendations in Brazil; c) To fund investigative journalism from a well-recognized journalism agency to further deepen the discussions raised in Briefing 1, producing in-depth materials about food systems and climate agenda; d) To develop podcast episodes on topics related to Briefing 1 targeting key stakeholders on the climate agenda.
|
| 30/09/2021 |
£20,000 |
|
SLOCAT PARTNERSHIP ON SUSTAINABLE, LOW CARBON TRANSPORT |
Tackling transport emissions has positive impacts. The benefits of transforming mobility paradigms spans across the notion of planetary health that includes human health and the health of our planet. Whether it is curbing emissions, reducing deaths in road crashes, enabling healthy lifestyles, supporting mental health with reclaimed streets or better integrating spatial and transport planning; the transport-air pollution-health-climate nexus is a multiplier.
Aim: Strengthening the nexus to advance two complementary objectives by March 2022:
Capitalise on the interdependence between the enablers and disruptors of transport systems transformation and health to influence climate action policy and investment frameworks.
Facilitate medium-, long-term strategic collaborations beyond the transport community.
Intended Outcomes
Mutually-reinforcing benefits of transport, health & well-being and climate action better understood.
Economies of scale and costs of inaction soundly established and clearly communicated.
Structured collaboration between a diverse group of experts, thought leaders and policy-makers.
Transport policies and investments defined with an integrated look at health implications and vice-versa.
Target Audience
Policy makers, sectors associations, knowledge and academia, governments, multilateral organisations, NGOs, philanthropy and industry
Global, national and local level actors engaged in the international processes on climate change and sustainability (e.g. COP26 and the Second UN Conference on Sustainable Transport).
|
| 30/09/2021 |
£19,956 |
|
PUBLIC HEALTH FOUNDATION OF INDIA |
The proposed work aims to convene stakeholders-health professionals, academia, civil society organisations, think tanks and policy makers to disseminate the recommendations from the policy brief on climate resilient health systems developed by the Health and Climate Network(HCN). The Public Health Foundation of India(PHFI) and its sister organisation- Centre for Chronic Disease Control(CCDC) are strategically poised to deliver the stated objectives given the extensive networks and collaborations already existing as a platform for transformative work with the health systems in India. PHFI's Centre for Environmental Health , recognised as a Centre of Excellence by the Government of India's Ministry of Health and Family Welfare within its National Program for Climate Change and Health, is engaged in providing technical inputs for development of an implementation framework for green and climate resilient health systems which will be customised for use across every state in India. CCDC's Health and Environment Leadership Platform(HELP), established collaboratively with Health Care Without Harm works with private hospitals to commit to decarbonisation as part of the Race to Zero initiative of UNFCCC for COP 26 and beyond. The team will leverage recommendations from the specific brief and related briefs on energy, transport and nutrition to enhance uptake and implementation.
|
| 30/09/2021 |
£300,000 |
|
ROYAL SOCIETY |
To ensure continuity of a resource valued by both the scientific and education communities, in 2021, the Royal Society Education Committee supported a request for the Society to apply to the Wellcome Trust for legacy funding that will enable it to take over the Science Education Tracker (SET). The Society proposes that it leads the next phase of this research study, while exploring options for future funding and sustainability. SET is a detailed online survey of young people in England aged 11-18, which explores views and attitudes towards science education and STEM careers. The Royal Society has contributed to both previous SET Tracker studies and has secured approval internally for a similar scale of additional funding, were this application successful. As a trusted organisation, independent of government, and with a long-term commitment to science education, the Society will ensure the legacy of SET and maintain the principles and purpose as part of the Wellcome Trust's legacy. The Royal Society will provide governance and oversight of initiative, working with Engineering UK as delivery partners, notably through its research team to oversee procurement and project management. Engineering UK will provide in-kind support to the project equivalent to the Society's own funding.
|
| 30/09/2021 |
£348,227 |
|
C40 CITIES |
This research will contribute to a more complete narrative for why a rapid and sustainable energy transition is needed. Critically, this work will question the calls for a medium-term reliance on natural gas as a transition fuel. There are legitimate cases for gas as a transitory fuel, but large-scale investment over the next few decades will prevent the world from reaching the 1.5oC climate target, will increase air pollution and negative health impacts, and will increase the risk of stranded assets.
This work will explore optimal urban transition pathways for gas (given that cities are key markets for natural gas), balancing the benefits of gas as a transition fuel with the need for a rapid transition to clean energy. Acknowledging the complexity of such a transition in the various different global contexts of C40 cities, we will develop a number of optimal transition pathways, creating decarbonisation narratives that reflect climate, health and development needs.
Project aim: to model the optimal pathways for a sustainable and equitable transition away from natural gas (based on modelling climate, air quality, health and economic impacts), and utilise the research results to enable cities to make the case for change at COP27.
|
| 30/09/2021 |
£238,000 |
|
MUSEUMS ASSOCIATION |
The Mindsets Engagement and Fund programme is designed to contribute to the development of science centres, alongside museums, as relevant organisations that represent, support and work with their communities. Science centres will join a mixed cohort that participates in an engagement programme exploring how to apply the "Mindsets" for the science centres and museums of the future and will request funding individually or within partnerships formed within the cohort to run two-year projects up to a value of £150k. External and internal evaluation will run alongside the programme to measure its impact and explore changemaking in the science centre and museum sectors. This application is for part funding for a wider programme in a collaborative partnership with UKRI and the Liminal Space creative agency. A narrative description of the wider programme with associated logic model, budget and timeline is enclosed in attachments to this application.
|
| 30/09/2021 |
£515,058 |
|
SERVAREGMP |
The proposed project will establish a manufacturing process to produce ZAC-3, intended to be an effective, low-cost IgG1 MAb against cholera, at very low cost and in a thermostable formulation that mitigates or eliminates the need for cold chains. This project concludes with the use of the developed biomanufacturing process to generate sufficient ZAC-3 for use in pre-clinical efficacy and toxicology studies. |
| 30/09/2021 |
£435,000 |
|
UKRI-MRC |
Not available |
| 30/09/2021 |
£248,605 |
|
UNIVERSITY COLLEGE LONDON |
The climate crisis affects us all, but not equally. Those who have contributed least to climate change, suffer the most from its health consequences. Racial injustice exists independent of the climate crisis, however climate change provides a new channel through which these discriminations can manifest. In this grant we will explore the intersection between climate, health and racial justice, engaging with the ‘most affected people and areas’ (MAPA).
To realise climate and health justice, MAPA must be central to discussions on reimagining solutions. We will centre our conversations on health inequalities identified by MAPA, prioritising those who are already suffering the worst physical and mental health impacts. We will listen first, via stakeholder meetings in Brazil, the Philippines and Uganda, and then conduct art-based engagement with young people in these sites. The work will be underpinned by evidence collated for an academic review paper and we will develop an educational module that can be used longer term. We will also encourage co-learning across the three sites, where young people can help to empower each other. Our work will target the Conference of the Parties 27 (COP27) meeting, where we will hold an event and also run webinar and podcast series.
|
| 30/09/2021 |
£149,775 |
|
UNIVERSITY OF HERTFORDSHIRE |
The Primary Science Quality Mark, based at the University of Hertfordshire is seeking a discretionary grant of £149,775.00 from Wellcome to enable it to increase its ability over the next two years to improve leadership in primary science in UK schools most affected by the Covid-19 pandemic. This will address gaps in provision and increase children’s access to exciting, inspiring and relevant science education that leaves them well-prepared to progress further in science, and well-informed about science in their everyday lives.
|
| 30/09/2021 |
£586,671 |
|
WORLD ECONOMIC FORUM |
Not available |
| 30/09/2021 |
£203,010 |
|
UNIVERSITY OF OXFORD |
Reporting and sharing cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national, and global levels. We recently developed and tested in seven hospitals in seven countries a pilot application, "AutoMated tool for Antimicrobial resistance Surveillance System (AMASS)", that allow clinical microbiology laboratories to analyze their routinely collected microbiology and hospital data files (in CSV or Excel format) onsite and generate AMR surveillance reports (in PDF) for immediate use and anonymous summary data (in Excel) for depositing in a data repository website.
Here, we propose to (1) enhance AMASS so that it can generate additional outputs; including crude excess mortality due to AMR infections, crude excess mortality associated with AMR infections, proof-of-principle outbreak detection, and Weighted-Incidence Syndromic Combination Antibiogram (WISCA), (2) improve AMASS codes so that it complies with best-practices in software development and FAIR (Findable, Accessible, Interoperable, Reusable) Data Principles, and (3) pilot implementation and evaluate AMASS in 20 participating hospitals in low and middle-income countries (LMICs).
The project will collaborate with Oxford Tropical network, ACORN and WHONET to ensure that the project will be beneficial, compatible and easy-to-uptake by a wide range of hospitals in LMICs.
|
| 30/09/2021 |
£40,727 |
|
CBM UK |
The Africa Centre for Disease Control (CDC) is part of the African Union strengthening the capacity of Member States to respond quickly and effectively to disease threats. They are looking to incorporate a mental health strategic plan into their organisational strategy revision, planned for 2022. This was not included in the first 5 year plan (2016-2021), and the result was a relative neglect of the field to date. There is currently strong mental health leadership, a new Mental Health Division, and a commitment to include mental health in the Africa CDC budget based on a strategic plan. Africa CDC asked CBM to help support this project and the Wellcome Trust have given their agreement to support this consultancy project financially whilst the project management will be done by CBM UK.
The key deliverable for this project is a Strategic Plan for Mental Health, that will align to Africa CDC’s overarching strategy and operational processes. It is costed to enable real-world application over five years. Africa CDC have indicated that such a Strategic Plan, presented to the African Union for approval and adoption, is likely to receive funding necessary for its implementation.
|
| 30/09/2021 |
£21,716 |
|
UNIVERSITY OF EDINBURGH |
To develop and produce a health-environment nexus policy guide that outlines opportunities for global actors to engage with, and link environment and health issues across multilateral environmental agreements (MEAs). This project will target national policy makers, including ministries of health, environment, and foreign affairs.
The guide will:
identify key fora where health and environment issues overlap, provide summaries of relevant priority areas and important policy debates at the environment-health nexus within these fora
focus on the following reference themes: social determinants of health, One Health, and Planetary Health including infectious diseases, non-communicable diseases, mental health, and the climate and biosphere crises, and gender equity
set out negative confluences in climate and health junctures
provide input for the Glasgow Financial Alliance for Net Zero to incorporate planetary health indicators into global financial assessment environmental, social, and governance (ESG) tools
the guide seeks to provide meaningful, succinct, accessible, clear and targeted information to enable health, and environment experts to engage in and follow global processes at a high level, focusing on intersections where policy approaches could incorporate health and well-being issues.
|
| 30/09/2021 |
£25,250 |
|
UNIVERSITY OF EDINBURGH |
This award supports the expansion of the Malawi Medical Humanities Network (MMHN) through strategic integration within Malawi University of Science and Technology (MUST), Malawi. This new space will facilitate the development of a dynamic research agenda and curriculum, whilst establishing international exchange programmes across the inter-related fields of medical and health humanities and disability studies. MUST's support will position MMHN to engage national collaborators to further pursue interdisciplinary partnerships and develop dynamic learning-based knowledge exchange platforms. This award will enable MMHN/MUST to organise the development of a robust agenda and activities portfolio to 1) facilitate the development of a culturally-informed, translational medical and health humanities approach to address effective modes of community care, 2) to strengthen membership engagement across the country, 3) to promote collaborative and interdisciplinary research projects, 4) to develop competitive scholarship in theory, methods and practice and 5) to showcase national projects that directly address interdisciplinary approaches to public health and community wellness and approach challenging and taboo health issues. Overall, this fund will support the network's transition into a sustainable platform offering greater support to create innovative spaces for interdisciplinary dialogues and define world-leading African crossovers between the arts, humanities, social sciences and health studies.
|
| 30/09/2021 |
£25,750 |
|
UNIVERSITY OF STRATHCLYDE |
The Society for the Social History of Medicine (SSHM) has a strong record of supporting single and standalone activities organised by our wider community, beyond our biennial and postgraduate/early career researcher events. We have tried and tested criteria for funding to include the necessity to support postgraduate and early career scholars as well as awareness of inclusivity. Wellcome network funding will enable SSHM to direct the Society’s experience into a new and exciting sphere of support: directing funding to networking and networked events. These serial activities promise the space to be both innovative and sustained; a space that has often been limited in the field of the history of medicine and health. What these sustained conversations will do is provide room for creativity and thinking, offering transformative scholarship and assuredly facilitating links and work that would otherwise prove impossible, especially due to our current availability of £1500 per conference funding application, limited so as to support as many activities as possible. We propose to fund between four and seven networks with a maximum of £6000 per award, with two rounds of applications for support.
|
| 30/09/2021 |
£25,750 |
|
UNIVERSITY OF STRATHCLYDE |
The Society for the Social History of Medicine has a strong track record of providing field-leading conferences in the history of medicine and health, together with postgraduate and early career training and events. Our proposed programme of new and innovative events will allow us to begin new areas of work in the areas of anti-racism, mid-career support, and discussions about career precarity. Wellcome funds will enable scholars to meet at a crucial time for the field, at a time when, with the continuing risk of Covid-19 and other disease outbreaks, the history of medicine has perhaps never been so vital. Bringing scholars together for physical meetings is essential to create the safe space needed for such sensitive discussions as anti-racism, facilitated by a clinical professional and academics experienced in this area, and regarding concerns about careers. The impact of Covid and changes in funding for universities mean many mid-career scholars are in need of support and mentoring, and those without permanent positions are in need of a safe space to discuss the future of the field and the impact on, and potential for, their own work and careers.
|
| 30/09/2021 |
£25,687 |
|
UNIVERSITY COLLEGE LONDON |
Racism, xenophobia and other forms of discrimination are important and powerful determinants of health that affect populations across the world. The non-profit group Race & Health was set up in 2020 to help combat the adverse health consequences of discrimination through academic work, advocacy and education.
Funding from The Wellcome Trust will enable us to expand the work of Race & Health. We will create a multi-disciplinary global network of experts that will form a ‘Lancet Commission on Racism, Xenophobia and Discrimination’. The commissioners will work collaboratively to produce solutions to improve health. Funding will help establish the network and enable virtual meetings and a physical meeting. Aligned to this, we will work to expand the reach of Race & Health, disseminating our work to the public through our newsletter, and new webinar and podcast series.
|
| 30/09/2021 |
£25,750 |
|
UNIVERSITY OF ABERDEEN |
Established in 2019, the Menstruation Research Network UK has been able to partake in and document a change in the discourse, policy, and media surrounding menstruation in Britain and the world. Since then, Scotland has passed the Period Product (Free) Provision Act, the UK has formed the Period Poverty Task Force, and the Welsh and Northern Irish governments have outlined similar policies. The network has been involved in these debates, lending interdisciplinary expertise about menstruation to policy makers, academic colleagues, and activists. Today, the continuation of our work is more necessary than ever, as menstrual discourse moves from a focus on products to larger debates about underlying structural issues, such as legal rights, sustainability, and diversity. We propose to continue our network by hosting three blended workshops at the University of Aberdeen, University of St Andrews and Liverpool John Moores University. These events will invite international keynote speakers and diverse stakeholders in and out of academia over the course of four years. Our aim is to strengthen and broaden the network in the UK, link with international colleagues, plan ambitious grant applications, provide mentoring to students and early career academics, and information for policy, media and community engagement.
|
| 30/09/2021 |
£25,438 |
|
BRITISH SOCIOLOGICAL ASSOCIATION |
We propose the development of a British Sociological Association’s Medical Sociology Study Group ‘research sandpit’, hosted at the group’s annual conference. A facilitated three hour event will enable disciplinary leaders to share opportunities relating to available funding, publication opportunities and disciplinary vacancies, whilst other attendees will have the space to discuss their employment availability, career aspirations and questions about establishing, developing and maintaining a career in Medical Sociology. The Sandpit will be hybrid, hosted online and in person at the wider Medsoc conference location. It will also be available to individuals who are not attending the conference as a free ticketed standalone event.
Discussion, both in person and online, will be stimulated by the display of research posters, and facilitated activities to ensure that attendees are encouraged to engage and maximise the impact of the event. The Sandpit will extend extant networking opportunities provided at the conference, where previous networking innovations have been replicated at the larger BSA annual conference including a well-established mentoring scheme. This event will directly address accessibility brought into relief by the recent pandemic, and our responsibility to ensure that we are creative and innovative in ensuring that Medsoc is a trail blazing organisation for inclusivity.
|
| 30/09/2021 |
£25,750 |
|
UNIVERSITY OF DURHAM |
Through this Discretionary Award, the Northern Network for Medical Humanities Research (NNMHR) will make funding available to support critical medical humanities research networks. These networks, which involve early career researchers in leading or coordinating roles, will help generate new ideas, methodologies, collaborations and areas of further investigation within the critical medical humanities, nationally and internationally. We will support prospective applicants by running workshops online to explore what makes a successful research network, to reflect upon the benefits and limitations of online working, to address barriers to access, and to share best practice. We will support successful applicants by offering them mentoring, networking resources, and opportunities for profiling their activities. Going beyond the simple distribution of funding, this Discretionary Award will help catalyse exciting and innovative ideas and approaches within the medical humanities research community.
|
| 30/09/2021 |
£25,741 |
|
UNIVERSITY OF DURHAM |
Extending beyond its geographical focus on the North of England and Scotland, the Northern Network for Medical Humanities Research (NNMHR) now contributes nationally and internationally to development of the critical medical humanities. This Discretionary Award will support the activity of the NNMHR over the next four years, with a focus on
supporting early career researchers to develop, deliver and participate in research-related activities and training;
co-hosting with Durham University’s Institute for Medical Humanities two large-scale international congresses with a significant online component; and
connecting medical humanities researchers with regional cultural institutions in order to forge new collaborations.
|
| 30/09/2021 |
£25,008 |
|
INSTITUTE OF MEDICAL ETHICS |
The Postgraduate Bioethics Network (the Network) is an interdisciplinary community of bioethics researchers. We strive to connect researchers from all backgrounds, fields and institutional settings.
Our vision is to:
Evaluate, evolve and expand our work to ensure sustainability of the Network and its steering committee.
Provide high quality and accessible network- supporting experiences virtually and in person
Ensure that the Network acts for both a diversity of people and of ideas.
This grant will allow us to achieve our vision by facilitating a range of activities and opportunities for development. We will build on the success of the annual Postgraduate Bioethics Conferences (PGBC) by refocusing on the networking aspects in 2022 and 2023, and incorporating feedback, especially PGBC2021, hosted virtually by Liverpool University.
We will offer further editions of the Bioethics & Media Workshop, oversubscribed in 2021. Two activities that we propose were identified as needs during that workshop: the Bioethics & Media Database and Writing Community.
We seek to build closer relationships with Network alumni by providing space for mentorship and collaboration.
Towards the end of the grant, we will hold a strategic planning event to evaluate our progress in achieving our vision and to plan for the future.
|
| 30/09/2021 |
£251,547 |
|
INTERNATIONAL CENTRE FOR ANTIMICROBIAL RESISTANCE SOLUTIONS |
ICARS is initiating a project with the Ministry of Health in Zambia aiming to reduce inappropriate antibiotic prescription in Urinary Tract Infections (UTIs), through implementation of a stewardship programme in facilities such as tertiary hospitals, community hospitals, and community pharmacies. The interventions will target prescribers and consider health system factors. However, a gap still exists in current AMR activities in Zambia for engagement with and involvement of the public to address perceptions and practices that impact AMR. This gap is holding back public awareness of AMR issues, as well as building and understanding within the scientific community of the drivers and impact of AMR on communities. This challenge can be tackled through a responsive dialogue process that can address patient perceptions, practices and community-driven solutions. Linkages between the ICARS project and the responsive dialogue process will ensure connections and engagements to ministry officials and policy makers, who are already a part of the ICARS work. This project aims at piloting the Wellcome Responsive Dialogues on Drug Resistant Infections in Zambia. It will be designed by ICARS with input and support from Wellcome, and commissioned to a Zambia-based research institute, with participatory and social research expertise, to design and implement it.
|
| 30/09/2021 |
£2,201,199 |
|
NEW VENTURE FUND |
Covid-19 exposed major gaps in our ability to aggregate and use data for pandemic prevention, detection, and response. Current approaches require pooled data, which is costly, time-consuming, and legally challenging. Distributed and privacy-preserving methods of analysis are an alternative for generating insight and present new opportunities to use commercially held "health-adjacent" data critical for pandemic analysis and modelling. However, despite the appeal of distributed and privacy-preserving methods of analysis, there are few working examples focused on disease analysis and none that are globally adopted.
This proposal is to build, deploy, and scale innovative solutions – including infrastructure, tools, and analytical techniques to unlock data and enable distributed analysis. Phase 1 will focus on developing the novel software and privacy-preserving methods that will be deployed in Phase 2:
Funding top teams to develop a suite of generalizable, open-source epidemiological software and tools
Challenge funding call to develop privacy-preserving approaches for deployment on commercially sensitive/privately held data, which could be scaled and deployed in Phase 2.
200 Days Architecture Challenge aimed at Big Cloud Providers to design the technical architecture for Phase 2.
data.org will provide the central convening and coordination role, including grant-making, convening interdisciplinary specialists, project management, and strategic communication.
|
| 30/09/2021 |
£649,700 |
|
DALBERG GLOBAL DEVELOPMENT ADVISORS LIMITED |
See attached document with additional information to answer this question.
|
| 30/09/2021 |
£724,258 |
|
VILLAGEREACH |
Despite significant progress of the Expanded Program on Immunization in preventing fatal diseases in children in low and middle-income countries, coverage has stagnated over the past decade. We propose a community based participatory and mixed methods research project in diverse settings in Mozambique and Malawi to determine drivers of childhood immunization dropouts as well as context-specific v. scalable solutions to improve full immunization coverage. The research sites will include both urban informal and rural settings. In site selection, we have considered the different ways in which vaccination services are provided. We will implement this study in four-iterative phases:
Identify barriers to childhood immunization access and uptake
Co-develop solutions with communities and understand communities’ roles in generating evidence and solutions
Implement the co-created solutions for up to one year
Evaluate the implementation and early impact of the co-created solutions
We will collaborate with community members, health workers and government stakeholders as participants and partners, and leverage existing partnerships at the global level. Our collaborative approach of engaging caregivers as co-researchers, ensures tailored approaches, which account for context considerations in solution development and promotes community buy-in and commitment to solutions. Tools and learnings will be packaged for broad dissemination.
|
| 30/09/2021 |
£7,323,772 |
|
DRUGS FOR NEGLECTED DISEASES INITIATIVE |
The COVID Moonshot project focuses on global equitable access to a safe, low-cost oral antiviral treatment that quickly clears SARS-CoV-2 infections and future coronavirus-related diseases. Current therapeutics in clinical trials require intravenous administration and are developed mainly by organizations focusing on a commercial return. This proposal will research an oral treatment to significantly improve patient outcomes in low-resource settings, removing the need for a cold chain or injection and enabling stockpiling of therapeutics for both this and future pandemics We will develop a novel inhibition of main protease (3CL protease) of coronaviruses in order to prevent viral replication, aiming to create a generic drug "straight from the pipeline," facilitating decentralised manufacturing and distribution allowing for rapid patient access. We target effective oral treatment for early stages of disease to reduce viral load, mortality and morbidity (e.g. long COVID). The goal is to progress a compound to Phase I readiness, anticipating clinical trials in 2022. This proposal involves the established Moonshot team complemented by DNDi’s expertise in IP and access strategy, preclinical project management, and drug development. The project aims to maintain the proven open science model adopted from the outset. |
| 30/09/2021 |
£168,401 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Not available |
| 30/09/2021 |
£3,136,000 |
|
ENTHUSE CHARITABLE TRUST |
The ENTHUSE Charitable Trust's charitable purpose is to improve science education, or related subjects, for young people, through the professional development of teachers. Over the period to 2023, ENTHUSE will:
continue to provide science CPD accessible by all teachers and others from state-funded schools, with a particular focus on engaging schools, colleges, teachers and young people most in need of STEM education support so helping close the achievement gap and promote social mobility while raising standards across the board;
build strong, visionary leadership in STEM teaching across primary, secondary and post-16 settings to achieve sustained system-wide improvement, raising standards and expectations;
encourage a culture of career-long, STEM-specific professional learning across the teaching profession, raising morale, and enhancing retention;
significantly raise awareness among schools, colleges, teachers, young people and families of the value of STEM study and STEM-related research and careers, and of the academic, technical and apprentice routes into those roles.
The ENTHUSE Charitable Trust is seeking a budget of £3.136m, with the deployment of Wellcome funding part of a wider mix of income, aligned to the above priorities.
|
| 30/09/2021 |
£1,542,993 |
|
GAVI, THE VACCINE ALLIANCE |
Vaccine MAPs have significant potential to improve equitable coverage of vaccines, due to their innovative product attributes and anticipated ease of use, which could be very valuable in the fight against enteric diseases such as typhoid. TCV-MAPs could also be an attractive target for the industry because they promise to be technically feasible and may be commercially attractive. To assess and quantify the potential value of a TCV-MAP, this project will develop a Full Vaccine Value Assessment (FVVA) including the potential public health need for a TCV-MAP, its programmatic impact and socio-economic benefit. If the proposed FVVA demonstrates high value for TCV MAPs, it could accelerate TCV-MAP development and preparation for uptake in countries. The processes and methodologies reviewed or developed during this FVVA could be useful for the assessment of other vaccine MAPs or other vaccine-delivery product innovations. |
| 30/09/2021 |
£99,999 |
|
OPEN LIFE SCIENCE |
Open Life Science (OLS, https://openlifesci.org/) offers a 16-week long cohort-based training and mentoring programme that enables researchers to learn about, reflect on and integrate open science principles in their work. The Open Research Fund will support the continuation of OLS and the delivery of three cohorts of the programme in 24 months. In addition to supporting the volunteer members (up to 30 projects, 30 mentors and 15 experts per cohort), OLS will recruit a full-time staff (1-FTE) for 18 months to conduct a long-term impact study and provide administrative support to the leadership team.
A successfully completed Open Research Fund activity in OLS after 2 years of funding period will have enabled:
(i) research-based evaluation and enhancement of the OLS curriculum, training materials, mentoring formats and value-based approach to community development,
(ii) incentivised integration of contextual (sociotechnical and cultural) knowledge of mentors and project leads in the open science project they develop in the program,
(iii) enhanced representation and equitable participation of health researchers and community builders from the Global South in a shared vision for the global open science through collaboration,
(iv) assessment of the long-term impact of OLS on the careers of the OLS participants and adoption of contextualised open science practices in research work in their regional contexts across low- and middle-income, as well as high-income countries, and
(v) publication of a series of reports capturing different outputs, building open source evidence base and inviting support for the sustainability of OLS over the next 5 years.
|
| 30/09/2021 |
£99,000 |
|
WITS HEALTH CONSORTIUM (PTY) LTD |
This project seeks to address existing data sharing concerns of African public and population health researchers. It also motivates for the implementation of Africa-led initiatives for data sharing. Using acquired knowledge on global best practices and regional concerns, the project will design sustainable mechanisms to incentivise data sharing. This will involve leveraging our strategic partnerships and adopting artificial intelligence (AI) tools to implement solutions to some of the concerns. We will improve data sharing value chain; simplify access and utilization of data; and strengthen capacity and advocacy towards incentivised data sharing.
Using AI tools, we will develop a virtual and physical environment for active and passive identification and curation of a list of publicly funded research data in public and population health in Africa; link researchers and research institutions to reusable publicly funded data; increase awareness and address fears and misconceptions about data sharing; and advocate for institutions to provide best practice rewards when data is shared.
These activities will result in improved knowledge, attitude, and practices on data sharing by researchers, institutional data custodians and institutional management; increased collaboration and knowledge generation among researchers; and incentivisation of data sharing at institutional level. The project will promote scientific data findability, access, and reusability while simultaneously addressing data governance and trust concerns, fear of data misuse and exploitation, and ensuring compliance with privacy, security, and ethical standards on data sharing.
|
| 30/09/2021 |
£97,867 |
|
UNIVERSITY OF OTTAWA HEART INSTITUTE |
The completion of the proposed research program will result in two key outputs: 1) a core outcome set of open science (OS) metrics relevant to, and developed by, the biomedical community; and 2) a usable flexible, tailorable, and automated tool, developed using user-centred design best practices, that reports on these core OS metrics.
Establishing a core outcome set of OS metrics is a vital step to move forward discussion around how to measure research(er) quality. Without consensus on what to measure, or how to measure it, even well intended institutions can’t easily consider incorporating metrics beyond those traditionally used (i.e., journal impact factor or number of publications). A core outcome set does not limit organizations from tailoring the collection of OS metrics, but ensures a standard set across organisations to enable national and international standardisation and comparison.
By engaging with the research community at the onset of this program and throughout via an integrated knowledge translation approach, we can ensure that the tool we develop to report on the established core OS metrics meets the needs of the community and considers their concerns. Doing so ensures greater uptake. Further, through embedding considerations of equity, diversity, and inclusion in our design of the OS dashboard, we intend to create a tool that is globally relevant in biomedicine. This will ensure that our impact is as broad as possible and serves the entire biomedical community. By meeting our proposed aims, we will have achieved a ready to implement publicly available OS dashboard.
|
| 30/09/2021 |
£61,203 |
|
PUBLIC LIBRARY OF SCIENCE (PLOS) |
We aim to have significantly increased the availability of research data associated with peer-reviewed publications in a Findable, Accessible, Interoperable and Reusable (FAIR) manner. By pioneering the seamless integration of a data sharing tool into the scholarly publishing workflow and removing barriers, including cost, to researchers receiving data curation support, in the pathogens community, we aim to increase data repository use by at least 10%. We will also determine if prominent visual cues (links) on publications are an incentive for researchers to share research data in repositories without support from an integrated tool, and determine the ability of these visual cues to support data discoverability and reuse, in multiple communities. The outcomes will enable PLOS, and other scholarly publishers, to make evidence-based decisions about the costs and benefits of increasing sharing of research data in compliance with the FAIR data principles. This will enable PLOS to determine suitability of rolling out these solutions more widely among its journals, which could potentially increase the availability of FAIR data more substantially. We will also understand the attitudes and experiences of researchers in the target community with these two data sharing solutions; determine if these attitudes change after implementation of the solutions, and potentially identify new opportunities to support data sharing and reuse that can be explored in future research or initiatives. The reported outcomes and any accompanying data, such as from user surveys, will be openly available to support decision making by funding agencies, publishers, researchers, institutions and infrastructure providers.
|
| 30/09/2021 |
£463,969 |
|
YOUBELONG UGANDA |
Summary: Mental health services are most effective and equitable when designed, delivered, and evaluated in collaboration with people with lived experience of mental illness. Unfortunately, people with lived experience are rarely involved in health systems strengthening, and when they are, it is limited to specific components (e.g., peer helpers) rather than across-the-board collaboration in the continuum of health services. We are proposing a novel approach for collaboration with people with lived experience of psychosis that includes involvement at the primary care, community, and home settings. By collaborating on health systems strengthening across these multiple levels, we foresee a more in-depth contribution that can lead to rethinking how best to design and deliver care for people living with psychosis. We will pilot this multi-tiered collaboration with people with lived experience in Uganda because low-income countries represent the greatest gaps in access to evidence-based mental health care. We will conduct a pilot cluster randomized controlled trial of "Strengthening CAre in collaboration with People with lived Experience of psychosis in Uganda (SCAPE-U)". We will train people with lived experience of psychosis using PhotoVoice and other methods to participate at three levels: primary health care, community and home level. The primary objective is to evaluate the feasibility and acceptability of SCAPE-U. This pilot will also be used to prepare a future grant in which we will conduct a fully powered cluster randomized controlled trial that will evaluate health systems outcomes and service user outcomes, including quality of life, lower symptom severity, less disability, lower rates of relapse, and less hospitalization. |
| 30/09/2021 |
£59,735 |
|
GEORGE WASHINGTON UNIVERSITY |
Mental health services are most effective and equitable when designed, delivered, and evaluated in collaboration with people with lived experience of mental illness. Unfortunately, people with lived experience are rarely involved in health systems strengthening, and when they are, it is limited to specific components (e.g., peer helpers) rather than across-the-board collaboration in the continuum of health services. We are proposing a novel approach for collaboration with people with lived experience of psychosis that includes involvement at the primary care, community, and home settings. By collaborating on health systems strengthening across these multiple levels, we foresee a more in-depth contribution that can lead to rethinking how best to design and deliver care for people living with psychosis. We will pilot this multi-tiered collaboration with people with lived experience in Uganda because low-income countries represent the greatest gaps in access to evidence-based mental health care. We will conduct a pilot cluster randomized controlled trial of "Strengthening CAre in collaboration with People with lived Experience of psychosis in Uganda (SCAPE-U)". We will train people with lived experience of psychosis using PhotoVoice and other methods to participate at three levels: primary health care, community and home level. The primary objective is to evaluate the feasibility and acceptability of SCAPE-U. This pilot will also be used to prepare a future grant in which we will conduct a fully powered cluster randomized controlled trial that will evaluate health systems outcomes and service user outcomes, including quality of life, lower symptom severity, less disability, lower rates of relapse, and less hospitalization. |
| 30/09/2021 |
£49,583 |
|
UNIVERSITIES UK |
Not available |
| 30/09/2021 |
£261,943 |
|
UNIVERSITY OF DUNDEE |
Drug discovery is a slow process with a high attrition rate. A key challenge is the optimisation of fragment hits and chemical start points, which requires simultaneous optimisation of multiple parameters – activity, selectivity, physicochemical, pharmacokinetic and toxicological properties. Further only relatively few compounds can be made and profiled in a programme from the vastness of chemical space. Our overall vision is to produce a platform to speed up the drug discovery process to produce clinical candidates with a good developability profile. In this collaboration between the University of Dundee and University of Oxford, we are aiming to produce computational design methods that adequately sample chemical space, driven by prediction of both properties and biological activities of the compounds. The aim will be to rapidly design compounds to make, which have the highest likelihood of satisfying Target Candidate Profiles. This will then feed into a high throughput chemistry platform to rapidly make and test compounds designed, with emerging data being fed back into the design platform. This should reduce the number of design-make-test-analyse cycles and will be tested in Dundee’s Neglected Tropical Disease drug discovery programmes. |
| 30/09/2021 |
£375,808 |
|
UNIVERSITY OF OXFORD |
Ethical, legal, and social aspects of AI have received unprecedented international attention in recent years. Many technical and organisational tools, such as statistical tests for fairness or ‘Algorithmic Impact Assessments, have been developed to make AI more accountable and trustworthy. However, the efficacy of these tools in practice across different use cases and application types remains unproven. The proposed multi-disciplinary project will develop a ‘trustworthiness auditing meta-toolkit’ to evaluate the efficacy of AI accountability tools in healthcare and scientific research. Over three years we will (1) assess the social and institutional norms, legal mandates, ethical values, and technical constraints guiding the development and governance of trustworthy AI systems; (2) develop the necessary evidence base and technical/organisational tools needed assess the efficacy of AI accountability toolkits; (3) draft policy proposals and best practices that describe standards for effective and trustworthy usage of AI accountability tools; and (4) publish these outputs as an open access meta-toolkit for researchers, civil society, regulators, and industry. Case studies in healthcare and scientific research will be carried out with partner organisations to build and validate all aspects of the meta-toolkit. This project is proposed on a consortium funding basis in partnership with Sloan Foundation and NHSx.
|
| 30/09/2021 |
£277,363 |
|
UNIVERSITE DE MONTREAL |
Changes in biodiversity, both natural and caused by human activities, are intimately tied to changes in ecosystem status. The environment in which species live will affect their chances of movement, survival, and adaptation; for example, abrupt changes in vegetation cover can modify the risk of predation experienced by some species, and therefore change the relative abundance of their populations. But because species express a variety of biological functions, they too change the status of their ecosystem; for example, harmful algal blooms will disrupt the physical and chemical composition of water, which can lead to localized extinctions, and send rippling effects across the ecosystem. As such, the biological and the ecosystemic are indissociably coupled. Nevertheless, effectively coupling models at these scales has proven difficult, because of three core challenges: differences in scale, differences in how models are built, and volume of data required.
Biodiversity and ecosystem sciences have made progress on these challenges, and developing a field-specific case study to integrate models and pre-existing work will inform about the feasibility of a more general approach to model coupling. We believe this approach to be necessary for accurately identifying emerging challenges and opportunities in global ecosystem sciences, intrinsically tied to human wellbeing.
|
| 30/09/2021 |
£2,013,582 |
|
ELIFE |
In recent years, eLife has embraced the rise of preprints in the biomedical sciences and adapted its processes to make the review of preprints its central goal. We have developed Sciety, which allows researchers to discover refereed preprints from across the web, to highlight the value of preprint review as an alternative to traditional journal publishing. We aim to create a new publishing model where research is published as a preprint, then reviewed and curated by participating groups.
This proposal outlines the steps required to build out an end-to-end workflow to support this model. Over three years we will develop Sciety to support author submission, peer review management and community curation. Over the first year we will work with a ‘model customer’ to develop the full workflow, then spend two years enhancing and adapting the model for a diverse range of partners, including publishers and funders.
We will work with existing preprint servers such as bioRxiv, open source providers such as Coko Foundation, and journal providers such as PubPub, thereby fitting into the existing ecosystem rather than building a new one. This approach, combined with our existing work to build the community, will ensure the long-term success of the platform.
|
| 30/09/2021 |
£2,000,000 |
|
EAT FOUNDATION |
EAT is pleased to submit this request for a continuation of Wellcome’s support for EAT knowledge engagement and communications activities. In collaboration with SISTEMIQ, FOLU, and PIK, we continue to progress on the Food System Economics Commission building on the foundational work of the EAT-Lancet Commission, and FOLU’s Growing Better report. . Second, after consulting with numerous EAT partners, including the Wellcome Trust and the Lancet, we are pleased to submit a proposal for a five-year revision of the EAT-Lancet Commission, or the EAT-Lancet 2.0 (EL2.0). This will be a critical revision of the Planetary Health Diet (PHD), amongst other topics, EL2.0 will include: a focus on the diversity of local diets that fall within PHD ranges; a focus on food production practices to complement the important consumption focus work of EL1.0; novel work on the "socially just" dimensions of healthy foods from sustainable production system; and an important IPCC style intermodel comparison. We will invite a third co-chair to join Dr. Willett and Dr. Rockstrom to lead EL2.0 with a focus on the "socially just" elements of the Commission. Third, EAT thanks Wellcome for its continued support, including to core institutional functions.
|
| 30/09/2021 |
£2,284,586 |
|
UNIVERSITY OF CAMBRIDGE |
The recently emerged SARS-CoV-2 variants of concern (VOC) have altered transmissibility, virulence and susceptibility to neutralising antibodies, leading to concern over the potential for new variants to emerge that have increased resistance to vaccine-induced immunity. This has led to a renewed focus on the deployment of whole-genome sequencing surveillance to detect variants early, to stop or slow their spread, and to enable vaccine programmes to adapt.
However, despite increased genome sequencing, disparity in access to laboratory support and genomic sequencing across the globe has become increasingly evident: to date West and Central Africa produced ~2,000 sequences ( 400,000 from the UK. The VOCs such as P.1 in Brazil and B.1.351 in South Africa can emerge anywhere, further highlighting the urgent unmet need to develop sustainable solutions for COVID-19 sequencing in this underserved region.
This proposal builds on the experience of the ARTIC network and regional collaborators to support SARS-CoV-2 sequencing in West and Central Africa.
The key goals of this proposal are to:
Develop a hub and spoke network of SARS-CoV-2 sequencing labs in West and Central Africa.
Develop a suite of COVID-19 focused training materials and tools for whole-genome sequencing and subsequent data analysis.
|
| 30/09/2021 |
£291,279 |
|
UNIVERSITY OF BRISTOL |
We propose developing an understanding of how responsible research is conceived and realised, both across disciplines, and across institutions in Europe, grounded in the framework provided by the Singapore Statement on Research Integrity1. The project will include three main phases (described in more detail below):
Phase 1: Scoping responsible research across disciplines and institutions.
Researcher attitudes to responsible research will be assessed via a survey across a range of research disciplines. A similar process will be conducted across institutions, to understand how responsible research is operationalised and linked to training and governance activity.
Phase 2: Developing a responsible research community of practice.
Informed by Phase 1, we will develop a locally embedded and relevant modus operandi for each Responsible Research Steward, and provide infrastructural and governance support (in the form of advice to each of the 18 HEIs).
Phase 3: Implementing and evaluating responsible research stewardship activity.
Local Responsible Research Stewards will coordinate the inventory of research cultures and plural views on responsible research practices at their HEI, thereby informing them of which stimulus and support structures (Phase 2) can help them to build and maintain a diverse and relevant responsible research community of practice.
|
| 30/09/2021 |
£455,998 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Antivenom treatment of snakebite is failing to reduce the annual 138,000 deaths - predominantly in impoverished tropical communities. With a focus upon the most medically-important African and Indian snake venoms, we are developing toxin-neutralising, recombinant, humanised, thermostable monoclonal antibodies (mAbs) that will be more dose- and polyspecifically-effective, affordable and safer than antivenoms, and possess critical economies of scale and manufacturing incentives to secure sustained production/delivery.
We have collected sera and B cells (producing immunoglobulins of distinct structure and therapeutic/mAb-development promise) from:
multi-envenomed humans
cows, camels, baboons, mice immunised with the most pathogenic African and Indian venom toxins
horses used to manufacture African or Indian antivenoms.
Using High-Throughput platforms, we will rank B cells producing these globally-unique animal and human antibodies by in vitro toxin-binding affinity and toxin-function neutralisation, prioritising cross-generic/continental functionality. Genes from top-ranked B cells will be processed into recombinant mAbs (220-500).
Subsequent rounds of in vitro and in vivo (neutralisation of venom-induced lethality in a mouse model of envenoming) down-selection will output 20-40 mAbs for gene-manipulation to deliver ‘humanised’ and thermostable mAbs.
A final round of in vitro/in vivo selection will deliver 5-10 mAbs/3 mAb mixtures of proven pan-Africa/India polyspecific efficacy for downstream preclinical manufacture and clinical trials.
|
| 30/09/2021 |
£477,083 |
|
INSTITUTE OF EPIDEMIOLOGY DISEASE CONTROL & RESEARCH |
Our proof-of-concept study used MinION (Oxford Nanopore Technology), "Lab in a suitcase" to generate genomic data that we combined with mobility data mobile phone operators to provide an early picture of the dynamics of the COVID-19 epidemic in Bangladesh. We showed evidence of repeated introductions by returning migrant workers and international travelers leading to the emergence and rapid country-wide dissemination of SARS-CoV-2 lineages or variants. Bangladesh urgently needs an integrated genomics network suitable to identify and track known or novel variants. Our proposal is to establish a country-wide network for SARS-CoV-2 genomic surveillance. We will do this by extending the number of MinION-based sequencing platforms to seven federated sites linked to the Ministry of Health and Family Welfare, representing facilities in different administrative areas (6 of 8) comprising Bangladesh. The advantage of these devices is their portability and ease of use, and the flexibility of the platform beyond SARS-CoV-2 in the context of future epidemics. We will use the expertise we have developed to train researchers, adopting a "train the trainer" model of capacity building, in sequencing, bioinformatics, and epidemiological modeling, such that we are able to respond to COVID-19 as it evolves, as well as to future pathogen threats.
|
| 30/09/2021 |
£100,000 |
|
WELLCOME SANGER INSTITUTE |
In 2020 The Pan American Health Organization (PAHO) established and now coordinates the COVID-19 Genomic Surveillance Regional Network. It includes 21 collaborating countries of which 10 do not have any appropriate in-country sequencing capacity and instead send their samples externally for sequencing to the network reference laboratories in Brazil and Chile. Here we propose to build direct sequencing and analytical capacity in all participating laboratories to generate relevant genomic data that can be used for public health decision making. Where batch sequencing capacity already exists we propose to use MinIon platforms to extend the within-country capacity to investigate changing patterns of disease. Combined, this will dramatically increase our understanding of the known and new SARS-CoV-2 variants circulating in this region. We will develop a hub-and-spoke organization with PAHO at the center forming the hub for coordination, training and data flow and the Network laboratories forming the spokes. Laboratories with existing genomics expertise will help build genomics surveillance capacity in those that don’t. Combining local and international expertise we aim to develop a regional network able to produce actionable SARS-CoV-2 data now with the potential to become a sustainable network able to track other diseases of regional importance in the future.
|
| 30/09/2021 |
£998,810 |
|
STEM LEARNING LIMITED |
Our vision for Explorify: is to be a sustainable and dynamic resource that is a core part of the primary science teacher’s toolkit – enabling teachers and school leaders to develop primary science as a strength, and inspiring children to engage with science.
Explorify has established itself as a substantial and influential part of the primary science environment – particularly for teachers taking their first steps in teaching primary science. We will build on this, expanding its reach, impact and long-term sustainability through:
Maintaining the current Explorify user experience so that it remains free of charge, simple to register, easy to navigate and requires minimal teacher preparation;
Updating content and adding activities in response to changes in primary science education and UK curricula, reflecting topical issues, and in response to feedback and suggestions;
Increasing the reach of Explorify, engaging more users through our established networks and partners, whilst seeking opportunities to create new associations and outlets through which to raise awareness of Explorify;
Positioning Explorify alongside wider professional development opportunities to develop a comprehensive and flexible CPD journey for Explorify users, including science subject leaders;
Developing a sustainable business model which enables Explorify to remain free to UK audiences.
|
| 30/09/2021 |
£1,406,528 |
|
CSIR- INSTITUTE OF GENOMICS AND INTEGRATIVE BIOLOGY |
The global challenges posed by COVID-19 are best tackled through global cooperation between researchers, clinicians and funding agencies. One such challenge is generating timely, high-resolution monitoring of the SARS-CoV-2 viral evolution and using such data to guide public health response in a timely manner. The discovery of current variants of concern (VOC) in UK, South Africa and Brazil is because of a high quality sequencing program (UK) or vaccination related investigations (South Africa, Brazil). Indian SARS-CoV-2 Genomic Consortia (INSACOG) is revealing the possibility of local VOC driving fresh outbreaks.
We proposes a network of satellite genomic sequencing MicroLabs in India, Bangladesh and Sri Lanka that will be integrated by virtual cloud-based workflows as well as physical linkages to national MegaLabs for quality assurance and operational support. This would help scale up global monitoring of emerging SARS-CoV-2 strains in one of the world’s most populous region and guide global R & D efforts for COVID-19 diagnostics, vaccines and therapeutics.
Given the relevance of SARS-CoV-2 surveillance to especially the diagnostics and health systems pillars of WHO’s ACT-Accelerator, partners such as Wellcome Trust can play an important role in furthering this effort. There is an urgent need to create distributed local capacity via MicroLab hubs.
|
| 30/09/2021 |
£388,926 |
|
UNIVERSITY OF COLOMBO |
The global challenges posed by COVID-19 are best tackled through global cooperation between researchers, clinicians and funding agencies. One such challenge is generating timely, high-resolution monitoring of the SARS-CoV-2 viral evolution and using such data to guide public health response in a timely manner. The discovery of current variants of concern (VOC) in UK, South Africa and Brazil is because of a high quality sequencing program (UK) or vaccination related investigations (South Africa, Brazil). Indian SARS-CoV-2 Genomic Consortia (INSACOG) is revealing the possibility of local VOC driving fresh outbreaks.
We proposes a network of satellite genomic sequencing MicroLabs in India, Bangladesh and Sri Lanka that will be integrated by virtual cloud-based workflows as well as physical linkages to national MegaLabs for quality assurance and operational support. This would help scale up global monitoring of emerging SARS-CoV-2 strains in one of the world’s most populous region and guide global R & D efforts for COVID-19 diagnostics, vaccines and therapeutics.
Given the relevance of SARS-CoV-2 surveillance to especially the diagnostics and health systems pillars of WHO’s ACT-Accelerator, partners such as Wellcome Trust can play an important role in furthering this effort. There is an urgent need to create distributed local capacity via MicroLab hubs.
|
| 30/09/2021 |
£3,069,373 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2021 |
£3,000,000 |
|
UKRI-EPSRC |
This partnership between Wellcome and UKRI will support the Physics of Life funding call. Which aims support internationally leading research that requires collaborative, interdisciplinary working to address key challenges at the interface of physics and life sciences.
The call will fund high-quality proposals that demonstrate deep integration of cutting edge experimental, theoretical and/or computational physics within life sciences research to advance our understanding of living systems in biological or biomedical contexts. |
| 30/09/2021 |
£3,728,812 |
|
UNIVERSITY OF OXFORD |
We propose to set up and validate a pharmacometric platform to provide quantitative assessment of antiviral effects in low risk adult patients with recent onset uncomplicated COVID-19 and high viral burdens. This assessment is based on measurement of oropharyngeal viral clearance rates. This will be a randomised, open label, group sequential adaptive platform trial to quantitate the antiviral activity of currently available potential (i.e. repurposed) treatments in low-risk adult patients with early COVID-19, through adjusted qPCR of serial oropharyngeal samples. It will be a mainly outpatient study conducted in three locations; one each in the Americas, Europe and Asia. The interventions to be evaluated in this first phase are hydroxychloroquine, lopinavir/ritonavir, ivermectin, miglustat, remdesivir, intranasal heparin, with the Regeneron monoclonal antibody cocktail or Peginterferon-lambda as a positive control. This will identify drugs with a > 90% probability of accelerating virus clearance compared to no treatment and will reject drugs with |
| 30/09/2021 |
£277,163 |
|
CENTRO DE ESTUDOS DO INSTITUTO DE PSIQUIATRIA |
The first goal of this award is to achieve an inexpensive, accessible and scalable
solution to detect clinical high risk for psychosis in individuals within the general
population. This solution will be based on an algorithm that analyses an individual’s
speech collected by means of a mobile smartphone or by over-the-web recorded
interviews. This algorithm will deliver a high accuracy score ( > 80% accuracy) that can
detect whether an individual is at clinical high risk for psychosis. The second goal is to
establish an algorithm that can predict whether individuals at clinical-high risk transition
to psychosis. In the longer term these tools will enable early detection of psychosis. |
| 30/09/2021 |
£3,828,366 |
|
OPHIREX |
Ophirex seeks funding from the Wellcome Trust to support an India-focused Phase 2 human trial to evaluate the safety, tolerability, and efficacy of oral varespladib-methyl with standard of care after venomous snakebite in subjects aged 5 years and older.
Technical Goals:
Goal 1. Qualify and on-board 4 – 8 trial sites in India.
Goal 2. Complete trial start-up activities including trial database, training, DSMB, and project operations.
Goal 3. Complete regulatory submission and approval from Drug Controller General-India (DGCI).
Goal 4. Complete trial and Clinical Study Report
The program will advance broad-spectrum treatments for snakebite based upon Ophirex’s privately developed toxin-targeting portfolio and provide affordable, superior care to rescue life and limb. All tasks are focused on supporting eventual New Drug Application submissions in India and, separately the US to enable file transfers to other regulatory authorities (such as individual countries in Asia and sub-Saharan Africa as well as via WHO precertification).
Key attributes of this First-In-Class antidote are:
1) Broad spectrum sPLA2 inhibition for first-line treatment of snakebite
2) Excellent safety profile for population at risk
3) Ease of use and administered anywhere
4) Shelf-stability for at least one-year
5) Low cost of manufacture compared to biological products
|
| 30/09/2021 |
£856,768 |
|
UNIVERSITY OF GOTHENBURG |
Antibiotic resistance surveillance is critical for guiding empirical treatment and evaluating interventions. As current methods rely on analyses of bacterial isolates from many individuals, surveillance is resource-demanding and thus absent or very limited in most low- and middle-income countries (LMICs). We hypothesize that microbiological analyses of sewage, containing excreted bacteria from thousands of people, can be a resource-efficient complement for population-level antibiotic resistance surveillance with particular value in LMICs. This is supported by our recent European studies showing good correlation between resistance rates in clinical and sewage E. coli isolates. Here we aim to further develop the sewage monitoring system by targeting additional clinically important bacteria in sewage and investigating the value of including gene-based analyses. We also aim to validate the methodology in three sub-Saharan African countries by benchmarking to local clinical surveillance data generated during the project. The relationship between sewage and clinical ESBL-producing strains, one of the most urgent resistance threats, will be studied in more detail by applying whole genome sequencing. By also engaging relevant stakeholders, the overarching goal is to pave the way for future implementation of sewage monitoring, which could significantly increase the basic data for surveillance of antibiotic resistance in LMICs.
|
| 30/09/2021 |
£999,674 |
|
UNIVERSITY OF OXFORD |
There does not exist currently a clear pathway for the pharmacometric evaluation of new Chagas disease treatments, and thus evidence-based drug and dose selection. Compounds currently in pre-clinical development (Wellcome HIT NTD flagship) cannot be assessed for efficacy in vivo in an efficient way. This project will provide a platform for phase 2 assessment of these new compounds. The success of our project could accelerate clinical development substantially and, by ensuring evidence-based dosing, will reduce the risks and improve the value of the phase 3 trials. This could have an enormous impact on the treatment of Chagas disease. |
| 30/09/2021 |
£318,039 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Critically ill patients require a continuum of care spanning from early recognition and system activation through facility-based care in emergency and intensive care units. There are few resources to support critical care strengthening in low- and middle-income countries (LMIC); existing tools have largely been designed in and for high-income settings and are poorly suited to the distinct resource and capacity constraints, disease burdens, and ways of organizing and delivering critical care in LMICs. WHO proposes to address this by developing a Critical Care Toolkit composed of two major elements. First, an expansion of the Essential Resources for Emergency Care to encompass the spectrum of emergency and critical care: a guidance document for policymakers, planners, and health professionals developing and improving critical care systems. This will explicitly define the elements needed to establish key critical care functions. The second will be a training course oriented to LMICs. The course will teach the basics of critical care delivery across the continuum, strengthening provider capacity. The toolkit will support effective critical care systems, those that integrate mechanisms to ensure a systematic approach to every patient, provide rapid access to equipment and supplies, and use structured processes for timely recognition and management of threats. |
| 30/09/2021 |
£449,970 |
|
NEOPENDA PBC |
Through user-centric design, Neopenda aims to create needs-based solutions that benefit underserved populations, enable high quality patient care, and provide nuanced data insights for stakeholders. With the funding requested for this project, we will modify a wireless vital sign monitoring system for health facilities into a vital sign measurement tool for lower level health facilities and community health workers. |
| 30/09/2021 |
£5,041,583 |
|
YORK UNIVERSITY (CANADA) |
Drug-resistant infections have the potential to threaten tens of millions of lives, yet, in many countries, efforts to promote sustainable antimicrobial use and implement national action plans have stalled. As the antimicrobial resistance (AMR) threat grows, it is increasingly important to integrate scientific evidence into the national and global AMR responses. We propose to develop a Virtual Policy Think Tank that serves as a bridge between AMR science and policy, leverages global science and insights, and delivers relevant and rigorous evidence that responds to urgent global policy needs. The Think Tank will undertake three streams of work to build coordinated and innovative progress toward global AMR goals. A rapid response stream that responds to rapid evidence requests from governments and other actors will support the implementation of robust, evidence-informed AMR action plans. A capacity-building stream will support the regular use of scientific evidence in AMR policymaking processes. A policy proposal stream that engages academics from around the world will build new solutions for intractable AMR policy challenges. The Think Tank will act as a global leader and resource for evidence-informed AMR policy with the aim of ensuring sustainable antimicrobial use for all.
|
| 30/09/2021 |
£533,825 |
|
MAKERERE UNIVERSITY |
Much of critical care revolves around respiratory support. Indeed, AHRF contributes the highest proportion of intensive care admissions worldwide. Therefore, any strategy to optimise critical care in Africa begins with care of the patient with Acute Hypoxemic Respiratory Failure.
This study provides an opportunity to introduce a cost-effective intervention that would also constitute a significant component of holistic frugal critical care in Africa.
This study is a pilot in the following manner, in addition to answering the primary question of which intervention is suitable, it will provide insights to the logistics of applying such interventions in places with under-staffed healthcare workers. In addition, use role of newer and safer lung diagnostics such as lung ultrasound shall be employed to ensure quicker diagnosis and to assist in patient stratification.
These answers shall inform preparations for larger multi-country trials that will test the efficacy of either one of the interventions (BREATHE) or their combination (COSTA). This is also likely to be the first adult acute respiratory trials network in sub-Saharan Africa.
This work has the potential to impact care of the critically ill patient in Africa.
|
| 30/09/2021 |
£2,639,537 |
|
BETH ISRAEL DEACONESS MEDICAL CENTRE |
With this funding, we hope to achieve a decrease in mortality for the 20 million critically ill adults in sub-Saharan Africa with acute hypoxemic respiratory failure.
In the setting of COVID-19, governmental and nongovernmental organizations are working toward improving oxygen availability through large PSA plants and bedside oxygen concentrators. While sources of oxygen are increasing, what remains unknown is the impact of using different delivery systems for oxygen, which include low flow nasal cannula and facemasks, HFNC, CPAP, and invasive ventilation. Low flow systems are limited in the degree of oxygen support they can provide and are therefore only appropriate for mildly hypoxemic patients; non-invasive CPAP carries a significant aspiration risk for patients with altered mental status and requires close monitoring by trained staff; mechanical ventilation requires even more significant infrastructure, consumables, and human resources to operate safely. In HICs, HFNC has been shown to reduce the need for mechanical ventilation, and in some cases reduce mortality. In LICs, where safe mechanical ventilation is largely unavailable, we predict a robust mortality reduction.
This funding will yield definitive evidence for HFNC’s impact on mortality, and develop the resources to widely disseminate that evidence, including comprehensive strategies for implementation and scaling.
|
| 30/09/2021 |
£6,783,629 |
|
CARDIFF UNIVERSITY |
First-in-Human, Phase 1 safety, tolerability, pharmacokinetic and pharmacodynamic/target engagement studies of MDI-478, a positive allosteric modulator (PAM) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype of ionotropic glutamate receptor (AMPAR). The aim is to demonstrate that MDI-478 is safe and well-tolerated and demonstrate pharmacodynamic effects and/or target engagement sufficient to support Phase 2 efficacy studies". |
| 30/09/2021 |
£15,613,391 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
Ensembl is the world’s most comprehensive genome informatics resource. We have powered genomic analyses for over twenty years through our data, know-how, software and deep ties to the research community. Today, as genomic medicine is scaling up across the world and the effects of the sixth mass extinction become increasingly apparent, genomics has a critical role to play in addressing key societal challenges. To meet these challenges and stay relevant in a fast paced environment, we are preparing for landmark innovations in our processes, including (i) a transition to the graph-based human reference genome; (ii) an increased use of cutting-edge technologies including machine learning to more accurately annotate genomes; (iii) an expansion of the number of supported genomes from hundreds to tens of thousands; (iv) an extensive redevelopment of our comparative genomics infrastructure; (v) a complete overhaul of our release cycle to release data as quickly as we can annotate it; (vi) the launch of our new website; and (vii) the release of new APIs that will replace our Perl API for external users.
Keywords: genome annotation, bioinformatics, database, biodiversity, functional interpretation of genetic variation, model organisms, genome regulation, agricultural genomics, FAIR data, open source software, open and reproducible science.
|
| 30/09/2021 |
£2,532,166 |
|
UNIVERSITY OF DUNDEE |
"Schistosomiasis is a neglected tropical disease, caused by parasitic worms that live in the blood vessels around the intestines or bladder. Approximately 230-440 million people are currently infected and the disease causes approximately 300,000 deaths per year, either directly or indirectly, and many other health related problems due to chronic infection, including cognitive development issues with children and exacerbation of the effects of other infectious diseases. There is only one drug, praziquantel, registered to tackle this disease, creating an urgent need for the development of new drugs to treat this disease, to improve the efficacy and also in case of resistance developing to praziquantel. Furthermore, there is little known about drug discovery for this parasite. In this Project the University of Dundee, Aberystwyth University and Cardiff University are developing new assays and optimising existing assays to facilitate the drug discovery process. The team has discovered a series of chemical start points through previous work which will be progressed through the improved pathway with the eventual aim of discovering a late lead, a molecule that has the potential to be developed for treatment of schistosomiasis." |
| 30/09/2021 |
£1,968,101 |
|
ST GEORGE'S, UNIVERSITY OF LONDON |
The overall goal of this project is to develop simple tools to help individual countries make the best use of their own AMR surveillance data to inform local action. The project will use a range of modelling methods of existing global data sets that include information on clinical infection management and outcomes, antibiotic resistance, consumption and use. The proposal aims to learn from the development of clinical surveillance networks in other disease areas such as tuberculosis (TB) and will use a public health approach to provide a conceptual framework for future surveillance implementation and policy goals.
This project combines research expertise on antimicrobial resistance, usage modelling and policy development. It aims to model the existing data sets to provide a framework for future clinical patient centred AMR surveillance that can inform empiric prescribing guidance and support local individual country policy decisions on future targets and ambitions. The proposal has been developed to link closely with current and planned WHO initiatives and the work of other key stakeholders. The project includes an early pilot phase, developing and testing the models in collaboration with multiple partner countries.
|
| 30/09/2021 |
£335,050 |
|
UNIVERSITY OF OXFORD |
The global community has mobilised in an unprecedented way to deliver research in response to the threat of COVID-19. In February 2020, priority areas for research were advanced under a coordinated mechanism convened by the World Health Organisation. For social science a cross cutting research agenda was proposed in recognition of the vital role played by individuals, communities and populations worldwide in slowing disease tranmssison and providing care for COVID-19 and beyond. Research initiatives, including over 300 social science studies funded by GloPID-R members alone, have been advanced against these social science priorities. Building on earlier successes in supporting epidemic-relevant research, the research arm of GOARN, the Global Outbreak Alert and Response Network, has actively coordinated this work with WHO. There is a pressing need to properly resource coordination and knowledge mobilisation of epidemic-relevant social science research. Further, there is an important opportunity to leverage the reach and expertise of GOARN and establish infrastructure for the COVID-19 response as well as for future scenarios to ensure that structures for epidemic-relevant research can take hold: the well worn phrase of building the ship while we sail it is unsustainable as an effective and efficient research response to infectious disease epidemics.
|
| 30/09/2021 |
£2,815,184 |
|
UKRI-MRC |
The UKPRP is an inter-disciplinary national initiative supported by an alliance of UK charities, Research Councils and the UK Health Departments, and established in recognition of the need for research into population-level strategies that will prevent non-communicable diseases (NCDs) and reduce inequalities in health. |
| 30/09/2021 |
£245,428 |
|
UNIVERSITY OF LIVERPOOL |
We will engage new parents and children and young people and their families in the Liverpool City Region through a series of highly interactive arts-based initiatives to understand how people perceive health, health inequalities and how data are used to inform policy, and to foster the ownership of the Children Growing up in Liverpool (CGULL) study in the wider community.
We will co-create engagement activities via engaging and creative arts, participatory research methods and events, and through a network of public engagement co-leads. We will create CGULL characters in books and digital media, host a museum installation on "Growing up in Liverpool", and conduct workshops on health inequalities and data use.
We will take activities, research and outputs to the communities that we serve. This public engagement work will enrich the core work of the cohort, enabling us to coproduce the next phase of the study and its engagement.
Working in collaboration with our partner organisations, including through Liverpool’s UNICEF Child Friendly Cities programme, Liverpool Health Partners Starting Well programme, local council and NHS trusts, we will provide a springboard for capacity across the city for trustworthy research and public engagement focussed on children and young people and health inequalities.
|
| 30/09/2021 |
£238,930 |
|
UNIVERSITY COLLEGE LONDON |
Research has indicated that the future use of emerging, data-driven, technologies in surgery is dependent on ensuring these technologies are designed with, and for, the public and patients.
Accordingly, we propose ‘In Theatre’- an interactive public installation and arts-based community engagement programme. This will use arts-based approaches to discuss challenging topics and break down barriers to engagement in a two stage project.
Stage 1: Deep listening – This will use societally engaged arts and creative practice to explore concepts of robotics and A.I. in surgery to better understand the public’s concerns, identify what they want to know more about and what they would like researchers to consider in future work. Learnings and outputs from this stage will inform the content, experience and overall design of the public installation.
Stage 2: Installation – Working with The Liminal Space, experts in public engagement delivery, we will create a three-week pop-up installation which will help residents in Tower Hamlets build their own understanding of these technologies and shape how they should be developed. This intervention will also make a valuable ‘learning environment’ for clinicians and researchers to gain further insights into the relationship people have with surgical technology beyond the clinical environment.
|
| 30/09/2021 |
£81,528 |
|
UNIVERSITY OF CAPE TOWN |
Total number of current applications in progress for LMICSSs by Administering Organisation (for all Programmes they administer): 1
Total number of current applications in progress for LMICSSs to be held at the AAP/Centre to which the application relates: 1
|
| 30/09/2021 |
£249,701 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2021 |
£1,484,750 |
|
SAVE THE CHILDREN (ELHRA) |
Not available |
| 30/09/2021 |
£31,219 |
|
MQ TRANSFORMING MENTAL HEALTH |
Interest payable to MQ |
| 30/09/2021 |
£0 |
|
WELLCOME SANGER INSTITUTE |
TDP-43 is a conserved RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 normally autoregulates its expression by binding to the 3’UTR of its cognate transcript. We have linked disrupted TDP-43 autoregulation to disease, showing that disease-linked TDP-43 missense mutations disturb TDP-43 autoregulation causing a gain of function, finding that ALS patients harbour non-coding variants in the 5’ and 3’UTRs of TDP-43 that could disturb TDP-43 expression and observing that TDP-43 misregulation in mice causes selective brain atrophy reminiscent of human ALS-FTD. We will follow these leads to understand the causes and consequences of TDP-43 misregulation and elucidate therapeutic targets and biomarkers for ALS-FTD. Specifically, we will dissect the TDP-43 autoregulation protein interactome in wild-type and TDP-43 missense mutant cells by performing in-cell protein-RNA interaction studies and native mass spectrometry. To determine the significance of ALS-linked UTR variants in regulating TDP-43 expression we will perform an in-vitro CRISPR/Cas9 mutagenesis screen with parallel genomic and transcriptomic sequencing. To understand how TDP-43 misregulation causes regional and cell type-specific neurodegeneration we will use in situ sequencing of mouse brain sections to obtain transcriptomic information with single cell resolution.
|
| 30/09/2021 |
£0 |
|
WELLCOME SANGER INSTITUTE |
The folding of genomic DNA from the beads-on-a-string like structure of nucleosomes into higher order assemblies is critically linked to nuclear processes, but it is unclear to what degree it is a cause or consequence of function. We aim to understand whether the Nucleosome Remodeling and Deacetylation (NuRD) complex regulates chromatin structure to control transcription, or whether it is NuRD’s regulation of transcription that results in global changes in chromosome structure.
We have calculated the first 3D structures of entire mammalian genomes using a new chromosome conformation capture procedure, which combines imaging with Hi-C processing of the same single cell. Our objectives are now:
To study: 1) how interphase mammalian genome structure is established in G1; 2) the factors that drive this formation and; 3) how this organisation is regulated by chromatin remodellers (such as the NuRD complex) as mESC’s differentiate.
To build a dedicated bespoke microscope for 3D double helix point spread function detection with light sheet activation, optimised for 3D single-molecule/super-resolution imaging of proteins such as the NuRD complex.
To combine 3D super-resolution imaging and the biochemical processing steps of single cell Hi-C to directly correlate binding of protein complexes to regions of the structures.
|
| 30/09/2021 |
£0 |
|
WELLCOME SANGER INSTITUTE |
The goal of the Human Developmental Biology Initiative (HDBI) is to be an enabling initiative to support wider research in human development. The UK is well positioned to take a lead in this, given its expertise in model organism developmental biology, the successful operation of the Human Developmental Biology Resource (HDBR) and clear regulation of human embryo research. HDBI will develop a set of core experimental and computational methods for studies in embryonic and foetal tissues. It will do so by focusing on generating foundational data on cell lineage in human development. To promote wider access to human developmental biology research techniques, HDBI will work closely with HDBR to develop the required technologies, creating two research hubs in proximity to the HDBR sites in London and Newcastle. Understanding developmental cell lineage provides an essential basis for comparative studies of development between species, as well as a context for understanding the developmental origins of disease. In addition to technology development, HDBI data will complement insights from Wellcome’s Deciphering Developmental Disorders program, the Human Cell Atlas and the MRC Regenerative Medicine Platform, and provide baseline data for validation of in vitro differentiated human tissue models.
|
| 30/09/2021 |
£2,000 |
|
PANOS PICTURES |
Produce, print and install an exhibition of photographs by Tom Pilston documenting University College Hospital (UCH) staff working on the Covid pandemic. Exhibtion to be in UCH lobby in Euston Road
|
| 26/08/2021 |
£17,827 |
|
UNIVERSITY COLLEGE LONDON |
The feminisation of HIV is an increasing issue of concern, especially amongst Latin American migrant populations. As the predominant demographic of those living with HIV in the region are men-who-have-sex-with-men (MSM), there is a gendered Diversity & Inclusion gap. Women living with HIV have different needs & experiences than MSM, however due to gender-based constraints (e.g.childcare, home-based-working) they are less present/visible in my research environment, as well as within local NGO activities/projects.
How the activity will look:
Working alongside the United-Nations-Population-Fund (UNFPA), this two-day participatory workshop will bring female migrants living with HIV in Peru together to discuss and ‘story-tell’ specific experiences and needs that may be overlooked due to lifestyle constraints limiting participation in research and NGO projects. Relevant stakeholders will be invited and, learning horizontally from the experiences of migrants, we will collaboratively discuss how to address the feminisation of HIV in migrant populations.
We will professionally produce an informative-animation to disseminate outcomes/stories widely and easily through social-media. This will ensure that a) research environment and NGO activities are more hospitable to the gender-specific barriers to participation faced by migrant women; b) migrants themselves have opportunities for their voices to be heard and fed-back into research and NGO activities.
What we will achieve for:
Diversity & Inclusion Initiatives: Greater understanding of the migrant-based feminisation-of-HIV amongst relevant stakeholders, and greater inclusion of women in research where they are often left-out due to practical constraints.
Participants/Collaborators: Prioritisation of experiences and voices of female migrants living with HIV, thereby empowering them.
|
| 26/08/2021 |
£19,500 |
|
KING'S COLLEGE LONDON |
Similarly to other universities in the UK, in the Faculty of Life Sciences and Medicine (FoLSM) we see that the diversity of our post graduate research (PGR) community is inconsistent with the undergraduate (UG) population we have at King’s College London and, whilst students on our UG courses are diverse in ethnicity and socio-economic background, our PhD students are predominantly white Europeans and rarely the first in family to get a university degree. This an area in great need of levelling up.
The proposed Research Enrichment activity will tackle some of the barriers students from under-represented backgrounds face when pursuing PGR. The combination of a mentorship scheme, visits to research laboratories and a series of talks will endow students with essential transferable skills, contacts and support that will demystify the PGR recruitment process and help them progress to PGR and research-related jobs, including academic careers. Additionally, we will raise awareness of issues related to equality, diversity and inclusion within our current cohort of PhD students and research staff, empowering them to drive the change needed to create an inclusive research culture in academia. We will employ a mixed-method approach to collect quantitative and qualitative information to evaluate the activity’s effectiveness and will share our findings with our Centre for Doctoral Studies and WP division, other Schools within FoLSM as well as with the other Health Faculties within King's. Other dissemination activities will include electronic media such as blog posts and publication of a summary report of the outcomes.
|
| 26/08/2021 |
£8,838 |
|
UNIVERSITY OF YORK |
Due to geographical distance, and difference in wages and funding opportunities for scholars in Sudan, there has been limited direct engagement with the Sudanese colleagues during the applicant’s project, for which Sudan is the core area of research. Owing to the close links between past and present heritage crafts and their impact on health, it is paramount the project reaches the scholars and the public in Sudan. The project aims to deliver a ‘hands on’ multidisciplinary ‘summer camp’ at the University of York, for the Director of the first Bioarchaeology laboratory in Karthoum, Sudan, Dr Mohamed Saad, and one of his students. Such a laboratory, created by the British Museum (Dr Antoine), is the first laboratory of its kind in the region, aimed to empower a new generation of scholars in Bioarchaeology. A multidisciplinary team in York, led by the applicant and the visiting scholars, will prepare an open access ‘road map document’ to implement the inclusion and diversity of scholars and the public in the field of Bioarchaeology and Medical humanities in East Africa. This will be achieved with the full support of the applicant’s Department, which hosts a Centre of Excellence in African Archaeology (Dr. Wynne-Jones, Dr Stump). The road map document will be shared across a wide network of scholars involved in traditional knowledge, sustainability and health in East Africa. The visit will culminate with the participation of the scholars to the final project workshop (a 3 days event) planned for June 2022 at the British Museum.
|
| 26/08/2021 |
£20,000 |
|
ELIFE |
We will develop sustained capacity for scholarly peer review among early- and mid-career African researchers. To this aim, we propose to develop resources and a dissemination strategy for the delivery of a Best Practices in Scholarly Peer Review workshop, materials that once openly released can be adapted and replicated across research communities in Africa.
The proposed programme will follow three milestones. We will develop materials and teaching resources for a three-part workshop (M1) where African researchers are invited to join a path of guided learning to build their profile as constructive peer reviewers. To ensure scalability and maximize impact, we will implement a "Train the trainer" model (M2). We will leverage joint networks of all partners to recruit the first cohort of ten African researchers and invite them to train as trainers, co-create the materials and help adapt the resources to their needs and contexts, and c) deliver the workshop to their research community (M3).
In addition to peer-review training, workshop participants will be invited to join the eLife Early-Career Reviewers Pool, and offered support and onboarding materials to build a public profile as preprint reviewers as part of new reviewing communities on PREreview and Sciety.
As a result of this programme, the visibility of African researchers will increase, as will the recognition for their constructive peer-review contributions. Those, coupled with supportive journal policies, will help establish a rich representation of African scholars among reviewers in the traditional as well as the ‘publish, then review’ system of scholarly communication.
|
| 04/08/2021 |
£504,703 |
|
UNIVERSITY OF DUNDEE |
Cryptosporidium is a waterborne, protozoan parasite that is a significant cause of child morbidity and mortality in low- and middle-income countries. Cryptosporidiosis causes severe diarrhoea in children that leads to approximately 200,000 deaths per year and is a major contributor to malnutrition and growth stunting. There are no effective medicines for the treatment of malnourished children and immunocompromised adults suffering from cryptosporidiosis. The aim of this project is to develop a new way to test drugs for their ability to kill Cryptosporidium that more closely mimics the actual intestinal environment in patients. This more biologically realistic environment will allow us to discover new chemical start points for drug discovery. We will use human intestinal organoids, "miniature organs", that replicate the environment of the intestine in the lab. We will test compounds on a largescale, collect the data using microscopy, and evaluate the results using artificial intelligence. |
| 04/08/2021 |
£751,510 |
|
I3S - INSTITUTO DE INVESTIGAçãO E INOVAçãO EM SAúDE, UNIVERSIDADE DO PORTO |
Healthcare-Associated Infections (HAI) affect ~1.7M people in USA and 4.1M in Europe, contributing to 99,000 and 37,000 deaths/yr, respectively. Catheter-related infections are the most frequent cause of HAI, leading to life-threatening complications and colossal medical costs. Current prevention/treatment options – lock solutions, systemic antibiotic administration – are inefficient and lead to bacterial resistance, a huge threat to public health. We propose the development of "SmartCap", the first light-activated cap for catheter sterilization. Unlike standard catheter caps that are just used as physical barrier, the SmartCap kills 99% of bacteria without using antibiotics, hampering bacterial resistance. This reusable system is fully integrated in the cap and can be adapted to any catheter, standing out as a safe, long-term antimicrobial solution to prevent catheter infections. The SmartCap will contribute to patient well-being and quality of life, reducing associated risks, reintervention procedures, and hospitalizations, having a huge economic impact on the healthcare system. |
| 04/08/2021 |
£697,119 |
|
UNIVERSITY OF OXFORD |
Brain injury commonly affects young people after trauma or stroke. Minimally Conscious State (MCS) is a devastating consequence where wakefulness is minimal, leading to poor quality of life, and dependence on healthcare services (Bernat J). There are currently no treatments that improve arousal and care is restricted to nursing and supportive care. In MCS, brain electrical rhythms are disrupted. We have demonstrated that deep brain stimulation (DBS - implanting electrodes in the brain) can increase arousal by altering these rhythms. We have developed a bespoke DBS system that responds to sleep/ wake cycles. Our next step is to modify the technology to respond to abnormal brain rhythms and test its effects in MCS patients. The advantage of this approach is that stimulation can be adjusted to wakefulness or time of day. This is a platform technology which has implications for both disorders of consciousness and sleep disorders. |
| 04/08/2021 |
£504,942 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Delayed parasite clearance and treatment failures with first-line artemisinin-based combinations are widespread in Southeast Asia and alarmingly resistance markers have been detected in several African countries. New antimalarial drugs with novel mechanisms of action, active against resistant strains are urgently needed. We have identified potent inhibitors of malaria parasite phosphodiesterase (PDE) enzymes. They kill asexual blood stage parasites that cause disease, and two of our sub-series also kill gametocytes which mediate transmission, a property absent from most antimalarials. Our inhibitors act at a similarly rapid rate to chloroquine. Importantly, PDEs have been targeted successfully and safely to treat a range of human disorders and importantly our series has excellent selectivity against human PDEs. One of the attractions of the chemotypes we are developing here is that their profile in terms of drug-drug interactions is particularly benign. Thus, a new antimalarial targeting PDEs has clear potential in combination therapy. |
| 04/08/2021 |
£470,113 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Worldwide, there are approximately 150 million cases of Shigellosis annually, which is exacerbated by increasing resistance to the antibiotics used to treat Shigellosis. The WHO has highlighted that there are no currently effective vaccines for any Shigella species. The O-antigen, a sugar that coats Shigella cells is a validated vaccine candidate, particularly when conjugated to a carrier protein, but current methods to achieve this are complex and costly. Using our glycoengineering technology, we will multiply conjugate Shigella O-antigens to novel conserved immunogenic Shigella proteins we have validated to produce broad-spectrum Shigella glycoconjugate vaccines. These "double-hit" Shigella vaccines will be expressed in E. coli cells that act as mini-factories to produce affordable vaccines. Our Shigella-plus vaccine will be (i) safe, (ii) effective, (iii) broad-spectrum to cover all Shigella species and (iv) low-cost so that it can be deployed where it is most needed, providing an effective global solution to Shigellosis. |
| 04/08/2021 |
£501,078 |
|
UNIVERSITY OF CAMBRIDGE |
Non-alcoholic fatty liver disease (NAFLD) is defined as hepatic fat accumulation that exceeds 5% of liver weight. Accumulation of lipids in the liver in NAFLD plays a key role in the progression of cirrhosis and hepatocellular carcinoma, a hard-to-treat cancer and it is becoming the major reason for liver transplantation in the world. NAFLD is associated with obesity, type 2 diabetes and metabolic syndrome and estimated 25% of adults worldwide suffer from it. No effective treatment, apart from a significant change in lifestyle, exists for NAFLD. We propose to develop a drug that will reduce the production of lipids in the liver and thereby stop and reverse the progression of the disease. Our drug target is pyruvate kinase, an enzyme that is critical for lipid synthesis. We will improve our early inhibitors to be more potent and specific and thereby pave the way for the first pharmacological treatment for NAFLD. |
| 04/08/2021 |
£348,280 |
|
UNIVERSITY COLLEGE LONDON |
Glaucoma and trachoma are leading causes of blindness worldwide, with a combined > 200M people affected and close to 10M at immediate risk of permanent sight loss. For both diseases, surgical treatment success is directly dependent on the avoidance of postoperative scarring. However, there is no treatment to prevent scarring in trachoma and the current drugs used to prevent scarring following filtration surgery for glaucoma can have serious blinding side effects. We have designed an innovative product consisting of biodegradable microparticles loaded with doxycycline, a common drug, for local delivery at the time of surgery to achieve safe, targeted and sustained anti-scarring action. These have shown remarkable anti-scarring efficacy in laboratory tests, and we propose to evaluate their effectiveness in an animal model of post-surgical ocular scarring. The successful completion of this project will allow us to develop this treatment towards clinical trials, with a potential benefit to millions worldwide. |
| 04/08/2021 |
£286,964 |
|
UNIVERSITY COLLEGE LONDON |
Scoliosis surgery involves insertion of screws in the spine (called pedicle screws). Current techniques to insert these screws are not completely accurate. Even in international experts’ hands, 25-30% of the screws are misplaced. Misplacement of screws has a high risk of bone weakening, injuries to the spinal cord, nerve roots or blood vessels. Getting screw placement wrong has long term health implications for young patients, including lifelong disability. More accurate methods use computer navigation or image guidance techniques. However, these involve using more radiation (X-rays, CT scans) before and/or during the surgery. Surgeons and parents are concerned regarding the long term effects of ionising radiation in young patients. Our work helps to address this unmet health need by developing MRI based imaging techniques to design patient specific pedicle screw placement devices, which improve the accuracy of placing screws in the spine and removing the need for ionising radiation. |
| 27/07/2021 |
£394,010 |
|
UNIVERSITY OF EDINBURGH |
Studying neurobehavioural and metabolic disease requires precise measurement of movement/behaviour, energy balance, and systemic metabolism in living animals. Current platforms are imprecise, and mice are often studied under conditions compromising fidelity of disease modelling (e.g. "normal" room temperature imposes a thermal challenge, confounding modelling of human energy balance). We now seek a 16 cage indirect calorimetry system with environmental cabinet and 8-cage stable isotope module for precise, integrated quantification of murine metabolism, energy balance and behaviour. This offers:
5x faster cage flow rate than competitors, sampling every 2.5 minutes for respirometry at 0.001%/0.0001% (O2/CO2) resolution, allowing analysis in hypometabolic states (caloric restriction/thermoneutrality/small or aged animals). Ambient in-cage CO2 minimises hypercapnic compromise of behavioural testing, and home cage environment minimises acclimatisation/downtime.
Direct water balance measurement.
Laser-based, multiplexed detection of 13CO2/C18O2/CO2/H2O, permitting synchronised, rapid measurement of oxidation of > 10,000 substrates.
Behaviour capture at 1Hz, resolving disease-relevant abnormalities invisible to legacy systems. Outputs include behaviour time budget and position probability mapping. 1Hz integrated mass measurement detects feeding and drinking to 0.002 grams, quantifying "microfeeding" (c.30% food intake).
Computer architecture configured in a standalone network supporting synchronised metabolic/behavioural analysis even in large, long term experiments, increasing statistical power and permitting multiple hypothesis testing.
|
| 27/07/2021 |
£1,000,000 |
|
UNIVERSITY OF DUNDEE |
Cryo-electron microscopy (Cryo-EM) has become a powerful method to determine three-dimensional (3D) structures of macromolecular complexes. The technological developments to electron microscopes, detectors and processing software have enabled researchers to achieve high-resolution structures. Hence Cryo-EM has revolutionized structural biology to provide unprecedented insights into protein structure and function. Substantial investment has established national centres for data collection at the eBIC facility in Harwell and at the SCMI facility in Glasgow. To ensure that only the highest quality samples are selected for ultimate resolution data collection at the national facilities, it is equally important that the institutes that feed into them have excellent instrumentation for sample screening. To meet growing demand for Cryo-EM in Dundee this proposal requests support for the purchase of a Glacios Cryo-TEM with 200 kV X-FEG optics with an Autoloader for cryogenic sample manipulation and Falcon 3EC detector (or similar). In addition to efficient sample screening, this system supports high resolution data acquisition for single particle analysis, sample quality assessment, tomography, and other applications. This microscope will provide high quality screening for optimizing cryo-EM samples prior to data collection at National facilities, but also can determine structures at sub-3 Å resolution in house.
|
| 27/07/2021 |
£103,508 |
|
UNIVERSITY COLLEGE LONDON |
The IsoPlexis IsoLight platform is a unique, highly multiplexed single-cell microchip proteomics technology applicable to both basic and clinical research. Quantitative measurement of secreted proteins associated with a broad range of functional profiles is derived from over 1000 live single cells using intracellular protein detection via high-density antibody barcode arrays. It can precisely dissect the functional heterogeneity ('polyfunctionality') of immune cells with genetically and phenotypically identical signatures and several studies have shown that polyfunctionality determined at the single-cell level can identify critical effector cells associated with durable immunity against infections and cancer. Isoplexis analysis of polyfunctionality in the cell therapy space reveals that phenotypically similar T-cells can have heterogeneous functions and that the 'polyfunctionality index' can provide predictive signatures for toxicity and response to treatment. This state-of-the-art equipment will be housed at the UCL Royal Free Campus and will be used primarily for disease-focused and translational immunology research spanning the disciplines of immunotherapy, autoimmmunity, immunodeficiency, infection (including COVID-19) and cancer. This breakthrough single cell proteomics analysis platform will enable immunology and immunotherapy scientists at UCL to further enhance their understanding of endogenous and engineered human immune cells subsets in the pathophysiology of disease and in the response to treatment.
|
| 27/07/2021 |
£842,649 |
|
UNIVERSITY OF LEEDS |
The goal of this proposal is to establish a cutting-edge in-cell structural proteomics platform at the Astbury Centre that will enable the characterization of biomolecular structure and function in a cellular context. This will inform on the architectures of proteins and protein complexes, including interactions with nucleic acids and small molecules, directly in their native environment. We are requesting funding for the centrepiece of this platform, an Orbitrap Eclipse mass spectrometer with extended mass range and advanced fragmentation technologies. This equipment will enable us to deploy the suite of structural proteomics methods we have developed for in vitro protein studies directly to the cell. These approaches include in-cell covalent labelling to probe protein structure, such as by hydroxyl radical footprinting, and in-cell chemical crosslinking, including using bespoke photocrosslinkers, for interactome analyses. Such methods can only be implemented utilising the most sensitive mass spectrometry instrumentation available, and require advanced fragmentation methods to achieve the highest possible structural resolution. The proposed equipment will transform our ability to study molecular mechanisms of health and disease directly in the cell, and will result in translational opportunities, by identifying novel proteins, complexes and interactions that could be biomarkers or drug targets.
|
| 27/07/2021 |
£373,813 |
|
UNIVERSITY COLLEGE LONDON |
The requested equipment is a state-of-the-art multiwavelength photoacoustic imaging scanner for non-invasively imaging mice. Its distinguishing advantage over conventional optical imaging is that it avoids the deleterious impact of light scattering; it can therefore provide high resolution 3D images with molecular contrast at much greater depths (cm-scale) than light microscopy (
To benefit the widest possible range of users, it will be installed in the UCL Centre for Advanced Biomedical Imaging, a preclinical imaging centre that provides open access to a wide range of mouse models and state-of-the-art small animal imaging systems including ultrasound, SPECT/CT, MRI, bioluminescence and optical-projection-tomography.
|
| 27/07/2021 |
£340,339 |
|
QUEEN MARY UNIVERSITY OF LONDON |
In order to remain world-leading in the fast moving arena of single-cell approaches, UK researchers need access to the latest technology. Single-cell genomics and transcriptomics have fuelled an unmet need for affordable, single-cell, multiplexed protein maps that maintaining tissue architecture and integrity in a multi-user, high-throughput and flexible manner.
Launched in April 2020, The Cell DIVE Imager provides an automated solution for multiplexed immunofluorescence with industry-leading high content image analysis software enabling the visualisation, identification and integrated quantification of 60+ markers at the protein level. This equipment represents a new research capacity. Thus, our key goal is to establish the first multi-user Cell DIVE Imager platform available to researchers outside the USA.
We believe that the requested equipment satisfies all the technical requirements for accuracy, sensitivity and specificity. It also currently offers best value with respect to throughput, assay flexibility and cost, and enables multiple projects to be parallel tracked to support a multi-user base. Under the guidance of the lead applicant, the experienced QMUL Phenotypic Screening Core Facility will operate and maintain the equipment ensuring fair access to the 20 named co-applicants and collaborators and beyond, if capacity allows.
|
| 27/07/2021 |
£811,161 |
|
UKRI-MRC |
We are requesting funds to acquire a focused ion-beam and scanning electron microscope (FIB-SEM) with a cryo transfer system and an attached mass spectrometer for investigating biological material in three dimensions (3D) at high spatial resolution with chemical specificity. This cryo-FIB-SEM will be used for the three distinct purposes -
Firstly, serial block face sectioning and imaging of vitreous samples will provide images of key regions of tissues at unprecedented resolution (~5 nm). Secondly, this instrument will enable thick vitreous biological samples to be precisely thinned at cryogenic temperatures, producing lamella at high throughput with automation, which will be used in cryo-tomography applications for in situ structural cell biology. Thirdly, the instrument will have a secondary ion mass spectrometer attached, which will support molecular identification of the specimen, adding chemical specificity to high-resolution EM pictures. This versatile instrument will therefore provide a link between molecular structural data to 3D ultrastructure of cells and tissues, a complete transformational advance for the research of the MRC Laboratory of Molecular Biology (MRC-LMB).
This instrument will enable study of the structure and function of molecules in their native environment inside cells, providing insights into fundamental problems related to molecular biology and medicine.
|
| 27/07/2021 |
£1,204,973 |
|
THE FRANCIS CRICK INSTITUTE |
To understand how metabolites and drugs function in our bodies, it is essential to map their distributions accurately within tissues and cells. Secondary ion mass spectrometry (SIMS) is emerging as a powerful technology for this. We and others have collaborated with industry to improve SIMS instruments so that it is now possible to image tissues at micron spatial resolution with high mass resolution ( > 240,000 at m/z 200) and in situ detection sensitivity by at least an order of magnitude. We now propose three technology development aims with the goal of removing critical remaining obstacles to the wide adoption of SIMS in the biomedical sciences and pharmaceutical industry:
1) To optimise instrumentation and sample preparation for submicron-resolution cryo-OrbiSIMS.
2) To develop a toolkit of cryo-OrbiSIMS-visible chemical and genetically-encoded markers for cells and organelles.
3) To validate the OrbiSIMS marker toolkit across another SIMS platform - NanoSIMS.
|
| 27/07/2021 |
£928,892 |
|
UNIVERSITY OF EDINBURGH |
Bioimage analysis helps answer scientific questions by applying computational methods to images comprising millions – or, increasingly, billions – of pixels. As imaging technologies advance, new software tools are required to interpret these complex images.
QuPath (http://qupath.github.io) was created specifically to address the image analysis challenges of one emerging imaging modality: whole slide imaging. Whole slide images (WSI) are ultra-large digital scans (up to 50 GB), typically representing histological samples containing a wealth of information relating to health and disease. QuPath’s native support for WSI and intuitive combination of image processing and AI have established the software as a de facto standard for digital pathology and an essential tool for basic research.
The aims of this project are to:
Expand the range of algorithms available in QuPath to maximize the value of imaging data
Improve workflow development, validation and sharing to aid the translation of image analysis and AI towards clinical practice
Extend QuPath to new imaging modalities and applications to address unmet needs across a wide range of bioimaging applications
Together these represent a major upgrade to the software, transitioning QuPath from being primarily 2D and pathology-focussed into becoming an advanced bioimage analysis platform for next generation multidimensional imaging.
|
| 27/07/2021 |
£1,000,339 |
|
KEW ROYAL BOTANIC GARDENS |
Products derived from plants have scientific, medical, and economic significance.
Effective research, regulation, quality control, and consumer safety require precise, unambiguous references to these products. Regulations, databases, and research, however, employ contradictory, imprecise terminologies undermining integrity, retrieval, and exchange. Complex plant mixtures, for example, are regulated inconsistently as ‘drugs’ and ‘supplements’. Local terminologies duplicate effort, are inconsistent, and fail to reflect advances in molecular plant taxonomies.
Plants for Health (PfH) addresses the quality, interoperability, and findability of research and regulatory datasets concerning natural products by collating the terms used for ingredients, products, adulterants, and substitutes and mapping them to a scientific ontology. PfH will enable the detection and resolution of ambiguous terms and improve how research is targeted (eg. novel molecules) and reported.
"Medicinal Plant Names Services" is the default reference for herbal drugs. PfH will become so for all plant-derived products (c. 50,000 plants, 1.3 million terms) and serve many more audiences. PfH will include key traits, link to critical references, and provide digital accessibility.
10 institutional partners from diverse domains (e.g. WHO and WIPO) will help design, test, and deploy PfH, ensuring impact within their communities.
Health outcomes worldwide will improve through enhanced research, regulation, and knowledge exchange.
|
| 27/07/2021 |
£1,544,774 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
The PRIDE database, established in 2004 at the European Bioinformatics Institute (EMBL-EBI), is the world-leading proteomics data repository. PRIDE is also the leading partner in the ProteomeXchange Consortium, standardising public proteomics data submission and dissemination worldwide. PRIDE stores ~83% of all ProteomeXchange datasets, with ~5,300 datasets submitted during 2020 alone.
We request support to extend PRIDE, enabling the appropriate handling of clinical sensitive human datasets, through implementing controlled-access (CA) data capabilities. We will leverage infrastructure implemented for CA DNA/RNA sequencing data in the European Genotype Archive at EMBL-EBI, to create PRIDE-CA. Additionally, we will adapt the Beacon framework (developed for genetic variation at the DNA level) to support genetic variation data at the protein level, which is increasingly relevant in personalised medicine studies.
We will also develop the PRIDE Knowledge-Base (PRIDE-KB), a complementary resource to PRIDE, to store and disseminate high-quality proteomics data re-analyses, to generate new biological insight. We will implement proteogenomics data as the first use case supported in PRIDE-KB, reporting protein variants, isoforms and novel coding events for personalised proteomics approaches. To support this, diverse components will be developed and integrated, including new data archiving infrastructure, web interface, open data analysis pipelines and data inclusion guidelines.
|
| 27/07/2021 |
£981,393 |
|
UNIVERSITY OF LIVERPOOL |
The Tick Cell Biobank (TCB), the world’s only dedicated culture collection for cell lines derived from ticks and other arthropods, was founded in 2009. The TCB houses > 60 cell lines derived from ticks of medical and veterinary importance. We also generate and supply cell lines from neglected insect vectors including sand flies, biting midges, tsetse flies, triatomid bugs and mosquitoes. We supply arthropod cell lines to researchers all over the world and provide training in their maintenance, greatly increasing the chances of successful transfer and subsequent application in recipient laboratories. TCB Outposts in Asia (Malaysia), Africa (Kenya) and South America (Brazil) facilitate uptake of these valuable research tools in lower and middle-income countries.
This new project will
substantially enhance the existing collection through genomic and phenotypic characterisation of our novel, medically-important insect and tick vector cell lines
support, with the TCB Asia Outpost, continued generation and characterisation of novel arthropod cell lines with emphasis on human disease vectors (mosquitoes, sand flies, midges and mites)
extend the availability of the TCB and TCB Outposts as a global biomedical resource underpinning UK and international vector-borne disease research until 2026.
|
| 27/07/2021 |
£1,521,990 |
|
UNIVERSITY OF EDINBURGH |
We propose to develop the first miniaturised microscopes for high-speed (kHz) voltage imaging in freely moving animals. Voltage changes that mediate neuronal computations, and electrical signalling in non-neuronal tissues, are too fast to observe with miniature microscopes currently used for imaging in freely moving animals. To address this, we will build miniature microscopes that use Single Photon Avalanche Diode (SPAD) sensor technology to obtain frame rates > 10 fold higher than existing systems.
Our proof-of-principle ex-vivo data shows that SPAD sensors can image sub-threshold and spiking activity of neurons reported with genetically encoded voltage indicators (GEVIs). As the sensors used for these experiments have a similar footprint to the standard CMOS sensors in current miniature microscopes, it will be feasible to use SPADs to image fast electrical signalling even in freely behaving animals.
Our goals are: 1. To develop miniature microscopes that incorporate our established SPAD technology, along with custom made drivers and control software, to image 10s of neurons in freely moving animals. 2. To develop a second system using state-of-the-art SPAD sensors to image 100s of neurons in freely moving animals. 3. To validate the systems by recording from genetically identified neurons during spatial exploration and action selection.
|
| 27/07/2021 |
£1,338,559 |
|
UNIVERSITY OF EDINBURGH |
Drosophila is the only model organism with complex adaptive behaviours for which we also have a powerful genetic toolkit and extensive connectomic and transcriptomic coverage of the nervous system. This offers unparalleled opportunities to reveal the mechanisms by which brains control complex behaviour. Virtual Fly Brain provides a uniquely integrated, queryable view of Drosophila neuroscience data. Established pipelines with all major data providers enable rapid integration of new bulk data. Powerful UI and API allow users to find neurons and reagents from many sources, explore connectomes, visualise and download 3D image data. VFB provides an essential system ensuring key data is released openly and rapidly following FAIR data standards. However, it must cope with rapid increases in data scale and richness.
The next phase will:
Massively scale-up integration of multiple connectomics datasets, enhancing tools for search query and, via APIs, integration with analysis pipelines.
Integrate comprehensive single cell transcriptomics data and exploration tools.
Incorporate data-driven cell-type definitions and automated tools to map cell types across datasets, and annotate and share data.
Develop and integrate text mining pipelines to ensure complete mapping of papers and reagents to neuron types.
Extend APIs to empower users to analyse, annotate and share huge datasets
|
| 27/07/2021 |
£1,036,355 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
Established in 2018, the PDBe Knowledge Base (PDBe-KB, pdbe-kb.org) is a community-driven resource providing FAIR access to experimental and predicted 3D structure models and enhanced structural and functional annotations e.g. predicted functional sites. PDBe-KB supports fundamental biology, biomedicine, biotechnology and bioenergy by enabling atomic-level understanding of macromolecular function through its novel, consolidated presentation of all the available structural data and enriched annotations by means of "aggregated views". The PDBe-KB consortium has established common data standards for structural and functional annotations to improve data interoperability extending the impact of structural data e.g. to rationalise the impacts of disease-associated mutations, and thereby assist diagnostic and therapeutic strategies.
In this project we will:
Grow the PDBe-KB consortium to broaden the structural and functional annotations with specific emphasis on integrating residue mutation data in human and pathogen genomes.
Establish a new and comprehensive 3D-fold structure domain library (3D-SCAfold) through integration of CATH and SCOP domain data.
Ten-fold increase in the structural coverage of the sequence space using 3D-SCAfold for enhanced structure-based annotations with a specific focus on disease genotype data from human disease and pathogen proteins (e.g. SARS-CoV-2, Mycobacterium tuberculosis).
Develop novel visualisation tools, and a collection of aggregated views.
|
| 27/07/2021 |
£659,982 |
|
UNIVERSITY COLLEGE LONDON |
Our goal is to establish and validate a non-invasive imaging system capable of concurrently mapping brain and spinal cord electrical activity, non-invasively, at millisecond temporal resolution, during natural movement.
The proposed system will exploit novel magnetic sensing technology in the form of optically pumped magnetometers (OPMs). Using this technology, we have successfully developed a 100 channel wearable optically pumped magnetoencephalography (OP-MEG) system in a dedicated laboratory and shielded room at UCL. With OP-MEG, we have demonstrated that it is possible to make reliable measures of human brain function, even under challenging conditions such as participant movement or mapping deep structures, e.g. cerebellum or hippocampus. Yet all of this has been achieved with precision exceeding conventional MEG technology.
Building on this experience, we will augment OP-MEG with the ability to simultaneously record from the spinal cord – something that is not possible with existing technologies. The proposed wearable magneto-encephalography and spinography (MESG) system would be a world first. Concurrent imaging of brain and spinal cord electrophysiology, during natural human movement, and in diverse patient groups, would offer unprecedented opportunities for basic and clinical investigation of the human central nervous system in its entirety.
|
| 27/07/2021 |
£928,849 |
|
ROSALIND FRANKLIN INSTITUTE |
We will address the urgent and unmet need within the biomedical community for effective agents to combat the existing threat from coronaviruses and to be prepared for those that will arise in the future. We will also deliver a pipeline that will be applicable to other high threat respiratory viruses (Disease X). We propose to build a nanobody screening strategy that targets cross-reactivity from which we anticipate identifying (pan)-coronavirus binders. The pipeline will combine nanobody technology, structural biology and virology making use of the Diamond synchrotron at Harwell for X-ray data collection and the CL3 facilities in Oxford and Liverpool for handling live viruses. Together the results will enable the structure-activity relationships of anti-coronavirus nanobodies to be determined providing information that will guide sequence changes to increase nanobody binding and counter the effects of virus escape mutants or natural variants on virus detection and neutralisation. The demonstration of in vivo potency to SARS-CoV-2 and other than coronaviruses(cross therapeutic) is a key aim of the proposal and we will test any new potent neutralising nanobodies in an appropriate disease model.
|
| 27/07/2021 |
£1,435,494 |
|
UNIVERSITY OF BIRMINGHAM |
Membrane proteins provide a multitude of functions essential to the life of the cell, and yet extracting them in an active form remains exceptionally challenging. In recent times an amphiphilic polymer, poly(styrene-co-maleic acid) (SMA) has gained significant traction as an effective agent for extracting and stabilising membrane proteins in phospholipid nanodiscs. Unlike conventional methods based on detergents, the method also extracts the lipids surrounding the protein, helping to preserve native activity. Although the original SMA polymer provided a good solution for demonstrating the utility of this approach it is becoming increasingly clear that further development of the polymer is required to fully capitalise on the unique aspects of the method.
This project aims to address this by providing a technical resource for the community for generating improved, bespoke polymers matched to end users need allowing them to:
1) Tune the lipid environment within the nano-particle to optimise protein activity by introducing a variety of comonomers, including aromatic, linear aliphatic and branched aliphatic into the established maleic anhydride copolymer
2) Harness functionalised plug-n-play polymers that allow researchers to easily modify the polymers for downstream applications
These polymers will be tested by the community and delivered through an integrated commercial supply chain.
|
| 27/07/2021 |
£1,561,404 |
|
DIAMOND LIGHT SOURCE LTD |
We propose a Membrane Protein Laboratory (MPL) as a national resource focused on integrating, developing and harnessing new technologies to drive membrane protein biomedicine and structural biology. This proposal will build upon 15 years of MPL research excellence, technical developments at Diamond Light Source, and complement the strategic aims of Diamond-II and the Rosalind Franklin Institute. Integrative in situ outcomes spanning atomic to cellular scales will be central to technologies developed including time-resolved structural biology for drug discovery, single-particle and live-cell imaging. The MPL experimental platforms located in the Research Complex at Harwell (RCaH) will be vital to these efforts, delivering biomedically important membrane protein samples to drive technological developments, create new access routes for Diamond users and engage experts on the Harwell campus with the wider membrane protein community. Through an integrative technologies user access programme, we will support challenging, high-impact projects that have exhausted current strategies. Rapid-access proposals and INSTRUCT-ERIC (European Infrastructure for Integrated Structural Biology) will support MPL facilities access for the wider membrane protein community. In parallel Diamond and the Franklin will work with the MPL to establish a sustainability plan to enable core MPL activities to be independent of responsive mode funding.
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| 27/07/2021 |
£1,560,057 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
DECIPHER’s mission is to lead an international collaborative effort to collect, annotate, share and aggregate genotypic and phenotypic data on rare disease patients in order to catalyse the discovery of new disorders and to improve clinical diagnostic interpretation of genome variation. It is the only online data-sharing platform which provides live, rich contextualisation of genomic variation and phenotype data in patients undergoing research and diagnostic testing globally, including for underserved areas of the world. Since 2004, collaborating rare disease genomics projects and clinical genetic diagnostic centres have uploaded and openly shared consented data on more than 38,000 patients.
Our plans to improve DECIPHER include driving increased global sharing and aggregation of clinical and research data; integrating relevant new research datasets to accelerate discovery science; developing functionality to support variant interpretation of the non-coding genome; and improving gene-phenotype-disease modelling to drive discovery research and drug development.
We will migrate DECIPHER from the Wellcome Sanger Institute to EMBL's European Bioinformatics Institute (EMBL-EBI), taking advantage of EMBL-EBI's rich resource environment and expertise in delivering web services and training. DECIPHER will operate and grow in an efficient and sustainable manner, providing an essential bridge to research resources to strengthen their clinical impact.
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| 27/07/2021 |
£1,385,864 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
SureChEMBL is a large-scale, fully automated, chemical-structure-enabled database providing the research community with open, free and FAIR access to the patent literature. SureChEMBL contains ~140 million patents with ~50,000 added monthly. Of these, ~50 million patents are chemically annotated with more than 20 million unique chemical structures. Around 80,000 new compounds are extracted and stored monthly. The data in SureChEMBL can currently be accessed via a web interface that enables users to perform text and chemical structure queries, filter the output and then display the results. The complete set of chemical structures and patent associations are also available for download.
In this proposal we plan to significantly enhance SureChEMBL, enabling a wider selection of questions and use cases to be addressed, by: expanding annotations to include biological entities; developing methods to assess the relevance of information identified in patents and enable more accurate data retrieval and analysis; significantly improving the technical infrastructure and web interface with enhanced stability and usability; providing programmatic access through development of a RESTful application programming interface (API). The new, upgraded SureChEMBL will provide the broader life sciences research community with unparalleled access to a large and rich source of information and knowledge.
|
| 27/07/2021 |
£237,623 |
|
UNIVERSITY OF SOUTHAMPTON |
We will generate saturation transposon mutagenesis libraries of human pathogenic Chlamydiae (C. trachomatis (trachoma and LGV) and C. pneumoniae) and the 'model' species C. muridarum using TraDIS methodology. This approach has been successfully developed during my current Technology Development Grant with urogenital C. trachomatis. We have now refined the method so it will be straightforward to apply to other species, the application of the technology to generate a new series of key resources will greatly accelerate research. Our ultimate aim is to develop an ordered library of mutated/knock-out chlamydia isolates akin to the E. coli Keio collection. These mutants (knock-outs of non-essential genes) will be genome-sequenced in Southampton to mitigate off-target mutations. The collections will provide a unique and important biomedical resource, along with the saturation mutagenesis libraries and transposon delivery vectors. The transposon delivery vectors will form the basis for the development of further vectors for other chlamydial species. All resources generated during this project will be made available to the research community via the Chlamydia Biobank (www.chlamydiabiobank.co.uk) (BMR 101502/Z/13/Z). This will enable other researchers to test their hypotheses in the pursuit of gene function ascertainment - a critical step in identifying novel targets for drug or vaccine development.
|
| 27/07/2021 |
£919,761 |
|
UNIVERSITY OF BRISTOL |
We have created a prototype system – "U-RHYTHM" (Fig 1) – which enables, for the first time, circadian and ultradian rhythms to be investigated in free-moving individuals in their own home or work environment. Now that we have regulatory guidance from the MHRA Innovation Office that we can provide other centres with our current U-RHYTHM system for research use, we want to work with scientists from different research communities to enable them to develop important new lines of research for which there are no current enabling methodologies. We now need:
a) A much more user friendly version of U-RHYTHM that can be readily used both by the research
community and clinicians. The current version is very reliable in experienced hands but needs
specially trained personnel and would not be suitable for commercialisation.
b) To demonstrate its value in three new specialties:
Chronobiologists using its ability to measure dynamic changes in tissue metabolome, melatonin and glucocorticoids
Cardiovascular scientists who can utilise our ability to measure catecholamines, aldosterone and cortisol to improve diagnosis and pathophysiological understanding of hypertension.
Inflammation biologists needing to measure dynamic changes in tissue inflammatory mediators.
|
| 13/07/2021 |
£197,441 |
|
UNIVERSITY OF EXETER |
The project tackles the question of how digital technologies (DTs) are being adopted and adapted throughout the pork production and consumption process in China.
It explores the opportunities and challenges of using DTs, their effect on disease management practices, and their implications for food safety and OH challenges in Shanghai, Zhejiang and Jiangsu.
The project analyses the current conditions (behavioural, regulatory, economic and material) and interactions (institutional, human-animal) that drive or hinder the adoption and adaptation of DTs. It scrutinises how political and scientific discourses about the adoption of DTs are constructed, valued, and promoted to shape the uptake of DTs, and how DTs are being adopted, by whom, for what purposes, and to what effect.
The project focuses on farmers, vets, policymakers, high-tech companies, retailers and consumers to understand how the uptake of DTs transforms farmers’ and vets’ behaviours expedite a reduction in antimicrobial use, and how the adoption of DTs affects consumer and market practices.
The project adopts ethnographic approaches to examine the adoption of DTs by employing document analysis, in-depth interviews, participant observation and mapping methods to engage with key participants, thereby producing a geographically-specific dataset to advance the field and policies of OH and digital farming.
|
| 13/07/2021 |
£190,287 |
|
UNIVERSITY COLLEGE DUBLIN |
Keywords: Heroin, drugs, Ireland.
By 1990 heroin had devastated working-class communities across Dublin and, in some families, wiped out entire generations. But how did things reach that stage when three decades previously heroin was only known in Ireland as a symbol of distant, undesirable, foreignness?
This project will explore the history of heroin in Ireland, from its first public discussion (1918) to the end of the first heroin epidemic (1990). It will approach the history from two directions. First, analysing the public discourse about the drug. This will reveal, inter alia, different ways that heroin was used as a symbol of dissolute otherness, and how this shaped health policy and provision. Secondly the project will collect 100 oral histories to investigate how heroin affected everyday life in the communities at the centre of the heroin epidemic of the 1970s and 1980s. Finally, the project will use reception theory to integrate these approaches and achieve three key goals:
To understand how the public discourse shaped community members’ interaction with each other, the wider world, and healthcare providers.
To give marginalised communities a voice in the production of their own history.
To produce the first history of heroin-use in Ireland.
|
| 13/07/2021 |
£165,923 |
|
UNIVERSITY OF DURHAM |
This project is the first in-depth geographic examination of relationships between fatness, masculinities, and everyday life of diverse Filipino men situated in the uneven urban geographies of Metro Manila in the Philippines. Drawing hybrid connections from contemporary work on critical fat studies, critical masculinities, and Southern urban political ecology, I investigate urban cityscapes as complex obesogenic environments that shape the subjective experiences and everyday embodiment of fat amongst men. My approach combines textual and image-based analyses of ethnographic interviews to articulate the multiple ways by which fat is embodied in everyday practices of fitness and leisure as well as food and diet. Recognising the distinct contexts wherein Filipino masculinities are constructed, the overall goal of the project is to deepen situated knowledges of fat and masculine politics as integral to the reproduction, contestation, and transformation of urban ecologies.The importance of this intellectual intervention is aimed towards transforming gender and fat politics and rebuilding everyday equitable and holistic health among diverse groups of men in the city.
|
| 13/07/2021 |
£245,064 |
|
GOLDSMITHS, UNIVERSITY OF LONDON |
This research project is an inquiry into how caste structured medical discourses on alcohol between 1860 and 1950 in colonial South India. It examines the conceptualization of two local drinks, toddy and arrack as contaminating within medical theories and tracts that produced stigma. It focuses on two communities, Adi-Andhras and Adi-Dravidas (Telugu and Tamil speaking Dalits) in Madras Presidency as they bore intense forms of stigmatization. It examines the part played by medical ‘publics’ and ‘counter-publics’ – where the former served as liberal sites for voicing public opinion and the latter as forums for oppositional discourses of subordinated groups – in consolidating and contesting caste stigmas around alcohol. It investigates processes by which medical publics composed of surgeons, chemists, missionaries, Congress nationalists configured these two communities as polluted agents of drink. It critically inquires into multiple public health pedagogies employed by counter-publics comprised of Dalit communities who fought to purge themselves of alcohol-driven stigmas. The project explores the empowering possibilities of medical discourses on alcohol when driven by a regionally and globally informed Dalit social consciousness. While grounding Indian debates, it delves into how concepts of ‘publics’, ‘counter-publics’ and ‘stigma’ travelled across global drinking cultures and medical landscapes of alcohol.
|
| 13/07/2021 |
£197,042 |
|
UNIVERSITY OF LEEDS |
This project will establish the fundamental methods for the study of Byzantine disability, an area that has received almost no attention. Focusing on two pillars of power, the Church and the Court, it will examine how representations of diverse human capacities and appearances, including restricted mobility, blindness, and dwarfism, changed between 1000 and 1200, depending on gender, race/ethnicity, social and religious status. It will reveal how norms of able-bodiedness were reproduced, while emphasising the potential for disability gain that arose from disabled bodies and their relational configurations with other humans, animals, and technology.
This project will expose ableist historiographical assumptions by uncovering the beneficial effects of a Church that valued spiritual sensation above the physical senses and a Court in which the bodies of powerful emperors and eunuchs disrupted expectations of perfection and integrity. More broadly, it will examine what Byzantine disability can tell us about what it means to be human, focusing on the place of autonomy/heteronomy in a world that was more connected with animals than our own.
These Byzantine findings will be placed in dialogue with Classical and Western medieval sources, challenging existing understandings of premodern disability and creating new avenues for interdisciplinary work.
|
| 13/07/2021 |
£195,286 |
|
UNIVERSITY OF STRATHCLYDE |
The illegal drug Ecstasy (3,4-Methylenedioxymethamphetamine (MDMA)) arrived in Britain in the mid-1980s. Initially associated with, and assumed to be a catalyst for the nascent ‘rave’ scene, by the mid-1990s Ecstasy had transcended its subcultural origins and was a mass intoxicant. Despite government campaigns, harm reduction programmes, and the high-profile deaths of young people such as Essex teenager Leah Betts, by the turn of the millennium Ecstasy had joined the ranks of alcohol and cocaine as ‘party’ intoxicants that were a feature of British nightlife and leisure activities.
This project places consumers and consumption at the heart of an original historical account of the impact and legacy of this novel psychoactive substance. Using a combination of archival research and oral histories to explore representations of Ecstasy by public health and medical circles, in mainstream media, and in wider cultural discourse, it promises important new perspectives on how far consumers drive markets for psychoactive substances in contemporary societies. It brings recent developments in the history of emotions into investigations of drugs and intoxicants for the first time. Finally, it will take these conclusions about Ecstasy consumers into debates about the changing relationships between ‘pleasure’, ‘risk’ and ‘health’ in Britain since the 1980s.
|
| 13/07/2021 |
£375,164 |
|
UNIVERSITY COLLEGE LONDON |
The NHS is challenged to provide effective psychological services for traumatised populations. Iranians comprise the largest number of asylum seekers in the UK, with some having experienced torture, which results in enduring psychological distress for the victims.
This study aims to improve mental health services for traumatised refugees by exploring moral injury from the perspective of Iranian torture survivors.
Moral injury, a concept for survivors’ responses to the transgression of their moral beliefs, seeks to address trauma’s lasting impacts – examples are loss of a sense of self-worth, and the belief in a benevolent world as well as mistrust in all forms of relationships. This concept, however, lacks empirical data from victims and refugees.
I will undertake a phenomenological study to explore the impact of morally injurious events in Iranian torture survivors in the UK. Using snowball sampling, I will recruit and collect life-history narratives. This will be followed by focus groups with healthcare professionals and support workers to determine the clinical and policy implications of moral injury.
The findings will contribute to a culturally sensitive approach to therapy for torture survivors. To influence policy and practice, the advisory group will include torture survivors, trauma experts, and refugee community organisations.
|
| 13/07/2021 |
£238,155 |
|
UNIVERSITY OF EDINBURGH |
This comparative research investigates how care relationships and identities are (re)configured through the development and use of Socially Assistive Robots (SARs) by tracing AI and robotics innovation for care from the laboratory to final users, and focusing on embodied experiences of SARs across different cultural contexts. The study lies at the intersection between medical sociology, anthropology and STS, while scrutinising how robots may be used to assist a range of healthcare workers. It investigates: (1) the ways in which emotionality and sociability are being algorithmically configured in SARs; (2) how care recipients do and might perceive and respond to such algorithmic sociability, and what aspects of human care relationships they may want robots to mirror; (3) how our understandings of the role and value of human care may influence the development of SARs - and how might such care in turn be influenced, as ‘caring machines’ come into our world. This research will create knowledge of how SARs may shape and be shaped by different understandings of the role and the value of human care, and potentially transform how care is understood, approached, managed, and experienced. Ultimately it will contribute to conceptual frameworks needed to analyse and understand these transformations.
|
| 13/07/2021 |
£1,905,653 |
|
UNIVERSITY OF GLASGOW |
Malaria remains a major global health threat with over 200 Mio cases and 400’000 deaths annually, the majority of them due to infection by Plasmodium falciparum. Malaria elimination depends on strategies to eliminate the parasite reservoir and prevent its onward transmission to mosquitoes. Production of transmission stages (or gametocytes) is variable across parasite species and strains, conditions as well as being environmentally sensitive. Studies in P. falciparum revealed that epigenetic mechanisms regulate the plasticity in gametocyte production in response to changes in the within-host environment. Specifically, we discovered that limiting levels of the serum phospholipid LysoPC are translated into transcriptional upregulation of alternative metabolic pathways for phosphatidylcholine biosynthesis and the transcription factor ap2-g. Epigenetic activation of the transcription factor, ap2-g in turn triggers the transcriptional program for sexual development. LysoPC is an immune metabolite and reduction in systemic LysoPC levels is the result of inflammation, for example due to acute malaria. How exogenous LysoPC levels regulate both, expression of metabolic enzymes and the epigenetic switch underlying stage conversion in the parasite is the subject of the current proposal.
|
| 13/07/2021 |
£3,743,939 |
|
UNIVERSITY OF OXFORD |
The development of improved therapies for Parkinson’s disease (PD) requires new knowledge of why certain types of neuron dysfunction and die. Midbrain dopaminergic neurons (DANs) are particularly impacted by PD, and offer valuable opportunities for comparative investigations of factors underpinning vulnerability. Our interdisciplinary collaboration will address the overarching hypothesis that compartmentalised, activity-dependent Ca2+ handling in DANs is cell-type-specific, perturbed by disease burden, and contributes to preferential vulnerability in Parkinson's.
We will collectively deliver a step change in the understanding of calcium dynamics and related dopaminergic signalling in DANs. We will be the first to define cytosolic and organellar calcium dynamics throughout the whole extent of DANs during physiologically-relevant activity patterns. Our programme brings together leading scientists with complementary expertise, and integrated experimental platforms spanning mouse models and human stem cell-derived models, to identify the key mechanisms involved. Progressing from correlation to causation in the contexts of health and PD, we will define how and when calcium enters susceptible and resistant DANs, its handling by organelles in light of their other functions, and the importance of compartmentalised calcium for how DANs cope with PD burden. Our collaborative approach is strongly positioned to transform understanding of selective neuronal vulnerability in PD.
|
| 13/07/2021 |
£1,598,460 |
|
UNIVERSITY OF BIRMINGHAM |
I will test the hypothesis that a shared molecular mechanism drives brain structural plasticity and degeneration throughout life. Structural plasticity enables the brain to adapt to the environment, whereas structural homeostasis constrains change. This balance breaks down in brain disease – psychiatric, neurodegenerative - and aging, and stressors such as isolation, lack of stimulation and stress cause a degenerative drive. Discovering the molecular and circuit mechanisms underlying experience-dependent plasticity and degeneration, and their link to behaviour, is urgently needed to understand human brain health.
Building on my discovery of the Drosophila neurotrophin system – comprising neurotrophins, Tolls and kinase-less Trk-like Kek receptors – I will use Drosophila to link molecules, neural circuit modification and behaviour.
I will ask:
How does experience and behaviour alter the brain?
What is the molecular switch between structural plasticity and neurodegeneration?
Key goals are:
(1) To establish a molecular mechanism regulating structural brain plasticity, focusing on DNT-2 and -3 and their circuits involved in sensory experience, motor output and neuromodulation.
(2) To test a key molecular switch between structural plasticity and degeneration, focusing on Wek.
(3) To test and reverse with DNTs a neurodegenerative drive caused by isolation, immobility and lack of stimulation.
|
| 13/07/2021 |
£1,718,251 |
|
UNIVERSITY COLLEGE LONDON |
Allergic reactions to food and environmental substances affect more than 40% of the UK population, resulting in a major health burden and potentially fatal anaphylaxis. Many of the clinical symptoms are caused by overproduction of allergen-specific IgE antibodies. Interestingly, the IgE responses are normally low, transient and lack classical immunologic memory. Using new genome-wide approaches, we have discovered molecular mechanisms, which naturally inhibit the differentiation of IgE-switched B cells into antibody-secreting cells and limit their lifespan. These inhibitory mechanisms are triggered by spontaneous intracellular signalling by the IgE B cell receptor expressed on the surfaces of IgE-switched B cells and plasma cells and are different from the control of other antibody isotypes. We hypothesise that this suppressive signalling defines the self-limiting character of IgE responses and that its failure contributes to allergic disease. We will investigate this by elucidating the molecular mechanisms and dynamics of this signalling, and by determining its role in responses to allergens and in primary hyper-IgE syndromes. Our comprehensive characterisation of the molecular pathways underlying the behaviour of IgE-switched cells will illuminate the unique character of IgE responses and provide new therapeutic targets to selectively inhibit IgE production in allergic disease.
|
| 13/07/2021 |
£1,387,077 |
|
UKRI-MRC |
AMPA receptor (AMPAR) operation underlies learning, while receptor malfunction is associated with various diseases. Their uniquely versatile signalling arises from numerous auxiliary subunits that assemble into functionally diverse receptor super-complexes. The combination and stoichiometry of these components, and how they shape neuronal response properties, remains a central open question.
We will elucidate the pathways leading to activation of a predominant AMPAR, building on our cryo-EM structures of this receptor, associated with two structurally diverse auxiliary subunits. Using cryo-EM, MD simulations and single-channel recordings, we will assess the differential contribution of core- and auxiliary subunits to the receptor’s characteristic activation time course.
We will also investigate the mechanism of leading neurotherapeutics on gating, capitalising on our AMPAR structures associated with these ligands, and study the role of the receptor’s lipid environment through reconstitution into liposomes. We will complement these studies with time-resolved cryo-EM of gating intermediates, and structures of native AMPAR complexes, isolated from mammalian synapses.
These experiments will uncover the principles underlying AMPAR organisation and activation. We will derive a comprehensive kinetic model, delineating how activation is modulated by auxiliary subunits, lipids and neurotherapeutics. Elucidating the conformational states selectively targeted by these ligands will facilitate targeted structure-based drug design.
|
| 13/07/2021 |
£1,619,132 |
|
THE FRANCIS CRICK INSTITUTE |
Toxoplasma gondii infects any nucleated cell of any warm-blooded animal and ~30% of the human population. Why some Toxoplasma strains cause disease in humans but not in other species and vice versa is poorly understood, but linked to effector proteins the parasite secretes to remodel its host cell. A substantial proportion of host cell remodelling occurs on the transcriptional level, but which of Toxoplasma’s ~200 putative effector proteins mediate these changes, and how they affect different cell types and hosts is largely not known. We will use a novel technology we devised (EffectorSEQ) to correlate host cell transcriptomic changes to infection by various Toxoplasma mutants in a highly multiplexed manner. We will i) identify most, if not all, Toxoplasma effectors important for host cell transcriptional responses in different cell types and species and ii) use bioinformatics approaches to identify those that promote anti-inflammatory immune responses. iiI) We will investigate in detail the effector proteins that change infected immune cells signalling behaviour and thereby promote an immune environment that favours parasite growth and pathogenesis. Our result will lead to a comprehensive understanding how this important pathogen infects and causes disease in such a broad host range.
|
| 13/07/2021 |
£1,810,041 |
|
KING'S COLLEGE LONDON |
Macrophages are best known for their immune functions, but they also play important roles in development and tissue homeostasis – often referred to as trophic functions. There are two distinct lineages of macrophages that populate mammalian tissues; embryo-derived tissue-resident macrophages (TRM) maintain themselves in adult tissues by proliferation and self-renewal and coexist with monocyte-derived macrophages (MDM) from adult bone marrow. We recently showed that TRM form a niche that promotes the metastatic spread of cancer cells, suggesting TRM have specific functions linked to tumour progression. We hypothesise that TRM maintain hard-wired trophic functions that support the malignant progression of cancer cells and tumorigenesis. It’s therefore critical to determine the unique features of TRM and the mechanisms that maintain their homeostasis and functional programming during tumour development. In this project we will perform high-dimensional single cell analysis of TRM in mouse models and human cancer. We will develop new genetic tools to dissect the specific functions of TRM during tumorigenesis and the mechanisms that maintain their homeostasis and functional programming. These studies will give new insights into the biology of TRM and their roles cancer that may reveal new targets for therapeutic intervention.
|
| 13/07/2021 |
£1,416,647 |
|
UNIVERSITY OF EXETER |
This research will use novel insights from genomic analysis of individuals with congenital hyperinsulinism to provide new mechanistic understanding of the regulation of insulin secretion. Through preliminary studies I have identified non-coding mutations that affect the regulation of HK1, a housekeeping gene which is silenced within the beta-cell. These mutations pinpoint the first element to be discovered that regulates beta-cell specific silencing and highlights the role of ‘disallowed’ genes in pathophysiology.
To discover further regulatory mutations affecting the expression of a beta-cell ‘disallowed’ gene I will integrate genomic data with epigenomic annotation in my unique cohort of ~2000 hyperinsulinism patients with known causes excluded. I will study the impact of mutations in affected pancreatic tissue to gain insights into 1) the mechanism(s) by which they disrupt insulin-secretion and 2) the regulatory networks that are critical for maintaining tissue-specific suppression of genes. The results from these studies may be leveraged to discover novel targets to better treat hyperinsulinism and will improve knowledge of the role of the non-coding genome. This will be important for genetic discovery in other monogenic conditions where the major focus has been on the discovery of coding mutations in genes highly expressed within the disease tissue.
|
| 13/07/2021 |
£2,002,780 |
|
UNIVERSITY OF EDINBURGH |
Background: rapid advances in our understanding of psychiatric disorder genetics within European ancestries are leading to mechanistic insights, more accurate risk stratification and stronger causal inferences, but there is growing concern that these findings may not generalise to African ancestries and those who reside in low and middle income countries. We need to urgently address this knowledge gap if we are to reduce growing health disparities.
Vision: drawing on the substantial strengths of the UK Psychiatric Genomics Consortium (PGC) and a network of African investigators, we will develop processes for rapid sample collection and address critical scientific and clinical questions about the genetic architecture of depression in non-European populations.
Research plans: using state-of-the-art ancestry-aware genetic methods, we will address whether the genetic architecture of major depressive disorder in different African countries is similar and whether it mirrors that of European ancestry populations. We will develop a network of UK and African partners in the best clinical research practices. We will adopt a pragmatic approach to data collection and analysis through a combination of new sample collections and genotyping and analysing existing samples; building capacity at each stage of the research process.
|
| 13/07/2021 |
£1,031,556 |
|
KING'S COLLEGE LONDON |
Background: rapid advances in our understanding of psychiatric disorder genetics within European ancestries are leading to mechanistic insights, more accurate risk stratification and stronger causal inferences, but there is growing concern that these findings may not generalise to African ancestries and those who reside in low and middle income countries. We need to urgently address this knowledge gap if we are to reduce growing health disparities.
Vision: drawing on the substantial strengths of the UK Psychiatric Genomics Consortium (PGC) and a network of African investigators, we will develop processes for rapid sample collection and address critical scientific and clinical questions about the genetic architecture of depression in non-European populations.
Research plans: using state-of-the-art ancestry-aware genetic methods, we will address whether the genetic architecture of major depressive disorder in different African countries is similar and whether it mirrors that of European ancestry populations. We will develop a network of UK and African partners in the best clinical research practices. We will adopt a pragmatic approach to data collection and analysis through a combination of new sample collections and genotyping and analysing existing samples; building capacity at each stage of the research process.
|
| 13/07/2021 |
£960,918 |
|
CARDIFF UNIVERSITY |
Background: rapid advances in our understanding of psychiatric disorder genetics within European ancestries are leading to mechanistic insights, more accurate risk stratification and stronger causal inferences, but there is growing concern that these findings may not generalise to African ancestries and those who reside in low and middle income countries. We need to urgently address this knowledge gap if we are to reduce growing health disparities.
Vision: drawing on the substantial strengths of the UK Psychiatric Genomics Consortium (PGC) and a network of African investigators, we will develop processes for rapid sample collection and address critical scientific and clinical questions about the genetic architecture of depression in non-European populations.
Research plans: using state-of-the-art ancestry-aware genetic methods, we will address whether the genetic architecture of major depressive disorder in different African countries is similar and whether it mirrors that of European ancestry populations. We will develop a network of UK and African partners in the best clinical research practices. We will adopt a pragmatic approach to data collection and analysis through a combination of new sample collections and genotyping and analysing existing samples; building capacity at each stage of the research process.
|
| 13/07/2021 |
£1,659,251 |
|
UNIVERSITY OF EDINBURGH |
My work during the Covid outbreak has shown that genetic associations with critical illness can predict therapeutic targets, and that therapies targeting the host response improve outcome in carefully-defined subgroups of critically ill patients. I propose to extend this work to bridge the gap between genetic discovery and therapeutic application. In doing so I will build on established infrastructure and lay the foundations of a system for rapid identification and assessment of candidate drugs for respiratory critical illness. To achieve this I will:
Use genome-wide association studies to identify host genes associated with critical illness in viral pneumonia (Covid-19: 20,000 cases; influenza: 3000 cases).
Identify targets using computational approaches including integrated functional genomics and Mendelian randomisation.
Complete proof-of-principle analysis to test for differential genetic effects in new patient subgroups.
Refine and test candidate causal variants in vitro.
Establish technology for distal lung regional microdosing to validate targets in vivo in critically ill humans.
At the end of this fellowship I will have established a programme of translational genomics in critical care medicine going from genomic discovery to experimental medicine in humans.
|
| 13/07/2021 |
£1,764,240 |
|
UNIVERSITY OF OXFORD |
The endoplasmic reticulum (ER) is the largest membrane-bound organelle in cells, playing numerous essential functions including the biogenesis of secreted and membrane proteins, lipid synthesis and assembly of the nuclear envelope. A long-term goal of my lab is to dissect how these functions are coordinated and ER homeostasis achieved. Proteolysis through the ER-associated degradation (ERAD) pathway has emerged as key in maintaining ER homeostasis and this proposal aims at understanding its mechanistic basis, with a particular focus on membrane protein substrates.
ERAD is organized in multiple branches, thereby targeting a broad range of luminal and membrane substrates. The mechanisms by which luminal substrates are selected and processed by the ERAD machinery are well established. In contrast, the mechanisms by which ERAD targets membrane substrates are mysterious and several fundamental questions remain: (1) what are the preferences of the various ERAD branches for membrane substrates? (2) what are the molecular basis for their recognition? (3) how are membrane substrates translocated to cytosol for degradation? Addressing these issues will reveal key mechanisms of membrane protein quality control by ERAD. Given that defects in protein quality control are linked to various pathologies, from developmental diseases to neurodegeneration, our studies may have clinical relevance.
|
| 13/07/2021 |
£1,791,993 |
|
UNIVERSITY OF OXFORD |
Neuropathic pain (NeuP) affects almost 10% of the general population and current therapies are inadequate. Ion channels are key determinants of excitability within the sensory nervous system and so are attractive therapeutic targets. We need to understand the mechanisms by which ion channels drive hyper-excitability and NeuP in humans. Ion channel variants have been associated with rare Mendelian pain disorders; we have recently found that variants in ion channels also act as risk factors for more common NeuP disorders such as painful diabetic neuropathy. I will investigate ion channels (and their variants) identified from human genetic studies of NeuP. These will include voltage-gated sodium channels and, recently implicated targets, such as channels which maintain neuronal homeostasis in response to sodium. I will determine how these genes regulate excitability within the sensory nervous system and their interaction with environmental stressors (such as extremes of temperature) using electrophysiology, human-iPSC and animal models. These models will also provide a platform in which to screen potential treatments. I will explore the relationship between pathogenic variants, clinical and sensory phenotype. This will lead to new understanding of the pathophysiological mechanisms driving NeuP, facilitating identification of new treatment targets and better targeting of existing therapies.
|
| 13/07/2021 |
£3,723,378 |
|
UNIVERSITY COLLEGE LONDON |
This project will reveal how neural activity is structured in brainwide patterns to support diverse behaviors, using powerful techniques that record and interpret the activity of a myriad individual neurons. The brain is a high-dimensional system, but coarse measurements of macroscopic brain activity - from EEG, fMRI, LFP, and widefield imaging - reveal a surprisingly simple low-dimensional structure. By recording from large neuronal populations across the mouse brain we will determine: 1) how macroscopic activity patterns are organized across brain structures at the level of individual neurons and neuronal cell classes; (2) how they interact with the high-dimensional activity patterns that encode sensory signals, and modulate the transmission of signals across brain regions; (3) how they depend on the performance of different behaviors, and evolve over time as animals learn a task. The results will provide a new understanding of how neural activity is organized across a myriad individual neurons into the brainwide patterns that shape behavior.
|
| 13/07/2021 |
£1,896,758 |
|
THE FRANCIS CRICK INSTITUTE |
Cancer immune control relies on cytotoxic T cells that are primed against tumour antigens by crosspresenting type 1 conventional dendritic cells (cDC1s). We have found that the cDC1 receptor, DNGR-1, promotes crosspresentation of dead cell-associated antigens through a novel cell biological mechanism that involves signalling for phagosomal rupture. We propose to screen for further components of the DNGR-1–phagosomal rupture pathway with a view to harnessing them in anti-cancer immunity. Notably, DNGR-1 detects dead cells by binding to F-actin exposed by cell corpses, an activity opposed by secreted gelsolin (sGSN) circulating in plasma or produced by cancer cells. We will examine how the interplay between DNGR-1 and sGSN regulates anti-tumour immunity, including testing the hypothesis that DNGR-1-mediated crosspresentation selects tumour neoantigens associated with the actin cytoskeleton. Finally, as cDC1 are rare in tumours, we will assess the benefit of broadening DNGR-1 expression to other myeloid cells, either genetically or chemically. The latter will involve arming Fcgamma receptors, which may also signal for phagosomal rupture, with the DNGR-1 extracellular domain. Altogether, the proposed work will reveal fundamental mechanisms by which the antigenicity of dead cells is translated into anti-tumour responses and suggest avenues to exploit these mechanisms for cancer therapy.
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| 13/07/2021 |
£2,099,101 |
|
WELLCOME SANGER INSTITUTE |
BACKGROUND
Despite impressive progress over seven decades, the prognosis of many childhood cancers has now stalled. Novel treatments are required, which may be derived by studying the foetal origin of childhood cancer. My goal is to provide an exact phylogenetic and quantitative molecular understanding of the roots of childhood cancer that may be clinically exploited, for example, by revealing foetal specific antigens, mechanisms of subverted differentiation, or markers for screening.
HYPOTHESIS & QUESTIONS
My overarching hypothesis is that childhood cancer formation represents a perturbation of human development that extends beyond individual cells, which I will address through two questions:
(i) Do childhood cancers arise from pre-cancerous clonal expansions?
(ii) Do embryonic cancer-disposed lineages contribute to non-transformed tissues?
APPROACH
I will reconstruct from resection and post-mortem tissues the embryonic phylogeny of tumours from somatic DNA mutations and interrogate the molecular differences between normal, pre-cancerous, and cancerous tissues through mRNA and methylation sequencing at the resolution of individual histological units.
ANTICIPATED OUTCOMES
This work will reveal embryonic precursors of specific tumour types and molecular features of malignant transformation. Moreover, it will provide a blueprint for studying the origin of the entire spectrum of childhood cancers and other genetic developmental diseases.
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| 13/07/2021 |
£2,019,718 |
|
THE FRANCIS CRICK INSTITUTE |
A relatively small number of proteins have been suggested to act as morphogens, molecules that spread within tissues to organize cell fate decisions and tissue repair. Among them are Wnt proteins, which, surprisingly for signalling molecules, are relatively insoluble because of a palmitoleate moiety that is essential for signalling activity. A number of proteins are dedicated to Wnt secretion and transport in the extracellular space. In particular, Wntless escorts Wnt from the ER to the cell surface, and Dlp-class glypicans shield the Wnt lipid in the extracellular space before it engages with signalling receptors of the Frizzled family. We will combine structural, biophysical, and genetic approaches to characterise the key interactions that Wnt proteins and their lipid engage with during this journey. Thus, we will determine how Wnts are released from Wntless in secreting cells and allowed to form a complex with Dlp-class glypicans. We will determine the glycosaminoglycans that support the formation of the Wnt-glypican complex before elucidating the complex’s structure and identifying the key determinants of affinity. These measurements will lead to a mechanistic understanding of Wnts’ extracellular transport and subsequent hand-over to Frizzleds and form the foundation of a realistic mathematical model of Wnt gradient formation.
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| 13/07/2021 |
£4,055,445 |
|
UNIVERSITY OF CAMBRIDGE |
Efficient brain network computations rely on suppressing cell excitation—a process known as inhibition that involves neurotransmitter activity. GABA is the primary inhibitory neurotransmitter in the brain and is known to play a key role in learning and brain plasticity. Yet, our understanding of the role of GABA in regulating the brain network dynamics that support learning has been hampered by technology limitations and a fundamental disconnect between work in animal models and humans. To tackle this challenge, we propose an integrated work programme that bridges across species (mice, humans) and scales (local circuits, global networks).
We will a) match behavioural training protocols in humans and mice, focusing on perceptual learning, b) validate non-invasive Magnetic Resonance Spectroscopy (MRS-GABA) imaging capitalising on the precision afforded by neuroengineering tools (optical GABA sensors, electrophoretic GABA/drug delivery), c) combine GABA imaging with calcium imaging and electrophysiology to test the link between GABAergic inhibition and network activity, d) marry modelling and interventions (optogenetics, neuropharmacology) to test the mechanistic functions of inhibitory brain networks.
Our work programme will 1) advance understanding of the inhibitory brain dynamics that mediate learning across species, 2) decipher the origins of MRS-GABA, 3) optimise GABA imaging, enhancing potential for clinical translation.
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| 13/07/2021 |
£1,377,893 |
|
UNIVERSITY OF LEEDS |
The human genome encodes 40 genes for myosin that can be grouped into 12 different classes based on their sequence similarities. Many are implicated in disease from cardio- and myo-pathies and blood clotting deficiencies (Class 2), to deaf-blindness (class 7) and neuronal and gut disorders (class 5). Each myosin is specifically adapted for its cellular role, with adaptations to the motor and lever domains dictating how the myosin interacts with actin filaments to generate motility and adaptations to the tail dictating its cellular cargos. However, we lack an understanding of how the activity of these motor proteins is regulated. Here I plan to focus on class 2, 5 and 7 myosins, to uncover how myosin-2 function is regulated by filament assembly and disassembly, how myosin-5 and 7 function is regulated by the formation of compact inhibited structures, how strain affects myosin structure, modulating its ATPase, a broad mechanism that regulates the behaviour of all myosins, and I plan to discover when and where myosin is switched off in in cells, a fundamental question in biology.
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| 13/07/2021 |
£3,984,636 |
|
IMPERIAL COLLEGE LONDON |
Those responsible for the healthcare sector in countries in Eastern, Central and Southern Africa must decide what to do with limited resources to generate the greatest possible benefit to the health of the people they serve. We propose to develop new methods and collect new data to characterize the means by which the healthcare system produces health benefits in the context of a complex and evolving pattern of demand for healthcare. Our proposed approach is to build a detailed and theoretically-principled simulation model that couples a ‘Healthcare Production Module’ with an agent-based ‘Epidemiological Module’, that together would represent the mechanisms by which resources create healthcare that lead to health gains. We will use these methods to examine: how can the currently available resources (budgets and non-financial resources) for health be used to generate the greatest health gains; how could greater gains be achieved with more financial resources; and how should the healthcare system adapt in response to evolving burdens of diseases. We will work closely with national and regional institutions to translate the insights into strategic planning and policy and facilitate the routine usage of these methods by governmental analysts throughout the region.
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| 13/07/2021 |
£2,105,903 |
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UNIVERSITY OF CAMBRIDGE |
Stem cells in tissues as varied as the blood, gut, and brain spend much of their time in a reversible, mitotically dormant state called quiescence. Quiescent stem cells can be reactivated to resume proliferation in order to fulfil the needs of the organism during development and in adult life. A key point of regulation is the decision to switch between quiescence and proliferation. The response of stem cells to changing physiological conditions is mediated by inter-organ signalling, ensuring that growth and patterning are coordinated throughout the organism and that homeostasis is maintained. Uncovering the molecular mechanisms that control stem cell behaviour is crucial for understanding tissue regeneration under normal and pathological conditions and may make it possible to activate quiescent NSCs to regenerate neurons after injury or disease.
My goal is to understand the control of stem cell quiescence and reactivation in the brain, unravelling the steps that lead from systemic signalling, through inter-organ communication, to stem cell proliferation and the generation of new neurons and their circuits. Using Drosophila as a model system, it will be possible to deduce, in vivo, the sequence of events at the level of the organism, tissue, cell, and finally genome.
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| 13/07/2021 |
£1,224,434 |
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UNIVERSITY OF OXFORD |
The interferon (IFN) immune response induces an antiviral state by triggering the expression of IFN-stimulated genes and is the primary line of defence against infection. The proteins encoded by these genes fulfil a variety of functions, including degradation of viral RNA and reduction in protein translation. Unsurprisingly, viruses have evolved compensatory mechanisms to suppress the IFN response. One such family of viruses is Coronaviridae, responsible for the current COVID-19 pandemic. Suppression of IFNs by Coronaviridae has been attributed to the macrodomain module present within the multidomain Nsp3 protein. The macrodomain functions as an ADP-ribosylhydrolase to neutralise the actions of the antiviral members of the poly(ADP-ribosyl)polymerase (PARP) family. However, the mechanisms through which antiviral PARPs and macrodomains impact the IFN response remain unclear. This proposal will provide a molecular understanding of how antiviral PARPs suppress coronavirus infection and how SARS-CoV-2 macrodomains oppose their activity to evade IFN signalling and promote viral replication. Furthermore, comparative analyses of the macrodomains from different coronaviruses and their impact on interferon response may explain the variations in their pathogenicity. Collectively, our studies will inform interferon-based disease management strategies to prevent spread within and between infected hosts and provide novel biomarkers of susceptibility and antiviral drug targets.
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| 13/07/2021 |
£1,202,559 |
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UNIVERSITY OF EXETER |
Transcriptional regulation is critical for all cellular processes. It is usually studied by asking how RNA polymerase II (Pol II) is recruited to gene promoters then activated for elongation. This programme focuses on promoter-proximal termination (PPT) of Pol II in mammals that I hypothesise as a general means of transcriptional control, the evasion of which is required to produce functional mRNA. I will dissect two major PPT pathways in the first two aims, one of which we recently discovered. I will use genetically encoded degrons to study the relevant protein factors at high temporal resolution. Cutting-edge nascent RNA analyses will be employed to scrutinise their impact on transcriptional control, define their mechanisms and uncover their substrates. I will then transfer this approach into mouse embryonic stem cells to ask whether PPT regulates developmental gene expression during the transition between naïve and formative pluripotency. In the final aim, I will uncover the proximal Pol II proteome to reveal why polymerases are susceptible to PPT. I will also identify the RNA binding proteins that distinguish PPT products from other transcripts. My overall goal is to uncover how PPT controls RNA biogenesis and the extent to which it regulates gene expression.
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| 13/07/2021 |
£4,215,495 |
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UNIVERSITY OF CAMBRIDGE |
Despite > 60 years of antitubercular chemotherapies, tuberculosis (TB) has been the leading infectious cause of death. My laboratory pioneered the zebrafish - Mycobacterium marinum tuberculosis model to better understand TB pathogenesis. It enabled surprising discoveries about tuberculosis with immediate implications for new therapeutic modalities. Here, we will use the zebrafish to discover genetic alterations that impact upon immunity and inflammation in early TB. This will uncover human genetic susceptibilities to tuberculosis and druggable pathways underlying them. Our key goals are to:
- Map and characterize hypersusceptible zebrafish mutants identified in a forward genetic screen. We will identify their causative lesions and characterize which infection step is altered in them and how, so as to understand how these genes modulate infection.
- Identify gene-regulatory networks involved in early granuloma formation. RNA-seq analyses will provide a blueprint of gene expression changes associated with tuberculous granuloma formation, which we will link dynamically and functionally to the individual processes involved to determine their consequences.
- Determine mechanisms of human primary immunodeficiencies to mycobacterial infections using the zebrafish. We will model in the zebrafish known human genetic mutations that increase human susceptibility to mycobacterioses to determine their susceptibility mechanisms, particularly in early infection.
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| 13/07/2021 |
£1,610,225 |
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UNIVERSITY OF OXFORD |
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally. However, current prevention and treatment strategies for CVD are inadequate. In response there is a growing interest in wearable sensors that offer the potential to continuously, noninvasively, and painlessly measure key attributes of relevance to cardiovascular health - such as physical activity, sleep, and atrial fibrillation - in patients’ everyday lives. In this fellowship, I propose a new programme of research to use wearable sensors to provide novel insights into cardiovascular disease (CVD), with respect to its prediction, discovery of target mechanisms, and new methods to prioritise and assess the impact of potential treatments on day-to-day physical activity and sleep. This research will harness the power of reproducible machine learning in large-scale wearable sensor and human genomic datasets to advance the understanding of CVD. My research will provide the basis for new methods, target mechanisms, and tools to reduce the burden of CVD.
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| 13/07/2021 |
£2,602,647 |
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UNIVERSITY OF OXFORD |
In the final three years of my Principle Fellowship I wish to complete studies to improve the treatment and elimination of malaria. To counter the threat of antimalarial drug resistance emerging from the Greater Mekong sub-region I have recommended a switch to triple artemisinin combination treatments and developed the methods to conduct targeted malaria elimination in endemic areas. I propose a series of studies to assess the safety, efficacy and overall benefit of these new approaches. To support control and elimination I will develop and evaluate better methods of identifying, measuring and monitoring antimalarial drug resistance. To prevent relapses of vivax malaria (the main therapeutic challenge and obstacle to elimination) I will investigate safer methods of giving primaquine, and identify the optimum dose of tafenoquine. I will improve methods for the pharmacometric assessment of antimalarial drugs and I will apply similar proven principles to the assessment of much needed treatments of Chagas disease and COVID-19. I will develop a pharmacometric platform based on assessment of parasite and virus clearance rates respectively for assessing and comparing new drug treatments. This is necessary to inform the choice of drug and dose in larger phase 3 assessments, accelerating their development.
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| 13/07/2021 |
£2,136,164 |
|
UNIVERSITY OF EDINBURGH |
A role for 3D gene structure in regulating transcription has been hypothesised, but direct evidence remains limited. This restricts our understanding of the mechanisms through which chromatin misfolding leads to disease. To understand the relationship between structure and transcription in human cells we will integrate molecular biology approaches and cutting-edge mechanistic polymer models of chromatin. Such models are well-suited to explore parameter space, predict molecular properties, and generate hypotheses to provide a framework for laboratory experiments. Using minimal bioinformatic data, a new polymer model to predict gene structure and transcriptional activity in healthy or diseased cells will be developed and experimentally validated. We will then assemble the first genome-wide, 3D gene structure compendium and use it as a foundation to determine if structure has evolved to regulate transcription. Polymer models predict a range of possible structures. We will combine simulations and experiments to test whether such intra-gene structural heterogeneity regulates transcriptional noise and will identify the mechanisms involved through locus engineering. Finally, as the protein SAF-A interacts with RNA to regulate gene architecture, we will incorporate RNA fields into simulations and experimentally investigate the concept that protein/RNA gels can impact transcription, thereby characterising a novel feedback between structure and function.
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| 13/07/2021 |
£1,813,055 |
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UNIVERSITY OF GLASGOW |
The adult intestine is a major barrier epithelium and coordinator of multi-organ functions. Stem cells constantly repair the intestinal epithelium by adjusting their proliferation and differentiation to tissue intrinsic as well as micro- and macro-environmental signals. How these signals integrate to control intestinal and whole-body homeostasis is largely unknown. Addressing this gap in knowledge is central to an improved understanding of intestinal pathophysiology and its systemic consequences.
Combining Drosophila and mammalian model systems my laboratory has discovered fundamental mechanisms driving intestinal regeneration and tumourigenesis and outlined complex inter-organ signalling regulating health and disease. Building upon new findings from our research, here we propose to:
Identify and characterise stem cell intrinsic metabolic adaptations underpinning intestinal regeneration and tumourigenesis.
Elucidate interactions between the intestine and its vascular microenvironment influencing intestinal regeneration and tumourigenesis.
Characterise the role of enteroendocrine signals in the intestine and the whole-body in health and disease.
The work outlined in this proposal will reveal new drivers of intestinal regeneration and cancer and key processes through which the intestine coordinates multi-organ responses. This knowledge holds great potential to inform the design of integrative regenerative and anti-cancer therapies.
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| 13/07/2021 |
£3,313,863 |
|
UNIVERSITY COLLEGE LONDON |
Our overarching hypothesis is that mechanistic insights from preclinical models of Huntington’s disease (HD) and their genetic treatment are valid for early human pathogenesis and can therefore be realised as the foundation for transformative, preventive, clinical trials. A major obstacle to treatment is that degenerative conditions are usually diagnosed once compensatory mechanisms have been exhausted and irrecoverable cell death has occurred. TREAT-HD shifts the focus to mechanisms underlying earlier and asymptomatic stages of pathogenesis as a better time to initiate treatment. We test our hypothesis through three inter-linked aims (Figure 1) that establish the earliest consequences of mutant huntingtin protein (mHTT) in cells, mice and humans with the aim of developing novel therapeutics to delay or prevent symptom onset.
Aims:
1. Determine molecular mechanisms associated with somatic CAG-repeat expansion as targets for novel therapeutics by examining agents targeting DNA repair pathways in cellular and mouse models of HD
2. Determine early systems-level pathology and impact on symptomatology in young adult HD mutation carriers to test the hypothesis that neurodevelopmental effects on brain structure occur before progressive neurodegeneration
3. Integrate molecular and systems-level insights for therapeutic benefit by identifying and validating target engagement and efficacy markers for future clinical trials
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| 13/07/2021 |
£1,560,578 |
|
UNIVERSITY COLLEGE LONDON |
I aim to understand the molecular and cellular mechanisms regulating HIV-1 replication and spread in T-cells and how the virus manipulates cells to create a permissive niche. HIV-1 most efficiently disseminates between T-cells by cell-cell spread (CCS) that dominates infection. We have recently discovered CCS triggers target T-cells to become vastly more susceptible to infection, allowing HIV-1 to replicate in resting T-cells that are usually non-permissive for infection. By using CCS infection to bypass the need to mitogenically stimulate target T-cells (a process which drastically changes T-cell biology), we have discovered HIV-1 transcriptionally and phenotypically reprogrammes T-cells to induce a tissue-residency-like phenotype via Vpr, revealing new consequences of HIV-1 infection. Our key goals are now to:
Determine how CCS drives HIV-1 replication in resting T-cells, defining key viral and cellular factors and mechanisms.
Determine how HIV-1 navigates innate immune defences to infect resting T-cells, how this shapes permissivity, and how sensing operates in T-cells.
Dissect how HIV-1 reprogrammes T-cells, Vpr mechanism and the consequences for T-cell fate and function.
Our work will advance mechanistic understanding of how HIV-1 manipulates its most important target cell to drive replication and persistence, uncover exciting new biology and inform future therapeutic innovation towards cure.
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| 13/07/2021 |
£1,288,633 |
|
UNIVERSITY COLLEGE LONDON |
This research programme explores the cellular and molecular mechanisms responsible for metabolic support of neuronal computation in the brain. Experimental studies are designed to answer the following fundamental questions: (Q1) What are the mechanisms responsible for on-demand delivery of metabolic substrates to support the variable level of neuronal activity? (Q2) What are the mechanisms underlying metabolic control of cerebral blood flow? (Q3) What are the brain mechanisms of adaptation to acute metabolic insufficiency? These questions are addressed by focusing on three metabolic mechanisms/signalling pathways: (i) mediated by cAMP in astrocytes, (ii) underlying the effect of CO2 on brain vasculature, and (iii) responsible for mitochondrial production of nitric oxide by astrocytes in low oxygen conditions. Key identified component(s) of the hypothesised mechanisms will be blocked genetically, followed by two-photon optical recordings of the activities and interactions between neurons, astrocytes and cerebral vasculature, electrophysiological assessment of synaptic function, recordings of cerebral blood flow and cerebrovascular reactivity using MRI, physiological and behavioural phenotyping in experimental animals (rats and mice). This research is expected to advance our understanding of brain energy metabolism and may prove to be important for the development of preventive and therapeutic strategies to maintain cognitive health and promote brain longevity.
|
| 13/07/2021 |
£1,852,668 |
|
UKRI-MRC |
We wish to determine how the cytosolic antibody receptor and E3 ligase TRIM21 uses its potent antiviral and immune signaling activity to prevent infection by diverse viruses. We will use our newly developed protein deletion technology ‘Trim-Away’ to determine the ubiquitin machinery necessary to synthesize the diverse ubiquitin chain types that allow TRIM21 to drive proteasomal degradation of viruses and trigger innate immunity. We will build on our structural studies of TRIM21 to define the mechanism by which its pro-inflammatory signaling is regulated and how other ligases and deubiquitinases are recruited. We will exploit our recent discovery that TRIM21 promotes antigen presentation, by investigating its role in targeting antigens for proteasomal degradation and stimulating protective T cell responses during LCMV, Influenza and SARS-CoV-2 infection. Together this work will define new roles for TRIM21 in host immunity and decipher how TRIM21 uses ubiquitin to provide antiviral protection. The insight we learn from these natural mechanisms will further the development of new technologies like Trim-Away and may inform future antiviral and vaccine development.
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| 13/07/2021 |
£523,653 |
|
NATIONAL UNIVERSITY OF IRELAND GALWAY |
Nucleoli form around rDNA arrays at nucleolar organiser regions (NORs) located on the five acrocentric chromosome p-arms, providing positional cues for 10 of the 46 chromosomes in diploid human cells. Thus, nucleoli are a paradigm for two general features of genome organisation; specific associations between multiple chromosome territories and internal organisation of nuclear bodies involving multiple chromosomes. Exploration of this organisational paradigm is complicated by the shared DNA-sequence composition of acrocentric p-arms. Recently we have devised a methodology for genetic manipulation and functional testing of individual p-arms/NORs. Efficient ‘scarless’ genome-editing of rDNA is achieved on ‘poised’ human NORs within mouse mono-chromosomal cell-hybrids. Subsequent transfer to human cells introduces ‘active’ NORs yielding readily discernible functional customised ribosomes. We propose exploiting this transformative methodology to identify p-arm elements that drive acrocentric co-location at large nucleoli. We further aim to determine how rDNA arrays from multiple NORs partition within nucleoli. NOR genome-editing will also facilitate exploration of rDNA genome-stability and links with cellular senescence. Finally, we propose using top-down chromosome-engineering to construct minimal NOR-bearing chromosomes as a platform for future research. These studies will advance our understanding of the relationship between acrocentric chromosomes and the largest functional sub-domain in the human nucleus.
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| 13/07/2021 |
£2,065,070 |
|
UNIVERSITY OF YORK |
The life cycle of the Leishmania parasite requires transition between insect and mammalian hosts, where temporal cell type differentiation allows adaptation to changing environments. We have recently identified a number of Leishmania protein kinases and ubiquitination enzymes that are essential for successful differentiation and establishment of infection, regulating cell signalling and cellular remodelling. We will now tackle two fundamental processes that are fundamental to the parasite’s biology: The regulatory mechanism(s) that control cellular remodelling during differentiation and the requirement of co-regulation of the cell cycle and differentiation to enable establishment of infection To address this we will decipher the protein kinase-dependent signalling pathways controlled by activators and repressors intrinsic to successful differentiation, as well as the signalling pathways regulating kinetochore assembly during differentiation-induced re-initiation of the cell cycle. We will investigate cellular remodelling through characterisation of E3 ubiquitin ligases essential for differentiation. These studies will lay the foundations for developing proteolysis targeting chimeras and protein kinase tool compounds for investigating Leishmania biology and for drug discovery. The expected output of the project will be novel insights into the cross-talk between cell signalling and cellular remodelling through the co-ordinated action of phosphorylation and ubiquitination post-translational modifications.
|
| 13/07/2021 |
£2,150,992 |
|
UNIVERSITY COLLEGE LONDON |
The molecular mechanisms causing neuronal death in many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, are poorly understood. The key consequence of our incomplete understanding of disease pathogenesis is that there is a complete dearth of effective symptomatic treatments for these widespread global disorders, prompting the necessity for a step-change in treatment strategies to fight these pathologies.
In this view, we are investigating ALS as a disease paradigm to identify new, common targets for pharmacological intervention in these devastating pathologies. In work leading to this proposal, we uncovered alterations in axonal transport of several cytoplasmic organelles at pre-symptomatic stages of ALS pathogenesis, suggesting that these impairments may play a causative role in disease onset and progression. Crucially, we have restored axonal transport to physiological levels at early symptomatic stages of disease, thus demonstrating that these pathological changes are fully reversible. Our program of work aims to identify novel signalling nodes that modulate axonal transport in healthy and ALS motor neurons. This will allow us to test the hypothesis that counteracting axonal transport deficits observed in ALS and other neurodegenerative diseases, represents a novel, effective therapeutic strategy towards treating these currently incurable pathologies.
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| 07/07/2021 |
£1,249,141 |
|
UNIVERSITY COLLEGE LONDON |
Much of the global population now live in an obesogenic environment, characterised by ready availability of the ultra-processed, high-fat and high-sugar foods comprising the modern ‘Western diet’. This diet is a deleteriously effective trigger of the evolutionarily-conserved drive to maximise energy intake during periods of food abundance, leading to the chronic overconsumption driving the obesity epidemic. Overconsumption can be caused by impaired function in the neurobiologically-distinct processes of satiation and/or satiety. Satiation processes ultimately elicit meal termination, via a poorly-understood interaction of neuronal and hormonal gut-brain signalling pathways, respectively mediated by vagal afferent neurons, and blood-borne peptide hormones and endocannabinoid-like lipoamines. I will use the TRAP2 system for activity-dependent Cre-recombinase expression, combined with systems neuroscience techniques including chemogenetics and optogenetics, to map and selectively manipulate Western diet-recruited gut-brain neurocircuits in an unbiased manner. I will combine this model with single-nucleus transcriptomics, and targeted HPLC-MS/MS lipidomics, to functionally interrogate how neuronal and hormonal gut-brain neurocircuits recruited by Western diet interact to orchestrate meal termination at the cellular, molecular and behavioural levels in lean mice. I will then identify the molecular mechanisms driving dysfunction in this circuitry resulting from chronic Western diet consumption, to identify new approaches to prevent and treat obesity.
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| 07/07/2021 |
£1,382,660 |
|
UNIVERSITY OF LEEDS |
The proteostasis network is at the forefront of cellular defence against protein misfolding diseases and its decline with age is directly associated with cell death. Chaperones of the Hsp70 family are the workhorses of the proteostasis network and their powerful refolding capabilities are crucially directed to specific clients by Hsp40s(DNAJs). However, the mechanisms that Hsp40s use to regulate Hsp70 functions and how they recognise specific toxic substrates remain unknown. Here, using the DNAJB6b isoform (that is related to neurodegeneration and myopathies) and utilising/developing NMR methods ideal to study dynamic/transient events, I will reveal how Hsp40s drive the multifunctionality of the Hsp70 machine using long, low-complexity regions. In addition to cooperating with Hsp70, DNAJB6b is able to inhibit protein aggregation on its own. The mysteries of DNAJB6b substrate antiaggregation functions are encrypted in its self-oligomerisation properties. By combining in vitro NMR, MS, and cryo-EM data with cellular assays and organismal models, I will reveal the origins of DNAJB6b self-assembly and how it interferes with toxic aggregation of client proteins. The interdisciplinary approach of this proposal will unravel the molecular origins of DNAJB6b specificity and will open the way to engineering optimised chaperones and therapeutic agents tuned to target different disease-related substrates.
|
| 07/07/2021 |
£963,821 |
|
UNIVERSITY OF MANCHESTER |
Knee replacement surgery (KRS) is commonly performed (~100,000/year in UK) in patients with severe osteoarthritis. Despite a good outcome for most patients, 20% of patients experience chronic pain afterwards and 4.4% require revision surgery within 10 years for a variety of reasons.
My goal is to develop a software system to predict poor outcome and early revision in KRS. The system will facilitate (i) informed decision-making about surgery, enabling targeted interventions such as preventive pain management; and (ii) the identification of patients that need closer follow-up post-surgery, enabling more remote monitoring of patients.
Radiographic knee shape has been shown to be a predictor for the outcome of KRS. I have developed the BoneFinder®-technology, an internationally leading technology to automatically outline structures in radiographs. Using machine learning methods, a system will be developed to automatically measure the knee in pre-/post-operative radiographs, and to predict poor outcome based on the radiographic measurements, clinical and patient-reported data.
To facilitate implementation of such a system for patient benefit, it will serve as a use case to create a sustainable toolkit for translating medical imaging solutions in particular and digital healthcare solutions more broadly; aiming to reduce the translational gap between research and clinical practice.
|
| 07/07/2021 |
£1,041,010 |
|
UNIVERSITY OF BIRMINGHAM |
Prosocial behaviours – decisions that help others – are essential for health and society. However, these behaviours can change across the lifespan and in mental health disorders, most prominently in adolescent conduct disorder. To support healthy development and guide intervention we must understand the basic mechanisms. Across three workstreams, I will use two novel paradigms to test hypotheses about fundamental aspects of prosocial behaviour and how they can be changed. Crucially, I will be able to link these behaviours to brain function through fMRI-MEG ‘fusion’. This approach can uncover the spatiotemporal dynamics – where and when - prosocial behaviours are computed, for the first time. I predict that prosocial decisions will be distinctly represented from self-benefitting decisions early in temporo-parietal and later in prefrontal brain areas. These findings will inform when to apply brain stimulation to temporal-parietal and prefrontal areas, to examine their causal influence on prosocial behaviour. Finally, I will translate these findings to understand changes in prosocial decisions and neural mechanisms in the transition from adolescence to adulthood and in conduct disorder. These integrated experiments will uncover the neurocomputational mechanisms of prosocial behaviour across health, development and disorder, laying a necessary foundation for interventions to foster prosocial behaviour.
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| 07/07/2021 |
£1,084,360 |
|
UNIVERSITY OF OXFORD |
Subcortical brain regions are critical for motivation and decision-making but work in humans has largely focused on prefrontal regions. Important subcortical structures such as amygdala and hypothalamus have typically been treated as homogenous, despite consisting of multiple nuclei with differing functions. This is because human neuroimaging has lacked the resolution and signal-to-noise required for studying precise nuclei, and available causal techniques have been unable to modulate activity at the required depth.
Here, I will exploit recent technical advances and Oxford’s expertise in high-field neuroimaging and transcranial ultrasound stimulation (TUS), a non-invasive technique for focally stimulating deep-brain regions, to test whether nuclei-specific limbic-prefrontal subcircuits have dissociable functional contributions to complex motivation and decision-making in humans.
First, I will develop in-vivo parcellations for nuclei within amygdala and hypothalamus, permitting study of their differential functional contributions. Second, I will use computational modelling, 7T-neuroimaging and TUS to establish the causal contributions of nuclei-subcircuits to motivation and decision-making. Finally, I will compare decision-making and nuclei-connectivity between healthy and depressed cohorts. My work will allow translation between work in animals and humans and provide a new framework for understanding neural circuit dysfunction and behavioural change in depression, which affects precisely the circuits and behaviours studied here.
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| 07/07/2021 |
£718,737 |
|
UNIVERSITY OF OXFORD |
Severe malaria remains a major cause of preventable childhood mortality in sub-Saharan Africa. Improved understanding of human genetic susceptibility to severe disease and the effect of therapeutic interventions will save lives. A major difficulty for all quantitative research in severe malaria is the evaluation and classification of the severe malaria phenotypes in areas of high transmission. The diagnosis of severe malaria in young children and the distinction from bacterial sepsis is imprecise. I will develop a biomarker based diagnostic model of severe malaria that can be used as a research tool to improve the quality and accuracy of quantitative analyses. The biomarker model will be validated using Mendelian randomisation (natural experiment using genetic polymorphisms with known protective effects). I will then apply the biomarker model to evaluate the effect of blood transfusion in severe malaria and re-evaluate the role of glucose-6-phosphate dehydrogenase deficiency in the protection against severe illness. Underpinning all of the work will be the development of new statistical methods for case-control studies which have phenotypic imprecision in the case definitions. These methods will improve genome-wide association studies in severe malaria and help guide the design of early phase evaluations of new therapeutic interventions.
|
| 07/07/2021 |
£810,761 |
|
UNIVERSITY COLLEGE LONDON |
My fellowship will test the hypothesis that academic pressure is a common, modifiable causal risk factor for adolescent depression, self-harm and suicide. If my hypothesis is correct, academic pressure could be modified in whole-school interventions and through longer-term changes to policy.
I will test my hypothesis using advanced methods from epidemiology, data science and causal inference, to triangulate evidence across different settings, samples and designs. I will also collaborate with a multidisciplinary network of key stakeholders, to inform my research and translate my findings into school and policy interventions.
The key goals of my project are to:
1. Conduct the first longitudinal studies of whether academic pressure increases the risk of depression and self-harm and is therefore a novel candidate for prevention.
2. Investigate how timing within the school year relates to clinical presentations for depression, anxiety and self-harm, and adolescent suicide rates
3. Work with key stakeholders to:
Complete patient and public involvement
Define the components of academic pressure and its sources and drivers
Investigate what schools currently do to mitigate the impact of academic pressure on the mental health and well-being of students and teachers
Achieve knowledge mobilisation
Key words: adolescent, depression, self-harm, suicide, prevention, epidemiology, schools.
|
| 07/07/2021 |
£1,340,337 |
|
UNIVERSITY OF OXFORD |
Chromatin is partitioned into functional domains. Nucleosomes within these domains contain specific histone variants and post-translational modifications (PTMs) that modulate chromatin structure and dynamics. During DNA replication, parental nucleosomes are disassembled ahead of the replication fork, followed by their restoration on daughter strands from recycled parental and new histones. Local histone recycling at the replication fork is central to epigenetic inheritance but the molecular mechanisms underlying this process are poorly understood.
I have developed a real-time single-molecule imaging platform that allows simultaneous visualisation of parental histones and replication forks as they navigate through the nucleosomal environment of individual DNA molecules in Xenopus egg extracts. Using this approach, I showed that, upon collision with forks, histones can be locally recycled, evicted from the DNA, pushed by forks over tens-of-kilobases and even stall forks. Importantly, I found that free histone concentration is a key modulator of parental histone recycling at the replication fork.
I will exploit this novel single-molecule technology, and combine it with biochemical and biophysical methods, to uncover how histone variants and PTMs affect nucleosome dynamics during DNA replication. My work will provide mechanistic insight into replication-coupled histone inheritance and shed light on how chromatin structures are maintained.
|
| 07/07/2021 |
£1,326,121 |
|
UNIVERSITY OF CAMBRIDGE |
Flaviviruses such as Zika virus, dengue virus and yellow fever virus transmit their RNA genomes between arthropods and humans, causing widespread pathology and death. During infection, the viral RNA genome resides inside the host cells’ cytoplasm. However, whether the viral genome folds differently inside human and arthropod cells, and whether it interacts with the hosts’ own RNA remain largely unexplored. The aim of this proposal is to dissect the dynamics and function of the flaviviral RNA interactome. I will employ my recent developed COMRADES method to investigate the base pairing capacity and function of two related flaviviruses: Zika virus and yellow fever virus, and to address the following little-explored aspects in their biology: (i) Do viral genomes base-pair with host RNAs? What are the roles of host-virus RNA base-pairing? (ii) Do viral genomes base-pair differently inside different hosts? What are the functional implications?
The results will cast light on how RNA viruses utilise RNA base-pairing to enhance their replication and pathogenicity; offer new opportunities to develop antiviral therapeutics targeting the host-virus RNA-RNA interactome; and establish a new role for RNA base-paring in zoonosis.
|
| 07/07/2021 |
£1,347,093 |
|
KING'S COLLEGE LONDON |
Using an innovative cross-disciplinary approach, I will directly explore the pathophysiology, function, and mechanisms of respiratory motor recovery following severe spinal cord injury (SCI) and determine if restoration of this activity is sufficient to mitigate increased rates of morbidity and mortality caused by acquired infections.
Treatment strategies for SCI have focused on restoring spinal neuronal circuitry. I will determine if a novel treatment strategy which targets both neural growth/plasticity in the spinal cord and muscle mitochondrial activity, can restore systemic respiratory motor function after severe SCI. I will use innovative techniques including bi-planer X-ray videography and ventilatory pattern variance to assess the pathophysiology of the respiratory system following injury and recovery. Further, in physiologically relevant conditions, I will assess cyclical power generated by respiratory muscles, alterations in neuronal circuitry, and model changes in muscle oxygen transport to determine the systemic mechanisms behind respiratory deficit and recovery. Finally, most SCI patients show increased morbidity and mortality with reduced functional activity due to post-injury acquired pneumonia infections. For the first time, I shall assess whether my combined treatment strategy can overcome the deleterious effect of pneumonia infection and the mechanisms through which sustained systemic functional respiratory recovery can occur.
|
| 07/07/2021 |
£626,065 |
|
THE PIRBRIGHT INSTITUTE |
Viruses that use a single strand of positive sense RNA (+ssRNA) as their genomes number a breadth of human pathogens including Zika virus (flavivirus), poliovirus (picornavirus), norovirus (calicivirus) and SARS-CoV2 (coronavirus). A number of key, fundamental questions regarding how these viruses regulate usage of their genomes remain. Answering these questions not only provides new biological insights into host-pathogen interactions but could prove critical in identifying new strategies for control. These viruses use the same molecule of RNA for protein expression and as a template for replication. However, these processes occur in opposing directions i.e. translation in a 5′-3′ direction and replication in a 3′-5′ direction. This therefore necessitates a "lifestyle switch" for any single RNA molecule in a cell, the details of which are unknown. We will use a multidisciplinary approach including in vitro reconstitution, cell biology and infection studies to determine how lifestyle switching of genome usage is regulated during infection by +ssRNA viruses. This work will lead to a new paradigm in our understanding of the evolution of genome organisation and function in an important class of pathogenic viruses.
|
| 07/07/2021 |
£712,398 |
|
UNIVERSITY OF EXETER |
A major source of emerging infectious disease are virus host shifts, where a pathogen jumps into a new host species (e.g. HIV, Ebola, SARS-CoV-2). Research to date has focused on the role of host genetics. Here I will examine the role pathogen genetics (relatedness) and ecology (interactions between microbes) play in emerging infectious diseases, which will be critical to predict future host shifts.
The first goal is to understand how patterns of susceptibility correlate amongst different pathogen taxa. I will infect hosts with different viruses and other pathogens to test the importance of the host phylogeny in determining susceptibility for each pathogen. For example, if a host is susceptible to one virus, are they also susceptible to other types of virus, or is susceptibility pathogen specific? This is critical for understanding whether the characteristics of an emerging pathogen can be predicted based on our knowledge of other related pathogens.
Next, I will investigate how interactions between microbes can alter the likelihood of pathogen emergence. I will examine whether the outcomes of co-infection and microbiome-pathogen interactions are the same or different across host species. This has important consequences for understanding how biotic interactions could alter the outcomes of pathogen host shifts.
|
| 07/07/2021 |
£601,131 |
|
UNIVERSITY OF MANCHESTER |
Cellular responses to changes in the environment depend on Receptor Tyrosine Kinase (RTK) signalling and are tightly regulated. Such regulation is lost in diseases, including breast cancer. Importantly, different ligands binding to the same RTK, including Fibroblast Growth Factor Receptor 2b (FGFR2b) in breast cancer cells, elicit distinct cellular responses (proliferation vs. migration). The molecular basis by which FGFR2b signalling generates such functional selectivity is poorly understood, information that is crucial to develop better targeted therapies against deregulated FGFR2b signalling in breast and other cancers. Here, I will investigate whether each FGF/receptor pair initiates unique responses right from receptor activation at the plasma membrane to determine specific long-term outputs. I will combine structural proteomics, proximity methods to study localised signalling, phosphoproteomics, and functional assays in breast cancer cells to reveal whether each FGF induces unique structural re-arrangements of FGFR2b at the plasma membrane, over and above receptor dimerization, that recruit specific signalling partners; what ligand-specific signalling modules are recruited to FGFR2b; and how these signalling modules regulate the long-term effects of FGFR2b functional selectivity. Overall, this project will lead to breakthrough in understanding cell signalling specificity and reveal new signalling nodes amenable for therapeutic intervention in breast and other cancers.
|
| 07/07/2021 |
£818,932 |
|
UNIVERSITY OF CAMBRIDGE |
Despite decades of research, little is known as to how we can improve epithelial regeneration. Mounting evidence suggests that the physical changes taking place during tissue remodelling are critical to regulate cellular behaviour. However, it remains unclear how different cell populations sense and synchronise their response to mechanical cues in order to adequately adapt to tissue perturbations.
Using the oesophagus as a tractable model, my laboratory has provided new insights into the mechanisms regulating epithelial cell behaviour. Our work identifies naturally occurring changes in tissue mechanics as a central regulator controlling the establishment of adult homeostasis after birth. In the proposed extension, we will use an interdisciplinary approach combining in vivo lineage tracing techniques, single cell transcriptional analysis and organ culture systems to investigate whether these mechanical cues (i) coordinate the behaviour and cross-talk of different cellular compartments, and (ii) contribute to the regenerative decline described in adult tissues.
This work will lay the foundation to understand how mechanical cues orchestrate cell fate at the whole organ level and to help develop novel clinical therapies to improve wound healing, an unresolved aspect of modern medicine.
|
| 30/06/2021 |
£50,000 |
|
UNIVERSITY OF CAMBRIDGE |
The proposed work is – to our knowledge - the first integrated economic analysis of a single policy intervention and its potential to influence three interlinked threats: the global health crises of both non-communicable diseases and new infectious diseases such as Covid-19, as well as environmental degradation, including biodiversity loss and climate change.
The work will comprise modelling the consequences of carbon pricing, set at a level compatible with keeping climate change within planetary boundaries, with outcomes including land-system change, agricultural production, food prices, diets and health outcomes, and effects on infectious disease and biodiversity. The analysis will consider potential differential effects of carbon pricing across socio-economic groups, and between high, medium and low-income countries, as a basis for considering policy interventions to mitigate inequitable outcomes.
This analysis will contribute to the goal of The Lancet-Chatham House Commission which is to identify actions that can impact positively across the shared drivers of the three threats to human and planetary health described above. Importantly it will provide novel evidence for the ways in which co-benefits and
co-costs of interventions might form a significant part of the political and economic cases for intervening at national and international levels and optimising policy design.
|
| 30/06/2021 |
£128,102 |
|
THE ASSOCIATION FOR SCIENCE EDUCATION |
The purpose of the project is to test the impact and value of delivering subject-specific CPD in upper primary, lower secondary science through ‘bite-sized’ online courses linked to micro-accreditation. It will:
develop three online CPD units focusing on teaching more challenging ideas in science to pupils at upper primary and lower secondary level (ages 9-13)
test ‘proof of principle’ that a structured online CPD course comprising ‘bite-sized’ CPD units supports teachers of primary and lower secondary science in strengthening their subject knowledge (SK) and their pedagogic content knowledge (PCK); and indirectly improves pupils’ understanding of difficult ideas in science;
enable teachers using the CPD resources to gain micro-accreditation in those topics, recognising and certifying their skills and knowledge, and explore ways to promote the value of this accreditation to senior leadership and more widely, including as evidence towards other accreditations such as Chartered Science Teacher (CSciTeach);
test the ‘buy-in’ to the value of micro-accreditation by senior leadership in building up a pool of teachers who are skilled, confident (and ultimately deployed) to teach age and stage appropriate topics of the science curriculum; and as a tool to inform individual professional learning needs, promotion; and support targeted recruitment and retention strategies.
|
| 30/06/2021 |
£153,054 |
|
SHEFFIELD HALLAM UNIVERSITY |
There is a strong evidence base on effective continuing professional development (CPD) for teachers, but in spite of this evidence, there has been limited sustained change towards the goal of all teachers being able to participate in high quality professional development throughout their careers. To address this, greater understanding is needed of how to make change happen: the implementation of innovations and programmes in relation to policy and entitlements and the school environment; and the mechanisms and processes which underpin change.
Applying insights from implementation science and theory-based evaluation, our proposed research will identify a series of ‘mechanisms for change’ applicable to teacher CPD policy and practice in school environments in England, to guide CPD practice by schools and policy-makers. Four complementary project strands (a systematic evidence review; STEM CPD policy analysis; investigating effective change implementation in CPD, through mixed methods of survey and case studies; stakeholder engagement and dissemination) will lead to evidence-based guidance for effective implementation of CPD in England at multiple system levels, whether a local system (e.g. a single department or school CPD), larger system (e.g. programmes for a specific teacher subject group or phase) or the whole education system (e.g. increasing access to CPD).
|
| 30/06/2021 |
£137,623 |
|
HUMBOLDT UNIVERSITY OF BERLIN |
Mindscapes Curatorial Research Fellow
Full-time position with CARMAH, reporting to the Director
This post-doctoral fellowship appointment will assist with the research and development phase of a new project looking at aspects of mental health with a specific focus on Berlin. Alongside pursuing self-directed research, the fellow will work closely with members of Wellcome’s International Cultural Programmes team and Wellcome’s Germany Office under the direction of the International Cultural Producer Danielle Olsen to:
- Develop external partnerships across the city with partner organisations on the theme of mental health in Berlin investigating potential archives, collections, institutions and community led organisations that could provide a focus for transdisciplinary research
- Serve as connector across participant spaces and places, developing creative new links with international city partners (in Bengaluru, New York and Tokyo) as the project develops
- Assist in developing interdisciplinary and inclusive methods and processes between and across the Arts and Sciences on a mental health theme
- Participate in a launch meeting in July 2021 on a mental health theme with a Berlin City focus
- Explore crossover and hybrid experimental curatorial possibilities utilizing original creative work, events, and public programming.
|
| 30/06/2021 |
£132,988 |
|
UNIVERSITY OF NOTTINGHAM |
Schooling in England is complex and evolving. Large-scale academisation has fragmented local landscapes and created multiple models for knowledge exchange, increasing the risk that continuing professional development (CPD) for teachers becomes variable in terms of quality, equity of access, and impact. More recently, national CPD frameworks have been made more coherent, while local areas are being encouraged to coordinate CPD offers through new Teaching School Hubs.
Understanding how this systemic process of fragmentation and re-formation is impacting on CPD for schools and teachers is a pressing concern. The EQuaLLS project will focus on ‘local learning systems’ (LLS): place-based localities encompassing a mix of school structures and hub arrangements for teacher CPD.
Using primary mathematics as a case study, we will research 'to what extent, and how, do LLS operate to provide high quality, inclusive professional learning for schools?' In four phases, we will: i) harness existing knowledge; ii) identify three representative localities and 18 schools for study; iii) investigate equity and quality of primary mathematics CPD; and iv) analyse findings, identify implications and disseminate these widely.
The findings will inform policy and practice, helping school and system leaders to shape and navigate high quality, inclusive and effective local CPD systems.
|
| 30/06/2021 |
£140,158 |
|
UNIVERSITY OF OXFORD |
Antibiotic resistance in Vietnam is amongst the highest in the world, driven by high levels of antibiotic use for human and animal health. Community understanding and perceptions about antibiotics and antibiotic resistance is poor, and antibiotics are often prescribed inappropriately in healthcare settings. There is limited evidence for the effectiveness of public engagement approaches to promote appropriate antibiotic use, compared to more traditional education-based methods, or for understanding the pathways and facilitating conditions for successful behaviour change.
We will facilitate community-wide change in the way people prescribe and use antibiotics for human and animal health. We will compare three different One Health approaches to change behaviour: training for human and animal health-workers; a public information campaign for communities and farmers; and participatory action research groups. Activators in communities and healthcare settings will guide groups through a four-phase action cycle similar to Wellcome’s Responsive Dialogues approach, covering: 1. Understanding the problem of antibiotic resistance; 2. Planning and implementing strategies; 3. Monitoring strategies and generating evidence; 4. Evaluating strategies and planning future actions. We will evaluate the impact on knowledge and behaviour through qualitative and quantitative methods. We will engage local researchers and policymakers through formative discussions and dissemination meetings.
|
| 30/06/2021 |
£35,000 |
|
SANDPAPER FILMS |
My Planet Now is a cinematic short film and feature documentary for worldwide release that seek to break new ground and provide a genuine moment of global coming together on the climate crisis.
The films will tell the global story of the climate crisis in a uniquely human way by inviting ordinary citizens from around the world to film and share their personal stories of their relationship to the planet and experience of climate change. By making these people our co-directors and enabling viewers to experience the world through them, they will offer a sense of connection to the crisis that is unfiltered, intimate and immediate – strikingly different from typical climate crisis documentaries.
The films will marry stories from the frontlines with stories that offer hope and offer a constructive way forward. Critically, they will also bring attention, insight and understanding to the relationship between health and climate, in alignment with Wellcome’s strategic objectives.
The feature documentary’s large-scale, multi-pronged impact campaign will target global and national decision-makers, key stakeholders and the public (including specific target communities). A central theme will be the relationship between climate and health, and we have enjoyed positive initial discussions with WHO about this prospect.
|
| 30/06/2021 |
£6,880 |
|
MQ TRANSFORMING MENTAL HEALTH |
The MQ Mental Health Science Summit, in collaboration with Wellcome, is an interdisciplinary mental health science conference. It brings together people from all disciplines and sectors, focused on transforming mental health. Key to this is the involvement of people with lived experience of mental illness, early career researchers, and delegates from LMICs.
Attendance at the Summit is ticketed. Many delegates are attending in a work capacity, and so are both salaried and have their costs covered by their organisation. For certain groups of key delegates, the ticket price is prohibitive. This is particularly true for people with lived experience who often attend such events in a voluntary capacity and some of whom are insecurely employed, early career researchers who often do not have research grants available to cover conference attendance, and delegates from LMICs who are economically less able to have such funds available.
Following Wellcome' Cat Sebastian’s contributions to the organising committee, we are applying for £4,000 to enable subsidised places for delegates from these three groups to attend the Summit. This will enable 30 delegates to attend. Aa agreed, any funds not spent on bursaries for this year’s Summit will be used to widen access at subsequent events.
|
| 30/06/2021 |
£98,806 |
|
BOSTON UNIVERSITY |
Pharmaceutical companies understand the need for modeling stochasticity, by which we can improve the reliability and effectiveness of drugs across the whole population. Our 2020 review in Trends in Pharmacological Sciences, one of the highest impact journals in pharmacology, argued that deterministic models that ignore stochasticity bias clinical and pre-clinical trial analyses. The quantitative systems pharmacology (QSP) groups within drug companies are the core units that model and predict patient outcomes, dramatically reducing the research and development timeline by predicting which drugs will fail before clinical trials begin. These groups have recently adopted stochastic dynamical models in order to better achieve their goals. Discussing with CJ Musante, Global Head of Pharmacology at Pfizer, the main reason that stochastic models are not more widely used is due to a lack of software that addresses the needs of QSP modelers. Stochastic models are more predictive of patient outcomes, but computationally expensive. Moreover, turnaround times needed by QSP teams are too short to make use of stochastic models with current software. This proposal addresses this problem, proposing to build software tooling which automates the construction and solution of stochastic models in a way that is orders of magnitude faster than what exists today.
|
| 30/06/2021 |
£2,135,985 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Not available |
| 30/06/2021 |
£0 |
|
UNIVERSITY OF SHEFFIELD |
My research is about what influences people in Ghana to use cancer services. Cancer is an increasing problem in Ghana due to changes to lifestyle and population age. Many things influence cancer services use including, disease beliefs, stigma, healthcare trust, and costs. The Ghanaian health system seeks to expand cancer services in a way that benefits as many as possible, but challenges remain in understanding why some patients do not attend.
I plan to use mixed methods to explore what influences cancer service use and how this information can be useful for Ghanaian policymakers. A key stage will involve surveying public members’ beliefs and behaviours. I will analyse data collected to see how information about age, gender and job relate to peoples’ views and might influence whether they would use cancer services; I also hope to build profiles of types of people to help policymakers target help to those most in need. To further understand and check the analysis, I will use narrative interviews with a range of the public to listen to what they think and why they act as they do.
I will bring together the findings and discuss with policymakers how this could help inform their decision-making.
|
| 30/06/2021 |
£0 |
|
UNIVERSITY OF SHEFFIELD |
County lines (CL) trafficking is a model of illegal drug (heroin and crack cocaine) distribution that has emerged recently in the UK, whereby city-based dealing groups exploit the labour of children and adults, often in vulnerable circumstances in order to deal directly to smaller coastal and market towns. Involvement in CL is associated with experiencing a wide range of health harms including violence and sexual exploitation.
CL is causally complex. The many individual-level risk factors currently thought to lead to vulnerability CL exploitation (mental health issues, prior histories of abuse and neglect, being excluded from mainstream education, being in care, prior offending, drug addition, disability) are themselves determined by complex, interacting upstream socio-economic factors. In order to capture this complexity, I aim to take a systems modelling approach to CL trafficking – viewing the CL phenomenon as an emergent property of a dynamic and open, adaptive system. This model could then be used for ‘what-if’ policy scenario testing, estimating the possibility for cooperation or conflict between the goals and activities of a wide range of statutory bodies, and could guide the design of coordinated cross-sectoral interventions.
|
| 30/06/2021 |
£0 |
|
UNIVERSITY OF OXFORD |
Dietary sodium – typically, common salt – is essential to all animals for health and survival, but when consumed in excess it is profoundly damaging, being a leading risk factor for cardiovascular morbidity and mortality worldwide. Eating salty foods is often a pleasurable experience, leaving many individuals struggling to keep their diet healthy.
Whether the taste of salt is rewarding or not depends on the brain’s reward pathways, which make salt less rewarding when the body needs it less. However, periods of sodium deprivation can subvert this, often leading to consumption beyond physiological requirements. This response to a period of deprivation may explain why some individuals are unable to regulate their sodium intake in daily life.
To better understand the brain circuitry regulating sodium appetite, I will use a combination of animal behavioural and neuroscientific techniques. My focus will be on dopamine, a key neurotransmitter involved in the brain's reward pathways, in addition to electrical activity in the wider brain. I will observe these aspects of brain function during periods of sodium deprivation to shed light on their role in overextending the sodium appetite beyond healthy consumption, delivering new insights about the brain’s role in nutritional disorders and appetite regulation.
|
| 30/06/2021 |
£0 |
|
UNIVERSITY OF EDINBURGH |
Approximately half of the global population is currently at risk of malaria infection, with an estimated 0.5 million deaths annually. Malaria is caused by Plasmodium parasites, which have a complex life cycle involving a vertebrate host and mosquito vector. Blood stage parasites cause the symptoms of malaria in humans, and are therefore the target of most current therapies. In order to reduce the incidence of malaria, and therefore global disease burden, a drug to block transmission between the host and vector is needed. The complex regulation required in transmission stage parasites remains poorly understood. Ubiquitylation is a well-researched post-translational modification which is commonly associated with protein degradation, but also has a range of effects from protein re-localisation to induction or arrest of cell signalling events. The role of ubiquitin in transmission stage parasite development is unknown. We aim firstly to identify the ‘ubiquitome’ of Plasmodium bergheiparasites during transmission stage development using ubiquitin capture systems and mass spectrometry. We subsequently aim to investigate the role of these ubiquitylated proteins during transmission using genetic engineering. These results will improve our understanding of the role ubiquitin may play in the regulation of transmission stage parasite development, and inform future drug discovery efforts.
|
| 30/06/2021 |
£0 |
|
UNIVERSITY OF CAMBRIDGE |
In the early mammalian embryo, there is a clump of identical "naïve pluripotent" cells. After implantation in the mother’s uterus, these cells diverge into a multitude of different cell types during a process called gastrulation. During this process, the three main lineages of the mammalian body, ectoderm, mesoderm and endoderm, are formed and shortly after, the basic body plan and body axes are established. Here, we focus on formation of mesoderm that gives rise to cell types such as blood cells.
While every cell in our body is in principle equipped with an exact copy of the same genetic information, in the form of DNA wrapped around proteins called histones, it is poorly understood how protein complexes that modify these histones, such as the MLL/COMPASS complex, control the process of mesoderm differentiation.
To address this, I will use advanced imaging techniques that can watch individual MLL/COMPASS or the DNA sites to which they bind. I will use embryonic stem cells that mimic in a dish the changes that occur as pluripotent cells differentiate towards mesoderm.
We hope to understand the driving forces behind the transition from pluripotent cells towards mesoderm lineages, providing overarching mechanistic principles of lineage diversification.
|
| 30/06/2021 |
£0 |
|
UNIVERSITY OF SHEFFIELD |
Sub-Saharan African countries continue to bear the burden of cervical cancer. High cancer incidence and high mortality rates can be decreased by available evidence-based interventions, such as vaccination, screening, and early referral for treatment, if they are implemented on a large scale. The large-scale programs though are expensive and not always affordable in low-income countries.
In this study, I aim to examine the economic costs and effect of the World Health Organization cervical cancer elimination strategy in Nigerian health system by 2030. The strategy involves attaining immunisation coverage of 90% for Human papilloma virus (HPV) vaccination, cervical cancer screening coverage of 70% and 90% treatment targets for identified cases .
I will review existing literature, conduct key informant interviews and simulation exercises to provide evidence on the appropriate resources and infrastructural investments required to attain the targets for HPV vaccination, cervical cancer screening and treatments of pre-invasive and invasive cervical cancer in Nigeria by 2030.
The study will provide evidence to guide decision makers in Nigeria and other sub-Saharan countries in allocating resources to address cervical cancer control in a robust, evidence-based and equitable manner.
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| 30/06/2021 |
£0 |
|
CARDIFF UNIVERSITY |
Magnetic resonance imaging (MRI) it is a powerful technique which allows brain tissue to be explored indirectly. Despite more than 40 years of innovation, the standard clinical MRI protocol remains largely unchanged: a set of 3 images influenced by ‘relaxation’ phenomena, namely how quickly tissue returns to equilibrium when perturbed by a radiofrequency pulse. Radiologists detect pathology through differences in relative intensity. While recent advances can estimate relaxation times directly, facilitating quantitative MRI, the biophysical origins of differences in relaxation times are poorly understood. In brain tissue, differences in cell size, orientation and make-up have all been posited, but their contributions have not yet been fully characterised. I will use computer simulations and real MRI experiments to tease-apart these mechanisms. This will include validating the specificity of different imaging parameters in animal-models using histology and further evaluating their sensitivity in the human brain at different stage of development. My aim is to make quantitative MRI more interpretable, boosting its clinical utility both in neuroscience and medicine.
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| 30/06/2021 |
£0 |
|
UNIVERSITY OF BIRMINGHAM |
The inflammatory response is a sophisticated mechanism used by the body to protect against injury and invading microorganisms and requires the trafficking of disease-fighting immune cells from the bloodstream to the site of injury. Resolution of the inflammatory response involves removal of immune-related infiltrate which if left unresolved can lead to chronic inflammatory pathologies. Carbohydrate-binding proteins called galectins, are expressed by cells that line the blood vessels and play fundamental roles in both the initiation and resolution of the inflammatory response. Changes in the frictional force generated by blood flow through the blood vessels can be detected by these cells which leads to subsequent changes in gene expression and release of these immune-modulating proteins. We aim to investigate and characterise the factors that regulate the endogenous expression of galectins from endothelial cells lining the blood vessels and the functional role they play in vascular inflammation. We aim to use a combination of inventive in vitro, ex vivo and in vivo experiments that combine physiological flow conditions and inflammatory mediators, to study the role of endothelial galectins in vascular inflammation and the mechanisms that underlie this.
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| 30/06/2021 |
£0 |
|
UNIVERSITY OF BIRMINGHAM |
Maintenance of gut health is dependent on the complex interactions between different cell types in the intestines and the immune system. Communication between these cells ensures that the barrier between the body and the gut contents is not disrupted and enables threats, such as harmful bacteria, to be detected by one cell subset and eliminated by another. The interactions between these cell types are disrupted during inflammation and disease, such as colitis, cancer, and infection. Understanding these signals and how they are perturbed during disease is vital. Certain bacteria are detected using receptors called NAIPs; we aim to understand how activation of NAIPs subsequently affects the rest of the immune system and how this impacts disease development. We will delete NAIPs from epithelial cells in the gut and identify resultant changes in immune cells. We will test this in models of colitis, colorectal cancer and Salmonella infection. I will look at changes in gene expression following NAIP deletion and identify the soluble mediators which influence the immune response. This project will aid our understanding of NAIPs during inflammatory disease development and thus generate potential targets for treating these diseases in the future.
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| 30/06/2021 |
£0 |
|
UNIVERSITY OF BIRMINGHAM |
Cancers are composed of mutant self-cells that exploit their environment to grow. The immune system can identify these altered cells as harmful and kill them. However, in some patients this immune response can become dampened over time. This is due to expression of "immune checkpoints" on a population of white blood cells called T cells. These checkpoints act as brakes on the immune response. In recent years, scientists have developed drugs to block these checkpoints, with the aim of releasing the brake on the immune system to attack the tumour (called immune checkpoint blockade ICB). However, ICB is effective in less than half of patients. One of the effects of ICB is to encourage T cells to make the inflammatory cytokine IFNgamma, which aids in eliminating the cancerous cells. Our initial studies suggest that some important immune checkpoints, such as Lag3, are increased by the cytokine IFNgamma, which may limit the success of ICB therapy. We aim to understand how IFNgamma controls these immune checkpoints on T cells in animal models of cancer. By using mice where their T cells cannot sense IFNgamma we will test whether making T cells insensitive to IFNgamma can improve ICB therapy.
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| 30/06/2021 |
£0 |
|
UNIVERSITY OF BIRMINGHAM |
Thrombosis is estimated to contribute to 25% of deaths worldwide, yet our understanding of the mechanisms behind thrombus formation and related inflammation remain poor. This so-called thromboinflammation can occur as a result of severe infection, for example in sepsis and severe COVID-19. We aim to probe the lifecycle of the thrombus, and understand why it differs between different organs. To do this, we will use the well-established mouse models of Salmonella infection to study the composition of thrombi in different organs. We also aim to investigate the response of human platelets (the main component of many thrombi) to different strains of Salmonella, allowing identification of host and bacterial-specific factors that are affecting the thrombotic response after infection.
This research will help further our understanding of the mechanisms behind the dysregulated inflammatory processes that occur upon infection, including during COVID-19, that can lead to fatal consequences.
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| 30/06/2021 |
£0 |
|
UNIVERSITY OF BIRMINGHAM |
While the importance of smallest cells in blood, namely platelets, in blood clotting is well understood, there is increasing interest in their role in regulating the inflammatory response. Our preliminary observations have revealed platelet aggregation and recruitment within the meninges following infection with the fungus Cryptococcus neoformans, the main causative agent of cryptococcal meningitis. Meningeal inflammation is one of the main contributors towards death in patients with cryptococcal meningitis, and thus targeting this is a potential therapeutic strategy for a disease which kills over 180,000 people every year. This project aims to understand how platelets and leukocytes (e.g. meningeal macrophages) drive inflammation and disease progression within the central nervous system during fungal meningitis. Using techniques such as flow cytometry and microscopy, we will determine platelet-leukocyte interactions during fungal infection in the CNS and define the molecular mechanisms governing these responses. Previous studies have shown disrupting platelet-macrophage interactions worsens disease outcome in sepsis, thus there is scope for targeting these interactions therapeutically. The results from this project will significantly advance our understanding of the pathology of cryptococcal meningitis, a disease associated with high morbidity and mortality, whilst providing novel insights into the immune functions of platelets which are poorly understood.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BIRMINGHAM |
Biotin synthesis deficient mutants of Pseudomonas aeruginosa can be killed by the diabetes drug metformin. I previously hypothesised that metformin disrupts metabolism and energy production, but not enough to kill Pseudomonas. This loss in energy may be compensated for by biotin mediated energy production, and therefore when this is also lost metformin has antimicrobial activity. I aim to understand the mechanism of action of metformin, the resistance mechanism of biotin and to try produce a novel combination therapy using metformin and a biotin production inhibitor. I will test P. aeruginosa growth in different carbon source medias +/- metformin to validate if metformin mechanism of action is metabolism linked. I will also try to elucidate the target of metformin via a suppressor screen and the use of TRADIS. Alternatively, I propose 2D-TPP. To validate if biotin resistance is related to bio-energetic compensation I propose an extracellular ATP accumulation assay. Next, the biotin synthesis enzyme BioA would be purified and an existing drug library will be used to screen for inhibitors. Should time permit, I will elucidate the structure of BioA using x-ray crystallography. These studies will help produce or inform the production of a novel combination therapy for P. aeruginosa infection.
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| 30/06/2021 |
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UNIVERSITY OF BIRMINGHAM |
I will investigate the role of efflux pumps in antibiotic resistance by researching two themes. Firstly, by looking at the function, prevalence and impact of plasmid encoded efflux pumps. There have been increasing reports of plasmid encoded RND efflux genes. To our knowledge no one has collated the incidence of RND pumps found on plasmids, their spread or potential roles in antibiotic resistance via the efflux of antibiotics. Using a clinical Acinetobacter pittii isolate, I will define the functional role of RND efflux pump genes in the laboratory for example by using efflux assays to measure export and minimum inhibitory concentration experiments to define the substrate profile.
The second theme will explore two Acinetobacter species: A. baumannii and A. lwoffii. Both species inhabit the same niche (hospitals) and cause high numbers of infections in immunocompromised patients. We wish to understand why A. baumannii is drug resistant and A. lwoffii is drug susceptible. To do this we will look at the variations in the resistance and efflux pump genes in clinical isolates of both species and hypothesise why A. lwoffii has not yet developed drug resistance and if there are any indications that it might in the future.
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| 30/06/2021 |
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UNIVERSITY OF BIRMINGHAM |
Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality globally (Quaderi and Hurst, 2018). Worsening of typical daily symptoms (acute exacerbations) are frequently instigated by infection or pollution and are associated with a greater mortality (Toraldo and Conte, 2019). Antibiotic treatment is often used to alleviate exacerbations (NICE guideline, 2018).
The aim of this study is to collect longitudinal respiratory samples from COPD patients at baseline and post-exacerbation, including following antimicrobial treatment, and using the technique of shotgun metagenomics with long read nanopore sequencing, to probe the microbial community structure and investigate the presence and burden of antimicrobial resistance (AMR) genes. Method development will be required as respiratory samples have a significant proportion of human DNA which can make detection and analysis of microbial reads difficult (Hasan et al, 2016).
I will explore different extraction and human DNA depletion methods to enable a greater sequencing depth of microbial reads to be obtained, while minimising bias on community taxon distribution. AMR genes detected will be related to specific organisms and clinical data. This will help inform treatments used in the management of COPD and identify potential biomarkers to predict clinical outcomes (Leitao Filho et al, 2019).
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Antimicrobial resistance (AMR) and population aging are currently two of the greatest threats to the human race. While extensive research has been carried out on each individually, little is known about the impact of aging on AMR. This is somewhat surprising since a decrease in efficacy of antibiotics married with a population-wide increased susceptibility to infection due to aging could be catastrophic. During this project, I aim to characterise the relationship between host age and likelihood of contracting an infection which is resistant to one or more antibiotics, or the rate at which resistance develops during treatment. This will be carried out using electronic health records and meta-analysis. Mechanisms which may give rise to these relationships will then be proposed, tested using mathematical modelling, and further investigated using the model organism Drosophila melanogaster. Understanding the relationship between age and AMR may highlight certain patient groups where AMR interventions should be focussed, or where use of certain antimicrobials should be increased or reduced. Targeting antibiotic interventions in this way is hoped to slow the rapid spread of resistance which may be exacerbated by an aging population and preserve antibiotic efficacy to prevent a dramatic increase in morbidity and mortality.
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| 30/06/2021 |
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UNIVERSITY OF NOTTINGHAM |
Antimicrobial-resistant pathogens are of increasing concern, and the O’Neill report [https://amr-review.org] predicts that, by 2050, more deaths globally will be caused by antimicrobial-resistant infections than cancer. One solution is reducing antimicrobial dependence. Our approach is preventing formation of biofilms (communities of microbes attached to surfaces) on blood-contacting catheters. The immune system is then able to deal with the infection, preventing antimicrobial treatment (Jeffery and Mundy 2020).
Hook et al (Hook et al. 2012) identified polymers that resist biofilm formation in the absence of blood, now used to coat urinary catheters (Jeffery et al. 2019) with Wellcome Trust funding.
In vitro testing of candidate co-polymer coatings in bacterial culture in blood and the analysis of the adsorption of blood components on their surface will allow optimisation of biofilm resistance and haemocompatibility of the coating. Co-polymerising with protein biofouling resistant monomers will be conducted, leading to materials that perform both anti-protein biofouling and anti-biofilm functions. Determination of mechanical properties will ensure integrity of the coating during mechanical deformation. Once optimised, the coating will be tested in an in vivo foreign body infection model.
This technology has the potential for patients with blood-contacting catheters to experience fewer infections and associated risks.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
The resilience of the human hematopoietic system declines with age as it becomes more susceptible to age-related disorders or malignancies, produces lower blood counts and is less capable of fighting off infections. When subjected to chemotherapy, it can be severely challenged, but cell counts will usually recover in 2 to 3 weeks. However, in older patients, the recovery can be slower, and individuals over the age of 75 are unable to tolerate more intense regimens.
In my project, I will compare and contrast the clonal composition and functional characteristics of hematopoietic cells from patients before and after receiving chemotherapy. To achieve this, blood samples of consenting patients between the ages of 40 and 90 will be obtained before and after their treatment, and I will grow single-cell derived colonies and then profile their DNA and single-cell RNA. This will allow me to measure how perturbation of the systemic environment affects the clonal composition of blood, how the proliferative capacities of cells are affected and what functional changes occur in their transcriptomes.
This study will help us understand to what extent the fitness of hematopoietic stem cells is environment-dependent and how ageing affects the recovery time after chemotherapy.
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| 30/06/2021 |
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UNIVERSITY OF LEEDS |
Macromolecules under flow at the biological mesoscale (10 nm L t L > 1 mum, t > 1 mus) whereas atomistic scales (L t
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, currently affecting 145,000 people in the UK. It is known that specific mutations in certain genes can increase the risk of developing Parkinson’s disease. One such gene is GBA, which represents the greatest genetic risk factor for developing PD. Despite this, we still don't fully understand how mutations in GBA increase the risk of developing PD and progress is limited by the lack of relevant animal models of GBA-associated PD. The Wade-Martins lab has therefore developed a new mouse model to study GBA-associated PD. These mice harbour a human GBA gene, which contains a mutation called L444P. My project will use biochemical, electrophysiological and behavioural techniques to investigate how disease in these mice progresses with age. I will also assess the effectiveness of potential therapeutic strategies at restoring the function of GBA. The second phase of my project will characterise pathology in stem cell derived dopaminergic neurons from Parkinson’s patients. These neurons also carry the L444P mutation in GBA, which will allow the translation of pathological findings in the mice into human neurons. This project will contribute to the field’s understanding of the pathology of GBA-associated PD.
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| 30/06/2021 |
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UNIVERSITY OF NOTTINGHAM |
Bacterial biofilms pose a major threat to global health, due to their ability to evade antibiotics and host defence systems; therefore, leading to the development of chronic infections. The process of biofilm development is regulated by a series of molecular pathways, including cell-to-cell quorum sensing (QS) signalling. The disruption of this QS signalling pathway, through the use of QS inhibitors, shows great potential for the treatment of biofilm infections, while minimizing the selection pressure exerted on the bacteria. The incorporation of nanoparticle drug delivery systems enables the enhancement of antimicrobials delivery, including an increase in drug solubility and prolonged systemic circulation. Furthermore, these materials can be equipped with stimuli-responsive switches enabling a targeted drug delivery. Of particular interest is the use of poly(b-amino esters) (PBAEs) reported to selectively target and accumulate within bacterial biofilms. We hypothesize azoreductase enzymes, released by bacteria, can induce the opening of PBAE nanoparticles equipped with azobenzene moieties. This targeted cleavage of the azo bond would result in the release of encapsulated QS inhibitors, leading to the prevention of biofilm maturation. This delivery pathway has the potential of significantly enhancing the efficiency of antimicrobial delivery to biofilms, enabling the prevention of highly challenging chronic infections.
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| 30/06/2021 |
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UNIVERSITY OF NOTTINGHAM |
Antibiotic resistance is one of the greatest threats to human health faced today. Infections previously treatable with antibiotics no longer respond, and bacteria have emerged that are resistant to all currently available antibiotics (O’Neill, 2016). As such, it is imperative to find novel treatment options including new antibiotics but also to develop alternative methods. One such method is to use other bacteria for our own benefit. Bdellovibrio bacteriovorus is a small, highly motile bacterium with an interesting food - it preys upon other bacteria, eating them from the inside out, including many bacteria that cause harmful infections in humans. However more must be known about the predatory behaviour of Bdellovibrio before it can used in the clinic. This project focuses on chemical signals (polyamines) produced by Bdellovibrio, its prey, and its potential patient hosts. It asks how these signals alter the predatory ability of Bdellovibrio. This will increase our understanding of how Bdellovibrio senses its prey in host and natural environments and the signals it needs to continue the hunt. More detailed knowledge of this predatory behaviour in vitro will allow us to better predict how Bdellovibrio may behave in vivo inside a patient during future potential therapeutic uses.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Human mobility plays an important part in the spread of infectious diseases. Mathematical models can assess the risk that an emerging outbreak will spread internationally, providing decision-makers with information to support early surveillance and control measures. In this project I will aim to improve how well these models capture international mobility patterns by exploring the suitability of different measures of connectivity. I will compare flight passenger data (which is commonly used in international infectious disease spread models) with alternative transport passenger statistics and novel data, such as location data from mobile phones. I will use these data sources (both individually and in combination) in models to make predictions of the risks of imported and exported disease cases, and assess how well these different models can retrospectively predict the global spread of COVID-19. I will use these findings to develop a statistical model and tools that are ready in advance of future outbreaks to make rapid assessments of the risks that they will spread geographically. The project will lead to more realistic models of international infectious disease spread and thus improve the information that is available to support decision-makers in controlling future outbreaks before they become widespread.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Adolescents and young adults (10 to 24-year olds) account for a significant proportion of people living with HIV globally. Due to psychosocial and biological changes associated with individuals in this age category, they are more likely to have poorer treatment outcomes compared to younger children and older adults. Two interventions that have shown potential to improve outcomes in this age group include timely disclosure of adolescents’ HIV status to them and inclusion of the highly potent integrase inhibitor 'dolutegravir' into antiretroviral therapy regimens. However, there is limited knowledge on the psychosocial impacts of disclosure, and level of uptake and impact of dolutegravir use among adolescents and young adults in sub-Saharan Africa.
I aim to analyse data from a longitudinal, community-traced cohort study of HIV-positive adolescents in South Africa (Mzantsi Wakho) to assess the effects of timely HIV status disclosure on anxiety, depression, behaviour and suicide. I also aim to analyse routine HIV program data and develop a mathematical model of HIV progression, to estimate the level of uptake and effects of dolutegravir on treatment outcomes among adolescents and young adults.
My findings will help improve current HIV status disclosure guidelines and assess the progress in dolutegravir transition among young individuals.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Dengue virus (DENV) transmission is dependent on the vector capacity of mosquito populations (their ability to carry and transmit DENV), which is influenced by seasonally varying traits such as mosquito lifespan. Novel and effective DENV control measures include the release of mosquitoes infected with Wolbachia bacteria, which confers reduced vector capacity, and vaccination. The high global economic and health burden of DENV is increasing with growing urbanisation and climate change. To target control measures to areas with the greatest burden of DENV, accurate estimates of where DENV is spreading the most are necessary.
We will develop DENV transmission models which integrate mosquito traits fitted to data describing the number of reported DENV cases over time in South East Asia and South America. The models will be further developed (addition of spatial structure) to explore the impact of population movement on the spread of DENV. In addition, the potential impact of novel control measures will be evaluated, including the release of Wolbachia infected mosquitoes, to explore their impact on DENV transmission. This research is therefore of high relevance to public health and to the DENV research field.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Phylodynamic methods utilising genetic and epidemiological data, such as contact-tracing, hot-spot identification and modelling of strain-specific transmission dynamics, can provide a useful way for forecasting infectious disease outbreaks and transmission dynamics of interest. However, information from epidemiological investigations and genome sequences are rarely utilised together in current gold-standard methods used for outbreak assessment (2). We propose to develop novel phylodynamic methods for real-time outbreak detection of RNA-viruses (Sars-CovV-2, Influenza) using contact-tracing and predicted hotspot identification, as well as further developing understanding of transmission dynamics at the strain-specific level in a sustained outbreak over time. Sars-CoV-2 sequence data is sourced from COG-UK and linked to epidemiological patient data from PHE (3). Influenza sequence data is sourced from PHE, including strain-specific samples for Influenza A and B, and linked to epidemiological patient data from 2015 to present (4). Methods will be developed into publicly available R packages for application in future RNA-virus outbreaks. We aim to advance methods for incorporating genome sequence data into real-time forecasting of outbreak detection (5–8). Additionally, by increasing understanding of strain-specific transmission dynamics, we will advance understanding of seasonal infectious disease transmission at local, community and national level, and inform annual vaccine development in the UK (9).
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| 30/06/2021 |
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UNIVERSITY OF LEEDS |
The outer membrane (OM) of gram-negative bacteria is the first line of defence against exogenous threats, and helps confer antibiotic resistance and enable biofilm formation. It is an asymmetric bilayer, consisting of an outer leaflet of lipopolysaccharide (LPS) and an inner leaflet of phospholipids and cardiolipin, and is crowded with outer membrane proteins (OMPs). While much is known about OMPs in symmetric phospholipid membranes, the effects of LPS, membrane asymmetry and protein crowding remain largely unclear – although they have been shown to be important. I will explore the structure, dynamics and function of OMPs in native-like membranes through an interdisciplinary approach combining molecular dynamics simulations, cryo-electron microscopy and biochemical/biophysical approaches. Specifically, I will develop protocols to generate OM-like asymmetric vesicles. Exploiting cryo-electron microscopy and molecular dynamics simulation methodology, I will elucidate the effects of the physiological OM components on FusA (a model OMP) in a broad range of asymmetric membrane contexts. In addition, substrate binding and in vivo function of FusA will be determined. Together, this work will elucidate details of how the OM modulates OMPs, providing clearer pathways to understand gram-negative bacterial biology, the role of the OM in antibiotic resistance and to develop better therapeutics.
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| 30/06/2021 |
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UNIVERSITY OF LEEDS |
Tissue damage and infection can elicit a specific response in the bone marrow called emergency haematopoiesis, which results in the production of myeloid-type blood cells. This response is mediated by a protein complex signalling hub called the Myddosome. After damage or infection resolution, the termination of emergency haematopoiesis is crucial, as prolonged emergency haematopoiesis may result in chronic inflammation, autoimmune disease and cancer. As such, termination of emergency haematopoiesis is carefully regulated by orchestrating a series of signalling events.
Using a multidisciplinary approach involving structural and cellular biology, this project aims to understand the molecular and functional basis of Myddosome-regulating complexes that participate in termination of emergency haematopoiesis. To achieve this, I will use cryo-electron microscopy to gain high resolution structures and use mutational analysis to probe protein-protein interactions and their functions. Results from this project will provide structural and functional information which will enable us to design potential therapeutics against immune-mediated diseases and hematopoietic cell proliferation.
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| 30/06/2021 |
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UNIVERSITY OF LEEDS |
Interstrand crosslinks (ICLs) are the most toxic form of DNA damage, forming a blockage to essential cellular processes by preventing separation of the two strands of our DNA. DNA crosslinking agents that induce this form of damage have been at the frontline of chemotherapy for over 50 years. However, to protect our genomes from their constant exposure to DNA damage sources, our cells have specialised repair pathways to detect and remove ICLs. Understanding the molecular details of DNA damage repair pathways is therefore essential for advancing cancer research. Using a range of structural techniques and functional assays, including X-Ray crystallography and Cryo-EM, I will focus on a structurally uncharacterised complex involved in recruiting SMC (structural maintenance of chromosome) 5/6 to sites of double strand breaks (DSBs) introduced during the Fanconi Anaemia pathway, a major ICL repair pathway in proliferating cells. This complex, SLF1-SLF2, directly interacts with the E3 ubiquitin ligase, Rad18, which binds sites of DSBs marked by post-translational modifications, appearing to define a linear recruitment pathway for SMC5/6. This study will provide further insight into how toxic ICLs are resolved and could identify novel interactions that can be specifically inhibited for development of new cancer treatments to enhance chemotherapy.
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| 30/06/2021 |
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UNIVERSITY OF LEEDS |
The hepatitis C virus (HCV) infection induces an intracellular rearrangement in the host cell forming many vesicles referred to as replication organelles. In particular, double membrane vesicles (DMVs) are proposed sites for the HCV replication. The HCV polyprotein is composed of structural and non-structural proteins. Five of the non-structural proteins form the replication complex. I aim to determine the ultrastructure of the HCV replication complex by taking a multidisciplinary approach. I will use biochemical, biophysical and structural analyses, including confocal microscopy, super-resolution approaches and cryo-CLEM, to visualise how and where these non-structural proteins form the replication complex. I aim to investigate in detail whether the replication complex is formed inside the DMV or on the surface. I will also determine the topology of nascent HCV RNA which will provide extensive knowledge about HCV replication. These studies will help to explain the concerted action of non-structural proteins and their role in HCV replication.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
In the neurodegenerative disease multiple sclerosis (MS), the lipid-rich layer surrounding nerve fibres known as myelin is lost, in a process known as demyelination. While this is thought to contribute to neuronal loss seen in MS, it is not clear exactly how neurons respond to demyelination, which prevents targeting key mechanisms that could be responsible for neurodegeneration in disease.
In animal models of demyelination, it has been observed that synapses, the structures that allow neurons to communicate with one another, are lost. Synapses are also affected in MS, which could contribute to clinical disability and cognitive impairment. We expect that synapse loss is an early feature of the neuronal response to demyelination, and if prevented, may protect neurons from degeneration. In this study, we aim to understand mechanisms of synapse loss and neurodegeneration after demyelination, and to determine if they are direct effects of demyelination or mediated by immune cells that respond to demyelination. We will employ zebrafish as a model, because we can follow individual neurons and synapses before, during and after demyelination using live imaging. This research will allow us to investigate the relationship between demyelination and synapse loss and identify strategies to prevent neuronal loss from ocurring.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
The way a brain is organised stems from a combination of evolutionary and environmental influences. I aim to understand how these factors have shaped how different primate brains are organised. Specifically, I am interested in how visual experience and evolutionary adaptations have shaped the organisation of the occipital (visual) lobe.
To study occipital lobe organisation, I will reconstruct white matter tracts from MRI scans of primate brains. I will then use computational approaches to compare these tracts, finding which tracts differ between species. Using our knowledge of phylogenetic relationships and different animals’ lifestyles, I can test hypotheses about which tracts diverged at different points in evolutionary history, and about which adaptations are unique to different ecological niches. Afterwards, I will explore how ecological specialisations affect connectivity on a cellular level, in finer-grained detail than MRI can offer, by staining brain slices for axons and their myelin and analysing the innervation patterns of specific white matter tracts.
This work will yield insights into the evolution of the primate visual system and illuminate how it evolved to subserve uniquely human functions like reading. This work will additionally help us understand principles of brain diversity, with implications for evolutionary biology and translational neuroscience.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
The environment is continuously changing. Our nervous system is capable of integrating these changes over time, facilitating an adaptive interaction with the world. At any moment, our brains are retaining past experiences and estimating future events. In the words of the philosopher Gottfried Leibniz: the present is saturated with the past and pregnant with the future. For example, when two people are having a conversation, retentions of what has just been said are needed in order to construct what will be said in the immediate future.
During my doctoral research, I will try to answer the question of whether retention of immediately past events and anticipation of future ones influences present perception both in the visual and in the auditory domains. By manipulating task demands, I also hope to explore whether such effects are flexible and context dependent. To explore how different brain regions across the visual and auditory systems allow for retention and anticipation, I will record electrical brain activity of participants while they observe learned and unlearned sequences of stimuli, such that we can manipulate their anticipation of what is coming . This work will advance the understanding of how events in the environment are integrated in time.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
X chromosome inactivation (XCI) is the mechanism that equalises X-linked gene expression in mammalian XX females relative to XY males. It is triggered by the expression of the 17Kb long non- coding RNA Xist. Upon transcription, Xist spreads in cis ‘coating’ the elected inactive X (Xi) and recruits factors acting in concert to modify the underlying chromatin and repress gene activity. A crucial step for XCI is the limited in cis localization of Xist, ensuring its action is restricted to the Xi elect only. Previous studies revealed Xist to be tightly anchored to the Xi territory through interaction with nuclear matrix proteins, however the mechanisms governing this process remain poorly understood. I will investigate the nature and the single-cell dynamics of Xist interactions with its anchoring factors through the genetic dissection of their functional domains in mouse model systems, using a combination of molecular biology and advanced microscopy approaches, such as live imaging and super resolution microscopy. Our research will elucidate the single-cell interplay between Xist and its localisation factors and their potential role in influencing Xist behaviour, providing insights into the mechanisms governing Xist spreading and retention within the Xi territory.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Transcription factor (TF) networks are cardinally dysregulated in Acute Myeloid Leukaemia (AML), with many of these dysregulated TFs known to have developmental and homeostatic roles in normal haematopoiesis. I will focus on the E-twenty six (ETS) TF Pu.1 that is known to play an important role in myeloid and lymphoid development. Conventionally, Pu.1 is better known as a tumour suppressor during AML development but, more recent studies within the Huntly Lab have suggested an alternative role for Pu.1 in the maintenance of AML.
I will be using an Npm1c/Flt3-ITD double-mutant mouse model, which recapitulates AML, to study Pu.1 in relevant leukaemic cell populations. I propose to study Pu.1 using chromatin-related genomic and proteomic techniques and will integrate these with gene expression analyses across normal-, early AML- and late AML-derived cell types. I will then aim to corroborating my findings from murine systems in AML patient samples. An understanding of changes in gene expression and the 3D chromatin structure caused by the binding of PU.1 and/or its interactors will unveil novel mechanisms of transcriptional regulation in the AML setting. Looking into the future, the combination of these experimental approaches may enable the development of therapeutics to specifically target PU.1-associated pathways AML.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Infectious disease modelling (IDM) is a branch of epidemiology that uses mathematical models to predict the spread of disease, often through a population. It is especially useful for estimating the impact of prevention and control measures.
After attending recent international conferences, the clear take-home message is that IDM research does not always reach healthcare decision-makers in a usable format, in useful time. ‘Healthcare decision-makers’ include such organisations as the WHO; Centres for Disease Control; International health NGOs; and country-specific Governments and Departments of Health. The bridge between researchers and decision-makers is especially challenging in emergency epidemic-response situations, where crucial action must be taken immediately.
In applied epidemiological research, the goal should be to inform evidence-based healthcare decision-making - answering the policy questions that need an answer. How do we ensure this can be achieved effectively?
This PhD seeks to analyse the use of infectious disease modelling in pandemics and large epidemics, by scrutinizing existing models and working closely with both influential modellers and global healthcare decision-makers on a broad range of outbreak case-studies. We will identify existing challenges on the interface of these two fields and work to develop a document of best practice, implementing change at the international level.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Red blood cells (RBCs) and platelets are important cells in the blood required for oxygen delivery and blood clotting, respectively. Having too few of these cells, which can be caused by things such as cancer treatment, can lead to severe health problems. Although this is treatable using voluntary blood donations, in coming years more donations will be needed. Alternative options must therefore be developed. In answer to this, the Ghevaert group has developed a method (known as 'forward programming', or 'FOP') to artificially produce RBCs and platelets from stem cells in the lab. Unfortunately the cells produced by FOP are less functional than the adult cells found in our bodies, meaning that improvements must still be made. Using a computer program, I will redesign FOP so that it produces more functional RBCs and platelets from stem cells. This redesigning will involve changing the core ingredients used to drive FOP, so that FOP is more likely to produce adult cells. I will also investigate why it is so difficult to produce adult RBCs and platelets from stem cells. Consequently this work will guide future research in a more informed direction, and may provide a viable alternative to donated blood products.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Myeloid malignancies are a range of blood cancers caused by specific mutations in blood cells. These mutations cause affected cells to grow more rapidly and make up a greater proportion of our blood over time in a process known as clonal haematopoiesis (CH). Recent studies have shown CH is commonly found in otherwise healthy individuals with some fraction going on to develop myeloid malignancies. We have previously shown that some of these mutations are particularly common in elderly individuals, although how they lead to CH is currently unknown. My research will study human bone marrow samples and mice carrying these mutations to understand how they cause CH and why they are more common in the elderly. In particular, I hope to identify factors present in the bone marrow of elderly people that alters the behaviour of blood cells carrying these mutations and leads to CH. This could be used to determine which individuals carrying these mutations are at high risk of progression to myeloid malignancy and develop treatments to stop or reverse this process.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
To direct behaviour effectively, animals need to constantly update the value and predictions of the sensory stimuli they encounter. To solve this task, all brains have the ability to change sensory processing and behaviour according to previous experiences, a process termed learning. The aim of this project is to identify what changes in sensory processing underlie the integration of conflicting (rewarding and aversive) experiences which produce opposite behaviour. I will use C. elegans because it has small and anatomically well described circuits for associative learning that share functional features with those of more complex brains and can be manipulated with single cell resolution. I will combine behavioural analysis, genetic manipulation of neuronal communication and imaging of neuronal activity to dissect the mechanisms of neural plasticity that underlie a switch in odour preferences after sexual conditioning. This will consist in identifying the neurons within the circuit for odour processing that release a neuromodulator and establishing the changes in information flow arising from neuromodulation. These studies will provide a mechanistic understanding for integration and resolution of conflict during learning that will illuminate how this process occurs in more complex brains.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Fibrosis (scarring) is a necessary part of regeneration, a stable scaffold around which cells can reorganise themselves to regain function is essential. In the liver, there are different modes in which fibrosis occurs, we need to learn more about what makes them different.
844 million people worldwide have chronic liver disease, with about two million deaths per year. Chronic liver disease can progress to cirrhosis, liver cancer and death. Treatment is limited to removal of the underlying cause or liver transplantation. Importantly, the greater the fibrosis a patient has the poorer the outcomes. Therefore, developing antifibrotic therapies for patients with chronic liver disease will impact significantly on morbidity and mortality. Primary biliary cholangitis (PBC) is a chronic liver disease resulting in destruction of the bile ducts. We have identified a protein called CTHRC1, expressed on scar-forming cells surrounding the duct, in patients with PBC. These cells play a role in fibrosis and disease progression.
To investigate how CTHRC1 contributes to liver fibrosis in PBC I will use liver tissue and cells from PBC patients and mouse models of liver fibrosis to explore whether targeting the function of CTHRC1 could be a new treatment for patients with liver fibrosis.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Regenerative cardiovascular medicine is emerging as a novel therapeutic alternative to heart transplantation in patients suffering from chronic heart failure. This approach aims to restore cardiac functionality by exogenous transplantation of stem cell-derived cardiomyocytes. Although promising, challenges to cardiac repair remain, for example with respect to cell maturation and revascularisation. It has recently been shown in rats, that these challenges can be improved by co-transplantation of stem cell-derived epicardial cells. One plausible explanation for these improvements is paracrine-mediated effects. Paracrine signalling involves secretion of signalling factors in cells to alter the behaviour of surrounding cells, often in a gradient-dependent manner. Paracrine signalling factors include secreted proteins and miRNAs. They can be secreted into the extracellular space directly or packed into small extracellular vesicles, called exosomes. I aim to identify and characterise paracrine signalling factors of stem cell-derived epicardial cells, which promote myocardial maturation and vascularisation. Candidate paracrine signalling factors will be selected based on gene, protein, and miRNA expression and functionally characterised in vitro and in vivo. Identification of effective paracrine signalling factors will make it possible to address selected cardiac repair processes, resulting in new approaches to therapy.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Current research suggests that homo sapiens originated in numerous subdivided populations, opposing the traditional view that we evolved from a single region/population. Existing methods for detecting the size of ancestral populations are limited by their assumption that populations develop in isolation (without mixing with other populations), therefore necessitating new methods that can detect ancient population mixing.
My approach is to simulate different population ancestries – generally speaking, mixing vs non mixing – and see if any of the current methods for population size estimation hold any information in their model parameters that change in the presence of population mixture. Using these results, I will aim to analyse the extent of mixing in ancestral African populations by examining real genome data of extant peoples, such as the San and Yoruba. The impact of my research will be to shed more light upon the origin of homo-sapiens as we developed in Africa, 150,000 to 400,000 years ago.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Intestinal macrophages are crucial in maintaining gut homeostasis and, during health powerful regulatory mechanisms exist to maintain intestinal macrophages in an anti-inflammatory state, allowing them to exist in their antigen- and microbe-rich environment. However, macrophages are now also considered key drivers of intestinal pathologies, such as inflammatory bowel disease (IBD). Moreover, proinflammatory macrophages accumulate in the intestine and promote reduced epithelial-barrier integrity in response to distant inflammation, including cerebral ischemia (stroke). How macrophages can play such seemingly paradoxical roles remains unclear. One line of thought is that functionally-distinct macrophages subsets may dominate in certain contexts, i.e. health, inflammation and repair. Recent work from our lab uncovered at least two transcriptionally-distinct intestinal macrophage subsets, however their locations and functions within the gut wall in different contexts remain unclear. I aim to determine the roles of these macrophage subsets in intestinal inflammation caused by local insult or distant injury, as well as tissue repair. I will use immunofluorescence and flow cytometry together with novel genetic depletion models to assess the spatial and functional characteristics macrophage subsets in experimental IBD and intestinal inflammation caused by cerebral ischemia. These studies will determine whether the paradoxical roles of intestinal macrophages are explained by functional heterogeneity.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Cells must communicate with their neighbours, send, and receive various information as they build and regenerate tissues. This communication is often not well understood, for example during the very first steps of cancer growth. Pre-neoplastic cells (PNCs) (the first cells carrying oncogenic mutations that will lead to cancer) are surrounded by healthy neighbours and contacted by patrolling innate immune cells. I want to know how these interactions between healthy cells of the body and the very first cancer cells may lead to the arrest or support of tumour development.
Evidence from the Feng group shows that neutrophils and macrophages contact emerging PNCs in the skin, and that this interaction results in increased proliferation of cancer-cell colonies (van den Berg et al., 2019). A new synthetic-biology tool called SynNotch allows us to precisely report on direct cell-cell contact at the single cell level (Morsut et al., 2016). I will engineer this tool into the zebrafish, where it will allow us to report on cell-to-cell contact in real-time, and in the living animals. Using this tool, I will study the effects of PNC-immune cell contact.
Additionally, I will study the effects of contact between PNCs and healthy neighbour cells in cell culture.
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| 30/06/2021 |
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KING'S COLLEGE LONDON |
Pbx1 is a TALE homeodomain transcription factor whose diverse regulatory function makes it indispensable for organogenesis (Selleri et al., 2019). Its activity is essential for early pancreatic development as embryos with homozygous deficiency of Pbx1 exhibit pancreatic hypoplasia and cell differentiation defects prior to death in utero at E15.5 (Kim et al., 2002). However, the basic mechanisms underlying the requirements for Pbx in mammalian pancreatic development remain largely unexplored. Using a conditional Cre-Lox system, I will focus on Pbx1 deletion in pancreatic epithelium at various stages of mouse development and in the adult pancreas to determine its role in maintaining pancreatic cell type identity. I will also establish a human induced pluripotent stem cell model to assess whether developmental mechanisms involving Pbx1 observed in mice are also conserved in humans. Here, I will use CRISPRi-Cas9 gene editing to reversibly inhibit Pbx1 at different stages of pancreatic cell differentiation. Lastly, I will construct a gene regulatory network of the pancreatic epithelium using chromatin immunoprecipitation and RNA sequencing data at various developmental stages to test Pbx1 targets both in vivo and in vitro. This project has great potential for advancing the field of diabetes research, disease modelling and cell therapies.
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| 30/06/2021 |
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KING'S COLLEGE LONDON |
The nervous system is the most complex organ in our body with thousands of different cell types. How is such diversity generated? This remains one of the key questions in developmental biology, which ultimately will inform regenerative medicine and cell reprogramming. Single cell technologies have shed light on how progenitor cells may commit to a particular fate, challenging the long-standing assumptions that cell differentiation is a smooth, continuous process.
This project will dissect the molecular mechanisms controlling how progenitors give rise to different cell types in the sensory nervous system of the vertebrate head. Despite a wealth of information on signalling, cell movements and timing of this process, a mechanistic understanding of how progenitors diversify is still missing. This is therefore an ideal context to apply a systematic, single-cell approach to identify and characterise cell fate decisions.
I will obtain single cell gene expression and chromatin state data from the developing chick embryo and use this to predict developmental trajectories, branchpoints, and candidate transcription factors regulating these branch points. I will then use perturbation analysis to validate these predictions. Together, this will reconstruct the molecular circuitry, the gene regulatory network, that drives cell fate decisions in the sensory nervous system.
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| 30/06/2021 |
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KING'S COLLEGE LONDON |
Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy, and involves progressive muscle weakness and wasting, beginning in muscles of the face, shoulder, upper back and lower legs. FSHD is caused by inappropriate expression of a protein called DUX4 in adult tissue. DUX4 is a transcription factor, meaning that it controls expression of other genes. DUX4 upsets the carefully orchestrated pattern of gene expression that allows muscle to function effectively, causing cells to die. However, exactly how DUX4 expression induces muscle cell death/loss are not well understood.
Muscle normally repairs efficiently due to resident stem cells, but loss of muscle in FSHD indicates a compromised repair mechanism. I aim to characterize muscle stem cells in FSHD by examining protein and gene expression in muscle biopsies from FSHD patients. I also aim to explore the dynamics and effects of DUX4 expression on development and function of muscle stem cells, as well as subsequent myofiber formation and regeneration, using induced pluripotent stem cells from FSHD patients and in vivo models. This work will inform whether deficits in muscle stem cell function contribute to the muscle wasting observed in FSHD pathology, and explore potential regenerative therapies.
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| 30/06/2021 |
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KING'S COLLEGE LONDON |
In this project, we hypothesise that there exist a tight regulation of macrophage activation following tissue injury to create environments permissive to different stages of tissue repair. Making use of human iPSC-derived macrophages (iMacs), we aim to gain insight into how they become activated after tissue damage, particularly through scavenger receptors in collaboration with other pattern recognition receptors. By studying knockout iMac models, we will then seek to understand how the IL-10/PGE2 axis and regulatory T cells limit excessive activation. Lastly, we aim to deliver in vivo evidence that some of these pathways are involved in promoting either organ inflammation or homeostasis restoration by using carbon tetrachloride (CCl4)-induced acute liver injury mouse model. A full understanding of these mechanisms will guide the development of potential therapeutic targets that harness specific macrophage properties for clinical benefit.
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| 30/06/2021 |
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KING'S COLLEGE LONDON |
The influence of host genetic factors upon HIV-1 infection is still not fully elucidated. As the virus relies on the host cell machinery and proteins to replicate, host genetics are a key determinant not only of the proteins expressed but also of their functional capabilities – therefore dictating the outcome of virus infection. This research aims to link the natural occurring genetic variation found in the human population with the inherent variability in the capacity of cells from different individuals to support HIV-1 growth. The work will employ well characterised cells from a bank of human induced pluripotent stem cells to obtain macrophages, which are natural targets of HIV-1 infection. Experimental procedures will include characterising how the virus infects and replicates in macrophages, and employing a bespoke bioinformatics pipeline to compare the genome sequences and transcriptomes of cells showing extreme infection phenotypes. With this approach, we aim to identify novel host factors that can regulate viral replication. These results will add new insights into the understanding of HIV-1 infection and disease (AIDS) and suggest avenues to explore as potential novel therapeutic strategies to treat and control HIV-1.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Currently, diagnosis of psychiatric disorders is based on symptoms rather than underlying biological cause. However, symptoms can vary within a disorder and are common across many different disorders. Therefore, it is possible there are shared biological causes for overlapping symptoms across disorders. Immune system dysfunction has been suggested as a potential cause of symptoms and altered brain structure common to many disorders.
I aim to identify groups of individuals with psychiatric symptoms and a genetic predisposition to immune dysfunction. To do this, I will analyse multiple large datasets of people with detailed information about their genetics, brain structure (from MRI neuroimaging), mental health and lifestyle. I will then uncover which specific components of the immune system are different in these groups of individuals. Using epidemiological statistical methods, I will test whether immune dysfunction causes psychiatric symptoms and altered brain structure. I also aim to extend this research to include a large dataset of young individuals (9 -11 years), to determine earlier origins of such relationships between immune dysfunction, alterations in brain structure and development of psychiatric symptoms.
These studies will identify shared biological causes common to many psychiatric disorders to help improve diagnosis, prognosis and move towards personalised treatment.
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| 30/06/2021 |
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CARDIFF UNIVERSITY |
Schizophrenia is a psychiatric disorder which affects around 1% of the population. There is no one single cause of schizophrenia, but genetics is known to play a substantial role. The genes involved in risk for the disorder span many different genes. Mutations thought to be linked to schizophrenia are often seen in individuals without a schizophrenia diagnosis, and I plan to investigate the impact these mutations have on an individual’s characteristics. I will use large-scale datasets in which every protein-coding base pair has been sequenced, highlighting any mutations. I will use information on an individual’s characteristics along with this genetic data to investigate the impacts of mutations in schizophrenia associated genes in both people with a schizophrenia diagnosis, and in those without. I also aim to discover new genes linked to schizophrenia, which will provide insights into the underlying biology of the disorder.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Whether it be catching prey or making dinner, rewards in natural environments take time to pursue. This requires planning into the future, setting goals, and flexibly switching between different strategies when needed. In my PhD I will use computational models alongside fMRI and MEG imaging techniques to explore how humans plan and make decisions in temporally extended environments. In particular, I’m interested in the role of the human frontal lobes in prospective value-based decision-making and goal maintenance.
I will investigate the neural mechanisms by which humans pursue goals and suppress alternative courses of action, versus deciding to abandon goals. In addition, I will examine how individuals differ in this tendency to commit to goals, which may have relevance for our understanding of various psychiatric disorders such as OCD, apathy, and depression. In future projects I will use MEG to investigate the moment-by-moment brain activity responsible for tracking changing rewards, and using this information to make predictions about the future. Finally, I am also interested in how humans weigh up different types of value across time, such as the value of information or increased agency.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Cardiac electrical activity and contractile output have a complex relationship – electrical activity signals contraction and contractile output can then affect electrical signalling via feedback mechanisms. Computational modelling allows us to understand this relationship further, particularly regarding two important applications.
Cardiac toxicity is a leading reason behind pharmaceuticals being withdrawn during development, but current screening methods centred on animal testing raise concerns with ethics and accuracy. Recent developments have suggested computational testing is a viable alternative, outperforming animal models in predicting risk from dangerous arrhythmias. I will incorporate contractile mechanics into our drug testing pipeline such that we can also assess their effect on contractile output.
Sudden cardiac death (SCD) is a leading cause of mortality worldwide, usually caused by arrhythmias. Various treatments exist to prevent SCD, but accurate risk stratification tools are needed to identify those at high risk for developing arrhythmias causing SCD. Measures of contractile output, such as ejection fraction (EF), are used, but the relationship between them and arrhythmic risk is currently unclear, as most people experiencing SCD have preserved EF. I will use an electromechanical model to investigate the mechanisms underlying this relationship so that we can more effectively identify and treat this high-risk population.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Rheumatoid arthritis is an autoinflammatory condition that mainly affects the joints. Increased permeability of the blood vessels and recruitment of immune cells into the joint likely play a role at the onset of this disease. For immune cells to enter the joint, a signal sent by joint tissue-resident cells is required. A specific subtype of tissue-resident immune cells, called synovial macrophages are suspected to be the source of this initial signal. It has been shown that synovial macrophages consist of different macrophage populations with unclear functions within the joint and during arthritis development. Exploration of synovial macrophages via computational methods, namely single-cell RNA sequencing, revealed a subpopulation of macrophages defined by high gene expression of aquaporin 1(AQP1). This population was not previously defined in the literature and the overall role of AQP1 in macrophages is unknown. Furthermore, AQP1-positive macrophages expressed high levels of genes associated with bioactive lipid signalling previously shown to influence the inflammation in animal arthritis models. In my project, I aim to characterize the AQP1-positive macrophages, define their function and position within the joint, and finally identify the contribution of these cells in bioactive lipid signalling and induction of inflammatory arthritis.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Immune-mediated diseases (IMDs) affect around 10% of the global population. Treatment of IMDs generally consists of immunomodulatory drugs to suppress active disease, but can have variable efficacy and can be associated with sometimes severe side effects. An alternative treatment for IMDs such as severe multiple sclerosis (MS) and scleroderma, is autologous stem cell transplantation (ASCT), which is emerging as a safe and effective therapeutic approach, although disease recurrence and secondary IMD development can occur.
The objective of our research is to test precision genome editing approaches for the treatment of several different IMDs by editing haemopoietic stem cells (HSCs). Edited HSCs would be for use in an autologous transplant to reconstitute the patient’s immune system with genome-modified cells to both treat and prevent the recurrence and development of IMDs.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
The production of autoantibodies by our immune system can be protective. In some cases, it can result in brain inflammation with memory disturbances and seizures.
My work aims to understand the basis of these disorders by studying a prototypical condition associated with antibodies against Caspr2. To study Caspr2-antibodies, I clone out patient antibodies from their blood and cerebrospinal fluid and study their characteristics using a suite of biochemical techniques. I will relate this to the properties of the cells which make these antibodies, also isolated from blood and cerebrospinal fluid, to address questions about the underlying immunology such as which cells first make the antibodies and which cells carry the most harmful antibodies.
After cloning, the antibodies will be subjected to in vitro tests to study their effects on nerve cells. Those with most potent effects will be injected into mice to observe their influence on memory, mood and seizures. In addition, real-time recordings of epileptogenic activity in awake animals will be used to investigate how the antibodies can lead to seizures.
These studies will utilise patient-derived antibodies as a powerful tool to decipher their relative contributions to human neurological illness and offer directed future methods to target their production.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Membrane proteins are integral to synaptic signalling, a process that enables the communication between a neuron and its target cell. Understanding the structure and function of such proteins is key to deciphering the biochemistry of our nervous system, which in turn will aid the development of new therapeutics. In this project, I aim to solve the 3D structure of membrane proteins using either cryo-electron microscopy or x-ray crystallography. The candidate proteins include: a) muscle-type acetylcholine receptor, an ion channel that is implicated in congenital myasthenic syndrome and myasthenia gravis, and b) the SLC1A family of membrane transporters which includes glutamate transporters and neutral amino acid exchangers – members of this family are associated with neurological disorders (Alzheimer’s disease, epilepsy and Huntington’s disease), cancer and other metabolic disorders. I will also test the effects of various compounds on purified proteins. These compounds could become useful tools for future studies or even evolve into therapeutics.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Pseudomonas aeruginosa (P. aeruginosa) is a major human pathogen, needing urgent development of novel antimicrobials. It lives in bacterial communities called biofilms and severe infections are typical within hospital settings. Due to increased antibiotic tolerance of P. aeruginosa in biofilms, treatment is lacking and infections can be fatal, especially for those who are immunocompromised.
Lipopolysaccharide (LPS) is the main component on the outer membrane of the bacteria, which protects the cell and provides rigidity. LPS is important for bacterial survival as it interacts with our immune signals, protecting bacteria from being killed. LPS also contributes to antibiotic resistance, due to variations of LPS in different bacterial strains. Additionally, it forms part of the physical barrier within the membrane, preventing antibiotics from entering. Using biochemical and structural techniques, including CryoEM and CryoET, I will determine what P. aeruginosa LPS looks like in vitro purified, on the outer membrane of single P. aeruginosa cells and within the biofilm environment.
Accomplishing this will further our understanding of how LPS functions and reveal the structure of this essential drug target. Ultimately, this information will help us understand how to treat P. aeruginosa antibiotic resistant infections more effectively and provide insight for novel antibiotic development.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
The cell cycle and cellular differentiation, two of the most fundamental biological processes, have been shown to be interdependent in embryonic stem cells, and during the development of blood cells and neurons. I aim to understand whether cell cycle alterations are associated with cellular differentiation in other developmental contexts as well, and how both processes jointly shape the cell’s epigenome and higher-order chromatin structures. To this end, I will establish a murine embryonic stem cell line stably expressing fluorescent cell cycle reporters, which will allow me to jointly quantify cell cycle progression and perform single-cell RNA sequencing and single-cell ATAC-sequencing during cell cycling and cellular differentiation. I will also use a low input chromosome conformation capture technique to study the regulatory genome interactions around cell cycle genes and master transcription factors in the same cells, which will allow me to characterise the regulatory elements governing the expression of these genes. These studies will help us better understand the interdependence between the cell cycle and cellular differentiation, which might have important implications for stem cell research, regenerative medicine, and for our understanding of the fundamental processes governing organismal development.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Lipid transporters are a class of membrane proteins that perform critical functions in many organisms. These proteins transport lipid molecules from one leaflet of a lipid bilayer to the other leaflet. In bacteria, lipid transporters can confer resistance to antibiotics, whereas in humans, dysregulation of lipid transporters has been implicated in a number of neurological disorders, highlighting the important role these proteins can play in health and disease. However, the mechanism of action of many of these transporters is poorly understood, in part due to the difficulties involved in the structural studies of membrane proteins. Therefore, this project aims to look at two lipid transporters that are implicated in health and disease: the bacterial Multiple Peptide Resistance Factor (MprF) and the human transporter TMEM16K. The focus in both cases will be on structural elucidation using a combination of cryo-EM and crystallography. The information obtained from these structural studies will be used in combination with biophysical assays to advance our fundamental understanding about the function of these proteins, whilst providing the groundwork that could be used to develop future novel therapeutics to target these proteins.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Building on the identification of macrophages which modulate sympathetic nerve signalling in adipose tissue (AT), our lab has recently also discovered tissue-resident macrophages within other endocrine organs thought to be sympathetically-innervated – including the adrenal glands (AGs). A role has not yet been described for these AG-resident macrophages, which localise to regions of both the adrenal cortex and medulla. Interestingly, a ring of macrophages unique to the female mouse inner-cortex suggests possible sexually-dimorphic immuno-endocrine interactions. Using bulk RNA-sequencing, whole-mount imaging and in vitro assays, I aim to phenotypically and functionally characterise male and female adrenal macrophages. I will compare the transcriptomes of male and female macrophages sorted from either the cortex or medulla, and use differentially-expressed genes between the sexes to find novel markers of female inner-cortical macrophages – which may also allude to their function. In addition I will also confirm the presence or absence of AG sympathetic innervation, as a role for these macrophages in the modulation of adrenal sympathetic nerve signalling similar to AT cannot yet be excluded. This will provide new insights into sexual dimorphism of immuno-adrenal homeostasis, which may underlie the incompletely understood pathologies of sex-biased adrenopathies such as polycystic ovary syndrome or Addison’s disease.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
A central objective of population genetics is finding objects that describe the relatedness structure of a group. For closely related individuals these can be family genealogies. On a larger timescale they can be evolutionary phylogenies. In general, such tree-like structures can be obtained by calculating the smallest number of generations needed to go back in time to find a common ancestor between a pair of individuals, through a mathematical framework known as coalescent theory. However, due to random recombination events that occur in the genome between generations, the most recent common ancestor for a pair of individuals varies along the genome, resulting in different tree structures for the same group on adjacent sites in the genome. Due to the highly structured nature of coalescent trees it has proven very difficult to obtain a precise probabilistic description of these random tree sequences. Our project aims to develop statistical methods that can encode coalescent trees and recombination events into a more amenable mathematical form, thus giving a close approximation to the underlying stochastic process. Efficient representations of the coalescent will facilitate all analyses of population structure and have the potential to increase the accuracy of genetic imputations and disease association models.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Therapeutic antibodies – drugs made from defence molecules produced by the body – are becoming increasingly important in treatment of diseases ranging from cancer to hepatitis. These drugs work by binding to the molecules they target called antigens. In order to be effective, an antibody must bind its antigen tightly and this depends in part on how fast it binds the antigen. For example, it has been shown in a set of antibodies against malaria that the ability of antibodies to neutralise the pathogen is highly dependent on the binding rate. Our research will use a multidisciplinary approach to engineer antibodies with the aim of achieving faster binding. Using both computational tools and experiments that characterise the physical properties of antibodies, we aim to identify factors that contribute to the rate of binding. Next, we would like to use this knowledge to generate software to predict changes that can be introduced to an antibody to increase its binding rate. As a way to validate our conclusions, we plan to improve antibodies against malaria. These studies will provide us with insight into the factors that make good therapeutic antibodies and also provide a tool for use by the wider scientific community.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Over the last 10-15 years, large datasets containing genetic, physical and medical information for thousands of people (such as the UK Biobank) have allowed researchers to detect many genetic mutations that increase disease risk or explain variation in other physical traits.
An important limitation of most of the studies conducted so far is that they mainly use data from people of European ancestry. This is significant, because there is increasing evidence that genetic differences between populations limit the validity and applicability of findings from European samples in other populations.
We propose to address one aspect of this problem by exploring genetic variation that affects the accuracy of a set of relevant mutations in predicting a physical trait or disease within a single population. This is an important first step in understanding the causes of the poor portability of findings across populations.
We expect that our work will identify relevant new genetic mutations, or interactions between them, which impact particular traits and diseases (as well as corroborate previous findings) and that this information will then improve our ability to understand the causes of, and predict, disease risk in understudied populations.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Efficient clearance of dying and dead cells, a process called efferocytosis, is crucial for tissue homeostasis and a healthy, well-regulated organism. Dying/dead cells are cleared by cells called phagocytes, principally macrophages. We recently identified the leukocyte-expressed glycoprotein CD43 as a molecule that acts as a ‘don’t-eat-me’ signal for macrophages, and showed it was rapidly and completely cleaved from the surface of dying T cells. We also demonstrated that ADAM10 (A Desintegrin And Metalloproteinase Domain-containing protein 10) is the enzyme responsible for CD43 cleavage from dying cells, therefore removing the don’t-eat-me signal, triggering phagocytic uptake. CD43 cleavage by ADAM10 is a novel observation that may be more generally applicable to other ‘mucin-like’ glycoproteins with similar don’t-eat-me properties. To explore this, we will take two approaches: i) probe leukocyte surface molecules with similar biophysical properties to CD43 for ADAM10 cleavage; ii) take an unbiased broader approach using mass spectrometry (MS) to reveal other proteins cleaved by ADAM10 during cell death. Once identified, we will analyse their function in regulating efferocytosis of dying leukocytes. This will shed light on how these molecules modulate clearance of dying and dead cells to ensure healthy tissue homeostasis, and will yield insights into immune cell-cell interactions.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Cells respond and adapt to various stimuli through a variety of detectors, which receive the signal. To ensure that a signal is transmitted, key decision-making hubs that interpret the incoming signal and define the output are required.
I am interested in one signalling hub the TAK1-TAB complex, which is vital for cells to respond to an infection or other external signals and decides cell death or survival. Correct interpretation of the signal by the TAK1-TAB complex is vital: human diseases ranging from inflammatory diseases, certain cancers and neurological disorders arise from defects within these hubs.
I will use a toolkit of biochemical and biophysical techniques to understand how the TAK1-TAB complex is regulated and obtain molecular snapshots that will provide the three-dimensional structure of the complex before and after signal activation.
Understanding the structure of this key signalling hub will, for the first time, provide a glimpse into its regulation. Furthermore, the structure will provide an explanation of how certain genetic mutations in the assembly and architecture of the TAK1-TAB complex leads to certain diseases, notably Crohn's disease and amyotrophic lateral sclerosis.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Rhythmicity is fundamental for the existence of life and 24 h circadian rhythms regulate every cell of the body. Synchronizing biological processes to certain times of the day optimizes the host response to invading pathogens and asynchrony can increase the severity of infection. Another basis of human life is oxygen and following infection, viruses can experience environments with variable oxygen tension that can influence their replication and persistence. Previous studies from our laboratory have shown that the circadian system and oxygen signalling pathways can independently influence viral infection. My project will study the interplay between these pathways to understand their role in human immunodeficiency virus (HIV) infection. I will use laboratory models of active or latent HIV replication along with genetic and pharmacological agents that modulate hypoxia and circadian pathways to study their role in the viral life cycle. Our goal is to uncover new therapeutic approaches.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
In the cell, genetic information from the DNA is copied into RNA molecules in the nucleus of the cell before being exported to the cytoplasm, where the information they carry is used to make proteins. In eukaryotes, these messenger RNA molecules (mRNA) are modified before they are exported out of the nucleus. An enzyme called the Cleavage and Polyadenylation Factor (CPF) cleaves the mRNA at the end and adds a string of adenosines to create a polyA tail. This polyA tail is important for the stability of the mRNA, and the cleavage process ensures that the enzyme that makes the mRNA, RNA Polymerase II, stops at the end of the gene and goes back to the beginning to repeat the process of making mRNA. The aim of my project is to study how the CPF modifies mRNA and interacts with RNA Polymerase II to ensure functional mRNA are properly produced. I will use techniques such as electron microscopy and x-ray crystallography, as well as biochemical techniques, to look at the structure of CPF to understand how it works. Through this work, we expect to gain a more detailed understanding of this fundamental biological process.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
With a yearly 1.7 million new people infected with HIV, the HIV/AIDS epidemic remains a major global health threat. Characterising HIV transmissions using phylogenetic tools like phylogeography and phylodynamics aids our understanding of HIV infections, both evolutionarily and epidemiologically, shaping epidemic control measures through increased knowledge on transmission events and thus, their prevention.
Sub-Saharan Africa (SSA) constitutes 59% of all new HIV infections, and phylogenetic studies highlighting HIV transmission dynamics have historically been less common in this region due to limited sequence availability. However, the recent sequencing upscale in SSA will inform the poorly understood structure of transmission networks and HIV epidemic dynamics in the region.
I aim to use viral phylogenetics, epidemiology and mathematical modelling to investigate the evolutionary dynamics of HIV-1 transmission networks in East African epidemics: firstly, using HIV-1 sequences from a trial in rural Uganda and Kenya, I will characterise HIV-1 infections and analyse HIV-1 transmission networks and cluster dynamics; secondly, I will undertake a comparative analysis of HIV-1 phylodynamics amongst different East African study populations; finally, I will model local transmission dynamics and intervention effects in these populations.
Altogether this will ultimately inform the design and evaluation of HIV prevention interventions.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Despite clinical demand for hematopoietic stem cell (HSC) transplantations for patients with blood cancers or hematologic diseases, little progress has been achieved in in vitro generation or expansion of HSCs. Cellular reprogramming by overexpression of critical transcription factors has been impeded by our incomplete understanding of how HSCs develop in the embryo. The very first HSCs are generated from endothelial cells in the aorta-gonad-mesonephros region in the embryo, with only a few functional stem cells hidden among other blood progenitors. Separating true HSCs from other blood progenitor cells in the embryo has proven challenging because they have similar surface protein expression. Moreover, testing function and then sequencing cells is impossible and HSCs differentiate and alter their transcriptome in expansion. Therefore, new methods of identifying functional HSCs are needed to advance our understanding of these clinically relevant cells. I aim to develop a model that predicts HSC function based on the precise levels of gene expression. I will then test the predictions of the model and determine if narrowing the ranges of gene expression can distinguish HSCs from progenitor cells. Accurate predictions will inform future studies into in vitro generation and expansion as precise required gene expression levels will be uncovered.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Among all known emerging pathogens, RNA viruses are overrepresented and pose a particular high risk of emergence. New RNA virus species have been detected steadily since the 1950s and their discovery is projected to continue in the future. Studying the epidemic potential of new RNA viruses is therefore important, however obtaining relevant epidemiological data requires extensive field and/or laboratory studies. These studies could be better directed if a priori predictions about the epidemiology of RNA viruses can be made.
Here, I propose to investigate whether predictions about the epidemiology of RNA viruses can be made using machine learning and genome sequences. Using an existing database containing epidemiological relevant data on all human infective-RNA viruses, I will use multivariate statistical analyses to establish which epidemiological characteristics correlate with genomic biases calculated from genome sequences. Using this information, I will devise machine learning models to make predictions about the epidemic potential of RNA viruses. Lastly, I intend to investigate how genomic biases change over time during an epidemic and link these to changes seen in the epidemiology of RNA viruses. If successful, my research could inform targeted surveillance to combat emerging RNA viruses.
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| 30/06/2021 |
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UNIVERSITY OF DUNDEE |
Trypanosomes are single-celled parasites that causes lethal diseases in humans and livestock. The parasite is covered in variable surface glycoprotein (VSG) that enables host immune system evasion. VSG is often swapped by ‘antigen switching’, which is central for the parasite’s virulence.
My group found that the active VSG suppresses expression of other VSGs. As VSG genes are located near the ends of chromosomes, we hypothesise that the characteristic and highly repetitive sequences at chromosome ends are important for suppression. To facilitate studying this, I will manipulate the dosage of these sequences using new genome editing tools (CRISPR/Cas9).
Also, I will explore the function of the proteins that package these regions. Again, I will use CRISPR/Cas9 to create parasites with a single copy of each gene encoding these packaging proteins, allowing me to manipulate those genes as well. These proteins impact DNA repair, DNA replication and gene regulation.
This project will provide new insight into how chromosome ‘caps’ function, how VSG genes behave at these locations and may also reveal potential drug targets.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Cytotoxic T lymphocytes (CTLs) are important agents of immunity responsible for clearance of infected or malignant cells. The understanding of their activation is incomplete. Recent advances have unveiled their ability to sense the stiffness of the opposing surface, with stiffer surfaces resulting in larger forces being transmitted to the CTL, promoting activation, leading to CTL-mediated killing of the target cell. Furthermore, decreased stiffness of malignant cells has been observed and posited as an avenue for their evasion of the immune system.
I will create cell lines in which intracellular stresses can be visualized with state-of-the-art microscopy via force probes. I will activate CTLs to varying degrees and measure the effect on the force probes. I will knock out cytoskeleton-associated genes in order to screen for genes that are involved in CTL force perception. Interactions between T cells and target cells of manipulated stiffness will also be investigated as a means of understanding the role of target cell stiffness in malignant immune evasion. A final screen will be performed to identify gene mutations associated with this immune evasion in target cells.
This work will broaden our understanding of T cell function and provide us with useful avenues for cancer immunotherapy.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Plasmodium falciparum causes > 90% of malaria mortality, killing over 400,000 people annually. To multiply, P. falciparum parasites must invade human erythrocytes. Invasion begins with attachment of the parasite to the erythrocyte, followed by reorientation to position the parasite to invade. These early steps depend on two families of membrane proteins: Erythrocyte Binding Like proteins (EBLs) and Reticulocyte Binding Protein Homologues (RBLs). There are four members of each family in the P. falciparum genome that can individually be deleted without blocking invasion. EBLs and RBLs are therefore believed to be functionally interchangeable, but this has never been systematically investigated and all Plasmodium parasites maintain both families suggesting considerable selection pressure against loss of one family. To determine if the families have distinct roles, this project will characterise invasion of single and double protein knock-outs using advanced video microscopy tools, and visualise the localisation of proteins simultaneously using fluorescence microscopy. New antimalarial therapies are needed as P. falciparum has developed resistance to every antimalarial drug available and the only licensed malaria vaccine is
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Nucleic acids (DNA & RNA) are commonly known for their ability to store genetic information. However, when single-stranded, nucleic acids can also fold into sophisticated 3D structures including catalysts capable of speeding up chemical transformations. RNA-cutting catalysts can be programmed to target specific RNA sequences in order to turn off harmful mutant genes or destroy viruses. However, catalysts composed of natural DNA and RNA, among other limitations, are rapidly degraded in the blood, hampering their clinical applications. Recently, it has become possible to evolve such catalysts in the test tube using robust, artificial alternatives to DNA known as "xeno nucleic acids" (XNAs). Our aim, therefore, is to explore the use of biologically stable XNA chemistries to evolve novel enzymes ("XNAzymes") capable of degrading disease-associated RNA (aberrant mRNA, microRNA and viral RNA). We will establish systems for engineering XNAzymes using chemistries resistant to degradation and which (unlike protein enzymes) do not trigger unwanted immune responses. Currently, there are few clinically-suitable molecular tools for manipulation of cellular RNAs and they often lack precision, XNAzymes are thus promising alternatives.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Non-Hodgkin Lymphoma (NHL) accounts for 4% (14,100) of new cancer cases every year (UK) with a survival rate of 55% (2013-2017). Diffuse Large B Cell Lymphoma (DLBCL) is a common subtype of NHL which arises from high affinity B cells. The lipid signalling enzyme phosphoinositide-3 kinase delta (PI3Kdelta) is critical for the development of these B cells and is often mutated (hyperactive) in DLBCL.
We identified that hyperactive PI3Kdelta cooperates with the oncogene B-cell lymphoma 6 (Bcl6) to drive lymphomagenesis and that this was accelerated in the absence of a functioning immune system. Furthermore, restricting PI3Kdelta hyperactivity to CD4+ T cells was sufficient to drive lymphoma progression. I aim to investigate the cooperativity between PI3Kdelta and Bcl6 in B cell lymphomagenesis by combining flow cytometry and transcriptomic approaches to identify and characterise B and CD4+ T cell populations in our lymphoma models. Transfer of selected populations into immunocompromised mice, followed by tumour analysis by histology, will allow me to identify the cellular origin of the malignant B cells and the CD4+ T cell populations responsible for driving lymphomagenesis upon PI3Kdelta dysregulation. This study will illuminate the cooperation between PI3Kdelta and Bcl6 in B cell lymphoma with important future therapeutic implications.
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| 30/06/2021 |
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UNIVERSITY OF DUNDEE |
Intraepithelial lymphocytes (IEL) are T cells that reside interspersed between intestinal epithelial cells in the gut. They provide protection to the gut by coordinating immune responses towards pathogens and producing factors which maintain the gut epithelial barrier. However, dysregulated IEL function has been associated with increased gut inflammation promoting inflammatory diseases of the gut including coeliac disease and inflammatory bowel disease. The signals which activate IEL and the intracellular machinery used to communicate these signals to have an effect within the cell are relatively unknown. I propose to investigate the signalling pathways in IEL using techniques such as flow cytometry, mass spectrometry and RNA sequencing. I will stimulate IEL through cell surface receptors to initiate the downstream signalling events. I will compare the IEL response to stimulation with conventional T cell responses to determine similarities and differences in IEL signalling. I will look at proteins which have become phosphorylated upon stimulation and, using a RiboTag mouse, detect which proteins are translated as a result of the activation. I will also investigate IEL signalling in vivo. These studies will increase understanding of how IEL become activated and offer opportunities to manipulate these pathways in the treatment of disease.
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| 30/06/2021 |
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UNIVERSITY OF DUNDEE |
Biofilms are communities of microorganisms that attach to surfaces or interfaces which contain one or multiple species and can be beneficial or detrimental for human health. Biofilm formation is tightly regulated by controlling production of exopolysaccharides and extracellular proteins that combine with components including extracellular DNA and extracellular proteases to form a sticky matrix. I am interested in the role of extracellular proteases during biofilm formation. It has been hypothesized that extracellular proteases might be involved in matrix remodelling, cellular dispersal and/or in food acquisition in poor-nutrient conditions. Using the bacterium Bacillus subtilis, I will use biochemical and proteomics approaches to quantify how abundant and how active the extracellular proteases are during biofilm formation. I will also assess if extracellular proteases can be shared among the population and if they confer a selective advantage in certain nutrient environments. By combining live-cell imaging and mathematical modelling, I will also explore how extracellular proteases influence spatial distribution of mixed populations during biofilm formation. The insights garnered with this study will help to understand how exoproteases support biofilm formation in diverse environments and more globally help us to understand why biofilm can be so persistent.
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| 30/06/2021 |
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UNIVERSITY OF DUNDEE |
During embryogenesis, that is the process of embryonic development after fertilisation, cells divide many times, and at some point, these cells become different from one another. This process requires turning on specific genes that make distinct cell types, such as nerve or muscle cells. My project aims to find out how this happens focusing on a specific cell type called neuromesodermal progenitors (NMP) that can contribute to two different embryonic tissues, depending on exposure to specific signals. One such signal is the Fibroblast growth factor (FGF) which regulates neural induction. It is known that inhibition of ERK1/2 activity, a protein controlled by FGF, is involved in the activation of neural genes in NMP cells. This process requires the removal of a protein complex called Polycomb, that blocks the activation of these genes. However, how the Polycomb protein complex is removed is unknown. During my PhD project, an analysis of the proteins with changed activity upon ERK1/2 protein inactivation, will begin to dissect the molecular mechanisms regulating neural differentiation. My findings may facilitate improved protocols for directed differentiation of human cells in vitro and have wider implications for how cell state can be manipulated for therapeutic effect.
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| 30/06/2021 |
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UNIVERSITY OF DUNDEE |
Ubiquitin is a small protein that is attached to different targets affecting their subsequent behaviour. This addition can ‘tag’ the target for destruction by the cell, affect its localisation or promote various interactions with other proteins. E3 ligases are a group of enzymes responsible for the addition of ubiquitin onto a target, and I am interested in an E3 ligase termed HOIL-1. People who lack HOIL-1 accumulate abnormal glucose deposits called polyglucosan in their cardiac tissue, leading to heart failure. These observations suggest that HOIL-1 has a critical role in preventing the accumulation of such deposits and the overall goal of my project is to discover how this is achieved. In my initial experiments, I found that HOIL-1 is able to attach ubiquitin to glucose and thus, I hypothesise that by tagging with ubiquitin, HOIL-1 marks this molecule for destruction. People lacking HOIL-1 cannot initiate destruction and therefore accumulate the abnormal polyglucosan deposits. My aim for this project is to gain insight into how ubiquitin is added by HOIL-1. Furthermore, I aim to identify additional targets associated with HOIL-1. By discovering its targets, we can further understand its role within the human body and consequently, its potential role in disease.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Pulmonary arterial hypertension (PAH) is a fatal disease in which the blood vessels of the lung thicken and narrow, causing an increase in blood pressure and eventually right heart failure. In order to develop new therapies for PAH the mechanisms underlying the progression of lung vessel damage must be determined. Many PAH cases are caused by a mutation of one of many components of the bone morphogenetic protein signalling pathway, however the effect of these mutations on blood vessel stability is still unknown. This project aims to examine the role of semaphorin 3G (SEMA3G), a protein that we have shown to be regulated by the bone morphogenetic protein (BMP) signalling pathway, in maintaining blood vessel integrity. Endothelial dysfunction is central to a number of pulmonary pathologies including PAH. I will investigate the role of BMP9 and BMP10 in regulating SEMA3G expression in the endothelium and specifically the functional role the protein plays in endothelial and mural cell interactions. In order to determine this, I will develop 3D co-culture assays using pulmonary microvascular endothelial cells and pericytes. These studies will further our understanding of the mechanisms controlling vascular homeostasis and potential pathways that can be targeted in the treatment of PAH.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
One’s appetite and body weight are primarily controlled by neurons in a brain region called the hypothalamus, which respond to signals from the organs involved in digestion and metabolism. These signals reach the hypothalamus after being transported through another brain reigon, the median eminence (ME). New evidence suggests that non-neuronal cells, called oligodendrocytes (OL), may contribute to the ME’s control of signal entry to the hypothalamus; OLs intentionally die and are replaced throughout adult life and express receptors for peripheral signals, both behaviours which change based on nutritional status (i.e. when one last ate) and coincide with changes in permeability of the ME.
We aim to determine how obesity disrupts the function of OLs in the ME, and how this may alter ME permeability. We will block certain functions of OLs in obese mice and identify the physiological consequences, identifying genes involved in these processes. We will use this data to identify candidate mechanisms which may alter OL function and influence healthy physiology. We will also explore the possibility that a new class of obesity drug, which mimic the signalling of hormones naturally released in the body, have their therapeutic effect by targeting OLs and changing ME permeability.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Fat tissue plays a key role in storing energy as fat after feeding, and releasing this energy when needed (fasting). In order to change between storing and releasing energy, fat cells have to change the proteins at its surface to allow transport of nutrients in and out of the cell. In addition, fat cells release proteins that signal to other tissues in the body depending on whether food has just been consumed (‘fed’), or if the body has not received any food for several hours (‘fasted’). In this project we will study how the hormones, insulin (present in a fed state) and noradrenaline (present in a fasted state) change how proteins are localised within fat to promote energy storage/release, and how these hormones change the proteins fat cells secrete. In obesity the ability of fat cells to store and release energy and secrete different hormones depending if the body is in a fed or fasted state appears to be disrupted. By also studying this in cells treated to mimic the obese-state we will shed light on how changes to these processes may contribute to the metabolic disturbances associated with obesity (e.g. type 2 diabetes).
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Recent discoveries have suggested a dysfunctional immune system of the brain plays a significant role in a set of diseases known as microgliopathies. New disorders of this type are still being identified, but ones which have so far been uncovered lead to significant brain damage and decreased lifespan. Our group has discovered a developmental microgliopathy-like disease in a patient caused by a defect in a protein named LRRC33. However, we do not fully understand the impact this defect has on the brain’s immune system, how it affects different types of brain cells, and how it leads to disease onset. We aim to investigate these questions using a combination of animal models and patient post-mortem tissue. We will also seek to determine whether we can repair brain damage in our animal disease model by suppressing the brain’s immune system. Strategies such as these, along with improved knowledge of the biology of the disease, could potentially lay the foundations for development of treatments for these microgliopathies, of which there are currently none.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Kin recognition is an organism's ability to distinguish between genetically close or distant individuals1, which facilitates social attachment among kin2. This is crucial after birth when parental care is needed. Kin responsive neurons have been identified in the rat lateral septum3, a brain structure associated with human kin-affiliation4,5. Human and animal data suggest that endogenous opioids in the brain mediate social attachment and an endogenous opioid-releasing circuit extends from the hypothalamus to the lateral septum. 6–8 In my project, I will test to see if this circuit mediates maternal attachment in early life. I will first confirm preliminary findings from our team that opioid action in the septum is necessary for maternal attachment by activating/inhibiting the lateral septal opioid system and characterising the resulting effects on maternal attachment behaviour in rat pups. To understand the cellular mechanisms involved, I will characterise the activity of lateral septum neurons when endogenous opioids are released. Finally, to explore if the findings are translatable to humans, I will investigate associations between attachment types and septal structure and connectivity in infants. These studies may help elucidate the physiology of early attachment and ultimately provide a rationale for improving the environment of care in early life.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Neurodegenerative diseases cause progressive loss of nerve cells in the brain, resulting in impaired cognition and/or movement. There are currently no treatments for these diseases and therefore, another approach to developing treatments is required. With ageing, dysfunctional or "senescent" cells accumulate in the body and are involved in various neurodegenerative diseases. Microglia are specialised immune cells in the brain responsible for keeping surrounding nerve cells healthy. Microglia can become senescent, meaning they struggle to maintain nerve cell health. We hypothesise that senescent microglia regulate neurodegeneration. However, how senescent microglia differ in ageing and neurodegenerative disease is unknown and it is unclear how senescent microglia contribute to neurodegeneration. I will explore this using immunofluorescence, whereby senescent microglia and associated neurodegeneration can be identified by staining cells with specific markers. I will also induce and prevent microglial senescence specifically, using two specially designed mouse models, and assess neurodegeneration. It is also unknown what causes microglial senescence but ageing and long-term inflammation throughout the body likely contribute. I will investigate how microglia become senescent in mouse models undergoing ageing or long-term inflammation. This work aims to improve understanding of the role of senescent microglia in neurodegeneration and provide alternative targets for treatments.
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| 30/06/2021 |
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UNIVERSITY OF EDINBURGH |
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a disease spectrum. Individuals affected by these conditions may have problems with movement (symptoms of ALS), thinking and behaviour (symptoms of FTD), or a combination of both. Even families with the same genetic cause, such as a C9orf72 mutation, can develop very diverse disease symptoms and there is currently no way of predicting how someone will be affected. This uncertainty is not only difficult for patients; it also affects our ability to conduct clinical trials, as some treatments may only work on a subset of patients, and disease heterogeneity may confound outcome measures. It has recently been suggested that neuroinflammation influences disease presentation along the ALS-FTD spectrum. I aim to explore this by creating a cohort of deeply clinically phenotyped post-mortem brain tissue. I will investigate neuroinflammatory gene expression in key tissues, aiming to create a holistic image of neuroinflammatory dynamics along the spectrum. Finally, I will validate my findings in a human stem cell-derived model and explore specific therapeutic approaches to target neuroinflammatory dysregulation. These studies will help shed light on methods to treat individual patients and symptoms, improving the outlook for clinical trials in this field.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Cutaneous leishmaniasis (CL) is a neglected tropical disease with about 1 million new cases per year. It is caused by parasites that are transmitted by sandflies. There are a number of different forms of the disease, ranging from small, self-healing lesions on the skin, to permanently disfiguring facial lesions. It is not well understood how the parasite can result in such a wide range of outcomes.
Our aim is to gain a better understanding of the interaction between the human immune system and the parasite. We are doing this by investigating how key immune cells called macrophages interact with parasites isolated from different patients. This may reveal key differences between the different forms of CL. We are achieving this through a highly collaborative approach with experts in different fields.
We hope that this research will shed light on our understanding of the diversity of CL as a disease and why some patients develop severe, life-changing lesions.
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| 30/06/2021 |
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CARDIFF UNIVERSITY |
Neuronal dysfunction and degeneration are central to amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and co-existent ALS/FTD. However, it is increasingly being recognised that non-neuronal cells actively contribute to disease pathogenesis. Recent genetic studies have identified several ALS/FTD risk genes with immune roles, highlighting immune dysfunction as a key early pathogenic mechanism. We aim to investigate the role of one of these genes, TANK-binding kinase 1 (TBK1), in microglia, the resident immune cells of the brain. We will use stable microglial cell lines and human induced pluripotent stem cell-derived microglia, along with pharmacological inhibition and genetic manipulation of TBK1, to investigate the role of TBK1 in key microglial functions. In particular we aim to determine the role of TBK1 in microglial immune signalling, phagocytic activity, autophagy and mitochondrial homeostasis using cutting-edge high content imaging techniques and cellular assays. By doing so, we hope to define the role of TBK1 in microglia and further understand how deficits in TBK1 function may drive neuronal loss in ALS/FTD, with the ultimate aim of identifying novel therapeutic targets.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
During infections, such as malaria, which is caused by plasmodium parasites, platelets and red blood cells are destroyed. Hematopoietic stem cells, which are responsible for the production of all the cell types of the blood system, are then put under stress to produce high numbers of platelets and red blood cells. Hematopoietic stem cells are found in the bone marrow, surrounded by many types of other cells. This project aims to investigate how only a specific subset of stem cells becomes activated to replenish the platelet cell counts. I will study the expression and function of specific genes in cells of the environment of stem cells and in stem cells themselves using microscopy-based assays on tissue slices and genetically edited cells implanted into mice. I will use intravital microscopy to study behaviours of stem cells such as cell division and movement, in the bone marrow in the skull. The results of this project could lead to the development of improved treatments for malaria patients and patients with bone marrow transplants.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Respiratory viruses such as RSV, influenza viruses and the recently emerged SARS-CoV-2, represent a major global burden to public health. While infection with such viruses will often only result in mild "cold-like" symptoms, many will result in severe disease and require hospitalisation. Why some people get seriously ill while others only develop mild symptoms is not yet understood.
Recent studies in both humans and mice have suggested that the presence of white blood cells, known as neutrophils, in the lungs prior to infection with respiratory virus results in more severe disease. The aim of this project is to investigate how the presence of these neutrophils alter the immune response to respiratory virus and ultimately how this drives more severe disease.
To achieve our aims, we will use mouse models to characterise how and which parts of the immune environment in the lung that is changed by the presence of neutrophils prior to infection with respiratory virus and how this influence the severity of disease.
This work will help us to better understand why some individuals are more at risk of severe disease following respiratory viral infection and help the development of effective treatments and vaccines.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
During the earliest stages of infection, the initiation of transcription from an infecting virus genome is a critical event and essential for subsequent virus replication, progeny assembly and onward transmission. However, the same virus genome is simultaneously sensed by the host cell as a "pathogen-associated molecular pattern". This results in the activation of numerous cellular restriction processes to limit virus transcription and replication, as well as, stimulating anti-viral processes in surrounding cells. To understand the critical dynamics of these opposing processes, I will exploit innovative new techniques in bio-orthogonal chemistry and single molecule RNA analysis to investigate a model DNA virus, herpes simplex virus (HSV), at single cell and single genome level. Using these techniques in relevant cell models, together with knock-outs in key cell DNA sensors and virus mutants, I aim to understand the processes that operate at the earliest stages of infection, the precise importance and role(s) of various host DNA sensors and viral antagonists, and identify novel restriction factors and associated mechanisms of viral suppression. From high resolution and quantitative investigation of these events, I aim to establish new insight into the early innate immune response and contribute to the development of novel anti-viral therapies.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Human T-cell Lymphotropic Virus type-1 (HTLV-1) infects 5-10 million people worldwide. The majority of people infected remain asymptomatic carriers (ACs), while 2-6% of those infected develop adult T-cell leukaemia and another 2-3% go on to develop chronic inflammatory diseases including HTLV-1 associated myelopathy (HAM). CD4+ T cells carry 95% of the HTLV-1 proviral burden. While CD4+ T cell dysfunction has been implicated in HAM pathogenesis, the mechanism of tissue damage is still unclear. Limited research has been done on the HTLV-1-specific CD4+ T cell immune response and little is known about CD4+ T cell dysfunction during chronic viral infections. The overall aim of this project is the identification and deep phenotypical and functional characterisation of live HTLV-1 specific CD4+ T cells in healthy individuals, ACs and HAM patients. We have optimised an ex vivo assay to identify and isolate live HTLV-1-specific CD4+ T cells. The results obtained in this project will have implications for vaccination approaches against HTLV-1 and for the development of strategies that could reduce inflammation and control disease, as well as providing mechanistic insights into HAM immunopathology.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Deciding the best way to behave is often dependent on where you are. For example, cheering loudly when someone scores a goal is a good way to behave if you are watching a football match in the pub, but not if you are watching it on your phone in the library.
The ability to tell where you are is governed by a part of the brain called the hippocampus, while deciding the most appropriate behaviour is governed by the prefrontal cortex. By communicating intricately with each other, it is proposed that these regions allow you to modify behaviour based on your location. However, the hippocampus and prefrontal cortex are not connected to each other, and therefore we do not understand how they communicate so effectively.
In this proposal we will investigate that idea that this communication occurs through a region called the nucleus reuniens. We will investigate how this region connects with both prefrontal cortex and hippocampus; we will carry out computational modelling to investigate how this communication might occur; and then carry out behavioural experiments that will allow us to directly test how neurons in the nucleus reuniens allow the modification of behaviour based on where we are.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Tri-segmented bunyaviruses, which includes Rift valley fever virus and Oropouche virus (OROV), are responsible for a variety of human diseases ranging from self-limiting symptoms such as acute febrile illness, to lethal encephalitis and haemorrhagic fever. OROV is the first example of a virus shown to recruit endosomal sorting complex required for transport (ESCRT) components to virus assembly sites in the Golgi, through unclear mechanisms. During this project, I will develop virus-like particle assays to determine whether ESCRT recruitment is conserved across representative tri-segmented bunyavirus families. Once this has been established, I will investigate the molecular mechanisms that drive ESCRT recruitment to sites of bunyavirus assembly. I will do this by employing a range of proteomic approaches, that will utilise exogenously expressed bunyavirus envelope glycoproteins to identify potential interaction partners that are involved in ESCRT recruitment. Finally, I will conduct experiments using live OROV in collaborative research trips to Brazil, to understand how the virus changes the proteome of the cell during infection using a variety OROV mutants. These studies will elucidate a potentially novel mechanism of ESCRT recruitment during virus assembly and provide detailed understanding of bunyavirus-host interactions. Such new insights into bunyavirus infections may aid in development of antivirals.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
During nervous system development, neurons extend their axons over long distances to predefined targets. Research from the last decade has revealed a plethora of chemical signals that are involved in instructing axon guidance. However, it is now becoming increasingly evident that axons also respond to the mechanical environment that they grow in and this affects axon guidance. Moreover, crosstalk occurs between chemical and mechanical signalling. Thus, a holistic understanding of axon guidance would involve understanding both chemical and mechanical guidance cues and the crosstalk between them. A variety of chemical signalling cues which mediate attraction or repulsion are known to regulate axon pathfinding. These include Slits, Semaphorins, Netrins and Ephrins. However, chemical guidance cues do not act alone. The mechanical environment that the axons grow in, also influences axon pathfinding. One of the ways axons respond to the mechanical environment is through mechanosensitive ion channels (e.g. Piezo1). My PhD project aims at exploring the crosstalk between mechanical and chemical signalling in axon pathfinding, using the optic tract (OT) of Xenopus laevis as a model system.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
The cichlid fish in the African Great Lakes are incredibly diverse despite being genetically very similar to each other. We will study the development of colour pattern in Astatotilapia calliptera, which consist of arrangements of specialised colour-bearing cells, chromatophores. We will focus on the variable circular markings on the fin known as egg-spots, as these play a role in reproductive behaviour and therefore have direct consequences for species evolution. Four genes have been identified as associated with variation in egg-spots number and colour in A. calliptera. We will use CRISPR-Cas9 to knock-out these genes to identify their effect on egg-spot development. We will also check whether the same genes are associated with egg-spot variation between different cichlid species. We will then model the interactions between chromatophores - these interactions affect the movement, differentiation, and death of chromatophores during development, affecting the resulting colouration. We will use this model to test which mechanisms the genes act through. Understanding how the slight genetic changes between cichlids affect embryo development and lead to such different appearances can help us understand the huge diversity of species we see today, and how the porcesses of embryo development and evolution affect each other.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
In the adult brain, most cells that produce new neurons (neural stem cells) are found in an inactive state (quiescence). These cells can be awakened in response to various signals, including diet or injury. Importantly, active and inactive neural stem cells differ in the genes they express and the modifications present on histones, proteins that the DNA is wrapped around. Histone modifications play a crucial role in regulating gene expression. During my PhD project, I will examine these modifications in active and inactive neural stem cells in Drosophila, in which these cells are easy to identify and manipulate. Using Targeted DamID, a technique that makes it possible to identify protein-DNA interactions in vivo, I will profile the location of individual histone modifications neural stem cells and classify the chromatin in those cells into domains. I will use super-resolution microscopy to observe chromatin within the nuclei of neural stem cells. Finally, I will test the function of those genes that may be important for awakening neural stem cells or inducing them into the inactive state. Understanding the mechanisms that induce neural stem cell inactivity and reactivation can potentially give insights into new therapies for brain injury or neurodegenerative diseases.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
Bronchopulmonary dysplasia (BPD) is a chronic respiratory system disease with a particularly high incidence in preterm infants who receive mechanical ventilation and oxygen supplementation. BPD is characterized by less developed alveoli, the main gas exchange region. Clinical studies and animal experiments have identified hyperoxia exposure, ventilation trauma and genetic susceptibility as risk factors of BPD, though their effects on human alveolar development at a cellular level remain unknown. Based on the established progenitor organoid system derived from human embryonic lung tips, I aim to build an in vitro alveolar differentiation model and investigate the effects of BPD risk factors on this process. I will also use a mouse xenotransplantation model to assess the in vivo differentiation potential of human lung progenitors affected by BPD risk factors. These studies will help to delineate the impact of current respiration-supporting methods on human alveolar development. The elucidated cellular and molecular mechanisms can assist to reduce the risk and damage of BPD on preterm infants and improve long-term health conditions.
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| 30/06/2021 |
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UNIVERSITY OF CAMBRIDGE |
During early development, embryos begin to develop what will become the future brain and spinal cord in a process known as neurulation or neural tube formation. Errors in this process lead to common birth defects such as spina bifida and anencephaly, which can differ in type and severity based on location along the future spine. This process differs between the head and tail ends of an embryo, with the head rolling up from a flat sheet and the tail end forming a solid rod that hollows in humans and chick. Whilst much is known about these two disparate processes, the region where they join is poorly understood.
We aim to generate a better understanding of this junctional region, and the cellular and mechanical changes that govern its formation, through studying the wider cell movements and then focusing on mechanics and hydrostatic pressure differences. Using advanced microscopy of live and fixed tissues, we will assess cellular and tissue movements and use the data gathered to create a computerised physical model to predict tissue mechanics.
This work will provide new insights on the basic processes of neural tube formation and may also help understand the causes of some neural tube defects.
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| 30/06/2021 |
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CARDIFF UNIVERSITY |
The retrosplenial (RSP) cortex is a cortical area located behind the splenium, As a part of the hippocampal-diencephalic-cingulate network, it has been repeatedly implicated in episodic memory, spatial memory, and navigation. Pathologically, when damaged the RSP cortex produces both anterograde and retrograde amnesia. It is among the first regions to show neurodegeneration in Alzheimer’s disease and Mild Cognitive Impairment. However, despite the region's clinical and behavioral significance, its unique functional contribution to hippocampal-dependent processes is poorly understood. To delineate the RSP cortex functions from that of other structures, I will use a combination of chemogenetic and optogenetic manipulations in rats, to examine behavioral effects. Disentangling the RSP cortex functions will not only elucidate the intrinsic processes underlying cognitive function, but also potentially provide a new target for the treatment of memory disorders.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Two systems govern human behaviour: the ‘habitual’ system tends to repeat actions were previously rewarding, and the ‘goal-directed’ system relies on an understanding of how the world works in choosing the best action. Whilst there is evidence that this is true for simple actions (e.g. ‘eat cake’, ‘lock door’), we do not know if it holds when applied to goals (a collection of actions that work towards a goal, e.g. ‘start a business’). My research aims to investigate how we choose which goals to pursue.
To test whether the two systems above apply to goals, I aim to develop a new cognitive task that involves choices between actions and choices between goals, and study how these choices are controlled by the brain. I will use a combination of behavioural, neuroimaging, and neurochemical approaches to this end. I also aim to investigate whether there are differences in how goals are chosen between healthy individuals and patients with compulsive disorders including addiction and obsessive-compulsive disorder.
The broader goal of my research is to understand how the brain optimises both short-term and long-term behaviour, and potentially inform clinical models of compulsive disorders.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Social hierarchies are ubiquitous among animals. They ensure efficient allocation of resources such as food, shelter, and mates, and reduce the need for physical confrontations within a group. Recent research has uncovered how representations of social status are learned and encoded in the brain, specifically in cortical areas. These representations of social status inform which social behaviours are shown by animals at different levels of hierarchy. For instance, subordinates are more likely to exhibit social avoidance and defensive behaviours such as fleeing, and show more restraint when presented with rewards. Despite these findings, it remains unclear how cortical representations of social status affect downstream areas that are more closely linked to controlling status-specific behaviours. My PhD project will investigate how cortical representations of dominance status affect the processing of social stimuli in hypothalamic areas, and how this leads to altered social behaviour in dominant vs. subordinate males. This work will help explain how social status is translated into appropriate social behaviour by specific brain circuits, and how dysregulation of these processes might contribute to maladaptive behaviours.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Neurons transport messenger RNA (mRNA) over long distances within RNA transport granules, which are made of one or more mRNAs coated by RNA binding proteins (RBPs). It is thought that such granules bind directly to motor proteins for transport, however, recent studies show that they can ‘hitchhike’ onto intracellular organelles for indirect mobilisation. The overall goal of my PhD is to uncover how these two distinct pathways are integrated to ensure coordinated transport along neuronal axons. Moreover, I will determine how these pathways are affected in motor neuron disease (MND). Specifically, I will focus on the RBP named Staufen, which is an important component for RNA granule assembly and transport, and which has been suggested to contribute to MND onset and progression.
I aim to identify the mRNAs transported via either route under normal conditions and in MND. I will use a novel method in which proteins representing each transport pathway are modified by an enzyme that "tags" nearby proteins. Tagged proteins and associated mRNAs can thus be identified and used to investigate RNA granule composition associated with each transport pathway in healthy and diseased neurons.
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| 30/06/2021 |
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CARDIFF UNIVERSITY |
Alzheimer’s Disease (AD) is the most common form of dementia and over the last 10 years many genetic mutations have been identified that alter an individuals risk of developing the disease. In my research I will be using Drosophila melanogaster (fruit flies) to investigate genetic contributions to AD. I will manipulate levels of specific genes within the fly brain and investigate how this, in turn, effects levels of other genes throughout the brain using a technique called RNA sequencing. To complement this analysis, I will also be investigating the effects of such manipulations on behavioural traits associated with human AD, such as sleep and memory disturbances. Generating a greater understanding of these newly discovered risk genes will hopefully aid the pursuit for a successful therapeutic target.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Archaea are single-celled organisms distinct from bacteria, but that share a number of traits. Like some bacteria, many archaea have a surface layer (S-layer) surrounding the cell, which is a proteinaceous lattice that helps protect the cell from attack from viruses. Understanding how the viruses bind to the S-layer will help us to understand how they infect the cells.
Using cryo-electron microscopy (cryo-EM), an increasingly popular technique for obtaining structural information about proteins, we will study a variety of archaeal S-layers and some of the viruses that infect them. This data will then be combined with molecular dynamics (MD) for a multiscale investigation of how these S-layer proteins move and interact over time. By solving the structures of the S-layers using cryo-EM, then simulating the interaction of the proteins in the lattice using MD, we push method development to lead the way in cellular structural biology.
With this work we will develop the understanding of viral entry in archaea, and the structure-function relationship of S-layers which has implications on the evolution of life. Tomography will provide cellular context to structures, and direct the large-scale MD simulations, built up from smaller simulations of atomic structures solved by cryo-EM.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Nicotinic acetylcholine receptor (nAChR) subtypes such as alpha7 and alpha4beta2 have been implicated in a range of psychiatric illnesses, including schizophrenia and Alzheimer’s disease. During the past two decades, the identification of multiple nAChR allosteric modulators (drugs that alter the response of a receptor to its natural agonists) have attracted significant interest. A recent study conducted in this laboratory reported an in silico screening of the DrugBank database against a predicted alpha7 nAChR allosteric site. Amongst the compounds identified in this study, the Na-K-Cl cotransporter inhibitor furosemide was found to be a potent positive allosteric modulator (PAM) of the alpha7 nAChR in electrophysiological assays. The objective of the present project is to expand on our understanding of how the chemical composition of allosteric modulators such as furosemide and its structural analogues influences their allosteric modulatory properties at nAChRs subtypes such as alpha7 and alpha4beta2. I will attempt this via the synthesis of a library of novel compounds (including furosemide analogues). Subsequent electrophysiological and computational (e.g. computer docking) studies of these compounds with respect to their allosteric modulatory activity at the alpha7 and alpha4beta2 nAChRs will be undertaken with the aim of developing a clearer understanding of their structure-activity relationship.
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| 30/06/2021 |
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UNIVERSITY COLLEGE LONDON |
Proteins control most cellular functions, made possible by their unique and diverse range of 3D structures and the dynamics within them. Methods to determine protein structure have revolutionised the understanding of cell function and dysfunction on the molecular level as well as drug design, however, these methods generally require static molecules. One rapidly developing method to probe protein structure uses transmission electron microscopy to take highly magnified images of cryogenically frozen proteins which can be computationally combined into a 3D model, however, freezing the sample prevents any real-time dynamics. We aim to optimise this method with new liquid-phase transmission electron microscopy technology, to film and understand structural dynamics of proteins in real-time in solution. This will require the development of electron microscopy techniques to image the protein clearly, image processing techniques to analyse the movies taken and molecular dynamics to understand and verify the results seen. We, therefore, aim to develop liquid-phase transmission electron microscopy as a technique to probe protein dynamics in solution, allowing the study of protein function, dysfunction and dynamic responses to stimuli, for example, drug binding. This will focus on RNA polymerase as a model system with physiologically relevant dynamics.
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| 30/06/2021 |
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BIRKBECK UNIVERSITY OF LONDON |
Packaging the two metres of chromosomal DNA found in every human cell is achieved by wrapping DNA around histone proteins in complexes called nucleosomes. Generally, DNA wrapped within nucleosomes is rendered inaccessible to enzymes and DNA-binding factors involved in normal DNA processes such as gene expression, DNA damage repair and chromosome replication. Chromatin remodellers are large molecular machines that disrupt the interaction between DNA and histones, exposing the DNA and therefore making it accessible for fundamental biological processes. I will be focussing on a particular chromatin remodeller called SWI/SNF that uses chemical energy to move, modify and eject nucleosomes. Around 20% of human tumours have been shown to have mutated SWI/SNF, highlighting the complex as one of the most commonly affected targets in cancer. The aim of my project is to use structural (cryo-EM) and single molecule (FRET) analysis to probe the molecular details of the interaction of SWI/SNF with the nucleosome. Moreover, we will visualise SWI/SNF in action, in an attempt to understand how the machine remodels nucleosomes and leading to further understanding of its role in cancer. Our results will provide a platform for the future development of drugs that specifically target mutated SWI/SNF complexes in numerous cancers.
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| 30/06/2021 |
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BIRKBECK UNIVERSITY OF LONDON |
Sodium channels (Navs) are proteins which are found in cells around the body, including the central and peripheral nervous system and heart muscles. These proteins span the cell membrane and form channels which specifically allows sodium ions to cross the membrane under certain conditions. This influx of sodium ions in neurons is responsible for information processing and is critical for nervous system function. Genetic mutations in Navs can cause multiple diseases including epilepsy, chronic pain and cardiac arrhythmias. Generally, these mutations reduce the function of Navs, disrupting the balance of information, for example in the brain sometimes resulting in epilepsy. Specific drugs therefore need to be developed in order to re-establish this balance either by adding to Navs’ functionality or reducing it. We aim to use structural biology techniques, including x-ray crystallography and potentially cryo-EM to visualise potential drug binding sites. We will also look at common disease-causing mutations allowing us to identify drugs which will not only target a specific subtype of Nav but also a specific mutation. In particular we will be looking at repurposing already commercially available drugs. This work has the potential to identify drugs for Nav related diseases and provide new treatment options for patients.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Behavioural phenotypes are highly relevant to many diseases, particularly those involving neurodegeneration, such as Friedreich’s Ataxia or Parkinson’s disease. While these behavioural phenotypes arise from low-level molecular and cellular processes, they are highly complex. As a result, identifying structure within behavioural data can be challenging. Generative models are a type of model which are able to generate new instances of data, unlike discriminative models which can only discriminate between existing instances. As a result, these models must solve the more complex problem of whether a given data instance is likely, as opposed to what classification it most likely belongs to. This means they must learn the underlying distributions of the data itself, often capturing more meaningful correlations as a result. Building generative models of behaviour can therefore offer deeper insight into the structure of behaviour, as well as a means of analysis through synthesis, where the ability of a model to successfully reproduce naturally observed behaviour provides further validation of the model. These models can also be used to investigate the impact of disease on behaviour through attempts to ‘corrupt’ the model’s underlying processes and compare the output to experimental data obtained from individuals with a particular disease.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
Single Molecule Localisation Microscopy (SMLM) has enabled scientists to observe biological processes at a molecular level. These techniques typically generate 3D point cloud data which localise individual molecules within the specimen. The spatial statistics of these point clouds have then been used to classify, segment or co-localise molecules to support hypotheses regarding the underlying biological processes occurring in the sample. As this is currently achieved through non-deep learning approaches (eg: Ripley's functions, DBSCAN, graph based or shallow neural networks), I will investigate the applicability of existing deep learning solutions on SMLM point cloud data. From this set of existing work, I will design and evaluate possible improvements to these systems. Improvements in the performance of these models could provide better acuity in the post-processing of SMLM images, and thereby improve our understanding of the fundamental biological processes involved.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
The brain can learn a variety of motor skills, from using chopsticks to playing the piano. Some skills are easier to learn than others, and this may be affected by the skills that you already have.
We are interested in how motor learning occurs in populations of neurons. Networks of neurons work together to produce different neural activity patterns that drive learning and movement. The possible patterns that can be produced thus depend on the structure of the network, and this can be affected by existing skill sets.
We will use artificial neural networks to computationally model motor learning. We will train the model on different motor tasks and see how they adapt to learning new ones. This will be coupled with experimental data that measure neural activity in monkeys and mice during motor tasks. By understanding how the brain learns new movements, we can gain insight into applications of assistive devices and therapies for motor function.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Antibodies are proteins, naturally produced by the immune system, that bind other molecules. This interaction can block the function of the bound molecule and is exploited in anti-tumour treatments. For instance, antibodies can block immune inhibitory receptors. These receptors are responsible for stopping the immune system from killing infected cells and cancer cells. For various reasons, some cancer patients do not respond to treatments with antibodies. Some can be attributed to the relatively large size of antibodies and the presence of immune inhibitory molecules within the tumour.
The aim of our project is to develop a new anti-tumour treatment to unleash the capacity of the immune system to attack and kill cancer cells. Our goal is to use genetic engineering to design small antibody proteins that can bind more than one distinct immune inhibitory receptor simultaneously. By doing this, we aim to restore the natural ability of the patient to recognise and eliminate tumour cells.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
The contraction of the heart muscle is caused by the propagation of electrical signal throughout the heart. This signal is propagated from cell to cell through proteins called ion channels and gap junctions. Physiological and pathological heterogeneities and changes in the expression of these proteins, result in the conductivity field of the heart tissue being non-homogeneous and anisotropic. This can result in electrical waves that propagate abnormally and can cause atrial fibrillation, which is an irregular beat in the upper chambers of the heart, the atria, and one of the most common cardiovascular diseases.
The aim of this project is to test the hypothesis that data from electrograms, recorded by electrodes in direct contact with the heart, can be used to estimate the conductivity field of the cardiac tissue. Deep learning methods will be used to solve this inverse problem, first applied in synthetic data, and then validated in a biological setting.
By reconstructing the conductivity field of the heart muscle from electrograms, the currently-low success rate of the treatment of atrial fibrillation through ablation will be increased, since the clinicians will have a better indication of the position of the low-conductivity tissue that has to be ablated.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Damage to DNA occurs constantly within our cells. If this damage is not repaired, it can lead to mutations in our genome when cells divide, which can cause cancer. So, to protect the integrity of our DNA, cells have evolved a variety of mechanisms to fix these lesions.
One protein that plays a key role in these processes is Artemis, which acts in the repair of several different forms of damage by incising sections of damaged DNA. I will study this protein using a range of biochemical, genetic and cell biology techniques. These will characterise the reactions that Artemis catalyses at sites of DNA damage, whether it requires interacting partners or modifications to do so and will enhance our understanding of the functions of each of its domains. I will also be collaborating with chemists to develop inhibitors against Artemis.
By better understanding the mechanisms that protect our DNA at the molecular level, we can improve cancer treatments. Chemotherapeutic drugs often kill tumour cells by damaging their DNA and cancers can evolve resistance to these treatments by increasing their capacity for repair. Inhibitors targeting Artemis could therefore be used to help overcome resistance to chemotherapeutic drugs and radiotherapy.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
Understanding how complex multicellular organisms, made up from trillions of cells within multiple tissues, develop from a single fertilised egg requires turning specific genes on and off at the right place and time, in a pre-determined order. The entire process is encoded within the DNA sequence of the genome in each individual cell. In humans, there are about 20,000 genes, which encode functional units such as enzymes or haemoglobin, but these only constitute 1-2% of the DNA sequence in each cell. The DNA also contains surrounding regulatory elements that control the output of genes. There are 3 classes of such elements: promoters, enhancers and boundary elements. It is becoming increasingly clear that the roles of these elements overlap one another.
In this work, I will study the characteristics of promoter interactions and the resulting impact on gene regulation. I will be particularly interested in how promoters control gene expression by changing the three-dimensional architecture of the genome as well as the conditions by which promoters interact with enhancers. Ultimately understanding the process of gene expression will enable us to understand how these genes are normally switched on and off during development and how this goes awry in human disease.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
All adult blood cells are derived from prenatal blood stem cells produced in the embryo, where the process is dependent on a gene named RUNX1. Blood cell formation and the development of various blood cancers (leukaemia) are sensitive to RUNX1 levels. In my DPhil, I will characterise the mechanisms regulating RUNX1 levels in normal and malignant human blood cell formation. I will use a "test tube" experimental approach to model human fetal blood cell formation, by differentiating stem cells into immature blood cells (progenitors). I will characterize the dynamic regulatory changes in the RUNX1 genomic region at distinct blood progenitor stages. These data will form the benchmark for the examination of RUNX1 regulation in primary human blood progenitor cells and childhood acute lymphoblastic leukaemia (ALL) samples. Lastly, RUNX1 regulation will be perturbed through genetic and epigenetic engineering, to identify the contribution of aberrant RUNX1 expression to the development of childhood leukaemia. This comparative approach will help us understand not only regulatory mechanisms of normal human blood cell formation, and how well this process can be modelled in a test tube, but also how altered regulation of RUNX1 affects leukaemia development.
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| 30/06/2021 |
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UNIVERSITY OF OXFORD |
The genetic information of each cell is stored in the nucleus as DNA wrapped around histone proteins, a structure termed chromatin. Apart from packaging DNA into the confined space of the nucleus, histone proteins serve as a template on which chemical modifications can be placed. These modifications can determine whether the associated gene is actively being used to produce messenger RNA (mRNA) and subsequently its product. I am studying the four ‘writers’ of one such modification, tri-methylation of lysine 4 on histone H3 (H3K4me3). These four enzymes, SET1A, SET1B, MLL1, and MLL2, have major roles in activating genes, but they seem to do so in a way that is separate and distinct from their roles as the writers of this modification. To understand how these enzymes activate genes, I am using genetically engineered cells in which these enzymes can be rapidly degraded by treating the cells with a small molecule. By removing these enzymes separately and in combination, I can analyse how these enzymes contribute to the overall levels of mRNA and H3K4me3 of the cell using sequencing techniques. The results of this project will be expected to increase our understanding of how genes are activated.
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| 30/06/2021 |
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IMPERIAL COLLEGE LONDON |
As the field of systems biology continues to develop, huge volumes of molecular data are being generated, including 'omics' data which aims to characterise activity at various levels of the biological system, such as genomics, transcriptomics, and metabolomics. A key challenge is the integration of multiple omics datasets to obtain a more holistic understanding of how the layers of the biological system work together. Pathway analysis is a method for assigning molecular entities to their respective biological pathways, to better facilitate biological interpretation of omics data. Current tools for the integration of multi-omics data focus on integrating the data at the level of individual molecules. However, the integration of omics data at the level of biological pathways has not yet been investigated. As biological entities are known to interact within pathways, I propose the development of a novel method for combining multi-omics data by integrating the layers at the pathway level using statistical/machine learning approaches. This work will result in novel methods researchers can use for integrating omics data at the pathway level, with a focus on improving interpretability, sensitivity (the ability to detect biological signals), and predictive ability (using the model to predict e.g. disease status) of current methods.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
Wound healing is a complex process wherein the tissue undergoes inflammation, repair and maturation to re-establish initial equilibrium. When transition between the stages fails, the tissue remains stuck in an inflammatory state, deferring healing and greatly increasing the probability of systemic infection, which may lead to member amputation or even death. Chronic wounds are prevalent in diabetic patients and represent an individual as well as a societal financial burden. Despite of this, it is still unclear how to robustly regulate the process to exit the chronic state and few advanced therapies show evidence of improving the outcome compared to standard treatment. Electric stimulation (ES) is a promising non-invasive procedure that was shown to influence the behaviour of the cells leading the immune and repair response to skin damage. ES was shown to modulate exchange of calcium whose changes in level are correlated with wound stages. The project aim is to define effective time dependent ES regimes that promote the healing of diabetic ulcers by characterizing normal and diabetic-derived cells and their response to ES. Furthermore, calcium signalling will be investigated to reveal ES mechanisms driving cellular response.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
MYC is a protein which is known to contribute to the development of cancer. It is found in many different types of cancer cells at much higher levels than it would be in healthy cells. As a result, MYC has been identified as a protein that could be targeted to treat cancer patients. However, developing a drug that inhibits MYC directly has proved challenging. Therefore, scientists have instead focused on targeting MYC indirectly. For example, several genes have been identified that when inhibited, result in the death of only cells that have too much MYC, such as cancer cells. This means that healthy cells with normal levels of MYC will not be affected. An example of one such gene is SAE2. SAE2 is an enzyme which catalyses the first step in a series of reactions called the SUMOylation pathway. Although this is an encouraging observation, it remains unclear why inhibiting SAE2 kills cancer cells with too much MYC. Therefore, the aim of my project is to find out why and how SAE2 inhibitors kill these MYC-overexpressing cancer cells. This will help determine whether we can use SAE2 inhibitors to treat cancer patients whose tumours possess too much MYC.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
Mammographic density (MD) refers to the proportion of the breast occupied by radiographically dense tissue, as assessed by mammography. It has been shown that women with significantly higher MD are four times more likely to develop breast cancer than those with predominantly radio-lucent tissue. High MD is associated with increased stiffness of the stromal extracellular matrix (ECM) surrounding the breast epithelial ducts. Despite a clear mechanistic link between ECM stiffness and breast cancer risk, little is known about how mammary epithelial cells (MECs) sense and respond to the altered mechanical properties of the surrounding microenvironment.
We want to understand how MECs within the duct mechanically sense altered stiffness of their surrounding ECM by using 3D culture models combined with mathematical modelling. We will utilise 3D traction force microscopy (TFM) to measure the forces on MECs within a 3D ECM model of tuneable mechanical stiffness. We will use these observations, alongside other biological readouts, to parameterise an individual-cell based mathematical model of a 3D acinar structure. We will develop this model to provide quantitative predictions enabling mechanistic insight into the behaviour of MECs and the link between high mammographic density and increased breast cancer risk.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
Gene expression allows organisms to convert the genetic code in their DNA into proteins which carry out specialised functions in cells. In early embryonic development, cells tailor their gene expression programme to make specific sets of proteins which allow them to transform into a particular type of cell, for example, a skin cell or a neuron. Gene expression has multiple stages including how the process begins, the tuning and travel of RNA molecules along their journey, their conversion into protein as well as the mechanisms by which the cell disposes of them. My work focuses on these degradation mechanisms. We will use large datasets and computational methods including machine learning to estimate degradation rates across different genes throughout embryonic development in the fruitfly model organism and understand the mechanisms controlling these. Our findings will be validated using cutting-edge methods for imaging mRNAs. We will then use other experimental biology techniques including CRISPR-Cas9 genome engineering to change degradation rates of individual mRNAs and examine the effects on cell fates and developmental processes. This will provide us with a greater understanding of how gene expression is controlled, which has implications for many human diseases including cancer, and applications to regenerative medicine.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
Oesophageal cancer is the 14th most prevalent cancer and the 7th most common cause of cancer death in the UK. Oesophageal Adenocarcinoma (OAC) is the most common subtype within Western populations. A poor understanding of the disease drives poor patient outcomes.
The disease is thought to arise from a pre-cancerous state known as Barrett’s Oesophagus (BO). Changes in the regulation of transcription and chromatin environment have been identified in the transition from regular oesophageal tissue to BO to OAC. This includes evidence of reversion to an embryonic developmental cell state. Additionally, Little is known about the changes in gene regulatory networks and chromatin environment which initiates and maintains metastatic cancer state.
I will use functional genomics approaches to identify elements which play a role in transcriptional regulation such as enhancers, super-enhancers and silencers. This will include developing bioinformatics methods to scale up existing unsupervised clustering methods and experimentally validating bioinformatics results e.g. endogenous reporter assays for enhancers. I will compare the regulatory landscape in regular and metastatic OAC, and embryonic tissue from the oesophagus, stomach and duodenum. This will help elucidate the origins of OAC and molecular drivers of OAC metastasis and provide bioinformatics tools potentially applicable to other diseases.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
The family of BMP1/Tolloid-like proteases (B/TPs) is involved in a variety of important functions in mammalian tissue development. Firstly, B/TPs cut collagen precursors to allow their assembly in the extra-cellular matrix (ECM). Mutations or a loss of function of B/TPs result in several developmental defects or can result in death during the embryonic stage. The second role of B/TPs is activating different growth factors. These messenger molecules are involved in communicating with cells during the formation of different tissues, including bones and the brain.
Our work aims to understand how B/TPs carry out their function and how mutations result in diseases. To do so, we aim to determine the 3-dimensional structure of two members of the B/TP family using cryogenic electron microscopy. Furthermore, we want to understand how B/TPs interact with their substrates, as well as known effector proteins. We hope our results will allow for a better understanding of B/TP function and regulation and provide potential basis for therapeutic approaches for B/TP-associated diseases.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
In order to sense and respond to outside events, eukaryotic cells utilise many different proteins on their surface to finely control activities such as growth and movement. Key to regulating these processes is the uptake of these proteins from the cell surface, and their destruction at the lysosome in a process coordinated by the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery. The first of these complexes, ESCRT-0, recognises a universal signal (ubiquitin), which is attached to these proteins and marks them for destruction by directing them to the lysosome where they are broken apart and recycled. In order to understand how ESCRT-0 works, we need to know what it looks like. We intend to investigate this by using the technique cryo-electron microscopy, which will allow us to understand the shape of ESCRT-0 at the atomic level. We will also use an array of biophysical techniques to investigate how the structure of ESCRT-0 changes when it binds to ubiquitinated proteins, and whether this binding helps to promote the subsequent stages of the ESCRT process. Together, this should tell us what the role of ESCRT-0 is at the head of the ESCRT pathway.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
From active transport by motor proteins to passive transport in the crowded cytoplasmic environment, the movement of organelles within cells is critical for cell function. This transport exhibits non-Brownian anomalous transport: sub-diffusion and super-diffusion. Abnormal transport can lead to disease, and understanding how this occurs requires systematic quantification of organelle movement combined with predictions based on biologically motivated random walk models with multiple states of motion. To simplify tracking and analysis we will study organelle motility in neurons that are one dimensional, due to the thinness of the axon, rather than the fibroblasts we studied previously. We will obtain and analyse organelle trajectories by live-cell imaging of cultured human neuronal-like cells, and individual neurons in the nematode C. elegans. Then we will determine how selected disease-causing mutations in dynein regulators affect motility. We will develop new mathematical models for non-Markovian stochastic transport and fractional Brownian motion with random Hurst exponents, validating and improving models using experimental data. Lastly, we will generate new neural network/machine learning algorithms to better segment and estimate different states of motion and use these to predict the effect of dynein disruption on motility in human motor neurons that can be 1m long.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
White blood cells (WBCs) play a fundamental role in coordinating our immune system in response to infection. WBCs known as B cells produce antibodies and contribute to lasting immunity upon re-exposure to the same infection. Unfortunately, B cells are also responsible for various immune disorders and lymphatic cancers. This makes understanding the mechanisms controlling B cell behaviour vital for treating these diseases. B cell physiology is heavily regulated by a cell surface receptor known as the B cell receptor (BCR). We have uncovered a novel mechanism by BCR function is mediated through a specific enzyme that targets fat-like molecules called lipids. I aim to understand this previously unappreciated mechanism of regulation using a multidisciplinary approach. I will use biochemical and mass spectrometric approaches to determine how these enzymes are recruited to BCRs. I will genetically engineer cell lines which lack these enzymes to explore the functional impacts of their absence on BCR activation and signalling, measuring changes using flow cytometry and cutting-edge live-cell microscopy. Validating these enzymes as critical for BCR function will not only enhance our overall understanding of this complex process but also reveal new targets for therapeutic intervention.
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| 30/06/2021 |
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UNIVERSITY OF MANCHESTER |
Polarity, the asymmetric organisation of cellular components, is crucial for the function of many cell types. Newborn neurons in the developing spinal cord shed their tips to move to their final location, causing them to lose polarity and the ability to distinguish their front from their back. These neurons must then regain polarity to extend a long process, called an axon, which makes connections with other neurons. In the developing embryo, neurons polarise in response to external cues from the surrounding tissue, which determine the orientation in which the axon will form, and therefore the direction it will grow in, or if it forms at all. Thus, neuron polarisation is essential for the formation of neuronal circuitry; however, the mechanisms of vertebrate neuron polarisation within tissue are unclear. I will study the molecular and cellular mechanisms that direct this key cell-biological process using cutting-edge live imaging and super-resolution microscopy of developing neurons in the embryonic chick spinal cord. Not only will this work help us understand how the nervous system is built, but it will also enrich our understanding of the general cellular mechanisms of polarity transition in development and disease.
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| 30/06/2021 |
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UNIVERSITY OF BRISTOL |
Body tissues, such as the skin, must be able to rapidly repair themselves in response to injury. However, some individuals (particularly those with underlying health conditions) suffer from debilitating ‘chronic’ wounds that fail to heal, which are often persistently infected. These non-healing wounds are poorly understood and represent a significant burden to healthcare systems and economies.
Damaged tissues recruit immune cells to ‘clean’ the wound, removing dead cells and producing toxic oxygen molecules to kill invading germs. This inflammatory response is essential for normal wound healing. However, overproduction of toxic molecules could cause ‘collateral damage’ to our own cells (termed ‘oxidative stress’) and hinder repair. To combat this, we have evolved a powerful network of ‘biological shields’ to protect injured tissues, including antioxidant production.
My work will explore whether defects in this protective machinery are responsible for the failure of infected/diabetic wounds to heal and whether we can rescue healing by boosting protection. For this, I will use the fruit fly (Drosophila), exploiting their translucency (and genetic tractability) to study wound repair live ‘in vivo’. In parallel, I will use ‘genetic epidemiology’ to investigate their clinical relevance, by seeing if variations in equivalent human genes have links to disease.
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| 30/06/2021 |
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UNIVERSITY OF BRISTOL |
Breast cancer (BrCa) is one of the most common forms of cancer, affecting 1 in 7 women and accounting for 7% of all deaths in the UK between 2015-2017. Numerous risk factors have been associated with BrCa including age, family history and body mass index, as well as factors involved in women’s reproductive health. Reproductive events such as early puberty and later menopause have been associated with increased BrCa risk. Much of the current literature has assessed reproductive events independently without consideration of other reproductive events, and these event’s causal role in BrCa development has not been fully investigated.
My aim is to use multiple approaches to explore the role of reproductive events for improving understanding of BrCa. Firstly, I will assess how these reproductive events have an effect, either independently or in combination, on BrCa risk, across the life course. Secondly, I will use newly developed methods to further assess if reproductive events play a role in causing BrCa. Finally, I will assess to what extent epigenetic modifications, changes to the DNA which influence gene regulation, play a role in the relationship between reproductive events and BrCa. This work will improve our understanding of the causes of BrCa.
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| 30/06/2021 |
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UNIVERSITY OF BRISTOL |
Osteoporosis is a disease which weakens bones, making individuals more prone to fractures even after a minor fall. It is a prevalent disease, affecting around 1 in 3 women and 1 in 5 men which accounts for 28 million people over the age of 50 across Europe. Individuals suffering with osteoporosis put a significant burden on health care services as they can require long term hospitalisation after surgery, as well as social care packages and physiotherapy. Current treatments aim to stop bone degradation, whereas there are few treatments available to re-build bone and thus help prevent further fractures. New bone-building drug targets can be discovered by investigating the genetic changes which cause people to have naturally high bone mass. In my project, I will use human genetic datasets for genetic changes relevant to bone metabolism to select two novel candidate genes. I will use zebrafish as a model, since their rapid life cycle and transparent bodies allow for imaging of fluorescent proteins that help us understand how the candidate genes affect bone homeostasis. Cultured zebrafish scales will be used to screen for compounds targeted to these candidate genes to test their bone-building capacity informing potential novel osteoporosis treatments.
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| 30/06/2021 |
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UNIVERSITY OF BRISTOL |
Background
Mitochondria are membrane-bound organelles implicated in cellular energy generation and an increasing number of cellular processes. Critically, these processes rely on proteins being imported into the mitochondria via the mitochondrial protein import apparatus. ‘Stop-transfer’ import (Figure 1) is a means to achieve delivery of proteins to a mitochondrial sub-compartment termed the inter-membrane space (IMS). PTEN-induced kinase 1 (PINK1), a mammalian mitochondrial protein kinase and Mgm1, a mitochondrial protein in yeast, are both implicated in mitochondrial ‘health’ and are critical substrates of this pathway.
Approach
Thorough mechanistic characterization of stop-transfer protein import and the role of processing of these proteins is required to better understand delivery to the IMS in native and damage contexts. I will apply biochemical and biophysical (spectroscopic) approaches to report on import into the IMS using purified PINK1 and Mgm1 in mammalian and yeast cell-based import assays respectively, while also focusing on the role of interacting proteins during the import process, markedly TOM/TIM proteins and PGAM5.
Impact
Design of a probe to report on mitochondrial import into the IMS will reveal new details of the molecular control of stop-transfer import and its regulation, markedly for critical substrates such as PINK1 implicated in human disease.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Neutrophils are the most abundant immune cell in circulation. They are the first to respond to infection and tissue damage. Once activated, they migrate into affected tissues to kill microbes using effector mechanisms. These are: pathogen engulfment, secretion of toxic granules, or, releasing neutrophil extracellular traps (NETs). NETs are large, web-like structures comprised of DNA and neutrophil proteins. NETs trap microbes to prevent them spreading and therefore limit tissue damage. However, NET production is tightly controlled because they can also damage our own tissues. Moreover, uncontrolled neutrophil activity and NET release can exacerbate some diseases such as cancer and malaria.
Despite their disease relevance, how neutrophils ‘decide’ to react to microbes and inflammation is not well known. Therefore, the aim of this project is to understand which genes control neutrophil behaviour. We will test the hypothesis that the same set of genes that regulate cell division, also regulate NET release. Furthermore, we will also examine if neutrophil changes during cancer make them more prone to making NETs and contribute to disease progression.
This project will lead to deeper understanding of the role of cell cycle genes in NET formation and elucidate their role in neutrophil populations associated with inflammatory disease.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Wound healing is the process by which skin integrity is restored following injury. At any site of tissue damage, the body activates a complex series of events to heal the wound. Each stage is necessary for effective tissue repair. Inflammation has evolved to prevent infection by pathogens. Besides killing bacteria, signals from inflammatory cells also coordinate other aspects of wound healing. However, these signals may also have negative consequences such a scarring, and if inflammation is not resolved, this can lead to chronic wounds such as diabetic foot ulcers can result. During my PhD I will investigate how inflammation impacts on three lesser studied cell types in wound healing, melanocytes (pigment cells), adipocytes (fat cells) and the cutaneous nerves in skin. It is thought these three cells could play interesting, but as yet unknown roles in wound repair, which may aid repair or be pathological. I will use live imaging in the translucent zebrafish to look at how these cells interact with inflammation, and what signals may cause this. This work could reveal the impacts of inflammation at the wound repair site, which could have impact on wound treatment in the clinic.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
My project will aim to investigate the role of the human gut microbiome in health and disease outcomes, in particular to assess its role in the link between dietary composition and obesity. The human gut microbiome is a huge community of microorganisms that exist within our digestive systems that interact to aid digestion, protect against pathogens and create metabolites. Although previous evidence suggests the gut microbiome plays a role in health and diseases, much of the literature (arising from animal or observational human studies) attempting to assess this relationship has so far been inconsistent and unable to prove cause-and-effect relationships. I aim to combine epidemiological, genetic and causal inference methods to establish relationships between dietary composition and the microbiome and between the microbiome and health outcomes (focusing on obesity). Dietary composition is one of the key exposures dominating the literature as a likely regulator of the gut microbiome, with a diet high in dietary fibre for example being correlated with high microbial diversity. Lower microbial diversity has been observed in the gut of people with obesity, amongst other diseases. By filling the gaps in the evidence, this research has the potential to be translated into clinical practice and industry.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BRISTOL |
Many common diseases such as obesity, diabetes and hypertension are caused by a combination of genetic, environmental and lifestyle factors. Better understandings of the causal factors of complex diseases may aid disease prevention and health research. Conventionally, studies on disease causal factors rely on health intervention experiments which cost enormous time and labour. The recent availability of large-scale databases, which contains genetic, lifestyle and disease information on tens of thousands of individuals, allows researchers to construct polygenic risk scores (PRS) to represent individuals’ genetic liability to develop a trait or disease. This score could be used to investigate disease causal factors in Mendelian randomisation (MR) analyses, a genetics-based approach analogous to a randomized controlled trial. My PhD will involve constructing and analysing the PRS for complex diseases and generating a large resource of PRS and MR results which we plan to share with the scientific community. I will improve the method of PRS constructions and develop analytical pipelines to identify causal modifiable risk factors for diseases, key genes and pathways underlying disease mechanisms. Furthermore, I will also assess the capability of PRS to predict causal risk factors during childhood which may therefore have important implications for preventing later life disease.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF DUNDEE |
While most fungal infections are cleared by the immune system in healthy individuals, in immunocompromised people or in patients after invasive medical procedures these pathogens can cause life threatening systemic infections. With mortality rates around 50% our current treatments are insufficient. Thus, research to better understand these infections is required.
Candida albicans is the most common human fungal pathogen and a frequent cause of hospital acquired infections. Macrophages are one of the first cells in our immune system to identify Candida and initiate an antifungal response; but how infection affects intracellular processes in macrophages is not completely understood.
I intend to further investigate which intracellular processes are altered during Candida infection. In previous work, we studied the total proteins in macrophages during infection, and we found Candida infection appeared to dysregulate an oxidative stress mechanism, Nrf2/Keap1, in a novel way. We plan to further study this mechanism, as well as more broadly look for novel mechanisms of regulation. This project will contribute to understanding our immune system’s functional response to fungal infection and will bring us closer to creating new therapeutics to prevent systemic fungal infections.
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| 30/06/2021 |
£0 |
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UNIVERSITY COLLEGE LONDON |
Long-lasting changes in strength between synapses are a key element of learning and memory. The intracellular second messenger cyclic AMP (cAMP) plays a key role alongside Ca2+ in coordinating such synaptic plasticity. cAMP signalling operates in localised ‘nanodomains’ that are centred on the enzymes that synthesize cAMP – adenylyl cyclases. In neurons, two Ca2+-sensitive cyclases (AC1 and AC8) are particularly important in signalling underlying synaptic plasticity. These enzymes are relatively understudied, partly due to technical hurdles.
I will take advantage of novel crosslinking approaches, and state-of-the-art mammalian cell expression systems to overcome these hurdles and study the enzymes in three ways. First, I will use crosslinking of extracts from rat cerebellum (where the cyclases are abundant) to identify and characterise their molecular interactions. Second, I will employ inducible expression in suspension cultures of mammalian cells to express large amounts of the cyclases. This will enable me to study their three-dimensional structure – a key step in fully understanding their function. Third, I will use a high-throughput assay to screen for novel ligands of neuronal cyclases. This multidisciplinary approach will address a basic element of neuronal signalling that is critical in brain regions including the cerebellum, hippocampus, and the striatum.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF CAMBRIDGE |
In immune conditions such as sepsis, treatment options can be limited by a lack of understanding of the causes of the condition, as well as the vast differences in how the immune system of the patient can respond. While expression differences between genes explain some of the variance between patient outcomes, there is still a lot of variability unaccounted for, and how this relates to the genome remains to be studied. RNA sequencing performed on samples from large existing cohorts of patients will give transcript level information, revealing not only the expression levels but also information such as how the genes are differentially spliced between individuals. With paired medical records I will relate these observed transcript differences with patient outcomes, as well as infer how innate genotypes can modulate these effects. Provided microbiological information on the cause of the condition or infection will allow me to also understand the differences in human responses to infection type. This knowledge will lead to a more personalised treatment regime for patients based on the course of their illness and innate characteristics, as well as giving the option to better predict and address the cause of their illness.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF CAMBRIDGE |
Inflammatory bowel disease (IBD) is a disease of the gut affecting over 2.5 million people in Europe alone. Through genome-wide association studies, over 240 genomic regions have been identified as significantly associated with the disease or its two subtypes: Crohn’s disease and ulcerative colitis (1,2). However the mutations, genes and cell-types that drive disease progression, are still unknown and for many patients, IBD remains incredibly difficult to treat. The Anderson group has undertaken two distinct, large-scale projects in an effort to fill in many of the gaps in existing knowledge. Firstly, whole genome and exome sequencing of large cohorts of healthy and diseased individuals is being undertaken to better understand the disease-associated regions. During my PhD I will use this data to examine the effect that deletions, insertions and inversions of large chunks of DNA can have on IBD. The second major ongoing project is single-cell sequencing of terminal ileum, rectal and blood samples taken from healthy individuals and patients with Crohn's disease. In the second half of my PhD project, I will use the single-cell data to determine the genes, pathways and cells involved in Crohn’s disease.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF CAMBRIDGE |
Metabolic health depends on a myriad of genes and the environment. Variation in these genes across individuals can predispose them to obesity, Type II Diabetes (T2D) and other metabolic syndromes. Early works focused on how a few mutated genes could cause rare and severe metabolic diseases. A lot has been learnt about appetite and weight regulation by studying those genes whose mutations have large impact on metabolic health. However, common forms of obesity and T2D are attributed to multiple genetic variations, whose individual effects are hard to observe. We aim to understand how these mutations with little observable impacts affect our metabolic health. We hope to gain more insights into the fundamental genetics of metabolism from these rare mutations by combining data-driven epidemiological methods and molecular biology techniques. Epidemiological methods will statistically identify how the presence of some mutated genes correlate with alterations in metabolic health. Then, using molecular biology techniques, we will investigate the causations and mechanisms of these statistical correlations. To this end, we will clone the mutated genes in cellular models and measure the changes in their activities.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF BIRMINGHAM |
The migration of immune cells such as T-lymphocytes to areas of inflammation plays an important role in the inflammatory response. T-lymphocyte migration follows a circadian (daily) rhythm, with more T-lymphocytes migrating into tissues in the morning than the evening. If this process is not carefully regulated, this can lead to an exaggerated inflammatory response which contributes to diseases. PEPITEM is a small peptide hormone which inhibits T-lymphocyte migration and is made by another type of immune cells, B-lymphocytes. Patients with inflammatory diseases cannot make PEPITEM in sufficient quantities to control T-lymphocyte migration. Our preliminary studies indicate that a protein able to cleave other proteins (protease) is responsible for PEPITEM release from B-lymphocytes and that this might be under circadian control. In my project, I aim to identify the protease that leads to PEPITEM release, and investigate how the PEPITEM pathway follows circadian oscillations. I will look at the expression of genes and proteins involved in the PEPITEM pathway at different time of the day to see how this pathway is regulated by circadian rhythms. This project will help to understand the dysregulation of inflammation that occurs in many chronic inflammatory diseases.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF LIVERPOOL |
The lysosome, once thought to be a cellular ‘trash-can’, is now found to be the key to understanding the signalling controlling human ageing, neurodegeneration, and a range of diseases from diabetes to cancer. Developing tools to understand how the lysosome works will be key to future biological studies.
In this project, we will develop and analyse a new imaging probe which will allow us to examine calcium signalling in functional lysosomes in live-imaging, proteomic and lipidomic modalities to develop a fine-grained understanding of how lysosomes function in health and disease.
The genetic probe we are developing makes it easy to isolate, image, and manipulate lysosomes in living cells and in cellular extracts using one transfectable tool, offering many avenues of application to basic and industry-focused research. One key regulator of lysosomal calcium storage is the messenger NAADP, which we will examine in detail. We will produce coordinated maps of the behaviour of calcium levels inside the lysosome under conditions known to alter NAADP signalling, coupled with the metabolic and proteomic profiles of lysosomes in the same conditions and in mutants of the muscular dystrophy gene INPP5K: giving a comprehensive map of the regulation of this key signalling axis.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF LIVERPOOL |
Cancer immunotherapy harnesses the potency of the immune system to reinvigorate anti-tumour effects. CTLA-4 is a protein that acts as a brake on the immune system; blocking CTLA-4 can disengage the brake on immune cells, thereby freeing our immune system to attack tumours. Although therapies entailing a CTLA-4 blockade has led to promising results, they have yet to achieve their full clinical potential. To improve CTLA-4-targeting treatment, a thorough understanding of CTLA-4 function at the cell biology level is essential. Modulating the number of CTLA-4 present on the surface of immune cells is an emerging therapeutic strategy in cancer immunotherapy. Generally, protein levels at the cell surface are controlled by two major events: protein internalisation and transport to the cell surface. Very often, internalised proteins that will be degraded by the cell’s "garbage disposal system" are temporarily tagged by ubiquitin, which will later be removed by an enzyme. Here, we aim to explore how CTLA-4 traffics in the immune cells by 1) identifying the key proteins that regulate CTLA-4 levels on the cell surface and 2) characterising the enzymes that control CTLA-4 degradation using state-of-the-art screening approaches.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF LIVERPOOL |
Mitochondria are organelles within cells which are responsible for energy production. High energy demands or cellular stress can result to dysfunctional mitochondria. When mitochondria become damaged, they should be removed, in order to keep cells healthy. Cells have complicated mechanisms for recognizing and successfully destroying damaged mitochondria, as well as other dysfunctional organelles and proteins. The aggregation of dysfunctional organelles or proteins is the hallmark of many neurodegenerative diseases. A main degradation system in cells is autophagy, which essentially means self-eating, during which the damaged cellular components are isolated in a vesicle to be broken down. The autophagy of mitochondria is called mitophagy. The first step for mitophagy is the ‘decoration’ of mitochondria with a protein called ubiquitin. Ubiquitin in several cases acts a signal for degradation not only for damaged mitochondria, but for other dysfunctional organelles and proteins. In mitochondria, specifically, the addition of phosphate in ubiquitin is critical for initiating their degradation. Here, we want to define if these phosphoubiquitin tags are also found in proteins outside of mitochondria, and which proteins are capable of recognize these unique tags. These experiments will help us to understand deeper the fundamental process of mitophagy, which is disordered in Parkinson’s disease.
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| 30/06/2021 |
£0 |
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UNIVERSITY OF LIVERPOOL |
The liver is the main site for the elimination of medicines taken by people (a process termed drug metabolism). There are many enzymes involved in drug metabolism – one of these is cytochrome P450 2C9 (CYP2C9). CYP2C9 metabolises approximately 13% of all clinically used medications. One example is warfarin [1].
The activity of CYP2C9 varies between individuals which can affect drug efficacy and increase the likelihood for adverse drug reactions [2–4]. This is due to several factors including concurrent disease and the intake of other medications. Genetic factors also affect the activity of CYP2C9 – these are termed genetic polymorphisms. The function (i.e. whether they increase or decrease activity of CYP2C9) of almost half of these polymorphisms is not well-defined [5]. Preliminary work performed in the Pirmohamed lab has identified 16 high impact (e.g. frameshifts), 159 moderate impact (e.g. missense variants) and more than 8000 non-coding variants.
The key goals of the project are:
Correlate genetic variation in CYP2C9 to clinical outcomes using the UK BioBank, 100K Genomes Project and a well-characterised warfarin cohort
Assess the effect of genetic variants on metabolomic parameters
Prioritise variants for in vitro functional studies using CRISPR-Cas9, with effects on metabolism evaluated using LC-MS
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| 30/06/2021 |
£0 |
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UNIVERSITY OF LIVERPOOL |
Many drugs used to treat cancers and HIV cause life-threatening heart problems which limits their use. Research into how to reduce this risk has previously been difficult due to a lack of experimental methods which accurately mimic the human cardiac system. However, new 3D human-cell models have been developed which reproduce the adverse drug reactions seen in patients. These new models have been used to show that increased expression of an important protective protein NFE2L (NRF2), provides protection from the toxic effects caused by a commonly used breast cancer drug. We believe that by increasing the activity of human NFE2L proteins (NFE2L1-3), we may protect cardiac cells from other adverse drug effects. Here, we will combine 3D human cardiac models with gene editing methods and advanced cell imaging techniques to manipulate expression of all NRF family proteins and monitor the protective effects under normal and high-glucose conditions, which are known to reduce the protective effects of NRF2. The results from this study will aid the development of new therapeutic strategies to prevent or reverse heart toxicity from commonly used cancer and HIV drugs.
|
| 29/06/2021 |
£7,433,739 |
|
BRADFORD HOSPITALS NHS TRUST |
Adolescence and transition into adulthood are periods shaping life-long mental health, cardiometabolic risk, and inequalities. However, they are poorly studied and understood. By extending and expanding the Born in Bradford (BiB) cohort study through this period using innovative, co-produced approaches to collect and analyse data, we aim to understand better the interplay of factors that influence health and wellbeing, and inform/evaluate interventions to improve them and reduce inequalities.
Age of Wonder will be the only large whole city cohort capable of capturing the contemporary lived experience amongst multi-ethnic adolescents progressing into young adulthood, linked to their earlier life. It will build on a world-leading birth cohort situated the 5th largest metropolitan district in England with high levels of deprivation, ethnic diversity, supported by a connected routine data infrastructure covering 600,000 citizens.
We will collect repeated data from existing BiB participants and their peers (N~30,000). In-school assessments, clinical assessments plus online data collection and electronic linkage will capture information on mental, reproductive, sexual, neurocognitive and cardiometabolic health. Remote collection will continue to age 21. Repeat qualitative interviews and ethnographic observations will explore lived experiences.
We will collaborate internationally to broad-ranging research and discovery science and promote rapid application to policy/practice.
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| 23/06/2021 |
£60,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Schistosomiasis, a trematode infectious disease, is highly endemic in Malawi. Approximately 40-50% of the population are at risk of being infected with urinary and intestinal schistosomiasis, with transmission being dependent on humans encountering an intermediate freshwater snail host. As such, the spatial pattern in disease risk is strongly influenced by the natural environment. The overarching goal of this project is to combine remotely sensed and georeferenced snail survey data to quantify the relationship between the snail host and the environment, and to understand the impact of environmental changes such as land-use and climate change on transmission risk. Focusing on the highly endemic region of Southern Malawi, I will use geospatial statistical methods and publicly available satellite imagery to generate habitat suitability maps over a 30-year period (1990-2020) to visualize the changing patterns in transmission risk over time. Data on various climate change scenarios will be used to predict future changes in snail habitat for the region. I will undertake snail surveys and drone image capture to generate snail habitat suitability maps which complement the ongoing epidemiological surveys. Outputs generated will provide valuable insight into the spatial patterns in schistosomiasis risk, and mitigating future risk caused by environmental and climatic changes.
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| 23/06/2021 |
£60,000 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Private retail pharmacies are the first point of contact for most people seeking treatment for minor illness in LMICs. They play a significant role in delivery of public health interventions (PHIs). In Kenya, for example, retail pharmacies are involved in the provision of family planning services, HIV counselling and testing services and malaria treatment. Despite the role private retail pharmacies play in delivering PHIs, there is limited evidence on the attributes of PHIs that community pharmacists (pharmacists working in private retail pharmacies) value and the trade-offs they would be willing to make. Moreover, private retail pharmacies have competing interests aimed at maximizing profits. It is therefore essential that the contracts policy makers design for them are aligned with their incentives.
The proposed study aims to elicit the preferences of community pharmacists for attributes of PHIs in Kenya, utilizing a discrete the choice experiment (DCE) approach. A DCE is a stated preference method used to elicit individuals’ preferences for goods and services using hypothetical scenarios. The mixed-method study will involve 350 participants from 4 counties. Data will be analyzed using thematic analysis and conditional-logit model. Findings will inform policy makers in design and implementation of PHIs through private retail pharmacies.
|
| 23/06/2021 |
£261,547 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Transmission of ESBL-E in humans occurs through diverse routes. However, the relative contributions of each are poorly understood, especially in low- and middle-income (LMIC) hospital settings. Furthermore, attempts to quantify effects of transmission risk factors in LMICs have been challenged by inadequacies in data quality and/or modelling approaches.
In this Fellowship, I will investigate pathways to transmission of ESBL-E at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi to:
To characterise changes in patient and carer gut microbiota during hospitalisation;
Determine hospital reservoirs of ESBL-E and routes of transmission;
Explore the causal relationship of antimicrobial use, patient and hospital hygiene factors with gut microbiota diversity and acquisition of ESBL-E.
I will sequence the genomes of isolated bacteria and whole populations from stool samples of admitted patients and carers at QECH and analyse the genetic data and participants metadata using bioinformatic and causal modelling approaches to investigate pathways to hospital acquisition of ESBL-E.
The output from this study will inform the design of interventions for controlling ESBL-E transmission and provide a framework understanding nosocomial AMR transmission to enable generalisation of methods from to this study to other sites.
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| 23/06/2021 |
£43,372 |
|
WELLCOME SANGER INSTITUTE |
Transmission of ESBL-E in humans occurs through diverse routes. However, the relative contributions of each are poorly understood, especially in low- and middle-income (LMIC) hospital settings. Furthermore, attempts to quantify effects of transmission risk factors in LMICs have been challenged by inadequacies in data quality and/or modelling approaches.
In this Fellowship, I will investigate pathways to transmission of ESBL-E at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi to:
To characterise changes in patient and carer gut microbiota during hospitalisation;
Determine hospital reservoirs of ESBL-E and routes of transmission;
Explore the causal relationship of antimicrobial use, patient and hospital hygiene factors with gut microbiota diversity and acquisition of ESBL-E.
I will sequence the genomes of isolated bacteria and whole populations from stool samples of admitted patients and carers at QECH and analyse the genetic data and participants metadata using bioinformatic and causal modelling approaches to investigate pathways to hospital acquisition of ESBL-E.
The output from this study will inform the design of interventions for controlling ESBL-E transmission and provide a framework understanding nosocomial AMR transmission to enable generalisation of methods from to this study to other sites.
|
| 23/06/2021 |
£416,392 |
|
CENTRE FOR SEXUAL HEALTH AND HIV AIDS RESEARCH ZIMBABWE |
There is an urgent need to promote positive masculinity among boys in Africa, where negative gender norms underpin many areas of public health concern including unwanted pregnancy, HIV and violence. I aim to co-develop and evaluate a peer-delivered gender-transformative intervention for younger adolescents (aged 10-14 years) to promote positive masculinity and sexual health in Zimbabwe. Gender-transformative interventions can successfully promote gender-equitable identities especially in early adolescence when attitudes and behaviours are still malleable. The ultimate goal is to develop an effective scalable model to influence constructs of positive masculinity. The project will include both girls and boys, but with special focus on boys. I will first conduct research to identify and prioritise the gender norms to be targeted. I will then work with younger adolescents and other stakeholders to co-develop an intervention targeting the prioritised harmful gender norms and then pilot and refine the intervention. I will also develop context-specific and valid quantitative tools to measure gender-related social norms, attitudes and behavioural norms. I will conduct a feasibility trial of the intervention with in-depth process evaluation to explore feasibility and acceptability to inform the design of a randomised effectiveness trial (assuming that pre-specified criteria for feasibility are met).
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| 23/06/2021 |
£278,810 |
|
MOCHTAR RIADY INSTITUTE FOR NANOTECHNOLOGY |
In Indonesia, a patch of Eastern Bornean forest remains the home of the last active hunter-gatherer group in the region, the Cave Punan (Punan Batu), who live under karstic rock-shelters. They continue to hunt on a daily basis, primarily using dogs and spears, and to gather a range of forest tubers and fruits. However, deforestation is forcing the community to transition away from their traditional lifestyle towards a more sedentary and partially agricultural one. The transition from hunting and gathering to agriculture involves a radical shift in diets and physical activity levels, and could disrupt long-standing biology likely to have been shaped by natural selection, eventually leading to increased risk for lifestyle disease. Hence, the aims of this project are i) to characterize genomic adaptation to a foraging lifestyle in the Cave Punan, ii) to study the biological impact of lifestyle transition by observing the changes at the RNA and epigenetic level in communities along this lifestyle gradient, iii) and to contrast the gut microbiome diversity in communities with different lifestyles. This study will provide insights on how our ancestors’ way of life has left genomics imprint in contemporary foraging community, and how lifestyle changes would alter its biological significance.
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| 23/06/2021 |
£183,909 |
|
INSTITUTE OF BIOMEDICAL SCIENCES, UNIVERSITY DE SAO PAULO |
Trypanosoma cruzi, the causal agent of Chagas disease, has a complex digenetic life cycle. This organism is well adapted to handle environmental changes, presenting high metabolic flexibility. In this context, amino acids and their metabolism play crucial roles in cell differentiation, maintenance of cell volume and response to different types of stress. This proposal aims to identify the key steps of the amino acid metabolic network which are crucial for T. cruzi to complete its life cycle. With this purpose, we will use the bar-seq CRISPR-Cas9 genome editing strategy to generate mutant knockout cell lines for the coding sequences of 40 enzymes putatively involved in the metabolism of amino acids. Each cell line will be identified by a unique sequence barcode and they will be pooled to allow parallel phenotyping during cell differentiation and infection, both in vitro and in vivo. Relative fitness will be assessed by next-generation DNA sequencing. Identification of the enzymes that are essential for parasite development and infectivity will provide insights on the metabolic strategies T. cruzi evolved to adapt to diverse environments as well as novel targets for target-specific drug design and ligand structure-based screenings in the future.
|
| 23/06/2021 |
£274,523 |
|
UNIVERSITY OF OXFORD |
Typhoid fever remains a significant public health and economic burden in LMICs. The global spread of extensively drug-resistant (XDR) Salmonella Typhi has limited the effectiveness of antimicrobial therapy and threatened lives. Resistance of S. Typhi to azithromycin, the only remaining effective oral drug to treat XDR typhoid, recently emerged in South Asia, posing an immediate threat of untreatable typhoid fever. I aim to investigate the emergence and epidemiology of azithromycin-resistant (AzithR) S. Typhi and determine its impact on typhoid treatment. I will perform genome sequencing of ~500 S. Typhi isolates from the ACT-South Asia Trial conducted in Nepal, India, Bangladesh and Pakistan to investigate the evolutionary and epidemiological dynamics of AzithR S. Typhi. I will conduct laboratory experiments to understand the evolutionary drivers of AzithR S. Typhi and measure the impact of AzithR mutations on bacterial growth dynamics, antimicrobial tolerance, and fitness. Further, I will assess the correlation between clinical responses to azithromycin and in vitro intracellular azithromycin susceptibility of S. Typhi isolates from the above trial. These research investigations are essential to understand the evolutionary and epidemiological landscape of AzithR S. Typhi, as well as clinical responses to azithromycin and appropriate dosages for guiding control measures and clinical practice.
|
| 23/06/2021 |
£819,410 |
|
UNIVERSITY OF CAPE TOWN |
Neurocysticercosis is caused by the presence of Taenia solium larvae in the brain and is the leading cause of adult-acquired epilepsy worldwide. The central goal of this research program is to determine what events control seizure susceptibility in brain-networks perturbed by neurocysticercosis. We will capitalise on rare access to human brain tissue in Cape Town by using human organotypic brain slice cultures (OBSCs) together with T. solium larvae. In Aim 1 we will determine how cestode larvae perturb neuroinflammatory processes by measuring the dynamics of cytokine release, glial cell activation and cell death. In Aim 2, we will use fast calcium imaging to test the effects of larval products on network excitability. This will be correlated with observations of morphological, electrical and synaptic changes within neuronal networks. We will also determine whether changes in chloride and hydrogen ion homeostasis underlie the development of seizures. In Aim 3 we will use powerful molecular techniques (including single nuclei RNAseq) to elucidate how T. solium larvae modulate gene expression in the human brain. By integrating our observations made studying inflammatory, neuronal and gene networks in the human brain, we expect to uncover novel insights into the cellular and molecular underpinnings of neurocysticercosis.
|
| 23/06/2021 |
£122,496 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Medical and nutritional management in acutely-ill undernourished children in developing countries aim to support rapid weight gain. However, such children remain at risk of death and poor catch-up growth post-hospital discharge. Little is known about mechanisms regulating childhood growth after acute illness. I hypothesise that persistent systemic inflammation (SI) is a key determinant of growth post-discharge among undernourished children. SI is associated with reduced linear growth in community cohorts, and is demonstrable at hospital discharge among undernourished children, potentially indicating untreated infections, microbiota dysbiosis, gut-circulation microbial product translocation, or enteric inflammation. My proposed work is nested within the CHAIN cohort that aims to characterise modifiable risks for mortality among acutely-ill children children and investigate its causes. I will examine relationships between growth and markers of SI, blood metabolomic profile, growth mediators, and microbial exposures comparing with well community children through a collaborative network between KEMRI-Wellcome; Kenya, the University of Oxford and the Wellcome Sanger Institute. Better understanding of relationships between SI and post-discharge growth is expected to inform therapeutic strategies to improve recovery.
|
| 23/06/2021 |
£244,713 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Medical and nutritional management in acutely-ill undernourished children in developing countries aim to support rapid weight gain. However, such children remain at risk of death and poor catch-up growth post-hospital discharge. Little is known about mechanisms regulating childhood growth after acute illness. I hypothesise that persistent systemic inflammation (SI) is a key determinant of growth post-discharge among undernourished children. SI is associated with reduced linear growth in community cohorts, and is demonstrable at hospital discharge among undernourished children, potentially indicating untreated infections, microbiota dysbiosis, gut-circulation microbial product translocation, or enteric inflammation. My proposed work is nested within the CHAIN cohort that aims to characterise modifiable risks for mortality among acutely-ill children children and investigate its causes. I will examine relationships between growth and markers of SI, blood metabolomic profile, growth mediators, and microbial exposures comparing with well community children through a collaborative network between KEMRI-Wellcome; Kenya, the University of Oxford and the Wellcome Sanger Institute. Better understanding of relationships between SI and post-discharge growth is expected to inform therapeutic strategies to improve recovery.
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| 23/06/2021 |
£54,000 |
|
WELLCOME SANGER INSTITUTE |
Medical and nutritional management in acutely-ill undernourished children in developing countries aim to support rapid weight gain. However, such children remain at risk of death and poor catch-up growth post-hospital discharge. Little is known about mechanisms regulating childhood growth after acute illness. I hypothesise that persistent systemic inflammation (SI) is a key determinant of growth post-discharge among undernourished children. SI is associated with reduced linear growth in community cohorts, and is demonstrable at hospital discharge among undernourished children, potentially indicating untreated infections, microbiota dysbiosis, gut-circulation microbial product translocation, or enteric inflammation. My proposed work is nested within the CHAIN cohort that aims to characterise modifiable risks for mortality among acutely-ill children children and investigate its causes. I will examine relationships between growth and markers of SI, blood metabolomic profile, growth mediators, and microbial exposures comparing with well community children through a collaborative network between KEMRI-Wellcome; Kenya, the University of Oxford and the Wellcome Sanger Institute. Better understanding of relationships between SI and post-discharge growth is expected to inform therapeutic strategies to improve recovery.
|
| 23/06/2021 |
£194,849 |
|
STELLENBOSCH UNIVERSITY |
Recent studies in Africa and India (countries with high TB- and HIV-burdens) reported increased frequency of zoonotic tuberculosis (zTB) in humans caused by other members of the Mycobacterium tuberculosis complex (MTBC) like M. orygis, indicating that M. bovis infection may be an inadequate proxy for zTB. Similarly, nontuberculous mycobacteria (NTM) lung disease in people is more frequently reported in Africa because of environmental NTM like M. avium complex. NTM are naturally resistant to various drugs commonly used to treat MTBC infection and are often indistinguishable from MTBC when conventional MTBC "specific" immunological tests are used in humans and animals. Consequently, the management and treatment of infected patients are substantially different and complicated by the absence of appropriate culture-independent tests for the combined detection and differentiation of MTBC and NTM. We hypothesize that zoonotic pathogens like M. orygis and M. avium complex are more abundant in livestock, their environments and nearby wildlife than previously thought, especially in areas with immunocompromised people, leading to potentially high transmission risk interfaces. The goal is to develop culture-independent detection and genotyping tests to enhance zoonotic Mycobacteria spp. detection and differentiation directly from livestock specimens collected from low-resource areas, their environment and near-by wildlife reservoirs.
|
| 18/06/2021 |
£13,029 |
|
QUEEN MARY UNIVERSITY OF LONDON |
This project will examine some of the many links that exist between reading and domestic healing in the collection of the Museum of the Home. The focus of the project will be the under-utilised collection of books relating to health and the domestic environment, dating from the seventeenth to twentieth centuries. For many, the primary location of their experiences of health and ill health was the home; in this context, the reader was the ‘patient’ and the book took the place of a medical practitioner. How were these texts intended to impact their readers’ domestic practices and their wellbeing – and how did readers interact with these texts? Influenced by Roy Porter’s ‘Doing Medical History from Below’, I will examine the intimate relationships between medical books and their readers, focusing on the ‘patient’s’ experience. Research produced during the Fellowship will inform a gallery redisplay, in addition to providing material for future development of the Rooms through Time galleries. The project will connect a wider audience of museum visitors to these stories through accessible written content as well as the Museum’s public engagement programmes, encouraging understanding of and reflection on a shared history of domestic health.
|
| 18/06/2021 |
£14,328 |
|
UNIVERSITY OF OXFORD |
Through a collaboration with the United Nations Environment Programme (UNEP), this 6-month secondment will bring insights from the fields of environmental justice, medical anthropology, and health geography into UNEP’s implementation plan "Toward a Pollution Free Planet". The point of departure for this collaboration is premised on an understanding of pollution as embedded in wider processes of industrialisation that causes social fragmentation and a diffused disempowerment of the communities it affects. As this represents an underexplored area of work in international policymaking, this secondment will focus on understanding and proposing implementation pathways that can lead to increased participation of communities in initiatives to curb pollution.
The outputs produced through this secondment will be integrated within UNEP’s Pollution and Health unit's work on integrated methodologies and tools. The first half of the secondment will be spent conducting a literature review on pollution and community action in the form of a report. The report will focus on identifying the factors that promote and hinder community participation, resilience, and agency. The second half of the secondment will be spent to produce an indicators framework to be utilized to assess the effectiveness of UNEP’s implementation plan in engaging the public and fostering participation and resilience.
|
| 18/06/2021 |
£15,306 |
|
UNIVERSITY OF YORK |
Socioeconomic inequalities in health are an increasingly central policy concern and accurate measurement is crucial in identifying effective policies to reduce health inequalities. I propose updating and refining previous OECD work examining inequalities in longevity by education in member countries around 2011. Updating the analysis involves using more recent data from national mortality registers linked to administrative data on education. Refining the analysis involves applying appropriate methods to allow for biases due to missing data. This is important since education data are often collected via the workforce, so there may be systematic patterns of missingness relating to non-participation in the workforce, which are associated with education.
The key goal is to devise a robust methodology for routinely calculating educational inequalities in longevity in a time- and labour-effective manner. The project contributes to the OECD mission of promoting wellbeing, and specifically the OECD work package ‘Health inequalities and inclusive growth’ and report ‘Health at a Glance’. It will also help the OECD become the main authority on educational longevity inequalities in member countries.
|
| 18/06/2021 |
£6,325 |
|
UNIVERSITY OF WARWICK |
My project will examine the potential use of blockchain technology in the delivery of public services, particularly in the areas of healthcare and welfare in Britain. A blockchain is a type of database that functions as a digital ledger, a way of recording transactions in a permanent, transparent, and irreversible format. Although blockchain technology has existed for decades, its real-world applications have only recently garnered attention from policy makers and politicians. Amidst booming interest in perhaps the most famous financial blockchain – Bitcoin – my project will look at how this technology could transform the nature and provision of healthcare and welfare services in Britain.
The type of information recorded and secured on blockchains is not restricted to financial transactions. It can relate to patient records, the movement of resources in a supply chain, legal documents, and an endless array of other information. As such, it has potential to revolutionise the way organisations utilise and manage data, eliminating problems like fraud and human error in the management of data. The project will examine these potential applications by interviewing key stakeholders, including academics, computer scientists and senior administrators in the NHS and the DWP.
|
| 18/06/2021 |
£27,439 |
|
UNIVERSITY OF LEEDS |
The applicant will collaborate with the World Health Organisation (WHO) Disability Unit in the Non-Communicable Disease department and the Mental Health Department, to research and contribute to the next WHO Global Report on Disability and Health. She will conduct a scoping review of the global health of people with an intellectual disability and write case studies, in relation to;
1. Availability and accessibility of health services
2. Consideration of the needs of people with an intellectual disability in emergency planning (eg virus outbreaks)
3. The impact of public health campaigns on people with an intellectual disability and
4. The quality of the data we collect about people with an intellectual disability.
The World Health Assembly resolution May 2021 will set the agenda on health and disability for WHO Member states for the majority of the next decade. The project provides the opportunity to be part of the team researching and writing the Global Report on Disability and Health and developing the recommendations that will have a global influence, while leading on the work about people with an intellectual disability. The team will collaborate on a peer reviewed publication and support the researcher’s networking and integration into WHO.
|
| 18/06/2021 |
£28,686 |
|
UNIVERSITY OF LEEDS |
This project is aimed at developing an understanding of public health models in relation to interventions designed to address health inequalities faced by autistic adults, who face a heightened risk of mental illness and suicide. I will explore possibilities of creating meaningful dialogue between 'difference-based perspectives' on autism and overlapping forms of neurological difference and existing frameworks that focus on difficulties/or deficits. This will centre on working with AT-Autism to create a body of evidence and a rationale for the creation of a national peer-support scheme for autistic students in higher education, focusing on students in humanities programmes. AT-Autism is developing a mentoring scheme in response to government strategies targeting the radicalisation of autistic young adults in criminal justice settings, and while my project aims to intervene at an earlier stage of policy development, it explores the kinds of evidence are used in assessing risk factors (the risk of experiencing mental health problems while at university) and protective factors. While learning more about policy and relevant legislation, I will provide AT-Autism with my own expertise in language and narrative to encourage recognition of the plurality of possible stories about autism, including those that situate autism as a positive identity.
|
| 18/06/2021 |
£11,049 |
|
INSTITUTE OF DEVELOPMENT STUDIES |
The global covid-19 pandemic has highlighted the scale of violence against women (VAW), and how far we still have to go to prevent VAW and provide quality responses to victims/survivors. Priority setting processes are an essential part of aligning funding with knowledge gaps. However, processes vary globally, are often not inclusive, and often dominated by the interests of funders in the global north.
The Sexual Violence Research Initiative (SVRI) is the largest network for VAW research, providing an essential platform to share research and connect. Engaging with the SVRI’s extensive networks, the key goal of this project is to engage global and regional groups in a discussion about the utility and efficacy of priority setting processes. This will be achieved by creating a space where priority setting processes can be critically examined with an emphasis on decolonising these processes and standardising priority setting methods to improve VAW research moving forwards.
The outcome will be a co-produced set of global principles for research priority setting which embody what has been learnt during the pandemic, reflect the work of regional and global groups and ensure that intersectional voices, including voices from researchers in low and middle income countries, are heard and represented.
|
| 18/06/2021 |
£13,029 |
|
BIRKBECK UNIVERSITY OF LONDON |
This project will catalogue and challenge the marginalisation of voices within mainstream British feminist movements (1). Based at the Feminist Library, this will culminate in an exhibition.
Public exhibitions are frequently sites of erasure and silence (2). British feminist movements similarly contain inequalities of speech (1), but the archive at the Feminist Library hosts one of the most diverse collections of feminist activism and scholarship in the UK. Organising an exhibition focused on marginalised periodicals will enable academic audiences to view feminist resources that are not reproducible in academic journals (3), and will facilitate a public dialogue around the dominant feminist narrative and associated political challenges (1).
Library staff and volunteers will act as a steering group for this project. I will catalogue and analyse archival materials and facilitate steering group discussion and reflections to provide insight into priority areas of marginalisation within British feminism. This will determine the focus of the exhibition.
References
Olufemi L. Feminism, Interrupted: Disrupting power. London: Pluto Press; 2020.
Clover DE. Animating ‘The Blank Page’: Exhibitions as Feminist Community Adult Education. Social Sciences. 2018 Oct;7(10):204.
Thomlinson N. ‘Second-Wave’ Black Feminist Periodicals in Britain. Women: A Cultural Review. 2016 Oct 1;27(4):432–45.
|
| 18/06/2021 |
£9,466 |
|
QUEEN MARY UNIVERSITY OF LONDON |
The aim of this project is to review current debates surrounding regulation of targeted online advertising. The movement to ban targeted or ‘surveillance’ advertising has gained momentum over the last five years, particularly in the wake of the Cambridge Analytica scandal and rising concerns about the impact of the attention economy on mental health and democratic norms. Advocates of banning targeted online advertising cite various social benefits, but such a ban would also be a major intervention that would strongly impact numerous business and digital publishers.
I will write a report in the form of a Parliamentary Office of Science and Technology Note, a 4-page briefing document for members of parliament. It will review the most recent literature surrounding targeted or ‘surveillance’ advertising and interview key stakeholders in academia, industry, government and the third sector. The report will detail the costs and benefits for both society and the economy and will consider how targeted advertising affects public trust in digital technology. I will then explore the practicalities and effectiveness of different levels of regulation in this area and consider these in the context of current government aims to further regulate the digital sphere.
|
| 18/06/2021 |
£24,244 |
|
UNIVERSITY OF CAPE TOWN |
During my secondment with MSF, my project will focus on equity in humanitarian responses to global health emergencies. Humanitarian organisations such as MSF are a critical part of the international response to global health emergencies. Increasingly humanitarian organisations are required to reflect on equity within their work. Questions of equity relate to, amongst others, how MSF works with other actors such as governments, engagement activities with affected communities, provision of health care services, the role of technology and research-related activities. This project has three objectives:
Policy review: I will conduct a review of policies that guides the response of MSF with a specific focus on how equity is operationalised.
Critical review and analysis: I will conduct a review and critical analysis of literature related to equity in humanitarian responses in global health emergencies. This review will summarise normative and empirical accounts, frameworks, and considerations of equity, including research as part of the humanitarian response.
Recommendations: Based on insights gained from objectives 1 and 2, I will develop targeted recommendations regarding equity for relevant stakeholders involved in MSF's work. I will also facilitate interactive sessions with MSF staff about their experiences of equity, which will also inform recommendations.
|
| 18/06/2021 |
£43,836 |
|
UNIVERSITY OF YORK |
Vets regularly experience ethical dilemmas when balancing the needs of animals, their owners and financial constraints. Moral stress, described as a feeling of conflict over what care it is appropriate to provide, may even contribute to the heightened risk of suicide observed in the veterinary profession. Charitable veterinary providers such as PDSA are currently working under extremely challenging conditions, with reduced capacity and increased demand caused by the COVID-19 pandemic.
Whilst ethical discussion groups and the use of ethical decision making tools have been proposed for supporting veterinary decision making, such practices have yet to be evaluated for their effectiveness in veterinary rather than equivalent human medical teams.
I will pilot the use of an ethical decision making tool within a supportive group environment to help PDSA veterinary teams explore their approaches to ethically challenging cases. Through in depth interviews, I will invite veterinary team members to share their experiences of moral stress and evaluate the effectiveness of small group structured ethical discussions.
My research will help PDSA develop strategies for improving veterinary mental health through supported ethical decision making. The research will also help us to better understand the causes and effects of moral stress in veterinary teams.
|
| 18/06/2021 |
£33,188 |
|
UNIVERSITY OF SHEFFIELD |
When people register as blood stem cell donors, they do so to save a stranger’s life. However, on rare occasions, donated tissue does not go on to clinical use, potentially being cryopreserved indefinitely. This presents a socioethical conundrum for registries, who have to make a decision about the future of this tissue, e.g., should it be destroyed, or used in therapeutic research? This secondment fellowship is a collaboration with Anthony Nolan, the world’s first blood stem cell, or bone marrow, registry. The secondment topic, co-produced with Anthony Nolan, is an exploration of this issue, which has become urgent as COVID-19 has increased instances of unanticipated cryopreservation globally.
The secondment fellowship comprises (i) exploration of perspectives of international stem cell donors on the potential futures of cryopreserved tissue beyond the clinic through focus groups with donors, and (ii) generation of critical social science to be disseminated to registries around the world through a report for practitioners. Findings will generate knowledge to inform global practice regarding cryopreservation, and the use of donor stem cells in therapeutic research. The secondment aims to build collaborative relationships with non-academic organisations for future social science research on the global stem cell infrastructure.
|
| 18/06/2021 |
£30,636 |
|
UNIVERSITY COLLEGE LONDON |
Though Black and Minority Ethnic (BME) populations have been significantly overrepresented in COVID-19 mortality statistics, they are vastly underrepresented in NHS management. It is critical to address this lack of diversity amongst decision makers to ensure equitable representation, as current NHS leadership is not adequately representative of the workforce or communities for whom it cares. Principally this project asks: what is the scope and capacity within non-clinical NHS management and NHS decision-making to understand and address BME healthcare worker experience in the face of emerging and changing health care structures, and how can it be improved for the future of equitable health service delivery and diversity in the workforce?
Working with the Nuffield Trust, key project goals are:
Investigate the current understandings and approaches to race and ethnicity within non-clinical London NHS Management teams. This will be achieved through embedded ethnography within 1-3 London NHS Trusts; chosen for diversity of workforce.
Encourage more open dialogue to navigate ethnic and racial concerns when it comes to mitigating COVID-19 and other future health risks. This will be achieved through an open-access, widely available report and associated workshop-toolkit that will be published online and circulated to management teams and stakeholders.
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| 17/06/2021 |
£12,839 |
|
UNIVERSITY OF SHEFFIELD |
Gestational trophoblastic diseases are rare conditions that span the worlds of reproduction and oncology. A lack of awareness surrounding gestational trophoblastic disease impacts patients, as they attempt to make sense of the condition whilst simultaneously undergoing diagnosis, monitoring and treatment.
For some patients, sense-making involves engagement with visual representations of GTD. These include biomedical diagrams illustrating its genetic causes. Patient accounts of these diagrams can provide alternative perspectives to research on GTD, as visual material can provoke feelings and responses that are not captured by traditional qualitative methods.
This project will involve collaborative work with patients, scientists and artists to reimagine the medical illustrations used to represent GTD and other forms of cancer. The project will provide participants with insight into biomedical explanations of cancerous conditions, and support them to develop creative ways of sharing illness experience.
Activities will comprise an initial creative workshop, ongoing artistic support and dissemination events. Through the workshop and artistic follow-up, patient participants will share experiences and produce their own visual representations of disease. The display and discussion of participants’ creations in an online gallery, and through a live digital event, will allow these to be shared with practitioners and relevant charities. This will enable patients’ stories to be heard in new ways and raise awareness of GTD, as well as informing the fieldwork and analysis conducted for the wider research.
This engagement work will involve continuous evaluation to ensure the activities have been enriching for patient participants, relevant stakeholders, and for the researcher’s skills.
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| 17/06/2021 |
£73,445 |
|
UNIVERSITY OF LEEDS |
We propose a programme of activities that will communicate project findings to a range of audiences. The programme will impact especially on public awareness and understanding of disability’s interaction with technology and the experiences of disabled users. It is centred around three strands:
Bespoke exhibits at major science festivals, beginning with Sheffield Festival of Mind 2020, then New Scientist Live in October 2023 and subsequently portable to other festivals across 2024.
Feature programme at 2022 Leeds International Film Festival (LIFF) focused on fiction and documentary films that explore disability, embodiment and technology.
Commission of artist Sarah Browne to produce creative moving-image artwork, in conjunction with the LUX Arts Agency, the largest distributor of contemporary art film and video in Europe. The final work will screen at festivals across the UK and Europe and be hosted on the project website.
Each strand will be developed with existing partners (named in the original Collaborative Award application) and disability arts groups and disabled mentors in Leeds, Sheffield and Dundee.
The activities will engage thousands of people. When the programme has finished, we will have communicated our research to audiences with interests ranging from developments in new/future technologies to contemporary art and film. Our interaction with the public will allow for individuals to volunteer, through our website, to participate in the project’s public consultation workshops on the co-design of research outputs across 2022 and 2023. We will feed all event response data into our publications and reports in the final year of the project.
|
| 17/06/2021 |
£89,311 |
|
UNIVERSITY OF LIVERPOOL |
ATtaining EQUity of Access TO Research (At The EQUATOR) will transform research culture to ensure equity of access to research. Initially focussing on women of childbearing age, using activities aligned with MILK and establishing key capacity at the Infectious Diseases Institute (IDI), community members will have input and involvement at all stages of research, from conception through dissemination. Co-creation of resources to enable meaningful two-way dialogue will include posters, video clips, infographics, drama and song in both an urban and rural population. Evaluation of impact, primarily through focus group discussion (FGD) at inception, midpoint and end, will include novel and interactive methods of feedback from community members.
.
At The EQUATOR will achieve this through:
.
A: Institutional Level (Capacity Building)
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Skills and capacity audit of personnel and projects at IDI at baseline – projects, people, level of understanding of PE & I, barriers
Public engagement training – initially outsourced then co-creation of relevant materials
Social media training
Developing standard operating procedures with guidance on PE & I at all phases of research from conception through dissemination
Establishing a PE & I working group within the IDI Research Department
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B: Community Level
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Strengthening the Community Advisory Board (CAB) structures (from ad hoc to regular)
Identification of key community leaders
Mapping community networks and communication channels
Community consultation at grant application and protocol development stages
Identification of key community members for co-creation activities
Community engagement alongside site initiation visit
Regular community meetings during execution of project
Dissemination event
Dialogue to establish ongoing research priorities
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| 17/06/2021 |
£69,000 |
|
IMPERIAL COLLEGE LONDON |
The ongoing COVID-19 pandemic has changed our world and lives, in many different ways. Restrictions on social contacts and closure of schools have brought with them a significant disruption to children’s daily routines, including exercise patterns and eating habits. The anxiety associated with social isolation, in combination with an increased sedentary lifestyle, has led to serious concerns about the long-term impact of COVID-19 on the global childhood obesity crisis. Our interactive science workshop "You’ve got guts!" will focus on positive messages centred around what keeps us healthy and why our guts play a central role in promoting health.
Our workshop is a stimulating virtual as well as real-life learning experience designed for pupils aged 8-11 in our local community (White City). In collaboration with experts in science communication and professional science animators we will create several animated features conveying key aspects of gut health and healthy diets. The animated features, combined with direct two-way dialogue between pupils and scientists, will help pupils gain a better understanding of the connection between diet, gut health and overall well-being. Workshops will be virtual initially, but, as current lockdown restriction are eased, will be disseminated more widely as part of local science festivals and events in dedicated engagement spaces. Scientists involved in this project will gain valuable training and experience in PE with young audiences. Our PE activities will help develop and deepen links between our Institute and local schools, strengthening our Institution’s reputation and visibility in the local community.
|
| 17/06/2021 |
£24,256 |
|
CENTRO INTERNACIONAL DE ENTRENAMIENTO E INVESTIGACIONES MEDICAS |
The radio drama: "Myths and Realities of Cutaneous Leishmaniasis" will consist of 6 episodes of 10 minutes each in Spanish language and it will be a co-created product of the interaction with the inhabitants of the municipality of Tumaco, particularly with local health workers and patients. The creation and dissemination of the radio drama will be carried out in collaboration with the local community broadcaster: Tumaco Stereo, and through it, the importance of early and timely treatment in the management of cutaneous leishmaniasis (CL) will be promoted in Tumaco, a municipality that is endemic for CL and that is affected by socio- economic exclusion, and an intense armed conflict, which make accessing health education difficult.
|
| 10/06/2021 |
£1,924,730 |
|
KING'S COLLEGE LONDON |
The proposed Centre in Medical Engineering focuses on medical imaging, and is a renewal of our existing Centre. Our vision is to bring together teams from multiple scientific disciplines to identify and solve complex multi-factorial challenges, focusing on the most important clinical and biological issues. By combining expertise in biomedical and clinical research with excellence in underpinning sciences of imaging engineering & physics, computational and mathematical approaches and imaging chemistry, we will deliver impact that improves the understanding, diagnosis and treatment of neuropsychiatric, oncological and cardiovascular diseases. The Centre will have a unique combination of characteristics that allow delivery of this vision. The current critical mass of imaging scientists combines with cutting-edge facilities across multiple imaging modalities, strong industrial links and our location within a major hospital campus to create an exciting, synergistic environment where the most challenging questions can be addressed. In addition to producing world-leading outputs, the Centre infrastructure will accelerate translation to clinical benefit and industrial uptake. The Centre will act as a focus for recruitment of leading international talent and training of the next generation of research leaders, enhancing excellence. We will make a major contribution to public engagement, enhancing the strong current activity. |
| 10/06/2021 |
£2,490,921 |
|
UNIVERSITY COLLEGE LONDON |
Image-guided Intervention (IGI) has enabled greater surgical precision resulting in reduced tissue trauma, co-morbidity, complications, and hospitalisation time. However, significant limitations arise from the challenging use of IGI systems, and their predominant reliance on preoperative anatomical images. Disrupting existing IGI, we will deliver pathologically, anatomically, and physiologically optimal surgery by combining diagnostic-quality imaging/sensing with ergonomic smart instruments. The Wellcome Trust Centre for Surgical and Interventional Sciences (WTC-SIS) will launch a new phase in which anatomical cues, which have driven interventional therapies for centuries, are augmented by physiological and pathological insight. Three fundamental research themes will link the WTC-SIS interdisciplinary groups: Physiological navigation, focusing on fusing anatomical, physiological and pathological information for real-time guidance/monitoring. Clinician experience, focusing on optimising the clinical team cognitive/ergonomic workload. Precision instrumentation, focusing on designing interventional devices that both sense physiological/pathological information and interact with tissue. WTC-SIS will serve as a hub-and-spoke translational catalyst for indication-specific externally-funded projects across surgical domains. A single unified Centre (hub) will provide all relevant skills and know-how, from scientific expertise to good manufacturing principles. This will drive rapid translation in our clinical satellites (spokes) and industry engagement through the development of a Health Technology Assessment programme. |
| 10/06/2021 |
£5,146,064 |
|
UNIVERSITY OF DUNDEE |
The vision for the Centre is to help tackle the urgent unmet medical need and lack of drug discovery research for Neglected Tropical Diseases (NTDs) by creating the hub for NTD drug discovery and being the collaborator of choice for academics, Pharma and Product Development Partnerships (PDPs) in the translation of discovery science into drug candidates. The success of this vision will be evidenced by increased integration, efficiency and effectiveness of the discovery science, drug discovery and mode-of-action teams in Dundee, providing: Accelerated delivery of NTD drug candidates for our PDP partners, with an initial focus on visceral leishmaniasis and Chagas' disease. Improved paradigms for carrying out NTD drug discovery, including improved understanding of PKPD relationships and more predictive disease models. Improved methodology to determine drug modes of action and resistance mechanisms. Increased exploitation of novel drug targets through structure based drug discovery, involving collaborators worldwide. Training and support for international scientists in the theory and practice of NTD drug discovery. Increased public engagement and awareness of the impact of, and need for, new medicines for NTDs and a greater understanding of the nature and importance of drug discovery. |
| 07/06/2021 |
£1,096,432 |
|
IMPERIAL COLLEGE LONDON |
Background: Early-onset type 2 diabetes (diagnosed
Goal: I will decipher heterogeneity of early-onset type 2 diabetes in white and south Asian individuals using epidemiological and genetic approaches.
Proposal:
Determine whether early-onset type 2 diabetes is enriched for sub-phenotypes contributing to higher risk, using analysis of large datasets to examine ethnic differences in presentation and progression by age-at-diagnosis with application of supervised and unsupervised statistical methods.
Determine if the higher risk of early-onset type 2 diabetes in south Asian individuals is driven by excess polygenic risk, by undertaking a cohort study with application of trans-ancestry polygenic scores compared to controls.
Summary: This broad population-level study together with deep genotyping and phenotyping of affected individuals has the potential to produce new insights leading to better surveillance, earlier therapies, and fewer complications.
|
| 07/06/2021 |
£574,165 |
|
UNIVERSITY COLLEGE LONDON |
In Alzheimer’s disease (AD) there is a drive towards earlier clinical trials, before symptoms manifest, prior to significant neuronal loss. However current approaches for identifying those at risk of imminent decline and tracking progression lack sensitivity.
I previously identified a characteristic pattern of early cortical loss in AD. In the current fellowship I will develop sensitive quantitive cortical imaging biomarkers, and improve understanding of early AD-related neurodegeneration and its link to molecular pathology.
First, I will undertake multi-compartmental modelling of multi-shell diffusion MRI to track presymptomatic microstructural breakdown of cortical neurons, across three separate cohorts, and compare with established imaging markers.
Secondly, I will acquire ultra high field (7T) MRI and undertake quantitive multiparameter mapping to characterize extra-neuronal cortical microstructure, including myeloarchitecture and iron deposition, at sub-millimetre resolution.
Thirdly, I will assess associations between tau PET and microstructural imaging.
I will use my expertise in blood-based biomarkers and novel measures of cognitive decline to explore their relationship with cortical microstructure.
Goals:
Assess how microstructural change can be optimally assessed in-vivo.
Determine the nature, timing, and distribution of early cortical breakdown.
Use microstructural cortical imaging to estimate proximity to symptom onset.
Examine how neuronal breakdown is mediated by tau deposition.
|
| 07/06/2021 |
£861,960 |
|
UNIVERSITY OF CAMBRIDGE |
Neural stem cells (NSCs) in the developing embryo brain share transcription programs with glioma stem cells (GSCs) in malignant brain tumours, and both are susceptible to Zika Virus infection. In the developing brain this can result in microcephaly, whereas in brain tumours it could offer insights relevant to oncolytic virus development. However GSC and NSC susceptibility to Zika and other viruses depends on the microenvironment. In particular, microglia progenitors migrating into the embryo brain from the yolk sac are believed to bring virus with them, whereas my preliminary data suggests that mature tumour-associated microglia instead drive a virus resistance phenotype in GSCs. This project seeks to establish the mechanistic basis for the microenvironment regulation of virus susceptibility in normal and malignant progenitors, and to suggest therapeutic strategies for modulation of these.
|
| 07/06/2021 |
£379,655 |
|
UNIVERSITY OF CAMBRIDGE |
Cancers upregulate telomerase in order to lengthen telomeres and therby to propagate their survival and immortality. However, in 10-15% of cancers, telomere length is instead maintained by the alternative lengthening of telomere (ALT) pathway. A breakthrough in understanding this pathway came when ATRX (alpha thalassemia/mental retardation X-linked), a chromatin remodeller with various regulatory roles throughout the genome, was discovered to be mutated or lost in ~90% of ALT cancer cell lines and tumours. An important mechanism of ATRX function is in conjunction with DAXX, the histone 3.3 (H3.3) chaperone, whose mutations are also associated with ALT activation. ATRX and DAXX act together to deposit H3.3 and its binding partner H4 at heterochromatin, such as telomeres, aided by HP1. Deposition of H3.3 helps to maintain telomeres in a canonical state, preventing aberrent secondary DNA structure formation leading to activation of the ALT pathway.
My proposal is to elucidate, by cryo-EM, the structure of HP1-ATRX-DAXX-H3.3-H4 in complex with the nucleosome. This structure would provide functional and mechanistic insights into chromatin remodelling, and histone deposition by this central ALT associated complex. This field is clinically exciting, as targeting the ALT pathway is a promising therapeutic approach for cancer.
|
| 07/06/2021 |
£1,673,630 |
|
UNIVERSITY OF OXFORD |
Dengue causes up to 96 million clinical infections annually. Despite this burden, there are currently no licensed therapeutics. Severe dengue is characterized by shock, organ dysfunction, cytopaenias, and vasculopathy, which occur late in the disease, during viral clearance, driven by an excessive host immune response and hypercytokinaemia. One of the most targeted ways of controlling this excessive inflammation is through interleukin-1 receptor (IL-1R) blockade (anakinra).
My overarching hypothesis is IL-1 mediated pathways drive hyperinflammation and severe disease in dengue. I hypothesize that therapeutic IL-1R blockade in selected patients with dengue will improve clinical outcomes through attenuation of the inflammatory response. The accompanying immunology and transcriptomic analyses aims to reveal any additional pathophysiological pathways involved in severe dengue.
I will test this hypothesis by conducting a phase 2 clinical trial of anakinra in dengue patients with hyperinflammation. I will also perform detailed mechanistic studies, investigating the effect of IL-1R blockade on dengue pathogenesis by assessing kinetics of inflammatory markers, cytokine trajectories, inflammasome and endothelial activation markers, cellular immune responses and antibody studies in trial patients with and without anakinra treatment. I will also investigate immune cell genetic signatures by disease severity and if IL-1R blockade can normalize these signatures over time.
|
| 07/06/2021 |
£457,663 |
|
KING'S COLLEGE LONDON |
Intrauterine infection accounts for at least 40% of cases of spontaneous preterm birth. The most common route of pathogen entry into the uterine cavity is likely to be ascent of vaginal microbes as a result of compromised cervico-vaginal innate immune defences. All mucosal surfaces are protected to some degree by mucus barriers formed by polymeric gel-forming mucin proteins secreted from epithelial goblet cells. Accordingly, research has identified a potential protective role for cervical mucins and mucus barriers in the antimicrobial defence of the pregnant cervix.
This project will address the hypothesis that a compromised mucus barrier function confers an increased risk of infection-related preterm birth. Our key goal will be to investigate the specific role of cervical mucins in mucus barrier integrity and antimicrobial defence using knock out mouse models, as well as exploring cervical mucins from cervical samples (collected in our prematurity clinic) from women at risk of preterm birth. Furthermore, this project will investigate the use of a mucin-like biopolymer, which would mimic a healthy pregnant cervical mucus plug, as a potential preventative therapy for preterm birth using a mouse model of preterm birth.
|
| 07/06/2021 |
£594,603 |
|
UNIVERSITY COLLEGE LONDON |
Background: Impaired social functioning is a core feature of dementia and declines progressively through the disease course, but we do not currently understand the specific causes of this decline and have no effective treatments for social functioning. Social cognitive impairment, particularly impaired theory of mind, is a likely major cause of this decline and, if this is established, it could be a target for future interventions aiming to maintain social functioning.
Key goals:
To test whether theory of mind deficits, or impairment in other social cognitive domains, are associated with current and subsequent level of social behaviour and functioning in Alzheimer’s disease.
To develop novel approaches to the measurement of social behaviour and function in Alzheimer’s disease and establish their reliability and validity.
To examine neuroimaging correlates of theory of mind impairment in Alzheimer's disease.
Methods: I will construct a new observational cohort study of 207 people with mild Alzheimer’s disease and conduct a detailed social cognition test battery. I will assess social functioning and behaviour over 1 year using questionnaires, behavioural observation, and remote digital monitoring. To examine neural correlates of social cognitive decline, I will analyse already-collected structural and functional neuroimaging and social cognition data from my collaborator.
|
| 07/06/2021 |
£649,059 |
|
UNIVERSITY COLLEGE LONDON |
Hippocampal damage impairs episodic memory, but it is unknown precisely why. Research in non-humans suggests that damage to a specific hippocampal subfield (cornu Ammonis 3, CA3) impairs computational processes called pattern separation (the ability to distinguish between similar but distinct memories; PS), and pattern completion (the ability to recall a full memory from partial cues; PC). I have shown that focal bilateral human CA3 pathology causes extensive episodic amnesia alongside reduced functional connectivity between the hippocampus and episodic memory network. Episodic amnesia could arise from disrupted PS/PC during learning and/or retrieval, or, from aberrant interactions between PS/PC and other cognitive processes supported by the hippocampus, critical to episodic re-experiencing (temporal sequencing, visuospatial re-experiencing).
This Fellowship will use functional MRI (fMRI) in a well-characterized cohort of patients to investigate the effects of CA3 pathology on episodic learning and retrieval.
Goals:
To understand how CA3 damage disrupts the normal hippocampal-cortical interactions required for episodic learning and retrieval.
To investigate whether episodic amnesia arises solely from a failure of PS/PC or from disrupted interactions between PS/PC and other processes such as temporal ordering or visuospatial re-experiencing.
To seek mechanistic understandings of how CA3 pathology disrupts episodic memory retrieval across the lifetime using fMRI.
|
| 04/06/2021 |
£19,995 |
|
UNIVERSITY OF OXFORD |
Human colour vision arises when cone cells in the retina absorb light, and estimates of the spectral sensitivities of the cones are fundamental to the field. However, the current, so-called "standard observer" models of cone sensitivities are based on data from participants recruited in London from a narrow demographic. We question whether these pseudo-representative models have biased our understanding of human colour vision, and how to best address the on-going ethnic bias in participant recruitment for colour vision research.
The major aims of this project are first to quantify the recruitment bias in relation to ethnicity in colour vision experiments, then to build an evidence-base of cases in which such bias is problematic, and lastly to raise awareness of the issue towards adoption of better practice and the development of an inclusive biological model.
The two main challenges posed by historical and current research practice are (i) underestimation of the true variability that exists in humanity; and (ii) features of the standard observer model that are unrepresentative of specific populations. Addressing these challenges will improve basic science (e.g. controlling for factors that would otherwise obscure mechanistic understanding of biological processes) and have wider impact in applications of colour science (e.g. through the development of measurement standards that are appropriate for diverse observers).
The completed activity will document current knowledge of ethnic variability in biological colour vision, providing a resource to motivate further consideration of ethnic diversity in recruitment, and will provide a jointly-authored ‘roadmap’ for how best to achieve change.
|
| 04/06/2021 |
£19,300 |
|
UNIVERSITY OF LEEDS |
itDf works with the lived experience of people living with disabilities and aims to integrate disabled individuals, communities and family members, as well as NHS user groups into its research design. The project draws on a variety of disciplinary backgrounds and has adopted a reflexive stance on the methodologies that make the ‘entanglement and risk’ of multi-, inter- and cross-disciplinary work rich and productive. With such a multiplicity of perspectives, voices and values, and with a commitment to disability-informed practice, it is crucial that the project team develop facilitation skills, particularly the macro and micro skills and practices needed to create and maintain inclusion, engagement and participation throughout the project cycle.
At the end of a successfully completed period of D & I funding in 2024, we will have developed a programme of work that will match the project's need for better practice. We will also meet the aims of Wellcome’s new (March 2021) diversity, equity and inclusion strategy, placing people with disabilities as central partners in our research design and practice, In particular, the project team will:
As individuals have developed professional facilitation and mentoring competencies
As a team enhanced creativity and inclusion in project research co-design and produced a culture of continuous improvement, including regular participatory evaluation.
Have communicated the value of these approaches to project partners and colleagues in our respective institutions.
Have created a safe and secure space for people with disabilities to contribute to the project that recognises their difference, working methods and wishes.
|
| 31/05/2021 |
£30,000 |
|
ASSOCIATION OF MEDICAL RESEARCH CHARITIES |
Not available |
| 31/05/2021 |
£39,724 |
|
HUMAN CELL ATLAS, INCORPORATED |
This year’s Human Cell Atlas General Meeting will convene our community virtually to share updates and insights on new HCA research and initiatives, as well as to highlight the work of the HCA Biological Networks and continue to build on progress from the HCA Biological Network Seminar Series.
Key outcomes of this meeting will include a shared appreciation for recent advances and future needs that will facilitate the construction of an integrated atlas; progress toward strategic roadmaps for different organs, tissues, and systems; and an enhanced understanding of how the Human Cell Atlas will provide a healthy reference for the understanding of disease.
Event Overview
Day 1: Plenary talks and networking opportunities.
Themes: HCA Overview, Computational Advancements and Cross-Cutting Approaches
Day 2: Poster viewings, biological network interactive sessions, and breakout sessions.
Theme: HCA Biological Network updates, and plan to organize to build out roadmaps.
Day 3: Plenary talks, panel discussions and networking opportunities.
Theme: HCA and Disease Impact, and Defining 10-year plan.
A portion of the requested funds will also provide partial support for the 2021 HCA Asia General Meeting, to be held in November or December 2021.
|
| 31/05/2021 |
£104,589 |
|
UNIVERSITY OF OXFORD |
This work will complement the Global Research on AntiMicrobial (GRAM) project estimating the global burden of drug resistant infections (antimicrobial resistance, AMR). The work will establish the best practice in quantifying the burden of AMR through the comparative analysis of selected data sets from the GRAM project and synthetic data generated using mechanistic models. Key goals include comparative estimates of the burden of AMR for selected data sets and evaluations of the appropriateness of different analytical approaches for different types of data and different epidemiological processes. In particular, the work will determine: i) under what circumstances the assumption that resistant infections fully replace sensitive infections with the same species is appropriate for quantifying the burden of AMR; ii) under what circumstances the contrasting assumption that resistant infections add to the burden rather than replacing sensitive infections is appropriate; and iii) under what circumstances the intermediate assumption of partial replacement is appropriate.
|
| 31/05/2021 |
£163,036 |
|
LANCASTER UNIVERSITY |
In a context of austerity, pandemic and unemployment, 14- to 24-year-olds have above-average levels of anxiety, significant rates of depression and lower life satisfaction than previous cohorts. Building on our model of upstream socioeconomic pathways for health impact, this project examines prospective impact of Universal Basic Income, a system of unconditional cash transfers, on anxiety and depression among 14-24s. It brings together an established, multi-disciplinary team to:
Objective 1) create a ‘risk’ factor for anxiety and depression among 14-24s from existing data
O2) deploy the RSA’s Citizen Engagement Workshops and focus groups with disabled people to advance designs for a ‘transitional UBI’ for 14-17s, an overall scheme aimed specifically at mental health impact, and account for additional needs
O3) use the ‘risk’ factor to model the impact of the cash transfer schemes from 2) on anxiety and depression among 14-24s
O4) design research protocols to measure impacts in different schemes using the examples of ActEarly’s Bradford pilot and the RSA/Scottish Government’s prospective Dunfermline trial
This will lead to a series of publications, an end of project report published by the RSA and a set of impact measurement research materials. We will seek to ‘leverage’ these to secure further funded research.
|
| 31/05/2021 |
£1,982,664 |
|
THE GRADUATE INSTITUTE OF INTERNATIONAL AND DEVELOPMENT STUDIES |
I-DAIR is a Geneva-based global platform to enable inclusive, impactful, and responsible research into digital health and Artificial Intelligence (AI) for health. I-DAIR’s mission is the transformation of personal and public health through collaborative research and development of digital technologies. This proposal for a grant of GBP 2 million over two years (2021- 2022) to fund the key capabilities necessary for I-DAIR to fulfill its primary functions as an enabler of digital health and as a convener of key stakeholders for digital health. The grant will complement a CHF 7 million (GBP 5.4 million) investment by Fondation Botnar, which has allowed I-DAIR to start building a Project Team and begin a two year incubation phase, with launch scheduled for 2022. By enabling key strategic outcomes, Wellcome’s contribution will allow the Project Team to make the case for I-DAIR at launch as a global catalyst for digital health and artificial intelligence (AI) research and development (R & D), and for democratising the R & D landscape by bringing more attention to networks, needs and opportunities in low-and middle-income countries.
|
| 31/05/2021 |
£198,620 |
|
NATIONAL ACADEMY OF SCIENCES, AMERICA (NAS) |
The G20, as proposed by the Italian G20 Presidency, has mandated a High-Level Independent Panel (HLIP) to recommend actionable solutions for reliable and sustainable financing of the global commons for pandemic prevention, surveillance, preparedness and response. The Panel’s recommendations will be presented to the G20 Finance Ministers and Central Bank Governors Meeting in July. To provide the HLIP with support for logistics, coordination, outreach, and communication/engagement, The National Academy of Medicine (NAM) proposes to establish a joint Secretariat comprised of 4-5 individuals from the NAM and the Wellcome Trust. From February through October 2021, it is expected that the joint Secretariat will support the execution of the independent review by the HLIP. The work of the Secretariat during these eight months will include: 1) meeting logistics and organization; 2) meeting facilitation (agenda setting, conduct, and procedures); 3) outreach and communication with key political and other stakeholders; and, as needed 4) limited research/analytical/writing support for health-related content.
|
| 20/05/2021 |
£427,809 |
|
WEST SUSSEX COUNTY COUNCIL |
The project will make accessible for research eleven archives from post-war new towns in England, Wales and Ireland. Eight of these archives will be catalogued and all will be safeguarded through conservation and preservation work. The new towns included are: Basildon, Bracknell, Crawley, Cwmbran, Newton Aycliffe, Peterlee, Redditch, Runcorn, Shannon, Stevenage and Warrington.
The archives are held by nine partner organisations brought together through the Association of New Towns Archives and Museums. The Association builds on existing academic partnerships, and this project will develop those further. Key outcomes include not only itemised catalogues and protected collections, but also a collaborative dissemination programme.
This project will provide a substantial increase in the evidence base available for researchers seeking to interrogate the new towns’ legacy. The project is particularly timely in the context of the current public health emergency. New towns have much to contribute to current policy making in urban planning and public health including: new homes to reduce overcrowding; generous public green space; amenities within 15 minutes of the home; and supporting walking and cycling. There is renewed interest in many aspects of new town design as plans are made for social recovery in the aftermath of Covid-19.
|
| 20/05/2021 |
£180,137 |
|
UNIVERSITY OF SUSSEX |
Mass-Observation (M-O) has been recording everyday life in Britain since 1937. Since the start of the Covid-19 crisis, we have collected over 8500 pieces of narrative life writing, ranging in format from open-questionnaire responses and day diaries to diaries kept for several months by self-selecting volunteers of all ages from around the UK. This unique set of large-scale qualitative data offers extensive research value and potential to contextualise quantitative data generated throughout the pandemic.
This project will open up the extensive collections of qualitative data relating to the impact of Covid-19 on the mental and physical health and social welfare of volunteer writers around the UK. We will build a tool for discovery and exploration that allows researchers to interrogate these collections.
A database will comprise metadata on the writers and writing that enables researchers across disciplines to interrogate the content of the data, thereby contributing to our understanding of the social and personal impact on UK health and wellbeing during the Covid-19 pandemic. The tool is designed to open up access to the texts that have been submitted, allowing researchers to select relevant materials and export the data into their own choice of research tools for analysis.
|
| 20/05/2021 |
£230,958 |
|
NATIONAL LIBRARY OF SCOTLAND |
This pilot project will preserve and provide research access to 10,000 websites relating to health information (and misinformation), and will use this collection to enable more health research on the UK Web Archive.
Our project brings together four co-applicant institutions, and a network of other organisations and researchers, to tackle one of the most pressing research issues of our time: how can the story of changing online health information be captured and understood?
During the Covid-19 pandemic, online health advice, data and scientific evidence have been contested, revised, used and mis-used with global consequences – but the digital record of this activity is fragile and hard to access.
We will:
Curate a new research-ready collection of websites within the UKWA, with the theme of Health Information and Misinformation, ensuring a wide representation of diverse and otherwise under-collected sources.
Use this collection as a test-bed to explore options for metadata, computational analysis, ethics and rights issues.
Build a research network across disciplines including use cases, involving researchers in the process of building, evaluating and using collections.
Produce a project report with recommendations for future work and advocacy for change to make web archives more representative, inclusive and open for health research.
|
| 20/05/2021 |
£113,611 |
|
UNIVERSITY OF LEEDS |
Leeds Animation Workshop (LAW) is a not-for-profit cooperative company established in 1978 and run by women. It produces and distributes animated films on social, health and educational issues, with international distribution. Subjects include childcare, violence against women, bereavement, child protection, parenting and relationships, gender and equal opportunities, bullying and homelessness. LAW has created films for audiences with learning difficulties and provides training in basic animation for adults and young people.
The LAW archive is a unique survival. It is the only complete archive of a collective independent filmmaking organisation. The archive is key to understanding the production of public information films and provides a counterpoint to ‘establishment’ films of the period. This is an essential national and international resource for exploring intersections between feminist activism, creative practice, and public health information.
The project will:
Secure the archive in a publicly accessible repository, appraised, organised and repackaged to archival standards.
Create an online catalogue with detailed index points to enable network mapping and exploration.
Showcase interdisciplinary research opportunities, and create new research networks through the University of Leeds and beyond.
Embed the archive in research led teaching and lifelong learning, including online delivery.
|
| 20/05/2021 |
£493,456 |
|
UNIVERSITY OF CAMBRIDGE |
This two-year, collaborative project will open up to health researchers worldwide 187 medieval manuscripts containing medical recipes across Cambridge collections, and the currently inaccessible corpus of approximately 8000 Latin and Middle English medical recipes that they contain.
A combined programme of manuscript digitisation, cataloguing and conservation will provide multiple points of entry. Researchers will see recipes in their original form: through high-resolution images viewable via the Cambridge Digital Library (CUDL), and medium-resolution images available for free download and reuse via CUDL and International Image Interoperability Framework (IIIF) manifests.
Fully searchable XML descriptions of the manuscripts’ contents, physical characteristics, and histories will be published alongside, revealing the intellectual and material contexts in which these texts were circulated and received. Adhering to interoperable TEI guidelines, these descriptions will facilitate cross-collection discovery, building strong links with comparable manuscripts in Oxford and Manchester.
Hyperdiplomatic transcriptions, created using Transkribus, will provide a level of detail unmatched by existing finding aids, enabling keyword searching and granular, computational analysis of the recipes. The project will empower other organisations to undertake similar work with their collections by creating a robust and extensible methodology, and disseminating it through a website, workshops and symposium for researchers, curators and libraries.
|
| 20/05/2021 |
£308,990 |
|
GREATER MANCHESTER COALITION OF DISABLED PEOPLE |
The GMCDP archive collection reveals the changing perspectives, language and attitudes towards disabled people that have occurred over recent decades. It highlights changes in medical practices, discussions and debates around bio-ethics and end of life issues, campaigns for independent living, the self-organisation of disabled people, development of disability culture, and the significant impact of wider health determinants (education, income/poverty levels, employment, housing etc). The GMCDP Archive is the largest, most comprehensive archive of the lives and experience of disabled people and the activism in England (JT Assessment)
The project will:
Work with Archives+ to catalogue and classify the collection.
Make the catalogue available online.
Establish a viable and sustainable system for viewing the collection (providing physical access to research material).
Make parts of the collection available digitally online (e.g. seminal papers).
Ensure that all openly available material is presented for viewing in a range of accessible formats and that there is an on-going system in place to transcribe new and/or restricted material. A significant challenge, but essential element of the project.
Share our learning on making collections fully accessible by developing guidance and toolkits, delivering workshops and training to other collection holders.
Connect with relevant institutions to promote the resource.
|
| 20/05/2021 |
£281,758 |
|
UNIVERSITY OF BRISTOL |
The Welfare State International archive spans five decades and provides an unparalleled record of pioneering participatory arts practice for health and wellbeing a generation ahead of its time. This project will make available this uniquely detailed history of the evolution of community arts for wellbeing, and provide evidence and inspiration for future research and practice.
We are responding to demand from a broad spectrum of social science, health and arts researchers, and practitioners, to enable exploration of WSI's innovative methodologies. Through community engagement and co-creation, WSI gave the marginalised a voice and empowered communities. They evolved from radical travelling performers, by way of intensely researched place-based and co-produced performances, to become embedded community practitioners and celebrants. Their internationally acclaimed work shifted the parameters of arts practice and policy in the UK and beyond, kindling the arts for wellbeing movement and emerging practices in social prescribing.
A comprehensive archive catalogue will be produced and published online, alongside selected, co-curated digitised material responding to key research themes, increasing the resource’s usability in uncertain times. Repackaging will ensure long-term survival alongside remedial conservation for stabilisation where necessary. Audiovisual items will be preserved and digitised for access. Dissemination activities will create additional research impact.
|
| 11/05/2021 |
£98,426 |
|
LANCASTER UNIVERSITY |
Healthcare as an industry is one of the most environmentally destructive on earth in almost every respect (e.g. energy use, harmful gas emissions, and physical waste). The enormous environmental toll of delivering healthcare is fundamentally at odds with healthcare's goal of improving health and wellbeing. Indeed, it is the drive to achieve healthcare excellence with world class medical safety and effective treatments that is ultimately so resource intensive and polluting. This project aims to address the dilemma of how to ethically make medical decisions that adequately account for patients and the environment. In particular, I am interested in how we can ethically make trade offs between what is owed to individuals, collective groups, and future generations. For example, what might be best for the treatment of an individual may harm the environment and be detrimental to collective society or future generations. What is the best course of action? I use these three groups as lenses to examine three case studies of areas of environmental concern in medicine: the environmental cost of medical treatments; medical waste production; and the environmental benefits of remote treatment. My findings aim to inform this cutting edge area of applied ethics, healthcare policy and practice.
|
| 11/05/2021 |
£127,173 |
|
UNIVERSITY COLLEGE LONDON |
With 22.1% of global conflict-affected populations afflicted by mental disorders, Mental Health and Psychosocial Support (MHPSS) has become an increasingly important set of interventions (Charlson et al., 2019). However, care has remained removed from broader socio-political and historical context. This is despite that the psychosocial" is conceptualised as one’s psychological development within, and in interaction with, the social environment (Glass, 2000). In conflict-affected contexts where social environments become strained, structural issues of reconstruction are typically managed by "peacebuilding" actors. In other words, MHPSS and peacebuilding remain siloed, ignoring that peace and mental health are intrinsically linked. Furthermore, interventions remain top-down and externally driven.
Accordingly, this research builds atop interdisciplinary critiques of both fields and asks, "can community-based critical psychology approaches effectively integrate and improve MHPSS and peacebuilding practice in conflict-affected areas?". Focusing on fieldwork with conflict-affected youth in Bogotá, Colombia, this research will take a Participatory Action Research approach in collaboration with local partners and communities, whereby Critical Community Psychology theories will be applied for the development of integrated "psychosocial peacebuilding" approaches. Through the introduction of these theoretical and methodological innovations, a "skeleton" of a model can be developed to be "fleshed out" and implemented in other conflict-affected contexts.
|
| 11/05/2021 |
£107,696 |
|
UNIVERSITY OF OXFORD |
Since 2012, the UK’s ‘hostile environment’ immigration regime has sought to precaritise non-citizens’ lives, and thereby encourage their voluntary departure. In recognition of this explicitly violent objective, empirical legal scholars have increasingly sought to elucidate migrants’ experiences of adversity in the UK with attention to the legal structures and practices that comprise this regime. This research will seek to expand this focus to return practices. Previous research on return has overwhelmingly focused on deportation – which comprises a minority of returns from the UK – and neglected voluntary return, despite its statistical and conceptual significance to the hostile environment regime. As voluntary return also affects far more women than deportation, the practice carries additional importance for scholars of gender and migration. Through ethnographic and narrative accounts of South Asian women’s lived experiences of ‘voluntary return’ from the UK to Punjab, this research will foreground voluntary return’s impacts for women’s health, safety, wellbeing and relationships, and consider whether these experiences might be conceptualised as ‘gendered harms’. These findings will develop understandings of migrant women's autonomy, dignity and bodily integrity, and states' obligations to non-citizens under a political and legal system that sharply differentiates their rights from those of citizens.
|
| 11/05/2021 |
£95,026 |
|
UNIVERSITY COLLEGE LONDON |
Following the lapse of the Contagious Diseases Acts in the late nineteenth century - legislation that allowed for the routine inspection of prostitutes in order to reduce the rates of STDs - rising rates of venereal disease created, by the outbreak of war in 1914, an atmosphere of widespread sex panic that associated the disease with moral infection, particularly in metropolitan locales. My research proposes that the venereal disease epidemic of the early twentieth century was a significant medical and cultural event of particular concern to literary modernists in and around the city, including Joyce, Woolf, Eliot and Pound, and Lawrence, and activated a nexus of interrelated concerns such as anxieties surrounding birth control, prostitution, and non-procreative intercourse. This project will demonstrate how the eugenic language of social hygiene influenced modernist aesthetic strategies and suggest that literary modernism itself contributed to emerging ideas of sexual health by reflecting contemporary fears of illness and contamination. In doing so, it will deepen our understandings of the place of the literary in the production of medical knowledge at this time, and examine the crucial role of cultural forms in the dissemination and transmission of public health discourse in the early twentieth century.
|
| 11/05/2021 |
£99,326 |
|
UNIVERSITY OF HUDDERSFIELD |
Advanced nursing practice has been of tremendous value to British healthcare. The government, NHS managers and patients alike have placed high expectations on Advanced Nurse Practitioners (ANPs), and researchers have concluded that ANPs have risen to the challenge. However, it is ironic that while ANPs have been deployed across varying sectors of British healthcare, neither the government nor the NMC - nursing's regulatory body - has placed legal parameters around the role's boundary of practice. There is no doubt that professional boundaries in healthcare have shifted. Before the 1990s, nurses had been innovatively expanding their practice boundaries in response to service needs. Consequently, the ANP role evolved under changing healthcare needs. It could be interpreted that British medical history does not understand advanced practice. Therefore this study will draw on the example of the USA and interpret such evidence to be applicable to the British context. Nursing historiography currently lacks any historical analysis of the implementation of Advanced Nurse Practitioners, their role and advance practice's evolution. This thesis will correct this oversight and be the first to write a holistic historical analysis of advanced practice's scope of practice.
|
| 11/05/2021 |
£95,373 |
|
UNIVERSITY COLLEGE LONDON |
This work responds to a growing volume of research on the wellbeing of sexual migrants. Little attention has been paid to defining migration in this literature, which is often understood in a purely spatial sense. In this project, I claim that sexual migrants – whether from the UK or abroad – traverse temporal, as well as spatial, boundaries. This, I claim, has important implications for sexual wellbeing and risk. Through ethnographic research in a London sexual health clinic, including two sets of 15 semi-structured interviews with service users and ten interviews with clinic staff, I seek to uncover the extent to which abrupt shifts between timelines, such as coming out of the closet, transitioning, or moving to radically new environments such as halls of residence or retirement homes, contribute to sexual risk. This research will problematise racist and imperialist geographies of risk that locate risk in faraway lands, while also bringing to light corrective measures that will improve patient experiences and health outcomes of temporal migrants, from wherever they originate. These measures include a recalibration of eligibility criteria for targeted risk reduction interventions and an identification of further training needs for sexual health staff working with temporal migrants.
|
| 11/05/2021 |
£106,241 |
|
UNIVERSITY OF HULL |
This project proposes a new critical study of English hospice architecture, aimed at making evidence-based recommendations for inclusive hospice design. Although 40 million people need palliative care worldwide annually, relatively little research has examined the settings in which palliative care is administered or attempted to understand how patients, visitors and staff experience them. The widespread tendency in contemporary hospice architecture to make palliative care settings resemble domestic residences is rarely interrogated, despite potential problems surrounding the home’s complexity and the question of whose home is being imitated. A better understanding of hospice architecture is needed to establish how to design hospices inclusively for individuals from all socio-economic and cultural backgrounds, especially given documented disadvantage in access for some groups.
This project will employ an interdisciplinary methodology, examining English palliative care facilities through site visits and analysis of primary documents, and exploring how individuals experience these environments through ethnographic field work, including observation, interviews and focus groups.
This study will provide a novel examination of English hospice architecture, highlighting the voices of the users of palliative care settings. Findings will be synthesised into recommendations for policy makers on how to address the issue of domestic design inclusively in palliative care settings.
|
| 11/05/2021 |
£110,278 |
|
UNIVERSITY OF EDINBURGH |
Mental health activists and service-users have long argued for research and interventions to take into consideration structural determinants of mental distress such as violence and inequality. Yet, current scholarship on high rates of mental distress amongst women in Pakistan focus on proximal social determinants (factors pertaining to individuals and families).
This project challenges public health investigations that places responsibility of poor mental health of women in the region on family conflict, thereby misplacing causal accountability and missing the opportunity for large-scale transformation and social change. Taking poor mental health amongst women in northern Pakistan as a case study, this project examines how structural determinants such as gender inequality, poverty, and impact of development interventions, shape women’s mental health in northern Pakistan. The proposed research will comprise of in-depth interviews, participant observation and archival research in Gilgit Baltistan, where high rates of suicides/attempted suicides have been recorded.
The project draws on critical perspectives from the fields of global mental health, international development, and gender studies. It aims to provide evidence and insights to researchers, mental health service providers, advocates, and policymakers in delivering health and gender justice through informed interventions and policies in Pakistan, and more broadly, South Asia.
|
| 11/05/2021 |
£89,482 |
|
BIRKBECK UNIVERSITY OF LONDON |
This practice-led project, from a disabled artist-researcher, investigates humour as a form of activism within the UK Disability Arts Movement. Focusing on the under-researched National Disability Arts Collection and Archives, it will document the emergence and uses of critical or polemical humour between 1976 and 2010. This archival research, supported by conversations with the movement’s artists, will combine object-orientated creative practice and sensory enthnography with historiographical research.
Art history has neglected these artists, who created institutions essential to UK arts today. Overlooked by disability studies too, their transgressive humour critically engaged with changing ideas of disability. For the medical humanities, the research will create new knowledge of how disabled people have driven and understood changing ideas of disability. For critical medical humanities, this project will offer a new paradigm of disability arts research, specifically addressing the significance of the disabled artist-subject as researcher.
At a time when the experience of disability in the UK is increasingly individualised, understanding this humour’s agency, collectivity and its effectiveness in disability activism is urgent. This study will inform arts policy, re-position disability activism within art history, and inform critical understanding of how ideas of disability are influenced and understood by disabled people.
|
| 11/05/2021 |
£87,362 |
|
BIRKBECK UNIVERSITY OF LONDON |
This project will be the first comprehensive history of the Beaumont Society, a UK based trans support network. It will focus on the ways that members of the Society conceptualised their sense of self, both within the organisation and in relation to other trans and cis gender people and cultures. This research will be much more than a history of the society itself but will make significant strides in historicising trans identities and experiences in the UK, exploring the ways trans people negotiated the medical and health discourse that have historically legitimised trans identity, alongside other ways of understanding gender crossing in their everyday lives. These perspectives will in addition allow for reconsideration of wider themes of belonging and selfhood and the changing nature of social movements from the 1960s to the early years of the internet. Using a combination of archival research and oral history the project will be organised thematically, examining trans subjectivities through the everyday including domestic life, work, clubs and leisure, and other countercultural and political movements. The relationship of trans identities and experience to shifting gender norms will be a cross cutting theme.
|
| 11/05/2021 |
£131,210 |
|
UNIVERSITY OF ST ANDREWS |
My PhD research aims to deepen anthropological understandings of health, illness and disease in contexts where the Guarani-Mbya people, rodents and microorganisms become entangled through leptospirosis within the Jaragua´ Indigenous Land – a small territory surrounded by the city of Sa~o Paulo, Brazil’s largest metropolis. My project will be based on the ethnographic study of multispecies relations entangling indigenous people, Leptospira spp bacteria, governmental agencies of disease and rodent control, and health professionals. The project will focus on the examination of Guarani-Mbya perceptions of and practices around rodent-borne infection so as to unsettle the colonial vestiges of epidemiological reasoning that continues to inform understandings of zoonosis. This investigation of human-rodent relations will be path-breaking for Amerindian Studies, as, for the most part, these have focused on animal-human relations primarily in contexts of hunting and pet-keeping. The ethnographic data produced by the project will also be useful for reconceptualizing and developing rodent-management strategies and community-led programmes in other Amerindian contexts, contributing to critically expanding the One Health initiative towards an ethnographic-based, decolonized, community-led, and multispecies approach. [zoonosis, Amerindian Studies, rats, Guarani-Mbya, Brazil]
|
| 11/05/2021 |
£133,183 |
|
UNIVERSITY OF EDINBURGH |
Transnational medical practice is a common phenomenon in contemporary Tibetan medicine, especially among exile practitioners in India and Nepal. Both in the form of medical tours abroad or local treatments of foreign patients and via telemedicine, doctors provide transnational medical care. However, as a result of the deterritorialization of practice and practitioners or new phenomena like telemedicine and innovations in medical treatment options, varying degrees of changes in contrast to national treatment paradigms occur that raise questions about the efficacy or benefit for patients. This research seeks to explore and analyse transnational Tibetan medical practice and asks to what extent this trend transforms essential principles, perceptions, and representations of Tibetan medicine. The aim is to determine and question tendencies towards a modern or global Tibetan medicine, following Wujastyk and Smith's categories of modern and global Ayurveda. Using the methods of participant observation and semi-structured interviews with Tibetan medical doctors and patients, I will conduct a 13 months long multi-sited ethnographic fieldwork in India, Nepal, and Europe. Ultimately, the research will help to understand the challenges to and possibilities for globalised medical practice, contributing to the growing anthropological interest in global health.
Keywords: Tibetan medicine, transnational medical practice, therapeutic travel, telemedicine
|
| 11/05/2021 |
£86,903 |
|
UNIVERSITY OF KENT |
Mediterranean red coral has long been treasured around the world and is currently under threat from intensive fishing, oil drilling and rising sea temperatures caused by climate change. This project will explore the value placed on Mediterranean red coral, Corallium rubrum, a natural material sourced and prized in medieval and Renaissance Italy but also a culturally significant foreign import to Protestant England c.1600-1750. While coral is highly visible in early modern English sources, the historical importance of coral to English beliefs about physical and mental health is yet to be analysed. Drawing on a wealth of documentary evidence, material and visual culture, held in The National Archives, V & A, British Museum, Wellcome Collection, Science Museum and National Portrait Gallery, I will examine how coral was used as a medicinal ingredient, contributed to a domestic armoury against natural and supernatural threats, and was also a luxury commodity, perceived to be a material imbued with particular values, properties and powers in English society. Once considered to be a limitless natural treasure of the seas, the ecological threat to red coral in the Mediterranean makes understanding our long history of engagement with this precious species all the more critical at this time.
|
| 11/05/2021 |
£171,260 |
|
UNIVERSITY OF OXFORD |
My dissertation seeks to argue that the modern Western Scientific advancement was largely predicated on the supply of South Asian bones from India to Britain during the legal creation of the British Raj in 1858. In doing so, it attempts to link the trade of bones and bodies to what I call the ‘Red Industry’—a full-fledged socio-economic establishment employing numerous labourers, specialized in different units, which thereby assumed a pivotal place in the network of imperial capitalism, propelled by profit. Besides leading to the emergence of ancillary industries, wherein bones are seen as potentially esoteric, aesthetic and even agricultural resources, I argue that the ‘Red market’ also projected itself as indispensable with regards to the contributions in various socio-medical fields: forensic anthropology, phrenological works, osteo-archaeological discoveries and leading studies on Osteoporosis. Focusing primarily on the local perceptions of the dead, and the surrounding inter and intra-caste polemics on dissection, the work essentially seeks to bridge the long-standing gap between the trade economy and the overarching historical debates predominantly concerning bio-ethics and public health, while interacting with law, labour, society and medicine throughout the mid-nineteenth to the late twentieth centuries—the era of decolonization.
Keywords:
British Raj, South Asia, Public Health, Medicine
|
| 11/05/2021 |
£94,754 |
|
GOLDSMITHS, UNIVERSITY OF LONDON |
Meaningful dreams, visions and coincidences are a remarkably common feature of the dying process. While patients and families report their profound spiritual significance, mainstream clinical literature explains them in materialist terms. This project asks how health professionals respond to such events on the ground, whether they reflect this materialist approach or if there are examples of healthworkers engaging in more ontologically and epistemologically open ways. The research will explore how philosophical responses influence the day-to-day practices of care. It will also ask whether variation in interpretations of such events runs along existing lines of social or cultural difference among both healthworkers and patients. I will take a methodologically interdisciplinary approach combining an ethnography of a hospice in-patient unit (utilising my experience as a palliative care nurse) with narrative interviews of staff who have responded to deathbed experiences. Drawing on feminist care theory, science and technology studies and the medical humanities this study will explore the significance of responses to deathbed phenomena for both clinical knowledge practices and patient care.
|
| 11/05/2021 |
£83,492 |
|
UNIVERSITY OF THE WESTERN CAPE |
The project aims to explore the various social and political constructions of lay care work during the Covid-19 pandemic and the early stages of the HIV/AIDs epidemic in Cape Town. It will analyse the tensions and possibilities that arise when informal, self-organised and localised care work done by ordinary people interacts with the formal health system, considering how this represents a potential for social change in the health system and broader society. Analysis will draw on Feminist care theory and De Certeau's concept of tactics and strategies, situating the project in a broader critique of the ways in which the dominant neoliberal and capitalist order produces a crisis of care that marginalises care work and stifles possibility for meaningful collaborations between the formal health system and ordinary people doing this work. Research will involve archival and document-based data such as meeting recordings, media pieces, policy documents, academic and NGO reports, and documentary films regarding lay care work and community-based care during Covid-19 and the early stages of the HIV/AIDS epidemic (90s-early 2000s). It will also draw on in-depth interviews with participants who were actively involved in and/or able to reflect on the provision of place-based, lay care during both cases.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
A major challenge in establishing novel therapeutics for neurological diseases is the assessment of tissue health. The inaccessibility of the brain for biopsy has motivated the development of novel technologies, with diffusion Magnetic Resonance Imaging (MRI) emerging as one of the most promising techniques to non-invasively assess brain tissue. Diffusion MRI generates images sensitive to the microscopic motions of water within and around cells. It has demonstrated considerable potential to identify novel biomarkers in a number of neurological diseases.
Despite this promise, conventional diffusion MRI methods have failed to access certain key brain regions. In these regions, rapid signal-decay (short-T2) leads to low-quality images with the appearance of ‘black holes’. I propose to establish an imaging platform that enables us to assess tissue health in these previously inaccessible regions. I will achieve this using a little-known but powerful technique, ‘steady-state diffusion’.
Building on a framework I have recently developed, I will:
Transform steady-state diffusion images into those with clear biological interpretation.
Enable in vivo use by overcoming its extreme motion-sensitivity.
Reduce examination times by integrating the estimation of signal dependencies.
Utilising this platform, I will investigate the substantia nigra, a black hole brain region of critical importance in Parkinson’s disease.
|
| 05/05/2021 |
£300,000 |
|
THE FRANCIS CRICK INSTITUTE |
Intrinsically disordered proteins/domains (IDPs/IDRs) are highly flexible and lack a defined secondary or tertiary structure. Their highly reactive and versatile interaction surface contains diverse small linear motifs that enable IDP/IDRs to act as key regulatory protein interaction and signalling hubs. In addition, a new set of small proteins have recently emerged by the identification of thousands of microproteins or smORF-encoded peptides (sPEPs) from which a few validated sPEPs play crucial regulatory roles via protein-protein interactions and add a new regulatory dimension to multiple cellular processes. Due to the size of sPEPs and high flexibility of IDPs, conventional tagging, biochemical and cell biological approaches are not suitable for the study of these type of proteins. I will overcome this by implementing a pipeline to achieve the orthogonal site-specific incorporation of minimally invasive non-canonical amino acids in IDPs and sPEPs. With this approach I aim to study the protein-protein interaction networks, localization and function of IDPs and sPEPs involved in innate immune processes such as the antiviral response or neutrophil defense mechanisms against pathogen invasion.
|
| 05/05/2021 |
£300,000 |
|
KING'S COLLEGE LONDON |
The function of the cerebral cortex relies on the cellular balance between excitatory (pyramidal cells) and inhibitory neurons (interneurons), which is disrupted in disorders such as autism or schizophrenia. The emergence of cortical function relies on spontaneous synchronous activity among large groups of pyramidal cells and interneurons, which later desynchronize for efficient information processing. Prior to this shift in network activity, interneuron numbers are adjusted through activity-dependent programmed cell death mechanisms. The contribution of interneuron programmed cell death to the change in network dynamics and the identity of the cell types participating in these events remain unclear. I will address these questions by combining in vivo longitudinal functional imaging of the postnatal somatosensory cortex with cell type identification via multiplex in situ RNA localization. This strategy will allow correlating the identity of one neuron with its activity pattern and participation in network dynamics during early postnatal development. I will perform complementary experiments in mouse models engineered to contain abnormal numbers of cortical interneurons, thereby assessing the importance of neuronal numbers for­ cortical function. This project addresses the fundamental question of how neuronal diversity and numbers contribute to the emergence of functional circuits during physiological and pathological brain wiring.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Generalisation is central to intelligent behaviour. Recent work has shown the classic dichotomy of hippocampal function, relational memory and spatial cognition, can be unified through the language of generalisation. Here the structure of the task (spatial navigation, transitive inference etc) is learned and abstracted in order to be reused when entering new environments. Animals (and hippocampus) do more than just space and memory. They display complex behaviours that are reused and arbitrarily combined in novel situations. This raises the exciting possibility that animals learn the structure of behaviours and generalise them to new situations (e.g. the steps to baking a cake are reusable for making cookies). The common role of generalisation and abstraction would unify representations of behavioural (reinforcement) learning with spatial map-like learning.
My research will build detailed theories and precise computational models to find a formalism with a common language for representations of reinforcement learning and space. Though much of the reinforcement learning literature has focused on more intuitive notions of reward and value to find in neural data, my models will predict that neurons additionally represent the structure of the behavioural tasks. I will look for this neural signature in data from both old and ongoing experiments.
|
| 05/05/2021 |
£300,000 |
|
KING'S COLLEGE LONDON |
This project investigates the genetic basis of psychiatric disorders and neurological diseases with three key goals.
First, to gain insight into the molecular mechanisms underlying genetic associations with these outcomes through the integration of genome-wide association study (GWAS) summary statistics with a range of newly released functional genomic annotations. These include variant-level annotations such as the effect of genetic variation on gene expression, methylation and chromosome structure within relevant tissues and cell types, as well as gene-level annotations such as expression profiles across tissues, cell types and developmental stages.
Second, functionally informed polygenic scores, such as imputed and observed gene expression risk scores, will be stratified by enriched functional genomic annotations and used for clustering patients into aetiological subtypes, which will then be characterised using sociodemographic and clinical variables.
Lastly, this study will evaluate the utility of machine learning models containing functionally informed polygenic scores and cluster membership information for prediction of diagnosis, prognosis and treatment response. I will use data from a range of ancestral populations to improve the accuracy of genetic predictors in all populations. Together this project can inform novel drug development, identify clinical subgroups, and promote personalised medicine through improved prediction of clinically relevant outcomes.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF EDINBURGH |
The kinetochore is a molecular structure that segregates chromosomes by connecting them to spindle microtubules. In the first meiotic division the kinetochores of duplicated sister-chromatids mono-orient to the same spindle pole, allowing the segregation of the paternal and maternal chromosomes. In human oocytes, meiotic chromosome segregation is highly error-prone, often resulting in chromosomal abnormalities. This worsens with advanced age, leading to miscarriages or trisomies such as Down syndrome, especially in older women. My project aims to define the molecular adaptations to kinetochores that allow mono-orientation in meiosis and understand how these might be defective in human oocytes. I will develop Xenopus laevis oocyte cytoplasmic extracts as a system in which to assemble meiotic kinetochores in vitro and use biochemical analysis to determine their molecular components. Using cell biological assays in oocytes, I will determine how these components work together to mono-orient meiosis-I kinetochores. Furthermore, I will use patient donated surplus human oocytes obtained from IVF clinics to investigate how deficiency in mono-orientation contributes to age-related chromosomal abnormalities.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Human and animals make decisions to harvest the most valuable rewards. This process requires a precise valuation of choice options and appropriate action selection. Despite the fact that many brain regions have been implicated in different aspects of value computation and decision making, the roles of the claustrum, a region with extensive brain-wide connectivity, in value-based decisions have remained unknown. This fellowship combines circuit, behavioural and computational tools to determine the role of the claustrum in value-based decisions.
I will train mice on a value-based decision-making paradigm. First, I will assess the importance of claustral neural activity in choice behaviour by combining viral injection strategies and three-photon microscopy. Then, I will create a biologically realistic spiking neural network and simulate the effect of claustrum on multiple upstream regions. By using Neuropixels systems and optogenetics, I will delineate how long-range inputs from the claustrum contribute to the value signal in frontal regions by recording spiking activity while silencing claustral cells. These results will provide fundamental insights into the neural circuitry of decision-making.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Epigenetic lesions occur at the early stages of cancer development, and have important roles in tumour initiation and progression. However, our understanding of how cancer cells acquire, propagate and select such aberrant epigenetic states remains very limited.
Therefore, I propose to define the mechanisms by which initiating epigenetic defects drive tumour evolution in Acute Myeloid Leukemia (AML), a deadly bone marrow cancer with no effective treatment.
I hypothesize that initiating genetic defects in the DNA methylation machinery (TET2 mutations) catalyse epigenetic diversity. The resulting epiclones might acquire properties that increase cellular fitness, predisposing cells to undergo transformation and generating a substrate for selection. Using state-of-the-art single cell DNA methylation and transcriptomic technologies coupled with lineage tracing, I will quantify stably propagated epigenetic diversity in TET2 deficient cells (Aim1), and identify selective advantage of high-fitness epiclones upon cell-extrinsic pressures (Aim2). I will then characterize putative driver epimutations in longitudinal AML patient samples and demonstrate their functional role promoting leukaemic transformation using locus-specific epigenomic editing tools (dCas9-DNMT3A; Aim3).
This research will shed light into the fundamental molecular mechanisms driving epigenetic diversification and selection of cancer cells, with the potential to bring an entirely new dimension to cancer treatment by intercepting tumour evolution.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
This project aims to advance our understanding of how the human brain evolved to support our unique cognitive skills. Using multimodal neuroimaging, I will investigate the structure-function coupling in the human brain and relate it to species differences in brain organization across the primate lineage. I will focus on the temporal lobe as a model system given its vital role in higher cognitive functions and because it underwent strong reorganization during evolution. To characterize individual patterns of brain organization optimally, I will use a gradient-based approach, where manifold identification techniques are employed to model spatial trends of variance in the data. MRI-based gradient analyses will be complemented and validated by using microstructural information from the BigBrain-Project and from gene expression data. Lastly, I will compare human temporal lobe organization to that of non-human primates to assess how divergent principles of brain organization relate to uniquely human brain function.
In sum, the present project will explore temporal lobe architecture by (1) studying human macro- and microstructural brain architecture in a gradient-based approach (2) relating structural and functional features in a unified framework to account for patterns of organization at the individual subject-level (3) comparing these relationships to those in non-human primates.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF MANCHESTER |
Commensal microorganisms protect their hosts from pathogens, denying space and resources to would-be invaders. To bypass this host protection, many human pathogens deploy a needle-like apparatus—the Type 6 Secretion System (T6SS)—to inject lethal toxins into commensal cells, thereby establishing infection. Bacterial resistance to T6SS attacks is therefore expected to be a crucial predictor of pathogen proliferation and consequent disease severity. However, it remains unknown when, and how, bacteria evolve the capacity to resist T6SS attacks, hampering efforts to predict or leverage this host protection.
My project will address this knowledge gap by characterising the emergence of T6SS resistance in Escherichia coli. Combining in vitro and in silico approaches, I will first determine the specificity, fitness costs, and genetic bases of evolved resistance, against diverse toxins deployed by Acinetobacter baylyi, a well-studied T6SS attacker species. Next, I will examine how the evolution of T6SS resistance is affected by attacker toxin arsenal and attacker counter-adaptation, to explain why attackers typically deploy multiple toxins in nature. My ultimate goal is to provide a systematic understanding of how commensal bacteria resist toxin-mediated attacks. In the longer term, this may offer applications for the design of invasion-resistant bacterial communities, and improved biotherapeutics.
|
| 05/05/2021 |
£300,000 |
|
BABRAHAM INSTITUTE |
Memory B cells (MBCs) are central to co-ordinated immune responses required to resolve viral infections and mediate protection following pathogen clearance or vaccination. I propose that a newly described subset of atypical MBCs (defined by expression of CD11c and T-bet) preferentially reside within peripheral tissues, where they can differentiate in-situ to provide rapid and localised protection against pathogenic threats. This project will investigate the mechanistic basis for CD11c+T-bet+MBC differentiation following immunisation, testing the hypothesis that Th1 skewed T follicular helper cells (Tfh) regulate the divergence of CD11c+T-bet+MBCs from classical memory responses and their migration to non-lymphoid tissues. CD11c+T-bet+MBC induction will be characterised alongside subsets of Tfh subsets in vaccinated humans and mice, with fate-mapping systems and interventional mouse models used to dissect: (1) the tissue homing capacity of CD11c+T-bet+MBCs; (2) their contribution to establishing protective immunity; and (3) the involvement of CD4-derived signals to CD11c+T-bet+MBC differentiation. These will be complemented by state-of-the-art imaging technologies to visualise the spatial dynamics of CD11c+T-bet+MBCs and Tfh within germinal centre responses following immunisation. Together, these data will reveal whether Th1 polarised Tfh seed populations of CD11c+T-bet+MBCs in tissues to establish local protection against infection. Findings may facilitate tailored development of strategies to enhance immunity.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
The Drosophila brain provides a unique opportunity to study the neural mechanisms underlying navigation. Recent work has revealed much about the fly brain’s ring-shaped ‘compass’ region. Within it, a single ‘compass needle’ of activity represents the fly’s heading. When the fly is pursuing a specific heading goal, it locomotes in a straight line, often holding the sun at a specific arbitrary angle (e.g., 90°), which holds the 'needle' stationary. If the fly is pushed off course, the circuitry downstream of the compass kicks in to reorient the fly toward its goal, moving the sun back to 90° and the ‘needle’ back to its original state. How does the brain initialise a specific angular goal (e.g., holding the sun at 90°)? We hypothesise that an asymmetry in a specific brain region (called the asymmetrical body) provides a coordinate system for writing new spatial goals into working memory. This asymmetry may be used to initialise a new spatial goal with respect to a landmark at an arbitrary angle. I will i) use computational modelling to explore the predictions of this hypothesis, ii) use calcium imaging to test these predictions, and iii) use specific genetic manipulations to perturb this process.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Ventricular arrhythmia is the leading cause of death in diabetes, but its mechanisms remain poorly understood, leading to suboptimal therapy. I propose an interdisciplinary project to address this unmet need, combining multiscale human cardiac simulations and experimental studies. I will use my recent computational model of a human myocyte ToR-ORd, which was extensively validated for arrhythmia research, disease representation, and drug assessment.
Goal 1) To build a computational model of a single diabetic myocyte and use it to elucidate how distinct aspects of diabetic remodelling contribute to arrhythmia, also investigating the role of glucose level disturbance.
Goal 2) To demonstrate how remodelling of cardiac sympathetic signalling at the myocyte level affects diabetic arrhythmia vulnerability using simulations informed by newly collected FRET imaging data.
Goal 3) To integrate the single-cell results into 3D models of ventricles based on patient-specific clinical imaging data, investigating the diabetic remodelling of cardiac conduction properties.
Goal 4) To produce a computational tool to search for new drugs with promising antiarrhythmic effects in diabetes and to assess existing therapies, suggesting their optimisation.
In summary, the project is likely to impact future diabetic therapy and to bring new insights into the so-far poorly understood area of diabetic arrhythmogenesis.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF GLASGOW |
NK cells are innate lymphocytes with crucial roles against viruses and tumours. There is growing evidence that NK cells display immune memory, however many key open questions remain. While memory NK cells where shown in several models and proved to be protective in adoptive transfer experiments, the mechanisms behind these phenomena remain unclear. Answering such questions could reshape our understanding of immune memory and provide new strategies against infectious disease and cancer. Using state-of-the-art scRNA-seq, 3D imaging and precision mouse models, I plan to study NK cell memory following influenza infection. I aim to decipher 1) which subpopulations of NK cells acquire memory, 2) where memory NK cells are located within the lung architecture and which cells (adaptive, innate or stromal) they interacting with, and 3) how memory NK cells act in concert with other memory cells in secondary immunity in immunosufficient hosts. With my background in NK cells and innate memory and the excellent array of sponsors with complementary expertise in influenza, chemokines, computational analysis and 3D imaging, this project provides the ideal platform for novel findings in the field of NK cell memory, expansion of my skillset in cutting-edge techniques, and optimally enables my transition to independence.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF BRISTOL |
Sub-Saharan Africa (SSA) has the highest HIV burden in the world and will be the region most affected by climate change, with the largest projected decrease in rainfall and limited resources to deal with the consequences. Global warming will lead to more droughts and decreased food yields, resulting in increased food insecurity. Emerging evidence suggests food insecurity could lead to increased HIV transmission risk and sub-optimal HIV treatment outcomes, due to such factors as women resorting to selling sex for survival, access to HIV treatment being interrupted, and decreased HIV treatment absorption in the absence of food.
This project will:
- involve epidemiological analyses (regression, systematic reviews, meta-analyses) on large HIV datasets from SSA to improve the evidence base for the effect of drought and food insecurity on HIV treatment outcomes, HIV incidence and sexual risk behaviours in SSA.
- use mathematical modelling to simulate the existing impact of drought and food insecurity on HIV transmission and morbidity in several countries in Eastern and Southern Africa.
- model the potential effect of global warming in these countries on increasing the impact of drought and food insecurity on HIV transmission and morbidity, as well as the impact of potential interventions.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Polycomb group proteins are chromatin regulators which are essential for mammalian development and are often dysregulated in diseases including cancer. Polycomb proteins make up two distinct complexes, Polycomb Repressive Complex 1 and 2 (PRC1/2). In mammals these complexes have expanded and evolved into a complex interconnected system making it challenging to disentangle the core principles through which they function. I will utilize Salpingoeca rosetta, a choanoflagellate, to dissect a more "ancestral-like" Polycomb system and through a comparative approach unravel the basic core principles through which animal PRCs operate. Firstly, I will interrogate the composition (Aim1) and dissect the biochemical properties and enzymatic activities of S. rosetta (Sr)PRCs (Aim2) to reveal the conserved properties of animals PRCs. I will then utilize genome-wide mapping approaches to address the function of SrPRCs and, using mutants for PRC components, test whether their activities are coupled in the genome (Aim3). Together, these discoveries will provide essential new insight into the principles through which animal PRCs act and will shed light on how they become perturbed in disease. This in turn will inform new avenues for targeted therapeutic intervention in diseases where alternations to PRC function are pathogenic.
|
| 05/05/2021 |
£300,000 |
|
KING'S COLLEGE LONDON |
Stress-related psychopathology (e.g. depression and anxiety) affects one in eight children in the UK. It is therefore crucial to identify modifiable protective factors that can promote mental health in young people. Physical activity is a promising target for the prevention of depression and anxiety. However, the extent to which it can reduce the burden of mental disorders in young people is not known. This is due to the breadth of environmental, social, and genetic factors that could confound the relationship between physical activity and psychopathology. Furthermore, it is unclear whether physical activity can promote resilience to psychopathology in children who are at higher risk by virtue of genetic liability or adversity.
I will apply cutting-edge causal inference methods, such as G-methods, Mendelian randomisation, and twin designs, to test whether physical activity can promote resilience against the development of stress-related psychopathology, using data from large population-based cohorts of children from the UK, Netherlands, Norway, and Finland. Triangulating evidence from multiple analytical approaches will allow me to strengthen causal inferences from observational data and minimise potential biases associated with each method. In turn, the findings will indicate whether interventions targeting physical activity are likely to hold promise to prevent stress-related psychopathology.
|
| 05/05/2021 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Obesity and associated comorbidities are significant unresolved global health problems. Despite intense research and various social policies, most of the available non-invasive treatments are ineffective in the long term, and the best therapeutic option remains highly mutilating bariatric surgery. Thus, the unmet need is to identify novel, long-term safe treatments. The activation of the brown adipose tissue (BAT), an energy-dissipating organ, is a promising strategy to treat obesity if the challenges of accumulating enough BAT mass and optimised activity are resolved. Since obese people do not have enough BAT, it is crucial to identify at which step of the differentiation and/or activation the BAT of obese patients fails, and whether we can pharmacologically bypass these functional bottlenecks. Recently, Vidal-Puig's lab has optimised a unique differentiation protocol that recapitulates step-by-step the developmental path of human BAT from stem cells. I aim to use this tool to decipher the signals regulating the process and provide an accurate stage-by-stage molecular map of human brown adipogenesis. These data will help to infer novel pharmacologically targetable molecules to improve differentiation and activation of BAT in obese patients and provide essential information for its analysis and classification in patients based on its maturation and functional stage.
|
| 05/05/2021 |
£300,000 |
|
IMPERIAL COLLEGE LONDON |
Dizziness is common in older adults and is strongly associated with more frequent falls. Nonetheless, treating this condition represents a significant challenge as clinicians are often unable to identify a physical cause (and, thus, dizziness is ‘unexplained’). Pilot work implies that unexplained dizziness may stem from attempts to consciously process balance. However, a causal relationship has not been established. Further, the specific mechanisms through which conscious processing influences dizziness remain unknown. My goals are to (i) investigate whether conscious balance processing is causally associated with symptoms of unexplained dizziness, and (ii) identify the neuro-cognitive mechanism/s that likely underpin such a relationship.
I will conduct a programme of research to test the hypothesis that conscious balance processing influences dizziness through a hypersensitivity to sensory input, in that even minor fluctuations within ‘normal’ bounds are perceived as unsteadiness. I will measure symptoms of dizziness and assess sensory processing during baseline balance conditions, as well as during experimental manipulations that either promote or prevent conscious balance processing. Data will be compared between older adults with unexplained dizziness and age-matched controls. This work will advance our understanding of how neuro-cognitive factors contribute to dizziness, informing the development of novel therapies that target these mechanisms.
|
| 30/04/2021 |
£20,000 |
|
NEUROMATCH ACADEMY, INC |
Not available |
| 30/04/2021 |
£7,247,952 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
The O2 Taskforce is coordinating access to emergency oxygen for COVID-19 patients in LMICs. Since the start of the pandemic, affordable, sustainable access to oxygen has been a growing challenge LMICs. COVID-19 has put huge pressure on health systems, with hospitals running out of oxygen, has resulted in preventable deaths and huge burden on families of hospitalized patients. Oxygen is an essential medicine, and despite being vital for the effective treatment of hospitalized COVID-19 patients, access in LMICs is limited due to cost, infrastructure and logistical barriers. The O2 Taskforce has identified an immediate need of approx. US$ 90 million over the next 1 – 2 months, with a US$1.6 billion need estimated for LMICs over the next 12 months to support.
The proposal will secure funding ($10 million) for acute oxygen COVID-19 needs in LMICs as identified by the O2 Taskforce. The funds will support countries to access oxygen and to unlock available resources to build more sustainable, resilient oxygen systems. Activities may include technical assistance for implementation of oxygen services, investments for market interventions and for additional country assessments/development of country funding proposals. This investment is intended to accelerate and amplify the impact of follow on scale-up funding. |
| 30/04/2021 |
£39,956 |
|
UNIVERSITY OF LEIDEN |
Not available |
| 30/04/2021 |
£116,653 |
|
NHS CONFEDERATION |
Execute UK assigned tasks and responsibilities within the Joint Action to a high standard, establishing the UK as a valued and trusted partner.
Gather a body of evidence of NHS and UK expertise on data processing in the health sector to contribute to the development of the European Health Data Space.
Regularly convene and consult a wide range of UK stakeholders to ensure that UK health data interests across the sector are fully understood and represented.
Maintain regular updates and briefings on the scope and objectives of the development of the European Health Data Space, to maximise UK preparedness.
Identify and pursue opportunities to progress UK interests in the health sector, and on digital policy development more broadly.
|
| 30/04/2021 |
£115,255 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Snakebite has recently been recognised as a Neglected Tropical Disease, In addition to the limited availability of high quality antivenoms, one of the major challenges to improving outcomes is that there is currently no established mechanism for a) determining the key evidence gaps, b) coordinating the necessary research and evidence generation and c) providing appropriate scientific and technical advice to governments and Ministries of Health to inform appropriate policy development.
This application seeks to undertake the initial work necessary for planning how these public health and policy issues could be addressed in sub-Saharan Africa. It will comprise two main phases:
a) a wide-ranging scoping review and mapping of critical issues and priorities
b) exploration of the best approaches and structures to address the issues identified in phase 1 and development of a clear strategy and plan to implement a solution
The overarching aim is: To undertake the preliminary work necessary to identify the barriers to evidence-based decision making at national and regional level for snakebite in Africa and to inform the optimal design of a major research and policy initiative that will overcome these barriers.
|
| 30/04/2021 |
£199,522 |
|
UNIVERSITY OF OXFORD |
This award will support a series of interactions between academics from diverse backgrounds with a shared interest in mapping, analyzing and critically unpacking decolonization debates in global health research. Decolonization discussions and activism have become far more prominent over the last year, bringing both opportunities for positive transformation (through disruption, change and renewed interest in global power inequities) as well as challenges (including the ‘trending’ of the decolonization agenda leading to – at worst – the ‘colonization’ of the arena itself). Now, as much as ever, decolonization discussions and debates need to be critically examined. We will organize a set of exchanges and activities to: 1 Unpack and reflect upon the term ‘global health research’ using a decolonization lens; 2 Examine how tacit, or embedded, forms of knowledge from Africa are drawn upon and feature in global health research; 3 Imagine what a decolonized or African-centred, and ethical, research initiative in global health might look like; and 4 Share our learning, advocate for change, and identify an African home for future work. We will incorporate a covid-19 research lens, but only in recognition that covid-19 will shine a light upon or amplify far longer and deeper policies and processes.
|
| 30/04/2021 |
£190,026 |
|
UNIVERSITY OF STRATHCLYDE |
This programme of exchange and networking will:
i. Energise the Medical Humanities research ecosystem in South Africa as it evolves.
ii. Embed the research environment at the CSHHH Glasgow, and its current partners, in this process.
iii. Seed a cohort of early-career scholars in the Medical Humanities with experience of research, training and teaching collectively in both South Africa and the UK.
Context
Since 2018 members of the CSHHH Glasgow and the University of Johannesburg have worked together in the Medical Humanities. The Wellcome Trust and both universities invested in these activities. Following the success of this co-working, partners from the University of the Witwatersrand and the University of Cape Town joined the collaboration. The core objective is to connect the four institutions in order to jointly conduct research, training and teaching so that Medical Humanities research ecosystems continue to grow together in both countries.
Activities
The focus is on seeding those ecosystems through investment in the researchers of the future and fresh collaboration across the countries and institutions. The programme will enable;
1. Four Masters students and one Ph.D. candidate to be co-supervised by the PIs.
2. Enhanced networking and communications capacity, including new online resources and platforms.
|
| 30/04/2021 |
£201,902 |
|
UNIVERSITY OF BIRMINGHAM |
Neuroscience and genetics have failed to deliver new treatments for mental disorders. It has been suggested by the NIMH that progress in biomedical approaches has been hampered by our conceptualization and taxonomy of psychiatric disorders and psychopathology. A renewed emphasis on experiential components and first-person perspectives is required to address this problem. Historically, phenomenology, as a branch of philosophy, has provided this methodology and knowledge to the mental health sciences. However, phenomenological psychopathology remains somewhat fossilized in the humanities and social sciences of the mid-20th century. This co-led international award will (1) renew phenomenological psychopathology with the recent contributions of analytic philosophy of mind, hermeneutics, structuralist/post-structuralist philosophy, history, literature, values-based practice, developmental psychology and service user research; and (2) reinvigorate phenomenology for mental health as the philosophical science of subjectivity and first-person experience.
We will develop international scholars from across disciplines and career stages to develop their research leadership and management activities and to engage in Award activities including international exchange fellowships small grants and, knowledge exchange events. The award will commence the reconstruction of phenomenological psychopathology for the 21st century as a democratic discipline with a historicized and inclusive account of the experience of the mental disorder developed.
|
| 30/04/2021 |
£201,912 |
|
UNIVERSITY COLLEGE LONDON |
This collaboration between Brazil, Mexico and the UK brings together environmental, indigenous, biosocial, multispecies, gender and theoretical expertise in Medical Anthropology, to extend interdisciplinary engagement concerning how the Anthropocene epoch impacts on human health. Supported by a post-doctoral researcher in each of the collaborating centres, we will develop Medical Anthropology in four areas: i) indigenous experience and coloniality of the Anthropocene, ii) gender, reproduction and environmental justice, iii) multispecies ethnography and human-animal health, iv) COVID-19 and public understanding of the Anthropocene. From this research and in conjunction with open access publisher UCL Press, we will develop a tri-lingual digital resource for teaching and public reference.
Our collaboration will begin online with bi-monthly meetings followed in February 2022 by a three day virtual cross-disciplinary seminar with invited expertise in science, geography, politics and history. We will work collaboratively to examine how these disciplines can inform Medical Anthropology of the Anthropocene and to identify articulations with policy and practice as these impact on human and environmental wellbeing. In November 2022 we will hold a face-to-face workshop in Mexico to develop dissemination and publications including the digital teaching resource and a multilingual special edition of a Latin American Medical Anthropology journal.
|
| 30/04/2021 |
£201,781 |
|
UNIVERSITY OF BRISTOL |
Building on a developing track record of collaboration between Bristol, Kyoto and Yonsei, BRIDGES:BKY aims to address shared bioethical challenges, through sharing learning and expertise, to benefit postgraduate and early career researchers (PGR/ECRs). Our four challenge areas are: (1) ageing and end-of-life care; (2) clinical ethics support; (3) reproduction and genomics; and (4) theories and approaches in bioethics. These are shared (indeed, global) challenges, which invite new research, and in which the partners have complementary research interests. Guided by these challenges, BRIDGES:BKY will share learning and expertise, including on different methodological approaches to research in these areas. BRIDGES:BKY will leverage our existing links and partnerships to deliver new opportunities to PGR/ECR participants, drawn from across the partner institutions (and beyond), to participate in, and benefit from training workshops, conferences and a (virtual) visiting researcher scheme. Supported by teleconferencing and a dedicated website, activities will be virtual, with some in-person elements (where appropriate). All partners will host and contribute to these activities, through which PGR/ECR participants will develop their knowledge and skills, and their - and the partners’ - future collaborative research endeavours will be shaped.
|
| 30/04/2021 |
£492,566 |
|
UNIVERSITY OF CAMBRIDGE |
Control of the COVID-19 pandemic depends on the development and equitable roll-out of vaccines that remain effective over time. But the evolution of SARS-CoV-2 variants that exhibit variable degrees of immune evasion, and other characteristics including greater transmissibility and/or lethality, threaten to undermine our ability to control COVID-19. It is widely accepted that vaccines will need to be altered over time as the virus mutates. Effective vaccine re-development is dependent upon the availability of global viral sequence data, but there is a lack of sequence data for much of the world, including low, middle and high-income countries. The COVID-19 Genomics UK Consortium (COG-UK) (including the Wellcome Sanger Institute) will leverage its expertise to develop a comprehensive global learning programme on SARS-CoV-2 genome sequencing (COG-GLOBAL). This will be achieved by working with experienced on-line educators. Specific aims include the development of an open access, online modular global learning programme on SARS-CoV-2 sequencing and analysis, allowing users to follow pathways of learning according to professional expertise (laboratory scientist, clinical practitioner, data scientist & epidemiologist, bioinformatician or policy maker); and the development of train-the-trainer courses in collaboration with the Wellcome Connecting Science Advanced Courses, Wellcome Africa and Asia Programmes, and other contributors.
|
| 30/04/2021 |
£463,888 |
|
WELLCOME TRUST SANGER INSTITUTE |
Control of the COVID-19 pandemic depends on the development and equitable roll-out of vaccines that remain effective over time. But the evolution of SARS-CoV-2 variants that exhibit variable degrees of immune evasion, and other characteristics including greater transmissibility and/or lethality, threaten to undermine our ability to control COVID-19. It is widely accepted that vaccines will need to be altered over time as the virus mutates. Effective vaccine re-development is dependent upon the availability of global viral sequence data, but there is a lack of sequence data for much of the world, including low, middle and high-income countries. The COVID-19 Genomics UK Consortium (COG-UK) (including the Wellcome Sanger Institute) will leverage its expertise to develop a comprehensive global learning programme on SARS-CoV-2 genome sequencing (COG-GLOBAL). This will be achieved by working with experienced on-line educators. Specific aims include the development of an open access, online modular global learning programme on SARS-CoV-2 sequencing and analysis, allowing users to follow pathways of learning according to professional expertise (laboratory scientist, clinical practitioner, data scientist & epidemiologist, bioinformatician or policy maker); and the development of train-the-trainer courses in collaboration with the Wellcome Connecting Science Advanced Courses, Wellcome Africa and Asia Programmes, and other contributors.
|
| 30/04/2021 |
£85,186 |
|
PARIS PEACE FORUM |
The Paris Peace Forum will host a series of discussions to maintain the partnership developed by ACT-A (Access to COVID-19 Tools Accelerator) and the governance of global health at the top of the political agenda and further deliver concrete solutions while contributing to the construction of an overall governance framework in the sector. The proposal includes hosting discussions taking place in the framework of a pilot, year-long partnership between the Forum and Wellcome Trust. These discussions would mobilize stakeholders of the Forum’s community and beyond. The Forum would naturally seek Wellcome’s guidance and advice on the scope, topics, invitees, and outputs of these discussions. Stakeholders would be invited to participate in each discussion based on their institutional focus and expertise and on the basis of their capacity to contribute to and implement the desired outcomes. With the support provided by the Wellcome Trust, the Forum could convene two roundtables in 2021, to provide for sufficient time for preparation, eventually for follow-up actions in between and potentially to leverage to key moments in the annual Forum cycle: the Spring meetings of the Paris Peace Forum (May 2021) and the fourth edition of the annual event (11-13 November, 2021).
|
| 30/04/2021 |
£1,122,000 |
|
CAMPAIGN FOR SCIENCE AND ENGINEERING |
See attached document.
|
| 30/04/2021 |
£331,006 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
A highly effective vaccine against yellow fever (YF) is available and part of the Expanded Program on Immunisation in YF endemic countries. Following a change in WHO guidance in 2014, YF vaccination is now restricted to a single dose given in infancy and expected to provide life-long protection. Recent data have highlighted that this schedule might be insufficient as low antibody titres have been documented in infants who received a primary dose at the age of 9 months. A booster dose of the vaccine might be required in order to ensure long-term protection. Data to support future decisions regarding the ideal timing of a potential booster dose and its subsequent immunogenicity are now urgently required.
Our Aim is to assess if a YF booster dose is required for children who received a single dose of YF vaccination in infancy and if so, at what age this booster dose might be most effective to administer.
We will enrol three well characterised cohorts of children aged between 15 months and 8 years of age with available data on primary immune response to YF vaccination to determine ideal timing for a booster and examine underlying innate and cellular immune responses related to sero-protection.
|
| 30/04/2021 |
£2,965,791 |
|
MICROPHARM LIMITED |
The project will be directed by MicroPharm and will include contributions by scientists at the Liverpool School of Tropical Medicine. It is in direct response to the WHO's stated aim of reducing the mortality and morbidity of snake envenoming.
The aim of the project is to re-establish supplies of Fav-Afrique in its current format as an equine F(ab’)2 based antivenom suitable for the treatment of Category 1 venomous African snakes. Sanofi-Pasteur will continue to supply large pools of plasma from horses immunised with venoms from Echis, Bitis, Naja or Dendroaspis species respectively. The manufacturing procedures will be modernised and simplified to increase yield and decrease cost. Initial supplies will be available for clinical use in Africa by 2023.
|
| 30/04/2021 |
£59,260 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
LSTM is submitting an application for salary supplements in connection with two roles at MLW:
Director of MLW
Deputy Director
Total Number of Current Applications in progress for LMICSS from LSTM for all programmes: 1
Total Number of Current Applications in process for LMICSS to be held at MLW: 1 (comprising 2 nominees)
|
| 30/04/2021 |
£34,237 |
|
UNIVERSITY COLLEGE LONDON |
UCL currently has one (this) application in progress, to be held at UCL as the administering organisation
|
| 30/04/2021 |
£59,222 |
|
ANACOR PHARMACEUTICALS INC. |
There is significant need for new treatments for Chagas disease. The disease is caused by the parasite Trypanosoma cruzi, and the disease can be spread by insect vectors, blood transfusions and from infected mothers to their newborn children. Between 10 and 20 million people, mostly in Central and South America are infected with the parasite and the disease results in over 10,000 annual deaths. Chagas disease kills more people in Latin America than any other parasitic disease, including malaria. Increasing numbers of cases are also being documented outside the normal high transmission areas, including in the U.S. and Europe. Although in use for more than four decades, the two drugs available to treat Chagas--benznidazole and nifurtimox-- require a long course of therapy (60-90 days), have serious safety concerns (20-30% side effects result in treatment discontinuation), fail to cure in a significant number of patients (a result of natural resistance of some isolates to current drugs), and are contraindicated in pregnancy. Thus, there is a critical need for new drugs that address these significant shortcomings of existing therapeutics. Oxaboroles—pioneered by Anacor Pharmaceuticals--have emerged in preliminary studies as a class that can potentially fill this important need. The Wellcome Trust is funding a dedicated drug discovery effort at Anacor, partnered with the disease expertise in the laboratory of Professor Rick Tarleton of the University of Georgia. The objective of the project is to deliver a new drug candidate ready to enter clinical trials by 2016. |
| 20/04/2021 |
£1,341,438 |
|
UNIVERSITY COLLEGE LONDON |
Effective adaptive immunity is dependent on T-cell development in the thymus. The thymus undergoes age-related involution, leading to reduced T-cell output. This is suggested to compromise T-cell immunity and increase risk of disease severity in the elderly. However, it was unknown whether enhancing thymic function would ameliorate the immune defects observed in the elderly.
Transcriptional assessment of thymic epithelial cells (TECs) through development facilitated the generation of genetically altered mouse models in which thymic involution was prevented or reversed. Both models restored normal peripheral T cell populations, and, critically, enhanced the survival of aging hosts when challenged with Toxoplasma gondii. Therefore, TEC-mediated restoration of thymic function improves immunity with age.
Based on these findings, I propose to identify progenitor-successor relationships within adult TECs that maintain the adult thymus and identify age-associated alterations in these populations that could contribute to thymic atrophy. Moreover, I will investigate the mechanisms by which restored thymus function improves immunity in aged mice. Collectively, my proposal will provide an important understanding of how TECs shape immune responses in the elderly, and inform TEC-mediated approaches of thymic regeneration to aid prevention of the degeneration of T-cell immunity that accompanies aging.
|
| 20/04/2021 |
£1,376,391 |
|
KING'S COLLEGE LONDON |
Why are all brains different from each other and where does this variability come from? A plethora of animal experiments demonstrate the importance of environmental and genetic influence in creating behavioural variation. A third factor named stochastic developmental processes is less established. Despite recent advancements, a systematic review of variation in brain wiring, its origins, and behavioural consequences is still lacking.
My main research goal is to understand the contributions of genetic, stochastic, and environmental factors to variation in brain wiring and behavioural individuality. Recently, I have shown that stochastic, non-heritable developmental processes can result in individually variable wiring diagrams that are associated with individual behavioural characteristics. This system provides a tractable genetic and neuronal model for individuality.
Based on this work, I hypothesize that (1) stochastic developmental processes are a general neuronal property affecting synaptic distributions, wiring and behaviour, and (2) that stochastic wiring differences affect several behaviours ranging from visual guided responses to circadian activity patterns. Within this framework, I aim to answer two key questions on the origins of individuality:1. Is circuit variability a general nervous system property and what are its origins? 2. Does circuit variability contribute to other visual and non-visual behavioural paradigms?
|
| 20/04/2021 |
£1,343,501 |
|
UNIVERSITY COLLEGE LONDON |
Robustness mechanisms are ubiquitous in biological systems where they act to ensure a stable outcome despite intrinsic (genetic) and extrinsic (environmental) variabilities. However, the underlying mechanisms are often unclear. In my proposed research, I will investigate the mechanistic basis of how systems deal with change in the context of cell migration during development, immune responses, and cancer invasion. Cell migration models I will use for my study include: the posterior lateral line primordium (pLLP) migration in development and macrophage recruitment during wound immune response in zebrafish, and invasion of cultured cancer cells.
The main goals of the proposed original project are: (1) Characterizing the molecular mechanisms and network architectural designs that enable robust adaptation during cell migration in a multicellular organism, (2) Analysing the requirement of regulated membrane trafficking switching during chemotactic adaptation, and (3) Quantitatively defining the role of dynamic buffering in breast cancer spreading.
To achieve these goals, an interdisciplinary approach will be taken, combining live imaging, genetics, biochemistry and phosphoproteomics. I will generate datasets bridging molecular, cellular, and tissue scales to obtain a systems level understanding of adaptive responses. This work will have broad implications for understanding chemotactic adaptation in development, physiology and disease.
|
| 20/04/2021 |
£1,578,744 |
|
UNIVERSITY OF CAMBRIDGE |
In order to survive, animals need to avoid predators and skillfully navigate the environment. These behaviors critically depend on the sense of vision. In mammals, two distinct systems process visual information: the evolutionarily ancient superior colliculus and the modern visual cortex. We will define their relative functions in two natural behaviors essential for survival: (1)innate defensive responses and (2)spatial navigation.
1)We will study the visual cortex's role in controlling innate defensive behaviors triggered by the superior colliculus. We will focus on the mouse postrhinal-cortex (POR), capitalizing on my discovery that the superior colliculus has, through POR, a dedicated cortical space from which it receives direct excitatory feedback.(Beltramo,Science,2020). We will test the hypothesis that POR, relaying contextual information about the estimated threatening nature of visual stimuli, controls collicular function's plasticity. By silencing distinct cortico-collicular projections, we will determine how the visual cortex shapes the flexibility of colliculus-mediated innate behaviors.
2)We will investigate the contributions of the two visual pathways in spatial navigation, studying how visual input is transformed into the spatial maps found in the entorhinal/hippocampal formation. Perturbing the activity of distinct visual streams, we will establish how the superior colliculus and visual cortex influence the internal maps that guide navigation.
|
| 20/04/2021 |
£1,350,129 |
|
UNIVERSITY OF CAMBRIDGE |
Pregnancy complications affect as many as one in four pregnancies, yet there remains a critical gap in our knowledge of their underlying aetiologies. As the maternal-foetal interface, the placenta is essential for healthy pregnancy, with poor function being strongly associated with pregnancy complications. However, there is little mechanistic understanding of the molecular events regulating placental development. My research programme will investigate mechanisms of epigenetic programming and gene regulation in early placental trophoblast and reveal how these underpin the development of a functional placenta. Specifically, I will test the hypothesis that epigenetic programming in placental trophoblast is critical for (1) setting up the gene regulatory landscapes in placental cell types and (2) directing appropriate differentiation during placentation. I will apply cutting-edge ultra-low input sequencing methodologies to characterise gene expression, epigenetic marks, transcription factor binding and 3D chromatin folding in multipotent trophoblast cells in mouse embryos. Using single-cell sequencing and histopathology, placental genomic regulation and function will be evaluated in knockout mouse models for epigenetic modifiers, including several histone and DNA methyltransferases. This research will be fundamental to our understanding of placental development and provide novel insights into how errors in epigenetic programming can lead to compromised placental function in pregnancy.
|
| 20/04/2021 |
£1,029,715 |
|
UNIVERSITY OF SHEFFIELD |
Cell division in epithelial sheets is crucial for tissue renewal, yet unchecked division leads to tissue dysplasia and ultimately cancer. The aim of this project is to discover how cell division is regulated in normal epithelial tissue and how it is perturbed by oncogenic mutations to disrupt tissue integrity. In previous work, I showed how activation of an oncogene, Ras, directly impacts cell division by controlling the shape, contractility and mechanics of single mitotic cells. I now ask how this finding plays out in a complex tissue environment. To do this, I will employ a multi-disciplinary approach, combining imaging and quantitative cell biology with biophysical techniques to study cell division mechanics in normal epithelial monolayers and Ras-mutant pancreatic cancer tumoroids. I will ask how the actin cytoskeleton is regulated during epithelial cell division to permit dynamic cell shape changes while maintaining cell-cell adhesion and preserving barrier function. I will determine how k-Ras activation perturbs this, identifying key mechanistic links between Ras/ERK-dependent transcription and morphological phenotypes. Finally, I will address how these Ras-induced changes to cell division alter the growth and organization of 3D tissue structures in pancreatic cancer.
|
| 20/04/2021 |
£1,036,024 |
|
UNIVERSITY OF YORK |
Several pathogens, such as African trypanosomes or malaria parasites, undergo antigenic variation in order to evade the host immune response. A key feature for successful antigenic variation is the ability to express a single antigen at a time, in other words monogenic-expression. Trypanosomes express a single variant-surface-glycoprotein (VSG) from thousands of possible genes, a fine example of extreme biology.
Single gene choice remains one of the biggest mysteries of eukaryotic gene expression and the machinery responsible remained elusive in every organism. I recently identified a protein complex that sustains VSG-monogenic expression and is responsible for the spatial integration of the single active-VSG with an RNA-processing centre. I will study the function of this novel protein complex, identify other relevant factors and use VSGs as a model-system to study how nuclear compartments can be organised to enhance gene expression. To pursue these questions, I will apply a wide range of genetic and biochemical approaches that include proximity labelling coupled with mass-spectrometry, next-generation-sequencing, CryoEM, super-resolution and live microscopy.
The mechanistic understanding of how monogenic-expression is initiated and maintained is of great value as it is critical for sustaining infections by trypanosomes, as well as several other pathogens that undergo antigenic variation.
|
| 20/04/2021 |
£1,056,320 |
|
UNIVERSITY OF OXFORD |
A novel energy conserving mechanism, myosin super relaxation (SRX) has recently been discovered in cardiac muscle. SRX is a structural state of myosin, where myosin heads are folded away from actin, preventing force producing actomyosin interactions and contraction.
Little is known about the key regulatory systems that govern the formation of myosin SRX in cardiac biology. It is evident that phosphorylation of key sarcomeric proteins play an important role, but the cellular signalling that underlies these changes is poorly defined.
I aim to define these cellular signalling pathways and how they control sarcomeric protein phosphorylation. I will define how far reaching myosin SRX destabilisation is as a disease causing mechanism. To do this I will employ CRISPR/Cas-9 technologies to develop stem cell models of hypertrophic cardiomyopathy, HCM, a debilitating genetic condition that affects 1 in 500 people. I will augment these human stem cell models with human and murine tissue samples to define SRX abundance and regulation in acquired cardiovascular conditions including atrial fibrillation, heart failure, hypertension, myocardial infarction, and ageing.
In doing so I will define sub-sets of disease pathomechanisms in inherited and acquired cardiomyopathies to allow precision targeting of therapeutics, which will bring significant benefit to patients.
|
| 20/04/2021 |
£917,024 |
|
UNIVERSITY OF OXFORD |
Changing diets could lead to substantial benefits both in terms of health and environmental impact, with the urgent need to change food consumption being increasingly recognised. Drawing on evidence from interventions targeting unhealthy diets could accelerate progress towards more sustainable diets by quickly narrowing down the choice of interventions to improve food selections. However, we need to ascertain whether key differences between healthier vs. more sustainable foods (including social norms, preferences and knowledge) impact on intervention effectiveness, and/or contribute to inequalities in responsiveness to these interventions.
This programme of work will examine differences in the impact of interventions targeting (a) healthier vs. less healthy foods and (b) more vs. less sustainable foods, and whether impact differs by socioeconomic position (SEP). It will identify key moderators and mediators of the impact of interventions, and the extent to which these contribute to any differential impact by intervention target or SEP.
The programme comprises (1) a conceptual review; (2) experimental studies; (3) field studies in worksite cafeterias and in stores; (4) secondary analyses of purchasing data (e.g. from supermarkets). Identifying the moderators and mediators of dietary interventions will help prioritise the most promising interventions for sustainable and equitable diets.
|
| 20/04/2021 |
£580,111 |
|
BABRAHAM INSTITUTE |
The protein tyrosine phosphatases (PTPs) are important regulators of cell behaviour and function with kinases to control phosphotyrosine levels. Phosphatases are often seen as an off-switch in signalling, however several PTPs promote downstream signalling. The PTPs are known to be regulated by reactive oxygen species (ROS), which function as second messengers in numerous processes such as growth factor signalling and wound healing by targeting protein cysteine residues. After discovering direct substrates for a receptor-type PTP, we now find that its interactions with these proteins are surprisingly redox-sensitive. I hypothesise that PTPs function as redox-switchable scaffolds, promoting protein complex formation in response to ROS in cells. I will combine biochemistry, cell biology and optogenetic approaches with quantitative mass spectrometry to test this hypothesis. To this end, I will define the molecular details of a PTP redox complex, the signalling pathways that promote cellular PTP oxidation and the sufficiency of PTP oxidation to trigger cell signalling events. The results will shed light on a new signalling mechanism and could yield alternative approaches to therapeutically target the PTPs in numerous disease settings.
|
| 20/04/2021 |
£589,779 |
|
UNIVERSITY OF YORK |
Bacteria are highly adaptable and can rapidly exchange genes in response to environmental pressures. Gene transfer agents (GTAs) are an understudied mechanism of genetic exchange that package the entire bacterial genome into bacteriophage-like particles. Indeed, phenomenally high frequencies of GTA gene transfer have been reported in the natural environment. Indiscriminate transfer of genes could clearly have a major impact on bacterial evolution, fitness and antimicrobial resistance. Over the past decade, several pleiotropic regulators have been shown to indirectly influence GTA production and I recently discovered the missing link, GafA, that couples GTA production to host regulatory pathways. GafA homologues were found in numerous species and those homologues I tested also enhanced GTA production in their respective hosts. In this proposal I aim to define the mechanism of action for GafA in the model GTA host, including its interaction with the enigmatic RNA polymerase Omega subunit, and to explore the impact of GafA/GTAs in wider range of bacterial species. I will also study the relationship between GTA production and adaptive immunity to bacteriophage infection. Understanding the role and prevalence of GTAs is essential to assess their impact on issues such as AMR and novel interventions to slow its spread.
|
| 20/04/2021 |
£1,069,515 |
|
UNIVERSITY OF CAMBRIDGE |
Whipworms infect hundreds of millions of people causing trichuriasis, a major neglected disease. Whipworms are large metazoan parasites that inhabit a multi-intracellular niche within their host caecal epithelia, where they manipulate mucosal physiology and inflammation through interactions with the intestinal epithelial cells and stem cell niche. These interactions enable chronic infections where whipworms are tolerated for years; but at a mechanistic level, how they operate is not understood. My research aims to define these interactions and bring a mechanistic understanding to how they underpin whipworm invasion, colonisation and persistence in their mucosal niche. This work will build upon a novel model I developed using caecal organoids (termed caecaloids), the first to reproduce whipworm infections in vitro, to address two fundamental aims. First, to determine how whipworms invade and colonise intestinal epithelia using imaging and transcriptomic analyses of infected caecaloids. Second, to define how whipworms impact stem cell niche remodelling to promote their persistence using microscopy, FACS and transcriptomics of infected caecaloids and chronically-infected mice. This research will transform our understanding of the whipworm mucosal niche potentially yielding new targets for anti-parasitic therapies, and provide novel insights into how the intestinal epithelia repairs damage with relevant application toward intestinal inflammatory diseases.
|
| 20/04/2021 |
£106,648 |
|
WELLCOME SANGER INSTITUTE |
Whipworms infect hundreds of millions of people causing trichuriasis, a major neglected disease. Whipworms are large metazoan parasites that inhabit a multi-intracellular niche within their host caecal epithelia, where they manipulate mucosal physiology and inflammation through interactions with the intestinal epithelial cells and stem cell niche. These interactions enable chronic infections where whipworms are tolerated for years; but at a mechanistic level, how they operate is not understood. My research aims to define these interactions and bring a mechanistic understanding to how they underpin whipworm invasion, colonisation and persistence in their mucosal niche. This work will build upon a novel model I developed using caecal organoids (termed caecaloids), the first to reproduce whipworm infections in vitro, to address two fundamental aims. First, to determine how whipworms invade and colonise intestinal epithelia using imaging and transcriptomic analyses of infected caecaloids. Second, to define how whipworms impact stem cell niche remodelling to promote their persistence using microscopy, FACS and transcriptomics of infected caecaloids and chronically-infected mice. This research will transform our understanding of the whipworm mucosal niche potentially yielding new targets for anti-parasitic therapies, and provide novel insights into how the intestinal epithelia repairs damage with relevant application toward intestinal inflammatory diseases.
|
| 20/04/2021 |
£691,880 |
|
UNIVERSITY OF GLASGOW |
The activity of viral entry machinery is tightly regulated to ensure successful infection. We have discovered that the hepatitis C virus entry glycoproteins, E1 and E2 (E1E2), possess a hitherto unrecognised regulatory mechanism that controls virus entry and neutralising antibody (nAb) resistance. This is dependent on disorder and dynamics in the peptide tail of E2. We call this the entropic safety catch.
This is important for three reasons: i) it is a significant advance in our understanding of the molecular mechanics of E1E2 ii) rational immunogen design remains hampered by a poor functional understanding of E1E2; our discovery may inform ongoing HCV vaccinology iii) it establishes that viruses can harness structural disorder to regulate virus entry, nAb resistance and protein-protein interactions.
We will ask how the entropic safety catch functions during infection; examining its adaptive tuning in response to emergent nAbs, and investigating its evolutionary origins. We will use biophysical and structural analysis to determine the molecular basis that allows the safety catch to control entry. This work will uncover fundamental mechanisms by which dynamics and disorder govern protein function. This will be relevant to HCV, and likely other important pathogens, having implications throughout the viral proteome and beyond.
|
| 13/04/2021 |
£1,660,717 |
|
UNIVERSITY OF CAMBRIDGE |
Transmissible cancers are malignant somatic cell lineages that spread between individuals by the allogeneic transfer of living cancer cells. These cancers, whose three known instances in mammals affect dogs and Tasmanian devils, provide a unique perspective on cancer evolution and host interaction. I will investigate this by deeply sequencing whole genomes from 1100 tumours selected from across each cancer’s range, together with matched bulk RNA sequencing and targeted single-cell RNA sequencing. Time-resolved phylogenetic trees for each clone will be annotated with mutation and gene expression data, and the source and consequence of mutation explored. Host cell contribution to the tumour microenvironment, and its variation across hundreds of tumours, will be assessed using allelic and cell-type deconvolution. Combining genetic, microenvironment composition and clinical data, I will explain how the immunological interface between allogeneic cancer and host varies between individuals, and how this interaction controls the outcome of disease. The inherent heterogeneity and short lifespans of most cancers may obscure their underlying biological patterns. By capturing variation in hundreds of clonally derived tumours inhabiting different hosts, I seek to deeply probe the mutational, evolutionary and immunological principles of cancer.
|
| 13/04/2021 |
£1,422,364 |
|
WELLCOME TRUST SANGER INSTITUTE |
Transmissible cancers are malignant somatic cell lineages that spread between individuals by the allogeneic transfer of living cancer cells. These cancers, whose three known instances in mammals affect dogs and Tasmanian devils, provide a unique perspective on cancer evolution and host interaction. I will investigate this by deeply sequencing whole genomes from 1100 tumours selected from across each cancer’s range, together with matched bulk RNA sequencing and targeted single-cell RNA sequencing. Time-resolved phylogenetic trees for each clone will be annotated with mutation and gene expression data, and the source and consequence of mutation explored. Host cell contribution to the tumour microenvironment, and its variation across hundreds of tumours, will be assessed using allelic and cell-type deconvolution. Combining genetic, microenvironment composition and clinical data, I will explain how the immunological interface between allogeneic cancer and host varies between individuals, and how this interaction controls the outcome of disease. The inherent heterogeneity and short lifespans of most cancers may obscure their underlying biological patterns. By capturing variation in hundreds of clonally derived tumours inhabiting different hosts, I seek to deeply probe the mutational, evolutionary and immunological principles of cancer.
|
| 13/04/2021 |
£2,023,433 |
|
THE FRANCIS CRICK INSTITUTE |
How epigenetic pathways regulate development and disease remains a major question in human biology. A remarkable paradigm for understanding epigenetic mechanisms is X-chromosome inactivation, the silencing of one X chromosome in females (XX) that equalises X-dosage with males (XY). X-inactivation in eutherian (placental) mammals is mediated by the non-coding RNA (ncRNA) Xist. How Xist silences the X chromosome, and how expression of Xist is regulated, remain poorly understood. Marsupials diverged from eutherian (placental) mammals 160 million years ago, and exhibit distinctive developmental features that make them ideal for studying development and disease. Using our colony of opossums, we identified RSX and XSR, the marsupial equivalents of Xist and Tsix, providing a comparative system for understanding RNA-mediated chromatin remodelling. In this proposal, we will deploy the opossum model system to identify deeply conserved epigenetic mechanisms regulating mammalian X-inactivation and X-chromosome reactivation, and to elucidate how they interface with global epigenomic changes in the early embryo and germline. Our datasets will shed light on the evolution of mammalian lineage specification, pluripotency, imprinting and germline development. We will apply genome editing to marsupials for the first time, accelerating discovery in other research fields, including cancer biology, neurobiology and infectious disease.
|
| 13/04/2021 |
£2,141,297 |
|
UNIVERSITY OF LEEDS |
Immune receptor turnover and subcellular localisation are regulated by attachment of ubiquitin, which controls receptor internalisation and endosomal-lysosomal degradation. Receptor ubiquitylation is fine-tuned by ubiquitin-processing enzymes, ligands and adaptor proteins, which regulate immune signalling output in a spatio-temporal manner. We identified a new signalling complex called BRISC, which is a deubiquitylase (DUB) and required for recycling of interferon and Toll-like receptors (TLRs). BRISC partners with adaptor proteins SHMT2 and EPS15 to regulate interferon and TLR signalling, although the role for each adaptor is unclear.
My laboratory uncovered a fascinating molecular mechanism by which vitamin B6 regulates BRISC activity, thus revealing a new example of metabolic control of immune signalling. Here, we aim to uncover how BRISC activity is controlled and directed to immune receptors. Using an integrated structural biology approach we aim to understand how BRISC partners with new adaptor proteins to perform its functions. Using BRISC-selective chemical probes in cell-based assays we aim to ascertain BRISC’s role in elevated inflammation in normal and disease conditions. These new tool compounds represent an exciting opportunity to better understand BRISC activity, receptor degradation and immune signalling functions, and how DUBs can be exploited as therapeutic targets for autoimmune diseases.
|
| 13/04/2021 |
£1,378,334 |
|
UNIVERSITY OF LIVERPOOL |
Severe brain swelling leads to death in cerebral malaria (CM) but detection requires MRI. Almost no children with CM have access to MRI, therefore an alternative is required to identify patients for intervention. Optical coherence tomography (OCT) can detect raised intracranial pressure and ischaemic injury by imaging the optic nerve head, and retina respectively. We aim to study OCT as a method to identify patients at risk of death from brain swelling and disability from ischaemia; and to develop a low-cost OCT device with integrated AI image analysis.
We will conduct a controlled cohort study of 120 children with CM in Malawi to compare OCT to MRI in detecting severe brain swelling. We will follow them for a year with neuro-developmental assessments to investigate retinal OCT in predicting neurological deficits; and correlate retinal and cerebral atrophy. We will also assess OCT in quantifying raised intracranial pressure in non-malarial coma, and retinal haemorrhages for predicting worsening of brain swelling in CM.
We will use fibreoptic and micro-electromechanical advances to develop handheld OCT design and make a low-cost, robust device suitable for malaria-endemic settings. We will develop AI techniques to automatically segment and quantify optic nerve head swelling and intraretinal hyper-reflectivity (ischaemia).
|
| 13/04/2021 |
£1,671,997 |
|
UNIVERSITY OF LIVERPOOL |
Invasive non-typhoidal Salmonella disease (iNTS) has emerged as a major killer in sub-Saharan Africa, responsible for ~500,000 deaths since 20091. The disease primarily affects people who are immunocompromised by HIV, malaria, anaemia or malnourishment2, and has a high case-fatality-rate (14.5%1).
In Africa, iNTS is caused by one clade of S.Typhimurium and two clades of S.Enteritidis3–5. Despite many decades of research on gene function and infection biology of Salmonella, the pathoadaptive mutations that have driven the emergence of African clades are unknown. Such knowledge is vital to decipher iNTS pathogenesis and develop control strategies in the future.
To address this knowledge gap, I will decipher the mechanisms that African and gastroenteritis-associated Salmonella employ to survive and replicate within a core niche, human phagocytic cells. I will achieve this using our powerful combination of comparative genomics and transcriptomics, plus new innovations in experimental evolution and genome-wide, high-throughput fitness assays.
By understanding the molecular basis of the intra-macrophage lifestyle, I will determine whether these neglected African-Salmonella pathovariants have used common or divergent approaches to combat the antibacterial properties of human cells.
My Research Question is:
How do African Salmonella pathovariants survive and replicate so effectively in human macrophages?
|
| 13/04/2021 |
£1,871,095 |
|
UNIVERSITY COLLEGE LONDON |
The tight regulation of mitochondrial transport and anchoring in brain cells is essential for providing ATP at the correct spatial location to power neural function and computation, and for providing calcium buffering at sites of calcium entry or release. Using a multidisciplinary approach, combining imaging, biochemistry, electrophysiology and mouse transgenics we will determine the molecular and cellular mechanisms by which the cytoskeleton coordinates mitochondrial transport, localisation and remodelling in neurons and glial cells. The influence of this regulation on the development and maintenance of neuronal connectivity, function, plasticity and pathology will then be determined in vitro and in vivo. The main objectives are to define (i) the role of Miro proteins as central coordinators of the activity-dependent transport, positioning and remodelling of mitochondria through the microtubule, actin and septin cytoskeletons; (ii) how mitochondrial position and calcium buffering in neurons and glia impacts the formation, maintenance and plasticity of synapses; and (iii) the mechanisms by which disrupted mitochondrial dynamics lead to neuronal pathology and neurodegeneration. Our proposal will provide unique insight into how mitochondrial networks in neurons and astrocytes contribute to regulating the operation and plasticity of synapses and how their disruption leads to neuronal pathology in brain diseases.
|
| 13/04/2021 |
£2,760,782 |
|
UNIVERSITY OF EDINBURGH |
All living systems – cells or organisms – operate in and must adapt to constantly changing environments. RNA transcription, processing and assembly with protein complexes form the core of the gene expression system, but many key features remain unclear. At times, very substantial changes take place; for example, in response to sudden environmental changes, following infection or during developmental progression. To address unresolved questions in RNA biology, we developed biochemical techniques to identify key, relevant RNA-protein, RNA-RNA and protein-protein interactions. These will be improved and applied in the proposed work, supported by bioinformatics. RNA systems are highly conserved in evolution, so techniques developed in yeast can be adapted for human cells and applied to understand disease. RNA biology in a cellular context is subject to dynamic changes. Kinetic analyses will therefore be applied, particularly during changes in cell state.
Specific topics:
1: How is the nascent RNA linked to transcription termination and RNA processing
2: How does RNA metabolism respond to environmental stress?
3: How is host RNA metabolism remodelled during Coronavirus infection?
4: What are the roles of ncRNAs in neuronal development?
The insights generated, and the experimental and bioinformatics techniques developed, will underpin future work by many groups.
|
| 13/04/2021 |
£2,500,000 |
|
UNIVERSITY OF EDINBURGH |
The character of a cell is determined during differentiation by selective gene activation and silencing. In addition to high level decisions about which genes are on or off, it is now clear that levels of transcription in each differentiated cell must be precisely calibrated. This proposal seeks a comprehensive understanding of two proteins, SALL4 and MeCP2, that optimise transcription programmes in order to stabilise cellular states. Despite very different biological outputs, SALL4 and MeCP2 share striking similarities. Both are DNA binding proteins that recognise short, frequent DNA sequence motifs; both interact with histone deacetylase-containing corepressor complexes to modulate expression of many genes; and both are of proven biological and biomedical importance. Our intention is to study these proteins in parallel using a molecular genetic approach in order to elucidate fundamental mechanisms that consolidate cell identity before and after differentiation. To explore the generality of this form of transcriptional control, we will screen for novel transcription modulators that also interpret regionally variable genomic features by sensing short DNA sequence motifs. Our findings will have implications for regenerative medicine and reveal the molecular basis of diseases caused by deficiency of these and similar proteins, including Rett syndrome, Okihiro syndrome and cancer.
|
| 13/04/2021 |
£2,904,144 |
|
UNIVERSITY OF OXFORD |
Substandard and falsified (SF) antimicrobials are a massive but underappreciated global health challenge in great need of innovative research to inform interventions. We will build on our collective pioneering research, to construct an innovative, multidisciplinary research hub that will improve understanding and inform global policy and action. Leading specialists investigating illegal wildlife trade, forensic genomics and chemistry, social network analysis and modelling, will work together to answer two main aims:
1. How can innovative forensic tools be used to identify sources and trade routes?
How can novel genomic (‘pharmabiome’), chemical and isotopic analysis with social network techniques be used to characterise the epidemiology of SF antimicrobials to inform policy and action to improve our global pharmaceutical supply quality? We will conduct high-throughput sequencing and novel chemical analysis of falsified and genuine antimicrobials to determine their comparative pharmabiome/chemical spectra, followed by social network analysis of origins and trade routes.
2. What are the public health impacts of SF antimicrobials?
What are the modelled impacts of SF antimicrobials on patient outcome, global public health, especially engendering antimicrobial resistance and how can these be minimised? Using a One Health approach, which pathogen-antimicrobial pairs are at greatest risk of SF antimicrobials?
|
| 13/04/2021 |
£1,151,174 |
|
MRC LABORATORY OF MOLECULAR BIOLOGY |
Our cytosol could provide ample resources for invasive bacteria, yet is maintained in a remarkably sterile state. We recently discovered that cells deposit polyvalent protein arrays at bacterial surfaces to convert cytosol-invading bacteria into anti-bacterial signalling platforms. The deposition of M1-linked ubiquitin chains by the E3 ubiquitin ligase LUBAC recruits and activates IKK complexes, resulting in NF-kB signalling, while the deposition of guanylate-binding proteins (GBPs) recruits and is required for the LPS-dependent activation of Caspase-4, resulting in pyroptotic cell death and the release of IL-18. Here, we will explore this novel principle of cell-autonomous immunity to better understand cytosolic anti-bacterial defence.
We will therefore investigate
The origin and function of ubiquitin-dependent signalling platforms, with special emphasis on the ubiquitylation of bacterial lipopolysaccharide (LPS) by the E3 ubiquitin ligase RNF213, which represents the unprecedented ubiquitylation of a non-proteinaceous substrate
The origin and function of the GBP-dependent signalling platform, specifically its assembly mechanism and how it promotes activation of caspase-4 and other downstream effectors.
|
| 13/04/2021 |
£2,444,805 |
|
UNIVERSITY OF CAMBRIDGE |
Children with Still's disease, the paradigm of autoinflammation-cum-autoimmunity, are predisposed to developing a cytokine storm with excessive activation of T lymphocytes upon viral infection. Loss-of-function of FAMIN is the sole known cause for monogenic Still's disease. We de-orphaned FAMIN as an unprecedented purine nucleoside enzyme that combines ADA-, PNP- and MTAP-like activities with adenosine phosphorolysis – challenging fundamental principles of purine metabolism. Dendritic cells with absent FAMIN activity prime for excess antigen-specific cytotoxicity, IFNgamma secretion, and T cell expansion, resulting in exaggerated virus-specific T cell responses and immunopathology. Enhanced priming is already manifest with hypomorphic FAMIN-I254V, for which ~6.3% of mankind is homozygous, and which predisposes for Crohn's disease and leprosy. Here we will address FAMIN biology from virtually atomic to organismal resolution: We will explore how FAMIN operates in a cell, and how it controls energy metabolism, ascertaining redox and pH homeostasis. We will investigate how FAMIN in dendritic cells potently restrains T cell priming, and whether the FAMIN-coordinated biochemical mechanisms are involved in often fatal virus-induced cytokine release syndromes. This work will reveal an ancient biochemical mechanism that potently controls adaptive immune activation at a very fundamental level, providing insight into immunity to pathogens, autoinflammation and autoimmunity.
|
| 13/04/2021 |
£1,088,447 |
|
UNIVERSITY OF DUNDEE |
Protein phosphorylation regulates protein function in a switch-like manner. Although each phosphorylation site only exists in two states (on/off), the frequency of switching between these states can vary dramatically. Individual molecules that flash on and off rapidly can possess unique signalling properties, but these are difficult to study because dynamic information remains hidden from current analytical methods. We will use heavy-[18O2]-ATP and mass spectrometry to quantify, for the first time, the rate that individual substrates are phosphorylated and dephosphorylated over time. We will measure this globally and characterise different complexes during mitosis that rely on phosphorylation-dephosphorylation cycles to function correctly (BUBc/RepoMan/Centralspindlin/COMA). We will study how these cycles control signal-switching and protein binding-release events, which we predict are needed to order mitotic progression, generate gradients of activity and/or assemble protein complexes. These concepts will be tested with purified components, mathematical modelling and quantitative microscopy. Although we use mitosis as a model system, this work has far-reaching implications. If binary phosphorylation events generate more complex outputs by varying their on/off rates, then any pathway could use this property to transmit information differently. It is therefore crucial to investigate this phenomenon because these rates could be modulated to drive both signalling and disease.
|
| 13/04/2021 |
£2,337,836 |
|
UNIVERSITY OF LEICESTER |
Eukaryotic gene regulation depends upon a plethora of multi-protein complexes that both control the organisation of chromatin and establish specific patterns of post-translational modifications of histone tails. These histone marks are key to the processes of gene regulation. Deciphering the roles and mechanisms of the complexes that regulate chromatin is one of greatest challenges in understanding how genome activity is controlled.
We aim to understand the roles and mechanism of action of a family of essential, non-redundant histone deacetylase complexes that control chromatin accessibility across the genome. These HDAC complexes share a common catalytic engine, but contain very different accessory proteins and have diverse oligomeric states. Although these are essential complexes, conserved from nematodes to man, we have only a very limited understanding of their mechanism of action.
We will take two approaches to determine the mechanisms through which these complexes engage with their chromatin substrates and to understand how this determines their biological function.
We will use structural techniques to determine the architectures of three exemplar complexes in complex with chromatin. We will use genomic and proteomic techniques to explore how these structures mediate their distinct biological activities.
|
| 13/04/2021 |
£1,564,396 |
|
IMPERIAL COLLEGE LONDON |
The TPL-2/ABIN-2/NF-kappaB1 p105 complex is essential for transmitting Toll-like receptor (TLR) signals, turning on inflammatory responses via TPL-2 kinase activation of ERK1/2 and p38alpha MAP kinases. This proposal will investigate the roles in innate immunity of the newly discovered functions of the TPL-2 complex in stimulating phagosome maturation in macrophages independently of MAP kinase activation.
1) TPL-2 and ABIN-2 regulation of phagosome function in professional phagocytes.
Mechanisms of TPL-2 and ABIN-2 regulation of phagosome maturation in mouse and human macrophages will be established.
Roles of TPL-2 and ABIN-2 regulation of phagosome function in mouse neutrophils and dendritic cells will be investigated.
2) TPL-2 and ABIN-2 regulation of innate immune responses to pathogenic bacteria.
Roles of TPL-2 and ABIN-2 regulation of phagosome function in mouse immune responses to Staphylococcus aureus will be determined.
3) TPL-2 induction of phagosome maturation in inflammatory bowel disease (IBD).
The human MAP3K8 gene encoding TPL-2 is linked genetically to the development of IBD, an auto-inflammatory disease that involves an abnormal mucosal immune response to intestinal bacteria. The role of TPL-2 regulation of phagosome function in gut inflammation will be investigated, using human monocyte-derived macrophages from IBD patients/control individuals, and the Citrobacter rodentium mouse model of colitis.
|
| 13/04/2021 |
£1,182,524 |
|
MRC LABORATORY OF MOLECULAR BIOLOGY |
To sustain life, cells must first duplicate their genome and then segregate both copies into two daughter cells at division. This requires regulation. In eukaryotes, the timing of DNA replication, segregation and cytokinesis are coordinated by a cell cycle clock, which marks time through the rise and sudden fall in the activity of a conserved set of CDK-Cyclins. Interestingly, the archaeon Sulfolobus acidocaldarius possesses a cell division cycle like ours, with distinct phases of DNA replication and cell division separated by gap phases, while lacking obvious homologues of CDK-Cyclins. Since Sulfolobus and eukaryotes are thought to share a common ancestor ( > 1,000,000,000 years ago), and use similar machinery to fire origins and to complete cell abscission, this suggests that cell cycle regulation predates eukaryotes and the evolution of CDK-Cyclins. Building on our recent discoveries, in this proposal we aim to test this hypothesis by studying the role and regulation of proteasome-mediated protein degradation in resetting the Sulfolobus cell cycle. Through this work we expect to identify core common regulatory principles of cell cycle control and to identify cell cycle control machinery that has been conserved from archaea to eukaryotes - shedding new light on the origins of the eukaryotic cell cycle.
|
| 13/04/2021 |
£2,864,125 |
|
UNIVERSITY COLLEGE LONDON |
Higher cognitive functions by which we learn to understand our environment and behave flexibly within it rely on the construction, from sequential experience, of a coherent representation of our situation (aka an internal ‘model’ or ‘cognitive map’). I aim to understand the neural basis of his process via precise mathematical models that directly link low-level neuronal mechanisms to behaviour in prediction, planning, generalisation and memory. This project involves convergent computational and experimental work in mice and humans at the neuronal, systems and behavioural levels, using methods ranging from multi-photon imaging in mice, through virtual reality and neural-level electrophysiology in mice and epilepsy patients, to functional brain imaging in healthy volunteers. Three streams of work address the integration of sensory information and actions into a common representation, how representations of states structured by transitions allow path integration and prediction for planning, and how such representations interface with encoding and retrieval during memory. Success will provide a quantitative understanding of how neural activity in medial temporal, retrosplenial and medial prefrontal brain areas support these complex cognitive functions, and a starting point for relating cognitive symptoms to dysfunction of this neural system in conditions such as posttraumatic stress disorder, schizophrenia and Alzheimers disease.
|
| 13/04/2021 |
£3,118,574 |
|
UNIVERSITY OF OXFORD |
Rehabilitation after brain damage such as stroke depends in part on the brain’s ability to reorganise. It is therefore critical that we understand how brain plasticity after injury happens, and how it can be influenced.
Clinical gains with rehabilitative training should depend not only on gains made during practice but also on offline consolidation, particularly during sleep. Therefore, if we can identify modifiable processes of consolidation, and amplify those to boost consolidation, that would be predicted to improve outcomes.
Using rodent models to understand the mechanisms of offline consolidation, we will identify (1) modifiable electrophysiological signals (reactivation, slow waves, or sleep spindles) that occur with consolidation and (2) imaging read-outs of plasticity, including myelin plasticity, associated with successful consolidation. These will be taken forward into human studies to develop non-invasive closed-loop devices to manipulate functional processes of consolidation during sleep after stroke. This will pave the way for future trials to test whether low-cost interventions that boost consolidation and plasticity can deliver lasting clinical improvements.
|
| 13/04/2021 |
£1,854,976 |
|
BABRAHAM INSTITUTE |
Microglia are the main immunological cell of the brain. These residential cells possess both immunological and neurodevelopmental functions, and have pathological roles during age- and injury-associated dementia. We recently characterised a new addition to the neuroimmunological landscape: transiently-resident brain CD4 T cells. Brain T cells are required to trigger the post-natal differentiation of foetal microglia, licensing their neurodevelopmental functions. Much remains unknown about potential further interactions between brain CD4 T cells and microglia. We have adapted cutting-edge technology to enable the parallel study of brain CD4 T cells and microglia. First, will use an adapted flow-based ProCode approach to unravel the molecular control over CD4 T cell entry to the brain and acquisition of the residential phenotype. Second, we have developed a novel genetic tool for competitive chimeric analysis, allowing us to study microglia niche-sensing and the role of interaction with CD4 T cells on microgliosis. Third, we will single cell lineage tracing to dissect the clonal evolution of microglia, and the influence of CD4 T cell interaction on microglial clonal dominance during ageing and following traumatic brain injury. The results will generate new insight into neuroimmune inter-cellular dynamics, and will validate new tools with broad applicability to biomedical sciences.
|
| 13/04/2021 |
£2,030,820 |
|
KING'S COLLEGE LONDON |
We wish to define the key interferon (IFN)-stimulated gene (ISG) effectors for three pathogenic human viruses – HIV-1, SARS-CoV-2 and influenza virus – and understand the molecular basis for antiviral function. Specific ISGs will be identified in unbiased gene silencing (siRNA/ CRISPRi) screens, some of which we have developed. For HIV-1, we will initially focus on the antiviral mechanisms and post-transcriptional regulation of post-entry inhibitors we have identified, human-TRIM5alpha and MX2, including the central roles played by ubiquitination and phosphorylation. Our discovery that NCOA7 suppresses endocytic virus infection (e.g., SARS-CoV-2) provides the opportunity to study how the endolysosomal system can be dysregulated, potentially through altering vacuolar-ATPase activity. New screens for ISGs targeting SARS-CoV-2 or influenza virus will be undertaken using wild-type viruses as well as engineered strains carrying disruptions in candidate IFN- or ISG-antagonists. We will explore the molecular mechanisms and regulatory pathways used by the most potent ISGs using multiple complementary experimental approaches, including proteomic and approved drug screens, and determine how these viruses escape or survive ISG action. By understanding the ISG effectors that can control these viruses, we will gain fresh insights into viral replication strategies, disease processes and host immunity, and inform future antiviral therapeutic development.
|
| 13/04/2021 |
£1,604,303 |
|
UNIVERSITY OF OXFORD |
The theme of the proposed research is our understanding of the replication and assembly of Influenza virus, from a structural imaging perspective. The transcription and replication of the influenza virus genome occurs in the nucleus and the structure of the isolated polymerase reveals at a molecular level key steps in transcription and replication. The genome of Influenza virus is composed of 8 RNA segments each bound to the viral RNA polymerase and multiple copies of N protein to form ribonucleoprotein complexes (vRNPs). Newly replicated vRNPs are transported out of the nucleus, where they are trafficked to the cell membrane and assemble to form new viruses budding out from the cell membrane. How the production and assembly of RNPs is coordinated in the nucleus and the details of how the vRNPs are transported out of the nucleus to the cell membrane is unknown.
By integrating structural, biochemical and cellular imaging, I aim to understand with atomic-level detail, vRNP production, nuclear export and viral assembly. This will be done using crystallography and single particle cryo-EM, combined with high resolution cellular EM and X-ray tomography, correlated with cryo- fluorescence imaging of infected cells to understand these key stages in the viral cycle.
|
| 13/04/2021 |
£663,703 |
|
UNIVERSITY COLLEGE LONDON |
Mental health problems are a leading cause of ill-health, with 1 billion experiencing mental health or substance use disorders worldwide. In the UK, anxiety and depression contributed 8% of the years lived with disability in 2017 and are associated with the second largest costs to society after dementia. This morbidity is accompanied by substantial suicide mortality, which rose by 10.8% in 2018, with even faster rises amongst young people.
Socio-economic disadvantage is strongly associated with mental ill-health. Austerity and immigration policies (i.e. systemic "shocks") implemented in the UK since 2010 may have increased mental health problems, particularly in disadvantaged populations, including people from ethnic minority backgrounds and may have been further exacerbated by the COVID-19 pandemic. However, causal evidence is missing.
Data typically available to evaluate such issues are observational (without random allocation) and population-wide (without controls), biasing straightforward estimation of causal effects. To advance causal inference of systemic shocks (policies, COVID-19) on population health outcomes, we will develop a generalisable statistical framework to overcome biases inherent to observational data. We will then apply this to evaluate the cumulative long-term causal impact of these shocks on mental health outcomes using longitudinal and spatial data, with particular focus on ethnic inequalities.
|
| 13/04/2021 |
£3,100,312 |
|
QUEEN'S UNIVERSITY BELFAST |
The following will extend our previous successful trials on impact of vision care on children's education and adult productivity:
CLEVER (Cognitive Level Enhancement through Vision Exams and Refraction): The first randomized trial to assess impact of eye care delivery (near and distance spectacles) on reducing rates of cognitive decline with aging, enrolling 874 participants > = 60 years in Hyderabad, India.
Piloting and delivery of STABLE (Slashing Two-wheeled Accidents By Leveraging Eyecare): The first randomized trial on the impact of vision care (distance spectacles) on traffic safety in a lower-middle income country (Vietnam), involving 875 young myopic motorcycle users.
Piloting and delivery of THRIFT (Transforming Households with Refraction and Innovative Financial Technology): A randomized trial on the impact of free reading glasses to support use of smartphone banking apps in Bangladesh among 400 elderly recipients of government Old Age Allowance payments.
ZEAL (Zimbabwe Eyecare And Learning) formative research on hyperopia and educational outcomes in Zimbabwe: . This work involving 2000 school-aged children in order to prepare for an eventual randomized trial will assess a novel, low cost vision test we have designed to screen for hyperopia, while examining the impact of uncorrected hyperopia on children’s current reading levels.
|
| 13/04/2021 |
£1,963,217 |
|
UNIVERSITY OF CAMBRIDGE |
In cells from every domain of life, RNA acts to communicate hereditary information, to regulate gene expression, and to support network control. Therefore, the fates of diverse RNA molecules, their biogenesis and lifetime, play a critical role in determining complex cellular behaviour. We propose to investigate the processes that govern RNA fate in bacteria. We hypothesise that defined ribonucleoprotein complexes act in key steps of cellular control, including co-transcriptional ribonucleoprotein folding and surveillance of transcripts during translation. We will test this experimentally and will also seek to understand how such complexes might be linked to sensing and responding to cellular status, including metabolic remodelling.
To this end, we will study the structure and function of key RNA-processing complexes in model bacterial species. Our targets include both stable protein-RNA complexes, which will be isolated and examined by high-resolution structural and functional analysis, and more transient assemblies, which will need to be investigated inside the cells to capture their information-rich physiological states. Our work will help to elaborate rules that define the lifetime and biological impact of RNA and its contribution to complex cellular phenotypes, including infectious virulence and antibiotic resistance of various bacterial species.
|
| 13/04/2021 |
£2,035,864 |
|
UNIVERSITY OF OXFORD |
This research project aims to define the key roles of newly defined T cell subsets, and how they integrate signals between innate and adaptive immune responses to optimise host defence. Recent work on immune responses in human tissues has revealed the complex landscape of immunity and emphasised the role of poorly-defined unconventional T cell subsets. In the past 5 years my lab has defined some of these roles including 3 main findings - a striking sensitivity to innate cues, relevant for initiation of protective responses to viruses, a wide palette of functions including a role for barrier repair, and the ability to co-ordinate adaptive responses following experimental vaccination. In this application I aim to take these findings much further, harnessing a set of novel tools and aiming: 1) To define the mechanisms underpinning the link between MAIT cells (as a paradigm for innate-like T cells) and vaccine responsiveness; 2) To understand the mechanisms by which such cells may impact on outcomes of severe viral infection. Overall this work is highly relevant to major health challenges such as SARS-CoV-2, influenza, viral hepatitis and microbial infection - and to the vaccines needed to combat these challenges.
|
| 04/04/2021 |
£7,645,274 |
|
UNIVERSITY OF EDINBURGH |
ECAT-I (Edinburgh Clinical Academic Track – Inclusive) will build on the research excellence and mentorship developed during the successful ECAT Wellcome Clinical PhD programmes.
Our key aims are to recruit and retain healthcare professionals from diverse backgrounds, to foster research that is inclusive, innovative and imaginative and to support a positive research culture. We will extend the scope of the programme to include our world-leading expertise in social science, health data science and informatics and provide trainees with new opportunities for international collaboration. We propose to:
Provide excellent doctoral training and post-doctoral support to an inclusive and diverse cadre of researchers across a range of healthcare professions, from hospital and community-based clinicians to allied healthcare professionals.
Build a positive research culture in and around our ECAT trainees promoting creativity, inclusivity and integrity.
Support trainees through the challenges of maintaining research momentum post-PhD and continue to take a highly pro-active and targeted mentorship approach, promoting clinical academic career progression of ECAT lecturers to Career Development Fellowships or substantive academic posts.
Extend our scientific ambition and align it to the research needs of diverse health professions building capacity in social science, data science and informatics and fostering international partnerships.
|
| 04/04/2021 |
£7,454,880 |
|
UNIVERSITY OF MANCHESTER |
Our programme will deliver excellent doctoral training for all healthcare professions. We are building a comprehensive inter-disciplinary programme across biomedical discovery and experimental medicine, reaching into our leading skills in physical sciences, engineering and computational/data science.
We have fully refreshed our partnership across the Universities of Leeds, Manchester, Newcastle and Sheffield; seven out of eight new directors are new. We have forged fresh partnership with the Alan Turing Institute, integrated our comprehensive ties with industry, and deepened our links to the Francis Crick Institute. We have coalesced features that define our best research culture and developed a thoughtful approach to equality, diversity and inclusion to ensure we capture talent, regardless of background or profession. The training will be valuable to fellows, supervisors and directors alike and set best-practice that will permeate our partner organisations. We are particularly proud of a new initiative with the Nuffield Foundation/STEM Learning to host 16-19 year olds as part of widening participation in higher education and scientific research.
This programme is important to us. We need a research-intensive workforce trained to the highest standards equipped to innovate for a surrounding population with some of the greatest health needs and reduced life expectancy in the UK.
|
| 04/04/2021 |
£7,390,835 |
|
UNIVERSITY OF LEICESTER |
Leicestershire’s social and demographic features, including the highest proportion of non-white residents (55%) in the UK, provide a unique and important opportunity to address key health issues across an ethnically and culturally diverse population, recently amplified by the pandemic.
We will capitalise on our strong track record of supporting clinical academics, with a focus on nurses, midwifes and allied health professionals, to grow the multidisciplinary research base in the inclusive management of long term conditions across healthcare systems and academic partners. Projects will focus on research-practice gaps in our areas of our research expertise to holistically improve patient care. Integration of basic scientists, social scientists, clinical academics, clinicians and data scientists to develop collaborative and strategic research programmes, combined with an outstanding training environment will provide an intellectually stimulating, methodologically rigorous and supportive environment for PhD fellows.
We will establish a sustainable integrated framework for healthcare professional academic career pathways to build capacity in clinical research leadership and create an inclusive research culture. Formal evaluation will ensure sustainability and best practice sharing. The long term goal is to increase the visibility and breadth of healthcare professional researchers and to transform holistic patient clinical care addressing health inequalities.
|
| 04/04/2021 |
£7,247,676 |
|
UNIVERSITY OF NOTTINGHAM |
This unique partnership between four Midlands-based universities (and regional NHS Trusts) builds an innovative multidisciplinary doctoral training centre for healthcare professionals focussing on Mental Health & Neurosciences (MH & N), which will foster a progressive and dynamic inclusive research culture to support and develop 25 outstanding PhD scholars.
Our holistic approach ensures that scholars’ needs are central to a supervisory system, supporting their research skills and career development, while ensuring wellbeing and quality of life. Every multidisciplinary cohort will have multiple opportunities to meet professionally and socially for peer support and companionship during their PhD.
Scholars can choose to research a ‘theme’ representing the lifespan (children, young people and perinatal MH; common MH; severe MH; dementia; and physical health comorbidity with MH), using specific bio-psycho-social ‘approaches’. Profession-specific mentors will ensure scholars remain connected to their primary professional groups. Scholars will leave our programme as well-rounded clinical-academics with high-levels of MH & N research acumen, and enhanced communication and leadership skills.
Ultimately, we aim to:
(1) develop the next generation of multidisciplinary clinical academics in MH & N
(2) conduct and disseminate world-leading research
(3) create and sustain an ambitious Midlands-based, internationally connected, compassionate clinical-academic ecosystem, collaborating to address the key contemporary mental health challenges.
|
| 04/04/2021 |
£9,285,942 |
|
UNIVERSITY OF LIVERPOOL |
This programme will deliver high quality, bespoke doctoral training for 20 clinical scientists across multiple scientific disciplines to address health priorities in the Global South. Through careful selection, high quality supervision and training, and access to excellent facilities in both the UK and globally, we will develop a cohort of trainees highly skilled at implementing research in Low and Middle Income Countries (LMICs).
Building on 13 years of successful PhD programme delivery for medical doctors and, more recently, veterinarians, we will broaden the programme to include clinical specialties for which we have established supervisory capacity and research excellence. We will provide new avenues in Global Health training opportunities for midwifes, with expansion to other clinical professions as demand and support develops. The programme will be supported by strong doctoral training frameworks in place at University of Liverpool & Liverpool School of Tropical Medicine. Equality, diversity and inclusivity will be embedded at all points of the programme consistent with the practice of the two institutions.
Success will be measured by progression of fellows into academic positions and Fellowships during and after completion of clinical training and their subsequent emergence as independent research leaders addressing health priorities in LMICs.
|
| 04/04/2021 |
£8,724,456 |
|
QUEEN MARY UNIVERSITY OF LONDON |
This doctoral programme for Primary Care Clinicians aims to increase research capacity across contemporary primary care to create future research leaders who will develop innovative and evidence based practice and policy to improve population health and support the NHS. Five clinical PhDs per year for five years (in total approximately 18 GPs and 7 other primary health care clinicians) will be hosted across 10 NIHR School for Primary Care (SPCR) members, building on our successful previous Wellcome PhD programme. The NIHR SPCR represents the leading departments of academic primary care in England and provides extraordinary critical mass enabling a broad and inclusive supervisory pool, access to databases, international expertise and bespoke training. Doctoral students will have supervisors across two consortium members and will join 45 NIHR SPCR doctoral students appointed from 2021-2026 to form a supportive cohort of peers who have the opportunity for regular contact at training meetings and our very successful Annual Trainees Event. Equality and diversity are core values underpinning the Programme which promotes the development of networking and collaboration, builds strong and experienced research groups and provides a rich, supportive research environment for doctoral students to develop into successful clinical academics and future research leaders.
|
| 04/04/2021 |
£8,323,636 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Underrepresentation of patient groups and diseases in research is both a cause and a consequence of health inequality. People may be underserved by healthcare and underrepresented in research due to 1) social inequalities related to demographic and protected characteristics, 2) marginalisation related to socioeconomic, lifestyle or legal factors, or 3) health status e.g. mental health, or rare diseases. Disease mechanisms, phenotyping and novel therapeutics are often studied in homogeneous populations with chronic underrepresention of certain groups. If studies fail to include these groups, outputs will be less accurate, relevant or effective in underrepresented populations, thereby exacerbating health inequalities.
To tackle these problems and redress these inequalities we will support fellows’ individual and specific training needs so that they are more able to manage career transitions and have the confidence to apply their imagination to bold research with populations and in diseases that will benefit the most from their efforts. This DTP will:
Recruit the best and most motivated fellows from a diverse range of applicants into a progressive research culture environment.
Conduct world-class research with underrepresented populations supported by specific training
Tackle barriers to Academic Transitions:
(optional) Pre-Doctoral Training Phase
Bespoke Career Development Programme
Post-Doctoral Support Phase
|
| 04/04/2021 |
£8,568,661 |
|
UNIVERSITY OF GLASGOW |
This Programme will address the substantial challenges posed by increasing multimorbidity. Hosted in the Scottish societal context, where multimorbidity is a significant health concern, but examining globally relevant problems, it will create a generation of innovative world-class researchers empowered to find ways to prevent multimorbidity, discover pathways tractable to novel intervention, and optimise management. We will achieve this through PhD projects designed to build synergistic, multidisciplinary collaborations across participating institutions, promoting new thinking on this complex topic.
Fellows will be recruited from a range of clinical/health professional backgrounds and experience the mentorship/skills training and support that will enable them to become future research leaders and make transformative contributions to multimorbidity and its clinical management internationally. We will promote intellectual curiosity, scientific rigour, peer learning, research integrity, translation into practice, public engagement and the principles of equality and diversity while imparting cutting-edge analytical skills. Underpinned by the track-records and resources of the Universities of Glasgow, Edinburgh, Dundee, and St Andrews, we will offer exceptional opportunities for clinical research across the translational spectrum from examining aetiology and mechanisms, through data science and epidemiology, to applied clinical research in a unique collaborative training environment, promoting development of a critical mass of multimorbidity researchers.
|
| 04/04/2021 |
£7,679,110 |
|
UNIVERSITY OF CAMBRIDGE |
The aim of the programme is to train the next generation of healthcare professional researchers and future research leaders, addressing challenges to health. The Universities of Cambridge and East Anglia in partnership with the Wellcome Sanger Institute will offer healthcare professionals of outstanding calibre unrivalled opportunities for research training spanning basic science, translational medicine, interdisciplinary and applied health research in an environment which represents the largest concentration of biomedical research in Europe. We will offer pre-doctoral research placements and training as part of our drive to widen participation and support fellows to make informed choices of research and supervisor. Strong, ongoing, mentorship is central to our programme and we will actively foster a vibrant, positive and inclusive research culture. During their PhDs, in addition to acquisition of research skills, making significant discoveries and achieving a doctorate, we will empower fellows with bespoke training & development and support supervisors and mentors, to ensure a successful research experience. Postdoctorally, we will guide fellows, tailored to their individual progress, to make the transition into higher research fellowships and clinical pathways, enabling ongoing training with continuance of research momentum.
|
| 04/04/2021 |
£7,096,279 |
|
UNIVERSITY OF BRISTOL |
Building on our Wellcome-funded Clinical Academic Training Programme (GW4-CAT) that uniquely supports Medical, Dental and Veterinary professionals; we will deliver a scheme that combines world class PhD training with exit to mentored post-doctoral positions with protected research time, open to all health professions (GW4-CAT-HP). Capitalising on the world class facilities and absolute commitment of the universities of Bath, Bristol, Cardiff and Exeter (Great Western 4 - GW4), and our partner NHS Boards and Trusts and Vet School, our objectives for GW4-CAT-HP are to:
Recruit talented Fellows from diverse disciplines and clinical specialties, supporting them to make bold choices by accessing the wide range of world-class cutting-edge research environments across GW4 where they will be stretched intellectually and practically.
Foster a positive and inclusive research culture, through robust equality, diversity and inclusion (EDI) practice and enabling the highest standards of research integrity through support and formal training.
Ensure, through bespoke and structured long-term support and mentoring, that all our Fellows secure externally funded post-doctoral support and linked clinical academic posts provided in partnership with our NHS Trusts, Boards and Vet School, to achieve research independence and retain excellent researchers in clinical academia.
|
| 04/04/2021 |
£11,877,508 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Our goal is to implement a transformative global health research programme that nurtures a new generation of diverse researchers addressing existing and emerging health challenges in Africa, by working across professional and research disciplines, with equity as a core value. Our partnership between five UK universities (UKIs) and six leading African research organisations is well-placed to provide the facilities, skills, mentorship and networks they need to become future leaders in equitable global health research. Our consortium includes world leaders in our proposed research themes, including infectious diseases; maternal, child and adolescent health; non-communicable diseases; and mental health. The UKIs will support matched PhD students from our African partner organisations to create a blended south-north cohort, providing a networked community of Fellows with transcultural experience, and a diverse learning and research environment.
Fellows will conduct their research at one of our African partner organisations. Each fellow will have two co-supervisors (one based in Africa), and will have access to online courses and educational activities at the UKIs, research support activities run by our partner organisations, and a mentorship programme. We will establish a Digital Global Health Academy to provide researcher development, and to foster an enabling and equitable research culture.
|
| 04/04/2021 |
£7,831,772 |
|
KING'S COLLEGE LONDON |
We will train the next generation of clinical academics in mental health research in a richly interdisciplinary training environment. The programme will include doctors, nurses, clinical psychologists and allied healthcare practitioners who will take training fellowships across a diverse range of topics relevant to mental health science. For mental health science to flourish we need to encourage clinicians both from within and outside disciplines traditionally involved in mental health, and to encourage collaboration with non-clinical academics with technical and scientific skills often absent from traditional PhD programmes in mental health. Supervisory teams will always combine clinical and non-clinical academics. Three programmes of research will be available, representing emerging opportunities in mental health science: (1) translational neuroscience, (2) digital mental health and (3) social science and policy. Fellows will be trained in key topics to equip them to negotiate their future careers with an emphasis on generating impactful research. The training will enhance a culture which values diversity and inclusion, open and reproducible science and the critical importance of patient and public voices in research.
|
| 31/03/2021 |
£9,960 |
|
AFRICAN POPULATION & HEALTH RESEARCH CENTRE, KENYA |
Critical to realizing APHRC’s vision of transforming lives in Africa through research is public engagement with research and health concepts. We are submitting this Development Grant to facilitate the preparation of the Transformation pilot grant for which the team has been invited to apply. During the development, a mix of senior and junior staff from APHRC will work with expert consultants and engage stakeholders in the area of Global Heating and its impact on Health to develop the plan for fellowship support and training program for The Global Heating and Health Public Engagement Programme (G2H-PEP). The pilot of this Leadership Transformation Programme will produce a cohort of fellows who will have an extended network of contacts working on public engagement, and will have gained leadership skills and tools to ensure their wellbeing and resilience while developing as leaders in a living system. The overall objective of the program will be to produce a network of public engagement fellows interested in global heating and its health impacts. The co-design process will ensure that the pilot cohort goes through a relevant training program and receives the support necessary for meaningful engagement with the public.
|
| 31/03/2021 |
£10,000 |
|
DALBERG GLOBAL DEVELOPMENT ADVISORS LIMITED |
This proposal is to help develop an initial proof of concept of the Transformation Programme pilot for public engagement leaders. We propose working for ~4 weeks to help refine and build out what this proof of concept would look like - specifically as it relates to the flow, curriculum and approach of the pilot programme.
|
| 31/03/2021 |
£139,270 |
|
BRUEGEL |
A high-level panel, led by co-chairs Tharman Shanmugaratnam, Lawrence H. Summers and Ngozi Okonjo-Iweala, has been mandated by the Italian presidency of the G20 to propose reforms and other measures that will lead to more reliable and sustainable financing of pandemic prevention, preparedness, and response. To support the deliberations and decision-making of the panel, Bruegel and CGD will establish a team to lead the analysis and content development of the proposals. The work of the project team and the panel is aimed at eliciting concrete and cooperative action by the G20 finance ministers. The team will develop an outline for the final report of the panel for discussion and feedback with the co-Chairs. Furthermore, the team will carry out three background analyses that will enable the informed discussion and brainstorming among panel members and the development of financing proposals: i/ landscaping current financing and issues, existing asks and proposals, ii/ landscaping current financing and issues, existing asks and proposals and iii/ governance, organization, and incentives. Reflecting the panel’s views as well as the teams’ own analyses, a draft and then final report will be developed building on the initial outline and the background analyses and consultations.
|
| 31/03/2021 |
£166,200 |
|
ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE |
Snakebite is a strategic priority for RSTMH given its high levels of death and disability. Although there has been an increase in research funding recently, there is still an unmet need to encourage junior researchers to undertake a career in snakebite research. The RSTMH Small Grants Programme is a unique grant funding programme open to early career researchers from anywhere in the world that aims to fill a gap in the research career pathway. RSTMH grants are for up to £5,000 to those early in their careers (e.g. researchers, healthcare professionals, NGO workers, health economists, social scientists) who are working in a field relevant to tropical medicine or global health. These grants typically represent the first time someone has received funding in their own name and helps develop their research and management skills.
In 2020, Wellcome piloted a partnership with RSMTH to fund 10 grants in snakebite research. With Wellcome funding, RSTMH awarded grants to African, Asian, South American and European nationals across various snakebite research areas. Following on from the success of the pilot, RSTMH is seeking funding for a 3-year partnership with Wellcome to fund 10 projects per year and up to 30 in total in snakebite research.
|
| 31/03/2021 |
£46,492 |
|
SOCIAL GOOD FUND |
Climate change presents a unique and urgent threat to planetary health. Compounded by the COVID19 pandemic, we face a very real risk of losing 50 years of global development, exacerbating health, economic, and social inequities.
COP26 will provide a special opportunity for global leaders to set a course for a healthy and green recovery.
Informed voices from across the globe are crucial in driving decision makers to deliver ambitious climate action. Health workers are among society's most trusted and respected professionals, and the health case for climate action is powerful, offering millions of lives saved through reduced non-communicable diseases, health resilience, and adaptation, and fully offsetting the costs of mitigation through health cost savings.
Wellcome Trust funding will enable the Global Climate Health Alliance (GCHA) to amplify the voices of medical and other health professionals globally, including those in low and middle income countries (LMIC) which have been underrepresented in the international climate conversation, on the massive health opportunities of climate action.
We will build capacity, link new voices to media advocacy opportunities, and disseminate Wellcome coalition asks through our global networks, thereby influencing climate action at the national and international level in the run up to COP.
|
| 31/03/2021 |
£49,936 |
|
STOPAIDS |
Action for Global Health (AfGH) and Students for Global Health (SfGH) in partnership aim to increase our respective health networks' (reaching more than 50 organisations), and members' (in 34 student branches) contribution to a shared climate and health agenda through capacity building, mobilising, and increasing collaboration between key stakeholders (our members, partners and other actors) and supporting synthesised advocacy and campaign events in the lead up to COP26. In particular we will focus on increasing access to engagement with youth, global south and NMIC stakeholders on the intersection of health and climate.
We will partner to work with the 'Climate Change Coalition' to activate and engage cross sectoral partners including global south, LMIC and youth organisations around a shared policy agenda and build support for sustainable health and climate change strategies leading up to G7 and COP26. We will actively participate in the climate coalition and build our and other actors' resources to activate and mobilise support for health and climate. We will draw on the breadth and strength of our members collective experience and expertise to actively engage with and broaden understanding of the intersection between health and climate.
|
| 31/03/2021 |
£16,000 |
|
OPEN RESEARCH CENTRAL |
The open access movement has demonstrated that "openness" is a benefit to the creation, dissemination, and reuse of knowledge. Through a variety of policies and initiatives, there is renewed momentum for sharing research outputs as part of a more connected and collaborative open research ecosystem. However, there remains a need for consensus around how best to deliver a research dissemination system that maximises the benefits for both science and society, and the researchers upon which such a system depends.
Open Research Central (ORC) is a not-for-profit organization that aims to change the paradigm for primary research dissemination by bringing together key representatives across the scholarly ecosystem to define standards, build a movement to expand adoption of these standards, encourage the community to provide researchers with services that meet these standards and promote these standards.
To build further momentum and adoption globally of open research publishing approaches, the ORC Board wish to secure resource for 18 months to underpin more significant fund raising efforts to enable ORC to deliver on its mission, to develop and start to put into place a sustainability plan, and to support the Board in the day-to-day running and management of ORC.
|
| 31/03/2021 |
£146,002 |
|
CENTER FOR GLOBAL DEVELOPMENT |
A new high-level panel, led by co-chairs Tharman Shanmugaratnam and Lawrence H. Summers, has been mandated by the Italian presidency of the G20 to propose reforms and other measures that will lead to more reliable and sustainable financing of pandemic prevention, preparedness, and response. To support the panel's deliberations and decision-making, CGD and Bruegel propose establishing a team to lead the analysis and content development of the proposals, with logistical, outreach, engagement, and coordination support from a secretariat at Wellcome and the US National Academies of Medicine. The team will develop a short scoping note on the economic rationale behind prioritizing public investment in prevention, preparedness, and response, an outline of the final report for discussion and feedback from the co-chairs, background analyses (on landscaping current financing and issues, existing asks and proposals; setting a financing goal and assessing its value for money; and governance, organization, and incentives), a long list of 10-15 proposals for governance reform and/or new or existing financing sources and mechanisms (with pros and cons for the panel's consideration), and a final report reflecting the panel’s views and the teams’ own analyses.
|
| 31/03/2021 |
£236,035 |
|
UTAH FILM CENTER |
"THE ARM RACE: HOW WE CONQUERED COVID" (working title) is a documentary film that will be the dispositive chronicle of the global race to research, develop, manufacture and distribute COVID-19 vaccines in the most enormous coordinated effort ever undertaken. In this unprecedented moment in history, the film will celebrate the herculean efforts of the scientific, research and immunization community during a complex time of mistrust, vaccine hesitancy, and misinformation - when trust in science itself has come under fire.
The stories track development of vaccines, (including research built on previous work fighting outbreaks including Ebola and HIV/AIDS,) and how public health agencies from hospitals to the WHO are responding to the crisis. Our narrative goes beyond the lab, delving into the complexities of underserved populations, equitable access and inclusion. We see opportunities in additional content, leveraging existing assets, foregrounding the making of the film and our collaboration with the global public health community. This project will spark interest in science’s potential to solve global health challenges by documenting the largest public health effort in human history, while also offering insights into our successes and failures to help prepare the next generation to better respond to future pandemics.
|
| 31/03/2021 |
£910,964 |
|
P1VITAL PRODUCTS LTD |
Intensive care unit (ICU) staff face repeated exposure to traumatic work-related events and have reported high levels of posttraumatic symptoms during the pandemic. Novel, scalable and preventative interventions are required.
We are developing a "cognitive vaccine" approach for ICU staff against one key symptom – intrusive memories of traumatic events. These are unwanted, distressing and disrupt functioning.
Our novel, brief gameplay intervention is repeatable, flexible, non-stigmatising, scalable, and driven by mental health science.
This digital intervention is guided by an initial session of psychologist support, then self-administered; delivered same day or months post-trauma, suitable for repeated trauma exposure, fits with busy lives of ICU staff, without discussing trauma detail.
Part 1 uses a Bayesian design to optimise and co-develop procedures with ICU professionals and move at speed under pandemic conditions, allowing limited rollout (guided-version) in these unprecedented times.
Part 2 uses a pragmatic RCT (three arms: guided/non-guided/attention-control) testing clinical effectiveness and acceptability to inform clinical practice. If the non-guided intervention is effective (i.e. no psychologist support) it will accelerate the speed of rollout.
Meanwhile through global mental health workshops with stakeholder communities we seek to understand the views of various communities worldwide regarding implementation of this novel intervention form.
|
| 31/03/2021 |
£150,000 |
|
SAVE THE CHILDREN |
In the 2020 Spending Review HMG signaled its intent to renege on a manifesto commitment and cut ODA form 0.7 to 0.5% of GNI (on top of the budget cut that happened automatically due to economic contraction). To do this, HMG wishes to repeal the relevant in coming months.
Work to sustain the Government’s support for ODA is already delivering results with an increasingly credible threat of a government rebellion and sustained media interest. However, increasingly our political intel says we may be at risk of winning the vote and losing the argument. Put simply, ‘hard whipping’ of a rebellion, combined with some horse-trading between different groups, might be enough to carry a vote but it won’t stop the debate flaring back up. This grant would allow us to scale the emergency effort around the legislation while also creating a more enabling environment for the longer team:
by bolstering our public affairs capability in Qs 1/ 2,
by expanding our local organising effort to an additional ten constituencies from Q1-4 and
by expanding our comms plans from Q1-4.
A key part of this partnership would be Wellcome’s inclusion in regular political updates, intel and learning sessions.
|
| 31/03/2021 |
£79,188 |
|
UNIVERSITY OF TORONTO |
Checklists are simple tools that are often used to promote safety in clinical applications, because they can easily be integrated into a clinical workflow deployment without the need for extensive training or additional technology. Currently, machine learning in health focuses on large, complex deep neural networks. In comparison with deep neural networks, checklists are far easier to use, understand, and scrutinize. In practice, checklists are difficult to develop, and the vast majority of real-world checklists are hand-crafted by panels of experts.
Given the widespread integration of electronic health data over the past decade, our goal is to learn checklists from data for clinical tasks. The main application of our method, in partnership with Dr. Leo Celi at Beth Israel Deaconess Medical Center (BIDMC) in Boston, is to predict mortality in patients eligible for Continuous Renal Replacement Therapy (CRRT).
A generated checklist for CRRT is clinically desirable in the intensive care unit as a mechanism to trigger a multidisciplinary discussion with the patient’s family, to consider the value of the treatment weighed against the physical burden and cost. Thus we include operational considerations such as number of items in the checklist, the false negative/positive rate tradeoff, and fairness across protected groups.
|
| 31/03/2021 |
£1,464,291 |
|
DRUGS FOR NEGLECTED DISEASES INITIATIVE |
Through the rapid establishment of a translational pathway, DNDi and its partners aim at providing the next generation of candidate medicines for SARS-CoV-2 clinical trials as well as integrating back-translations to validate the most appropriate preclinical models. The project is planned to run from September 2020-December 2021, with a total budget of 1.97M GBP, split into three pillars of activities composed of short and medium- term deliverables:
Pillar 1 : Selection of the best combination of repurposed antiviral drugs to include into the 3rd arm of the ANTICOV clinical trial and the next back-ups
Pillar 2 : Support candidate progression through an integrated pharmacometrics package involving both Physiologically-Based Pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modelling approaches
Pillar 3 : Development of a translational platform and performance of a comparative analysis of selected drugs/combinations (including those from Pillar 1) to better understand and refine the screening cascade with best translational value; definition of a Target Candidate Profile (TCP) for SARS-CoV-2 mild infection
This project will cement a collaborative partnership in the SARS-CoV-2 translational space that will pave the way to future longer-term discovery projects and preparedness for additional future threats.
Key words: COVID-19 / Drug re-purposing / Translational drug development pathway
|
| 31/03/2021 |
£303,984 |
|
MILKEN INSTITUTE |
In partnership with the Wellcome Trust, the Milken Institute's FasterCures and the Financial Innovations Lab program will examine ways to engage, accelerate or modify existing models or design new models that can support the development and commercialization of new antibiotics. The project will look to thoroughly vet the barriers and incentives for implementing a more sustainable system, focusing on identifying fund models and financing mechanisms that are applicable across disease areas and markets. The Lab will utilize the Milken Institute’s network and expertise to thoroughly vet funding models to ensure they are operational and provide a platform towards implementation.
Using the Lab’s signature model, the project will: 1) complete independent research and stakeholder interviews on the nuances of the issue area to complete a landscape analyses; 2) host a moderated, in-person roundtable with interdisciplinary leaders, including non-governmental organizations, researchers, policymakers, investors, financial institutions, academics, and industry experts to generate market-based solutions, and 3) produce a summary report on the findings of the roundtable, including policy recommendations and models for financial incentives. By leveraging a diverse pool of knowledge, the Lab will develop solutions to help fund and expedite new, innovative ways of funding new antibiotic development and commercialization.
|
| 31/03/2021 |
£3,446,620 |
|
MASSACHUSETTS INSTITUTE OF TECHNOLOGY |
The goal of this proposal is to develop, implement, and evaluate machine learning algorithms for trustworthy clinical AI. The proposed technology aims to support a wide range of healthcare
applications, including diagnostics, treatment personalization, and prediction of treatment outcomes. These applications utilize diverse sources of data, including clinical notes, images, and test results. Rather than designing a disease/application-specific AI algorithm, we are interested in developing a capacity that can be readily embedded into existing AI models to improve their transparency and ability to incorporate human feedback as well as strengthen their data privacy guarantees. The Jameel Clinic team has deployed AI tools in many clinical areas. These tools would be our testing ground for measuring the effectiveness and flexibility of the proposed platform.
|
| 31/03/2021 |
£340,531 |
|
UNIVERSITY OF OXFORD |
By bringing GOARN Research and ISARIC partners together in the LMIC setting during COVID-19 we hope to strengthen the clinical, social science and operational research response.
Aim: to support the roll out of the ISARIC WHO natural history protocol (known as the Clinical Characterisation Protocol - CCP) across LMICs:
Overarching goals:
Support the roll out/uptake of the CCP across 5 countries per region, where feasible* (across four ISARIC regions of S America, Africa, S Asia & SE Asia).
Support the set up and running of local dynamic clinical data dashboards in at least 10 sites per ISARIC region
Share the aggregate data with WHO to assist with providing a global picture on the incidence and presentation of moderate to severe cases across a representation of the LMICs to inform clinical management and public health planning and control.
Support the establishment of follow up modules and programmes for discharged hospitalised cases in 5 sites per region to evaluate longer term health impacts of COVID-19 on individual, health services and society to inform prevention and care planning.
*Brazil are in an intense first wave and reaching out to another 4 S. American countries would be challenging at the time of writing.
|
| 31/03/2021 |
£1,335,301 |
|
NATIONAL UNIVERSITY OF SINGAPORE |
Drug-resistant infections (DRIs) have recently been recognised as a major challenge by the G20 and the UN General Assembly, with a disproportionate impact on the people of Asia. Potential solutions will require multidisciplinary and multi-country collaboration in order to successfully address in terms of innovative discoveries, implementation of policies and roll-out and evaluation of the best evidence based clinical practices.
The current model of clinical research in low and middle-income countries (LMICs) is to fund individual clinical trials on an ad-hoc basis, with each trial requiring significant investment in research infrastructure and skills development in addition to the trial-specific costs. This model is inefficient scientifically, developmentally, and financially.
In response to the challenge of AMR, Wellcome plans to set up a pilot clinical trial network (CTN) in SEA. The CTN will significantly increase the quality and efficiency of clinical trials in the region, resulting in an improved understanding of DRI, improved treatment of those infections and an increase in the supply of new drugs to fight AMR. The support hub for this clinical trial network will be based in Singapore.
|
| 23/03/2021 |
£54,887 |
|
UNIVERSITY OF MANCHESTER |
This activity will establish Salford's Ordsall Hall (OH), a free-to-access heritage property, as a dynamic site for developing public healthcare knowledge and engagement for its 35,000 annual users. It will also offer a case study of how other UK heritage organisations can encourage positive health outcomes for their users by making public healthcare a focal point of public and learning programmes.
OH's 2.5 acres of organically-managed gardens will become a site for cultivating and analysing plant species that were widely used in early modern sleep-care routines, from soporific tonics to foodstuffs. A series of workshops with OH's users will involve them in planting and cultivation, and in remaking experiments based on historical sleep recipes. The PI's team will use their digital microscopy expertise to reveal the material qualities of individual plants, which will enrich the research project. The workshops will generate material for learning resources, vlogs, and recipe cards for OH's users, in which Salford schools feature strongly (c.40 schools). This activity supports the Personal, Social and Health Education (PSHE) learning objectives now mandatory in UK primary and secondary schools, which emphasise the importance of, and connections between 'sufficient sleep' and 'time spent outdoors' for physical and mental health. The project will encourage positive health outcomes for OH's users by juxtaposing historic sleep-care practices with current healthcare concerns about sleep quality. Project outcomes will be scaled through the project website, and through strategic webinars with the Museums Association, GEM (Group for Education and Museums), and the Historic Houses Association.
|
| 23/03/2021 |
£27,709 |
|
UNIVERSITY OF READING |
The prevalence of self-harm in the UK has nearly tripled over the last decade (BMJ 2019). However, studies of self-harm have focussed on its biomedical causes to the exclusion of social and cultural factors. This project facilitates new ways of discussing self-harm through artistic practice.
In collaboration with ArtLab (the outreach arm of University of Reading art department) and The AnDY (Anxiety and Depression in Young People) Clinic, the completed project will have delivered a series of creative workshops for people with a history of self harm, their loved ones, and service providers. I will have accumulated artwork and qualitative feedback from these workshops which helps me to understand how my research relates to (and differs from) modern narratives about self-harm. As ‘co-researchers’, participants will explore and express their ideas about representations of self-harm and generate a greater understanding of one another’s perspectives.
These insights will be disseminated as a dynamic online exhibition of (anonymised) artwork and feedback from the workshops, made freely available to mental health charities and NHS trusts as a resource for promoting discussion about the socio-cultural aspects of self-harm. I’ll also discuss the project and the exhibition at local arts, science and heritage events such as the Being Human festival, encouraging greater openness about mental ill health. Additionally, my findings will be incorporated into a scholarly monograph on the topic of self-wounding in early modern England, specifically as part of an ‘epilogue’ which considers how historic experiences of self-wounding relate to modern self-harm.
|
| 23/03/2021 |
£81,762 |
|
UNIVERSITY COLLEGE LONDON |
Dementia is common in Parkinson’s, being six times more likely in Parkinson’s patients than in the general population. Despite this, those working in the Parkinson’s community avoid using the word or having discussions about dementia due to worries about adverse responses from patients. While a difficult conversation, new tools are needed to create awareness and open dialogue, so that we can better help patients and involve them in research and treatment targeted at dementia in Parkinson’s.
As a clinician investigating mechanisms of dementia in Parkinson’s, I struggle to navigate these difficult topics with patients, and the wider public. Dementia can feel like a new trauma for patients who have just become accustomed to living with Parkinson’s. However, I need to talk about cognitive decline in Parkinson’s to engage patients in the research. In clinic, early conversations about Parkinson’s dementia can help patients gain access to appropriate support, prepare for the future, and benefit from treatments to slow progression of dementia in Parkinson’s.
Therefore this project will:
Identify roots and triggers of discomfort linked with the concept of dementia within the Parkinson’s community
Co-produce information resources to support dialogue and awareness including: (i) a clinical tool to enable discussion of dementia between professionals and people with Parkinson’s, (ii) a hub of accessible, non-threatening information for people with Parkinson’s to learn about their risks
Embed toolkits in Parkinson’s UK’s resource packages and run a campaign to raise awareness of the risk of dementia and the toolkits.
|
| 23/03/2021 |
£99,680 |
|
KING'S COLLEGE LONDON |
Building on existing community engagement activities, each month for two years, we will run ‘PRECISE-DYAD open days’ to connect with study participants, their families and community members. The aim of this project is to dedicate time for interactive learning and discussions about pregnancy and mother and child health. These open days will take place in the communities where the participants live or at the health centre where the study takes place (The Gambia= 3, Kenya= 2). The choice of location will optimize participation by selecting centrally located/convenient locations.
The PRECISE-DYAD open days will be delivered as follow:
A variety of interactive activities including storytelling, plays and interactive games on topics related to pregnancy, mental health, brain function and nutrition. These activities will be led by the PRECISE-DYAD health care workers following appropriate training programs.
Printed material highlighting interesting PRECISE-DYAD study data relating to the community will be shared at the open days. A team member will provide an overview of the study data and encourage further conversation on topics of interest to the attendees.
Thank-you ceremony and tokens of appreciation will be provided to participants. These will be conducted at the end of ‘PRECISE-DYAD open days’ and will include wraps to carry children and polaroid pictures of the woman and her child, if present.
A video will be recorded by a local professional team to showcase community perceptions of maternal and child health.
|
| 23/03/2021 |
£40,757 |
|
UNIVERSITY COLLEGE LONDON |
Our knowledge of Latin America’s past is predominantly based on colonial and governmental sources, side-lining indigenous stories and myths that have been experienced and transmitted orally for generations. Through a collaboration between the British Museum’s Santo Domingo Centre of Excellence for Latin American Research (SDCelar) and Indigenous participants we will tell these stories, creating a virtual exhibition examining the coloniality of gender in their communities. Wixárika gender relations and how these were performed and transformed throughout history will be shared using interactive materials, with the aim that researchers, participants and museum users more clearly understand how colonialism shapes experiences of gender and health.
Research partners in the UK and Mexico will work with exhibition specialists Múcura and Wixárika participants to record their interpretation of the history of gender. Theatre, narratives and interactive experience-based artwork and will be used to generate content for the virtual exhibition. Evaluation will be formative and embedded, recording participants’ experience of analysing historical data and acting on their feedback.
Once completed, Global visitors to the exhibition will learn how colonialism intervened with gender structures, participants will understand how colonialism has shaped their experiences of gender, pregnancy and childbirth; and the research team will learn to critically examine their own positionality, facilitating genuinely participatory and decolonising interpretations of their findings.
Partnering with SDCelar gives Wixárika communities the ability to influence global knowledge networks and use this engagement to decolonise healthcare in their communities, with the potential for shaping future research and the focus of linked
academic publications.
|
| 15/03/2021 |
£1,064,246 |
|
UNIVERSITY OF THE WITWATERSRAND |
Africa has the fastest growing population in the world. At the same time the continent has some of the highest rates of infertility. Most people long to have children for diverse reasons. Those unable to have children seek ways to improve their chances of conceiving. These may include biomedical interventions, vernacular healing practices, changing or adding partners or making kin through adoption and child circulation. Yet despite the diversity of lived experiences and practices of reproduction across the continent, most research and interventions into reproductive health in Africa frame it primarily in terms of risk, pathology, mortality, and irresponsibility. Doing Natality engages a team from four African countries, working across demography, social sciences, medical humanities and science and technology studies, to develop a research agenda that centers the notion of "doing natality". We aim to explore practices of doing natality as articulation of love, care, beginning something new and securing better futures in raising children. We thereby open up a new space to interrogate and explore the usefulness of the notion of "doing natality" as heuristic, theoretical and methodological tool by asking what it means for African women, men and couples to have (or not have) children.
|
| 15/03/2021 |
£1,040,680 |
|
BATH SPA UNIVERSITY |
Social science research has long been criticised for failing to improve the life chances of disabled people. Current research agendas are determined ‘top down’ by policy makers, and researchers risk objectifying disabled participants by conducting research ‘on’ them (as opposed to ‘with’ them). Our radical and exciting proposal challenges the status quo by developing an inclusive agenda and establishing a Disabled People’s Research Network. Our vision is to place academic and non-academic disabled people at the heart of research development, and our entire project will be co-produced by working with disabled people’s organisations. Our activities will identify new salient questions and reinvent social science methodology by exploring how the arts and humanities can enable disabled people to evidence and share their lived experiences. We will develop more inclusive forms of knowledge exchange between universities and disabled people, and we will work with policy makers to maximise disabled people’s research impact. We will empower disabled people as agents of change and our activities will include a range of fellowships for disabled people and a highly innovative research training course led by disabled people. Our network will reinvent how universities work with disabled people, in addition to methodological and epistemological development.
|
| 15/03/2021 |
£1,016,937 |
|
UNIVERSITY OF LEEDS |
LivingBodiesObjects is an experiment in the making and understanding of interactions between bodies, technologies, objects and health, designed to test and extend the boundaries of Medical Humanities research. Working with a range of partners, it will take place in the context of multi-purpose/use laboratory spaces (both physical and virtual) that invite differing conceptions and practices of health experiences, and responses to them. The ambition of the project lies in the imaginative creation of these spaces and not in any pre-emption of the materials they might produce. The laboratories will be specifically designed to figure ideas and creativity, making spaces that provoke, facilitate and respond to the ideas and questions raised by bodies as they encounter different forms of technology. Centring on the ways in which individuals and communities collaborate to produce work within dynamic and generative locations, the laboratories will also link to more traditional laboratory activities such as equipment, testing and use. As a specific research development initiative, the project will further extend interdisciplinary health research practice at the University of Leeds, where its work will inform and further develop a research culture through the foregrounding of innovation in professional research management, career development and equality, diversity and inclusion.
|
| 15/03/2021 |
£996,460 |
|
UNIVERSITY OF HELSINKI |
The aim of this Research Development Award is to establish a leading centre for the social study of microbes. Since their discovery, microbes have been predominantly defined as pathogenic and threatening to human and animal health. Recently, however, societal, and scientific views about microbes, immunity, and antibiotics have started to acknowledge the beneficial and symbiotic qualities of bacteria, viruses and fungi. Existing social scientific language is insufficient and outdated in describing the complex and entwined relationships between humans, nonhumans, microbes, and environments. These relations with microbes raise profound challenges for the foundations of social theory.
Strategically situated within an emerging network of research, this application will establish an egalitarian and experimental research infrastructure to develop new social scientific concepts and methodology to address the challenge. The Centre will host international research fellows and an art residency, and organise social theory and methodology workshops, two academic seminars annually, and a yearly PhD Summer School to support younger generations of scholars. Not only is this work theoretically essential, it is also key to understanding and acting upon the way humans relate to microbes and other nonhumans, a vital objective for developing sustainable ways of planetary co-existence.
|
| 15/03/2021 |
£733,684 |
|
UNIVERSITY OF CENTRAL LANCASHIRE |
Three paradoxes in global research ethics seriously harm vulnerable populations.
First, health research works. Yet, to protect vulnerable populations from exploitation, they are often excluded from it.
Second, international collaborative research works. Yet, major trust issues block collaborations with vulnerable populations who have previously been exploited.
Third, the further apart researcher and end-user experiences are, the more urgent the co-creation of research becomes. Yet, successful co-creation methods for non-clinical health research with vulnerable populations in low and middle income countries (LMICs) barely exist.
All three paradoxes restrict non-clinical health research in LMICs.
Leaving no one behind in research will build an extensive research agenda to tackle all three paradoxes by:
radically rethinking the concept of vulnerability and what appropriate protection mechanisms for the vulnerable would look like.
enabling indigenous peoples and sex worker teams to define what vulnerability means to them and how they want to be protected in research.
developing a humanities method for non-clinical health research that would make research less risky for vulnerable populations.
The above will be achieved by a highly-experienced research leader and her UK team in a network with two African teams representing vulnerable populations.
|
| 15/03/2021 |
£1,019,767 |
|
LANCASTER UNIVERSITY |
New and emerging reproductive technologies have the potential, within a generation or two, to profoundly disrupt established social practices linked to human reproduction and parenting, as well as the concepts of relatedness and family. Better understanding the cultural, ethical, legal, and social issues that this prospect raises is the principal substantive research aim of this programme. We will examine three such technologies.
Ectogenesis could allow us to develop fetuses wholly outside the body, to create children who have not been ‘born’ (in the usual sense of that term).
Genome editing will mean that future children can be ‘chosen’ or ‘designed’ with far greater levels of precision than at present.
New methods of creating eggs and sperm will enable the creation of children with two genetic parents of the same sex, or who have multiple genetic parents, or perhaps no determinate genetic parents at all.
Using these cases as focal points, we will develop transformative new research methods and modes of interdisciplinary working - for example, by integrating speculative design methodologies with those of bioethics, law, literature, linguistics, and psychology. Our ultimate aim is for this to lead to a novel research paradigm for the study of disruptive emerging technologies.
|
| 15/03/2021 |
£1,058,630 |
|
UNIVERSITY OF CAPE TOWN |
In this project, we propose to create opportunities for African theory-building by fostering critical reflection, exchange of knowledge and perspectives, and collaboration and writing between African scholars from different disciplines, with a focus on exploring how African thought could influence critical engagement with the ethics of new and emerging health technologies globally. Starting with a recognition of incompleteness and the conviviality that requires, the focus of this project will be on a) developing conceptual accounts of how African thought could inform on key ethical questions raised by new and emerging health technologies, b) better understanding how we can ensure epistemic justice in our scholarship and which diversity matters; and c) understanding how particular African research contexts drive us towards academic activism. The programme seeks to create opportunities for exchange and joint reflection, in an aim to push the audacity with which African scholars can take ownership of, and lead, reflection on the ethics of new and emerging health technologies. The programme will dive into questions relating to African personhood, relational autonomy, epistemic justice and academic activism to explore how African ways of seeing and being in the world could enrich global conversations about science and technology.
|
| 15/03/2021 |
£1,190,927 |
|
UNIVERSITY OF MALAYA |
This programme aims to build a bioethics community in South East Asia (SEA) to establish a research agenda that brings to the forefront voices that are not well captured in current bioethics discourses, and shape policies and practices to enhance the wellbeing of individuals and communities. A distinctive feature of SEA is its diversity of language, ethnicities, cultural and religious traditions, and political and economic development. However, SEA voices are underrepresented in contemporary bioethics discourses and in the development of bioethics guidelines that have international relevance and impact. Led by the University of Malaya with initial partners in Singapore and Thailand, this initiative will initially focus on two thematic research areas: 1) emerging issues relating to healthcare for and research with mobile and marginalised populations; and 2) challenges and opportunities presented by emergent health and biomedical technologies.
The guiding principles of this initiative are threefold. First, to discover and bring into the bioethical discourse, the voices of the many cultural and religious traditions in the region. Second, to advocate for change and challenge orthodoxy; and third, to build a vibrant, inclusive and collaborative bioethics community in South East Asia.
|
| 10/03/2021 |
£18,459 |
|
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL |
Black, Indigenous, and People of Color (BIPOC) suffer most from the consequences of broken food systems (Petersen et al., 2019) and climate change (Morello-Frosch et al., 2009) yet are underrepresented among research leaders working to address such issues (National Science Foundation, 2018; Pearson & Schuldt, 2014). The Nutrition Research Scholars Program (NRSP) aims to build a pipeline of BIPOC scholars to become leaders in food, health, and climate research to inform policy.
Our activity will involve implementation of the pilot NRSP providing BIPOC students interested in nutrition and climate with research experience and mentorship from leaders in nutrition and food policy. We will implement a 12-week summer NRSP for two BIPOC undergraduate students to build research and professional development skills and prepare for matriculation in a PhD program. Short-term indicators of success will include objective measures (e.g., total professional development workshops and networking meetings attended) and subjective measures (e.g., satisfaction with the NRSP). Long-term indicators will include continuation of an annual NRSP, total scholars matriculating in related PhD programs, and development of a network of BIPOC scholars working with our research group.
Upon successful completion of the pilot, we will expand the program to other research groups within the UNC Department of Nutrition; disseminate program findings at nutrition conferences; and build sustainability by incorporating funding for NRSP scholars in grant proposals. With time, the NRSP will foster a pipeline of BIPOC nutrition scholars pursuing graduate training to work as researchers at the nexus of food policy, health, and environmental change.
|
| 26/02/2021 |
£79,672 |
|
UNICEF UK |
UNICEF proposes multi-country focus groups to gather insights on young people’s mental health and well-being. This reflects our and Wellcome Trust’s mutual commitment to engaging youth as partners in the design and implementation of action research that affects them. The proposed research will be featured in UNICEF’s flagship State of the World’s Children report, ensuring that the knowledge, expertise, and lived experiences of young people are part of the global dialogue on research, policy, and programming priorities.
Key research questions include:
How do adolescents perceive and understand mental health, both positive and negative?
What are the key emotional and behavioral challenges facing adolescents in communities around the world, and what do they identify as risk and protective factors?
What are the positive and harmful ways adolescent are coping with mental health problems?
What are the barriers and reinforcing factors to their help-seeking behavior?
What are adolescent ideas and solutions around structural, community, peer, and self-care approaches to mental health promotion, prevention, and support?
This research will create opportunities both for promoting positive youth development as well as increase youth voice in the scientific study and body of evidence around mental health of young people.
|
| 26/02/2021 |
£447,509 |
|
IFAKARA HEALTH INSTITUTE |
Community engagement is an essential component in clinical trials, and it is regarded as an ethical requirement of most ethics review committees before the trial protocols can be approved. However, there is a scarcity of studies that have objectively assessed the impact of best engagement practices on recruitment and retention rates.
Using an in-depth review of the literature, in-depth interviews, and focus group discussions with relevant stakeholders, we will develop clinical trial community engagement best practices. We will then establish and pilot an implementation assessment tool that would be used to assess the extent of implementation of these practices. Finally, we will conduct a randomized controlled study to assess the efficacy of best practices on the recruitment and retention rates of clinical trials in a randomized controlled trial, where trials in the intervention arm will be assigned to implement the new best practices, and control trials will implement their originally planned engagement approaches. The implementation assessment tool will be used to measure the extent of adherence to the newly established best practices in both arms. We will then assess the enhancers and barriers to the successful implementation of clinical trial best community engagement practices.
|
| 26/02/2021 |
£4,794,788 |
|
UNIVERSITY OF OXFORD |
The COVID-19 pandemic has once again exposed the lack of coordination and cooperation across the research and development efforts of the infectious disease community. A key indicator of this failing is the lack of international, interoperable data platforms to provide rapid insight into disease pathogenesis and treatment. Access to data is an important tool for accelerating evidence, product development, and scientific innovation.
Enhanced technology, infrastructure and systems for data platforms will increase Findability, Accessibility, Interoperability, and Reuse (FAIR), so that science can advance in a rapid, robust and innovative way, saving lives in the affected communities.
Recognising the importance and complexity of the task at hand, this project brings together the vast experience of IDDO, Vivli, and other key stakeholders to deliver a broad, effective, and sustainable data platform(s) for infectious diseases.
In this project, IDDO will:
Enhance its platform for improved findability, discovery, and persistence which ensures that data are available in the long-term;
Optimise and accelerate its data curation capacity;
Streamline and accelerate its data access workflow;
Develop a business plan to secure the sustainability and success of the platform
|
| 26/02/2021 |
£1,028,765 |
|
VIVLI (CENTRE FOR GLOBAL CLINICAL RESEARCH DATA) |
Data repositories (such as IDDO and Vivli) have played a significant role in making research data available for secondary use. However, access to data needs to be further enhanced for accelerated innovations on infectious diseases by addressing the friction in data contribution, discoverability, access, and reuse. There is a strong alignment between Vivli the Wellcome’s visions of improving the discovery and accessibility of Individual Participant Data related to COVID-19 in the short term, and for other infectious diseases in the long term. With this grant we seek direct support for discoverability and accessibility of data related to COVID-19, and to directly support Vivli to become an effective node in the "FAIR Data Network".
The grant will focus on the following primary objectives:
Recognition and credit for data contributions,
Accelerated access to Individual Participant Data (IPD) hosted by Vivli,
Discoverability of IDDO studies via the Vivli platform, and
Discoverability of IPD hosted by Vivli and its platform partners (including IDDO) based on rich metadata).
|
| 26/02/2021 |
£100,000 |
|
KING'S COLLEGE LONDON |
Treatments for inflammatory pain (IP) and neuropathic pain (NP) are frequently ineffective and have many side effects. Scientists in Professor Peter McNaughton's laboratory at the University of Cambridge have discovered that both IP and NP are abolished in mice when an ion channel is genetically deleted. This suggests that drugs blocking this ion channel will have value as novel analgesics.
IP is associated with injury, infection or chronic conditions such as arthritis; and NP is caused by nerve damage in conditions such as post-herpetic neuralgia and diabetic neuropathy. Both IP and NP can impose major limitations on lifestyle and working patterns and currently available treatments have major drawbacks. For example, non-steroidal anti-inflammatories cause gastric and renal damage; and opioids cause constipation and problems with tolerance and addiction.
The team aims to develop selective ion channel blockers, which avoid those that play essential roles in the heart and brain, and test them in animal models of IP and NP. In separate parallel studies they will use a known non-selective blocker to carry out proof-of-principle studies in human NP. |
| 05/02/2021 |
£129,030 |
|
UNIVERSITY OF STRATHCLYDE |
The opportunity to renew the Wellcome Trust (WT) Masters Programme Award comes at an exciting time for the M.Sc. in Health History (HH) at the CSHHH Glasgow. The purposes of the initial award were to; enable UK based applicants to study on the degree at a time of growing demand for teaching in the field; to drive connections with students from outside of the UK as Health History develops in Asia and Africa. The Centre has proven able to meet these objectives, having funded one South African and two UK students to date. All were integrated successfully into a student body that includes those from partner institutions in Shanghai through the WT funded Medical Humanities China-UK (MHCUK) programme. This proposal will secure further resources for the development of this increasingly diverse Medical Humanities student community at a time when the M.Sc. HH continues to grow new capacities for career-building and training in partnerships both within, and beyond, academia. Its international scope also prepares it to actively engage in the re-establishment of collaborations around the globe in the wake of disruption caused by COVID-19 by placing the next generation of Health History scholars at the heart of this process.
|
| 05/02/2021 |
£134,844 |
|
UNIVERSITY OF YORK |
Since 2016 the University of York’s MA in Medical History and Humanities has offered students invaluable perspectives on Medical Humanities, exploring the historical, literary, philosophical and political nuances of the field. Its thematic structure ensures a wide range of subjects and option modules are incorporated to provide interdisciplinary and international perspectives, and to facilitate inter-cohort learning from the diverse perspectives of students and teaching staff.
This successful course has been developed further in response to student feedback, advances in the broader field of Medical Humanities and the unique perspectives offered by staff research undertaken at the University of York and the Centre for Global Health Histories. The University specializes in interdisciplinary collaboration, and as a University for Public Good (as set out in its strategic vision statement to 2030), draws on a rich tradition of social justice and equality alongside internationalism and innovative thinking.
Renewal of the studentship grant is now being sought to further grow the course. Previously successful applicants have been of an extremely high calibre. We anticipate that the students who successfully win these scholarships will go on to match and exceed the successes of those who have completed the course thus far.
|
| 05/02/2021 |
£149,726 |
|
BIRKBECK UNIVERSITY OF LONDON |
This is a joint programme between HCA and ETCW, but also draws on expertise across the Humanities and Social Sciences at Birkbeck. It runs for one year full-time or two years part-time. Most students complete two core modules, two subject-specific option modules and a dissertation. But we also offer a coursework-only pathway, which is popular among students coming from health professions. Students taking this pathway complete the core modules and four option modules.
The MA addresses the cultural complexity of historical and current health issues, including infectious diseases, preventative medicine, mental health, disability, expertise, authority and medical ethics. Additionally, students learn about the emergence and organisation of the medical humanities as an academic field and the debates that shape its identity and purpose.
Many students use the MA programme to prepare for doctoral study or careers in health policy and management. Others use the MA to enrich established careers as health professionals, developing more reflexive practices and sensitive relationships with their patients. The original grant offered opportunities to students with disabilities and from disadvantaged backgrounds who would otherwise have been unable to afford postgraduate study. We would use the renewal to widen access and diversity, including opportunities for BAME students.
|
| 05/02/2021 |
£186,643 |
|
LONDON SCHOOL OF ECONOMICS AND POLITICAL SCIENCE (LSE) |
Renewal of the WT Award for the LSE MSc in Health and International Development (HID). To date the two WT scholarship recipients (one graduated, one current) were selected from shortlists of outstanding applicants demonstrating excellent potential for research careers. HID offers a multi-disciplinary social science approach to health. The core courses expose students to theoretical, substantive, and methodological debates in health-related research. The compulsory research design course supports students’ formation as independent researchers, preparing them to develop dissertations where they probe deeper into health-related issues on specific topics that motivate them. Optional courses from a range of disciplinary perspectives (political science, anthropology, development studies, social psychology) allow students to tailor their learning to their research career aspirations. The integration of health and development make the degree truly distinctive, and different from health degrees taught in schools or departments of health. HID graduates are analytically sophisticated, and able to grapple with complex health-related questions and evidence. Studentships are allocated on merit, but also on a highly motivated personal statement and experience. Our experience of WT studentships to date is that they allow the very best future researchers to gain confidence, flourish, and take the next steps in their health research career.
|
| 05/02/2021 |
£164,629 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
The Humanities and Social Science (HSS) Pathway supports students taking the MSc in Public Health at the London School of Hygiene and Tropical Medicine. The degree provides students with the knowledge and skills necessary to improve the health of populations, communities and groups within them. The course emphasises the use, development and critical evaluation of conceptual models, evidence and methods of analysis, and on the design of effective interventions and policies at all levels. Students holding the Studentship follow an HSS ‘Pathway’ through the degree. This involves taking specialist modules in HSS (such as history, anthropology and sociology) and producing a dissertation rooted in these disciplines.
The Pathway has improved award holders’ understanding of health and the value of HSS for interrogating this. The programme has allowed students from a humanities or social science background to develop the knowledge, understanding and skills necessary to comprehend the multi-faceted nature of ‘public health’. Renewing the studentship enables us to move the programme to the next stage by growing, diversifying and strengthening the cohort of award holders. This will help build a new generation of researchers who understand public health policies and practices and are also able to critique and contextualise them.
|
| 05/02/2021 |
£129,007 |
|
NEWCASTLE UNIVERSITY |
Our current MA award enables us to recruit and train students who would otherwise be deterred from studying at MA level due to a fear of incurring more debt. Despite securing studentships, and developing cogent, novel research ideas, these students doubt their ability to progress as researchers, struggle to acknowledge their own achievements, and question whether they belong in the university’s research community. Wellcome MA funding offers a rare opportunity to diversify the research community: while UKRI funding supports capable doctoral students, lack of MA funding prevents many promising students from progressing beyond a BA. Our renewal plan utilizes this opportunity, aiming to dismantle barriers that prevent talented researchers from progressing.
We also aim to prepare our students to tackle complex health challenges by highlighting the role of history and humanities within multidisciplinary and transdisciplinary health research projects. We have capitalised on institutional investment to create a sustainable and intellectually diverse cross-faculty Newcastle medical humanities network. This has enriched our medical humanities research-led teaching, facilitated cross-disciplinary supervision, and enabled students to tap into a growing number of relevant research resources, networks and activities. We will encourage our students to adopt innovative multidisciplinary agendas at the outset of their research careers.
|
| 05/02/2021 |
£114,062 |
|
UNIVERSITY OF BRISTOL |
Thank you for the opportunity to apply to renew our Masters programme award. We are seeking renewal so that we can continue to offer outstanding Bioethics training opportunities to promising young scholars.
Based in the Centre for Ethics in Medicine (CEM), our programme is designed for students who are interested in a research career in Bioethics, and its aim is to foster future bioethics research and develop future bioethics research leaders, through equipping MScR students with the diverse skills and knowledge needed for doctoral (and further) inquiry. We specifically aim to grow into a national feeder programme for research careers in bioethics, including as a feeder into our own PhD programmes, and support our students in applying for PhD funding.
To date we have funded three promising Bioethics scholars from diverse disciplinary backgrounds, two of whom have secured PhD funding and one is in the process of applying for it.
In our renewed programme we will be revising our selection criteria to ensure candidates can more easily adjust to unforeseen changes in their projects, offering enhanced initial training opportunities, and ring-fencing two studentships for healthcare professionals.
We look forward to continuing to support a next generation of Bioethics research leaders.
|
| 05/02/2021 |
£169,771 |
|
UNIVERSITY OF CAMBRIDGE |
In 2016 we began a new MPhil in Health, Medicine and Society (HMS). HMS provides students with interdisciplinary training in the history, philosophy, anthropology and sociology of health and medicine. Through taught modules, keyed to research essays supported by one-to-one supervisions, students are introduced to theories and methods, develop skills in conceptual and empirical analysis, and become acquainted with the scholarly literatures across all four disciplines. No other programme in the UK does this. Moreover, because it is situated within a vibrant international hub of humanities and social sciences research in health and medicine, students are supervised by leading scholars in the field. The programme is attracting applications from a diverse and talented body of students. The studentships we are applying for would help us to bring outstanding students from a range of backgrounds to Free School Lane, to equip them with skills of critical thinking in the humanities and social sciences, and to launch them into careers where understanding health and medicine matter.
|
| 05/02/2021 |
£140,046 |
|
UNIVERSITY OF WARWICK |
This application requests a series of studentships for the MA in the History of Medicine at Warwick over a three year period. Our case, in the document attached, is partly based on reviewing the type of degree that we have created, reflecting on its developing strengths and explaining why we feel the MA merits further support; but it also sets out how we plan to build on this foundation in developments that take us forward in exciting new ways. These relate to new staffing, a rethinking of aspects of curriculum in line with shifts in the field, a commitment to diversity, and our ongoing efforts to create a culture that has produced a stream of talent in the history of medicine as well as leaders in the fields of health policy and the medical humanities. We argue that the Warwick program has some unique strengths. We also however embrace the opportunity to propose a series of improvements to current practice. Our case is built around four main headings that reflect the guidelines. Our response places emphasis on enhancement, new approaches, and an underlying holistic vision that both we and our students benefit from them being integral to our research community.
|
| 05/02/2021 |
£144,840 |
|
UNIVERSITY OF BRISTOL |
The below proposal relates to the University of Bristol’s LLM in Health, Law, and Society. It provides:
Reflections on the impact of the award so far;
Explains how we would make the most of a renewal; and
Summarises my vision for the next three years.
The proposal involves critical self-reflection, explanation of how and why I continue to believe that the LLM is a worthy programme for this funding award, and an outline of how we would modify the running of the award in the coming years. Notably, the changes relate to: practical support for wider skills-development beyond the taught aspects of the programme; and the University of Bristol Law School’s commitment to supplement the fees on two of the scholarships to enable inclusion of students from Low and Middle Income Countries.
In the additional materials to this application, the proposal is complemented by demonstrations of institutional support, and links to wider materials that may be useful in considering the merits of the application.
|
| 05/02/2021 |
£138,975 |
|
UNIVERSITY OF SOUTHAMPTON |
The MSc in Global Health within the Faculty of Social Science at the University of Southampton is a multi-disciplinary programme designed to equip students with the necessary skills to understand and respond to global health challenges. Our previous award from the Wellcome Master's Programme Award in Humanities and Social Science enabled three talented students from low- and middle-income countries to attend this highly successful programme. They have gained an extensive understanding of key issues in Global Health from a social science perspective as well as strong quantitative skills that provide a firm basis for a successful career in research. They have also established enduring links with Global Health academics within the University who will continue to support and advise them.
We are now requesting funding for a further five studentships. Three will again be ring-fenced for students from low- and middle-income countries, while the other two will be open to UK students in order to build further capacity in global health research within the UK. In addition to gaining subject knowledge, quantitative expertise and transferable skills for the workplace, they will also be supported in planning their future careers and offered opportunities for networking and gaining specific training and experience.
|
| 05/02/2021 |
£140,199 |
|
UNIVERSITY OF MANCHESTER |
Founded in 1986, CHSTM is the largest British group devoted to the integrated historical study of science, technology and medicine. Our core belief is that these fields cannot be studied in isolation from each other or their wider socio-cultural contexts, and that history can enrich discussion of present dilemmas. Health and medicine are at the forefront of our work, initially supported through the Wellcome Unit for the History of Medicine (1986-2006) and recently through a range of PI-led research projects.
Our Master's Programme in History of Science, Technology and Medicine (HSTM) brings together first-class graduates from humanities, medicine and the sciences each year, and is underpinned by our commitment to research-led teaching. All academic staff contribute to the programme, and students are fully integrated into life at CHSTM through a range of seminars, conferences and public engagement activities.
A recent restructure of the HSTM curriculum, launched in 2020-21, increased our focus on current challenges, such as climate change, race and mental health, and doubled our student intake. This provides us with a unique opportunity to recruit outstanding candidates for the studentship and train the next generation of researchers to work at the cutting edge of health-related humanities and social science.
|
| 04/02/2021 |
£500,000 |
|
WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH |
The SARS-CoV-2 pandemic is a global health emergency that highlighted the need for new antiviral medicines and better pandemic preparedness. Our drug-discovery program focusses on a critical protein present in all coronaviruses, the papain-like protease PLpro. PLpro is essential for viral replication, but also stops our alarm systems to respond to viral infection, To achieve the latter, it removes ‘ubiquitin’ and ubiquitin-like signals required for inflammation and anti-viral signalling. Our world-leading experts in ubiquitin research, drug-discovery and infectious disease biology have leveraged our state-of-the-art facilities to identify new drug candidates to block PLpro. We have screened > 400,000 small molecule compounds and identified new chemical scaffolds that inhibit PLpro from SARS-CoV-2 without affecting human enzymes. Our program will deliver new antivirals to prevent or treat COVID-19 and also develop a library of efficacious drug candidates to combat future coronavirus outbreaks |
| 04/02/2021 |
£317,317 |
|
UNIVERSITY OF GLASGOW |
Inflammation is part of the body's defence system against a wide range of harmful stimuli.
Inflammation also plays an important role in human diseases, including stroke, Alzheimer's,
hardening of arteries, arthritis, and cancer. The ability to image inflammation inside the
human body would provide an improved understanding of this process and provide new
opportunities for diagnosing disease and guiding treatment. ABL-101 is a fluorinated oxygen
carrier which is being investigated for treatment of stroke. It is made up of a large number of
fluorine atoms that can be visualised in MRI using a detector that is tuned to fluorine (19F
MRI). Once injected, cells that are also part of the inflammatory response (macrophages)
take up ABL-101. ABL-101 could therefore be an imaging agent for inflammation. 19F MRI
uses a specially developed radiofrequency coil and some specialised programming that Dr
Santosh and the team at the University of Glasgow wish to assess as a vital step to
developing clinical uses. |
| 04/02/2021 |
£439,472 |
|
INTERNATIONAL VACCINE INSTITUTE |
Salmonella Typhi and Paratyphi A have a high incidence worldwide and coexist in many
areas, especially in South and Southeast Asia. S. Typhi causes an estimated 12.5 million
cases and 149,000 deaths and S. Paratyphi causes about 3 million cases and 19,000 deaths
annually. There is urgent need for better and affordable vaccines against these infections.
The aim of this project is to develop a bivalent Typhi-Paratyphi A vaccine to prevent
systemic Salmonella infections and enteric fever. Specifically, we intend to identify a bivalent
conjugate formulation, arrived through determination of optimal formulation &
characterization conditions, that induces equivalent or higher anti-OSP/Vi IgG titers than
monovalent OSP and Vi conjugate controls, and bactericidal activities against S. Typhi and
S. Paratyphi A, with/without adjuvants. |
| 04/02/2021 |
£519,278 |
|
UNIVERSITY COLLEGE LONDON |
Neuroblastoma (NB) is the most common extra-cranial solid cancer in children and contributes to 15% of childhood cancer deaths. Surgery to remove NB is often incomplete and poses high risks due to the significant involvement of vital organs and vessels.
We aim to develop a novel integrated surgical platform to eliminate cancer more efficiently and safely. With the synergistic use of highly innovative optical techniques, built around a core technology of using injectable probes, we aim to:
1. Specifically, "light up" cancer to help the surgeon in differentiating tumour from vital organs (colour-coded surgery).
2. Equip the surgeon with an innovative special scanner to chase small and non-visible cancer residuals.
3. Kill any minimal residual cancer, left by the surgeon, using a new technology based on light.
This original approach has the potential to improve the effectiveness of surgery in eradicating solid paediatric and adult cancers, leading to better survival and fewer complications. |
| 04/02/2021 |
£476,489 |
|
EPICENTRE |
Malaria remains a key driver of high mortality in sub-Saharan Africa, particularly in Niger. Malnourished children are particularly vulnerable to malaria, and more likely to die from it. Malaria drug resistance to several commonly used drugs has emerged and spread. As a new approach to treat multi-drug resistant malaria, we have proposed to increase the number of drugs to 3 in malaria treatments (i.e. triple-artemisinin combination therapies, TACTs). Epicentre Niger is one site in a multicentre RCT evaluating TACTs, and is uniquely placed given the high rate of malnutrition. We will use Wellcome funding to evaluate the pharmacokinetic properties of TACTs in this critical population of malnourished children, with the aim of understanding the complex relationship between malnutrition and drug efficacy. This funding will specifically target aid for a vulnerable and neglected population, while providing evidence to reduce the impact of two of the most devastating crises in the region. |
| 04/02/2021 |
£504,936 |
|
KING'S COLLEGE LONDON |
Coronary artery disease (CAD) is the most common cause of death in the UK. Modern medical
imaging scans, such as cardiac magnetic resonance imaging (CMR), allow an accurate, noninvasive
and radiation-free diagnosis of CAD and the early identification of patients that would
benefit from available treatments, before complications such as heart attack and heart failure
develop.
There are not enough doctors in the UK trained to accurately interpret these scans, and this
results in an underutilisation of CMR, also with significant regional variations. We will bridge
this gap by creating computer programs based on artificial intelligence that, acting as expert
digital doctors, will facilitate the interpretation of the scans and guide the clinical team in
the management of patients with suspected CAD. This technology will enable advanced
imaging to be rolled out in any hospital equipped with a suitable magnetic resonance scanner,
regardless of the presence on-site of trained doctors. |
| 04/02/2021 |
£320,413 |
|
ROYAL COLLEGE OF SURGEONS IN IRELAND |
Epilepsy affects around 50 million people worldwide. Temporal lobe epilepsy is the most common and drug-resistant form in adults. A particular microRNA involved in brain structure and function has emerged as a potential new disease-modifying target. This project will develop a gene therapy-based treatment to inhibit this microRNA. The study will adapt an already clinically-approved gene delivery technology to ensure the therapeutic is delivered to the right part of the brain. The outcome will be a clinical trial-ready gene therapy with a unique mechanism of action that can reduce and prevent seizures in this devastating form of epilepsy |
| 04/02/2021 |
£494,777 |
|
UNIVERSITY OF CAMBRIDGE |
Although cancer immunotherapy has come of age, such therapies are currently only beneficial for some patients, particularly those with tumours with lots of mutations. Therefore, new therapies desperately need to be developed. Our approach is to make tumours look like virally infected cells enabling a patient's own naturally pre-existing immune cells to recognise and destroy tumours. There are many advantages to our innovation. As it utilises natural immunity, it will be less toxic with fewer side effects compared to other treatments. The immune responses can be highly controlled. We can target solid tumours, which are often not treatable with current immunotherapies. Furthermore, our treatment will be cheaper than cell-based therapies. We expect our work to widen cancer immunotherapy as a valid treatment option to a larger cohort of patients, including those with disease resistant to current immune based treatments, and to bring tangible clinical benefits to patients. |
| 04/02/2021 |
£501,343 |
|
UNIVERSITY OF OXFORD |
Fat deposition in the liver is now the commonest chronic liver condition, affecting one-in-three individuals. It can lead to liver problems including cirrhosis and liver cancer as well as increasing your risk of heart attacks and strokes. Simple blood tests are often normal, and the current gold-standard test for assessing NAFLD severity is a liver biopsy. This is an invasive procedure that is associated with significant complications, including pain and bleeding. We have developed a urine test that measures natural steroid hormones and provides an accurate reflection of how the liver is functioning in patients with NAFLD. We wish to extend our findings to a large cohort of patients with NAFLD to ensure that our test is accurate and reliable. If successful, our urine test could be used by GPs and hospitals reducing liver biopsies and making a significant advance to patient care. |
| 04/02/2021 |
£310,300 |
|
CENTRE SUISSE DE RECHERCHES SCIENTIFIQUES - COTE D'IVOIRE |
Insecticide resistance in malaria vectors has been clearly identified as one of the major obstacles for malaria control. While developing new chemicals for bednets is expensive with no guarantee of success, a less expensive option can be developing a physical method for killing resistant mosquitoes. Studies using infrared cameras revealed that more than 75% of mosquito interactions with bednets occurred on the net roof; by exploiting this natural behavior, Dr Mouhamadou will develop an insecticide-based mechanical solution that kills mosquitoes regardless of their insecticide resistance status. Dr Mouhamadou will design and develop a long-lasting insecticide-treated mosquito trapping bednet for mass mosquito trapping and killing, the "LLI-TNet". The LLIN-TNet will be field-evaluated in Africa against wild free flying high resistant malaria vector Anopheles gambiae population. The goal is to develop a cheap strategy which can be widely used to overcome the problem of insecticide resistance in malaria vector control. |
| 04/02/2021 |
£756,386 |
|
UNIVERSITY COLLEGE LONDON |
The larynx is a sphincter whose main function is as a sphincter to prevent food, drink and saliva passing onto the lungs ("aspiration"). Therefore, neuromuscular and mechanical disturbances of laryngeal function lead to considerable problems managing secretions, eating and drinking and recurrent pneumonia. 30% of persons with acute stroke develop aspiration, whilst it is the commonest cause of death in patients with neuromuscular diseases and throat cancer survivors. Our vision is to transform the lives of those losing laryngeal sphincter function by combining the cutting-edge technologies of bioengineering and soft robotics into an implantable sphincter device. Our team partners leading surgeons, engineers and scientists with patients and business experts. Preliminary work completed includes: i) biomaterials testing in the laboratory and patients; ii) creation of a valve generating sound at speech frequencies; iii) electrical systems capable of accurately controlling speech, swallowing and breathing. Here, we integrate these components in a single, soft robotics based, device. We will (a) trial internal and external power solutions; (b) compare internal and external sensors for control; (c) compare electrical and magnetic actuator solutions; (d) include patients and healthcare workers in project planning and management; (e) identify the evolving pathways to healthcare implementation for complex implantable devices. If successful, this project will deliver the world’s first soft-robotics-based implantable healthcare solution and provide proof-of-concept for novel solutions to other, diverse and common unmet patient needs, especially those involving sphincters (e.g., incontinence).
C7 Post award |
| 04/02/2021 |
£503,771 |
|
UNIVERSITY OF ABERDEEN |
Over 1 million people die every year from a serious fungal disease. One major cause of these diseases is the fungal pathogen Candida. Treatment is restricted to three main classes of synthetic drugs which are poorly tolerated and have increasing problems due to drug resistance. Biologics, such as monoclonal antibodies (mAbs), have revolutionised the treatment of other diseases. We are developing first-in-class antifungal mAbs to address the unmet need for safer antifungal drugs which are effective against drug-resistant infections. We have cloned naturally occurring mAb genes from the B cells of recovered patients. These mAbs protect mice from Candida bloodstream infection and show great potential for treating drug-resistant infections. We will optimise these mAbs for therapeutic use and test in mouse models of drug-resistant infection, accelerating development of this urgently required new class of antifungals. Ultimately, these new agents have great potential to improve patient outcomes and reduce healthcare costs. |
| 04/02/2021 |
£764,285 |
|
UNIVERSITY OF CAMBRIDGE |
Advances in medical and digital technology are generating large volumes of patient mental health data. Interpreting these rich data is key for improved early diagnosis, patient stratification and new drug discovery. Specifically, in the case of dementia, diagnosis at early stages of neurocognitive decline has major implications for timely clinical management. We currently intervene too late and often target the wrong patients. Here, we propose an innovative AI-guided healthcare solution that uses machine learning to improve early precision diagnosis and prognosis from low-cost, non-invasive data. Our aim is to deliver a clinical decision support system that will: a) help clinicians assign the right patient at the right time to the right diagnostic or treatment pathway, b) improve patient wellbeing and reduce healthcare costs, as patients undergo fewer, less invasive, less expensive tests, c) guide patient selection for clinical trials to enhance their efficacy and pave the way to drug discovery. |
| 29/01/2021 |
£50,000 |
|
UNIVERSITY OF GLASGOW |
This grant will support the 2021 International Genetically Engineered Machine Competition (iGEM), by supporting UK undergraduate students from the synthetic biology community to take part in it.
The provided funding will be used to support the students’ stipends, some consumable and travel support for the teams that have successfully applied to the competition.
Wellcome has funded the iGEM programme for several years as this is an interesting model to develop interdisciplinary thinking and skills for students. Funding is provided in partnership with BBSRC who also make available a £50k contribution.
Wellcome (Luigi Martino) will be involved at the selection stage and receive a brief report about the respective activities at the end of the year.
COVID-19 effect on the competition. The hope is that this year’s teams will have the ability to undertake wet-lab-work. If this is made impossible by the potential restricted access to lab spaces, the selected teams will be asked to submit a written proposal reporting the design and strategy to build their chosen genetically engineered machine. |
| 29/01/2021 |
£773,978 |
|
UNIVERSITY OF OXFORD |
Aims and key deliverables;
To provide consistent technical support to national testing programmes for SARS-CoV-2 in Kenya, Malawi and South Africa.
To support epidemiological research, clinical trials, immunological studies and genomics work
To consolidate and maintain positive relationships with national policy makers.
Our respective Wellcome AAPs/Centre (i.e. MLW, KEMRI-Wellcome, AHRI and CIDRI-Africa) have responded to the COVID-19 pandemic by making resources and staff available for SARS-CoV-2 testing, accounting currently for significant proportions of the local and/or national testing capacities, especially during surges. It is ethically imperative to provide national support alongside research-driven testing, and we have found this testing provided an opportunity to develop stronger relationships with national Government, with the potential for research that is better aligned to informing policy and with a better position to communicate. The immediate need has been covered by re-allocating resources for paused activities. The proposal here will bridge the gap between our immediate response and more sustainable long-term funding. This will allow us to sustain the enhanced relationships developed through our response to the pandemic, and will avoid the reputational risks that might be associated with failing to support the obvious ongoing need while establishing more sustainable long-term projects and core provisions.
|
| 29/01/2021 |
£115,046 |
|
CODE FOR SCIENCE AND SOCIETY |
Research software is a critical component of open research, and an increased focus on research software challenges will further the objectives of Wellcome Trust’s Open Research programme to maximise research impact. The Research Software Alliance (ReSA) advances the vision that software is valued as a fundamental component of research. This proposal will support ReSA to bring research software communities together to collaborate on the advancement of research software, utilising application of the FAIR principles as a catalyst for this global endeavour.
This project seeks USD$157,250 to engage the research software community to apply the FAIR principles to research software. to achieve three aims:
FAIR4RS WG project direction to develop agreed FAIR for research software principles
FAIR4RS Roadmap leadership to map FAIR for research software projects into a longer-term strategic framework
People Roadmap to support the development of career paths and reward structures to complement the FAIR4RS Roadmap
This proposal will accelerate the development of an open research system that recognises and supports research software. This will provide researchers with the skills and resources to fully utilise research software, in a system where policy makers and funders value research software, and where organisations adequately reward staff with software expertise.
|
| 29/01/2021 |
£338,472 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Antivenoms are bespoke biologicals that have been the mainstay of snakebite treatment for 125 years. Requirements for production, safety and efficacy vary across regulatory environments. Shortages of effective antivenoms have emerged as important public health issues, particularly in Sub-Saharan Africa. The variability of current products in this market present substantial challenges. WHO is exploring a pathway for prequalification of antivenoms and identified a need to develop target product profiles (TPPs) to support optimisation of current and emerging products. TPPs can play a central role in the drug discovery and development process towards desired product characteristics, including access, equity and affordability considerations. At present, there are no available public-interest TPPs for snake antivenoms. We will develop public-interest WHO TPPs with preferred and minimally acceptable profiles for antivenom therapeutics, with an initial focus on Sub-Saharan Africa. The work will be a collaboration between WHO and DNDi following the 2018 WHO TPP Generic Methodology. The resultant WHO TPPs will be widely shared through diverse communication channels and publications, and listed in the WHO Health Product Profile Directory. TPPs will assist product standardization and guide more targeted research and development of antivenoms.
|
| 29/01/2021 |
£1,485,631 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Sub-Saharan Africa has a high snakebite burden, compounded by a lack of safe, effective and affordable treatments that are accessible to victims. Across seven East African countries (Ethiopia, South Sudan, Uganda, Kenya, Tanzania, Rwanda and Burundi) there are an estimated 89,940 (95% Confidence Interval: 74,511-105,385) cases of snakebite each year, while in seven West African nations (Cameroon, Nigeria, Chad, Togo, Benin, Ghana and Burkina Faso) there are 70,712 (95% CI: 58,348-84,791) cases annually. Access to snake antivenoms for the treatment of snakebite envenoming in sub-Saharan Africa has been declining since at least the 1970’s and current data provided to WHO suggests that
|
| 29/01/2021 |
£639,793 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Nepal, as for much of Asia, has high levels of labour migration, particularly to neighbouring India and the Middle East. The SARS-CoV-2 pandemic has caused a chaotic mass return migration event. While the government has attempted to quarantine and test returning migrants the fragile infrastructure has been rapidly overwhelmed and repeated migration waves have occurred into remote rural areas.
The epidemic in Nepal is now entering the rapid escalation phase. Despite this surge, the government has been forced to raise the lockdown, imposed since March 24th, due to the economic and political consequences. There is limited understanding of the pattern and extent of transmission in this context due to limited and sporadic testing.
Understand how return migration is influencing the epidemic dynamics in rural vs. urban contexts.
Understand how the reported data from the core government testing system compares to estimated community prevalence dynamics to predict testing capacity gaps and refine future response.
Determine sensitivity and specificity of GeneXpert Xpress testing using nasopharageal swabs or saliva against RT-PCR for SARS CoV-2 infection.
Sequence a cohort of 500 SARS CoV-2 samples to understand the patterns of repeated introduction, seeding and transmission occurring in rural and urban areas as the epidemic unfolds.
|
| 29/01/2021 |
£4,059,969 |
|
COALITION FOR EPIDEMIC PREPAREDNESS INNOVATIONS (CEPI) |
A large-scale study in the Democratic Republic of Congo (DRC) to deliver Janssen's candidate Ebola vaccine regimen VAC52150 (Ad26.ZEBOV, MVA-BN-Filo). The vaccine Ad26.ZEBOV (5x1010 viral particles[vp]) will be given as the first dose and the vaccine MVA-BN-Filo (1x108 infectious units [Inf U]) will be given as the second dose 56 (-14 day +28 day) days later, to adults, and children aged 1year or over. Evaluation of this intervention will include the estimation of the effectiveness of the two-dose vaccine regimen to prevent Ebola Virus Disease (EVD) and a qualitative component of the understanding and perceptions of individuals of this study. The primary objective is to estimate the effectiveness of vaccination of the population with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen for the prevention of EVD in adults and children aged 1 year or above. The study sponsor will be the London School of Hygiene and Tropical Medicine (LSHTM). The study PI will be Professor Jean-Jacques Muyembe-Tamfum from the DRC Institut National de Recherche Biomédicale (INRB).
|
| 19/01/2021 |
£325,774 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
This research will investigate the ethics of British public health over the period 1920-2020, through the lens of public health law. In so doing, it will develop the ‘public health humanities’ as a mode of designing and implementing interdisciplinary research in public health. My goals are to discover how the implicit and explicit ethical frameworks of public health law have changed over the period in question; to analyse how and why these changes came about; and to explore methods for investigating public health ethics from interdisciplinary perspectives. I will use documentary and archival sources to locate and interrogate moments of morally inflected controversy in public health law, and will work collaboratively with public health practitioners and researchers to explore novel methods of data generation and analysis. Attention to ethics and public health law in Britain 1920-2020 disrupts assumptions that ethics in this time and place has been neutral and unchanging, and examines relationships between shifting ethical frameworks and factors including the post-war welfare state and its subsequent roll-back, decolonisation, migration, epidemiology, HIV/AIDS, and bioethics. The project will historicise ethics, connect past and present, and provoke cross-disciplinary interrogation and integration, for the benefit of the humanities and public health alike.
|
| 19/01/2021 |
£263,061 |
|
UNIVERSITY OF EDINBURGH |
Who delivers health care, where and why? The COVID-19 pandemic has underscored stark global inequalities in answers to these questions. ‘Community participation’, an enduring pillar of interventions in the Global South, has been leveraged in response to COVID in Africa via Community Health Workers (CHWs). Key agencies who recruit Africa’s army of Community Health Workers (CHWs) have declared them to be COVID’s emerging ‘first line of defence’. This research will examine the structural factors that lead to the recruitment of CHWs and which contribute to the persistent undervaluing of CHWs’ work in Kenya. The research will innovate in its combination of discourse analysis, informed by critical/feminist/postcolonial thought, with detailed ethnographic fieldwork in Kenya's marginalized north. The research will firstly provide a critical reading of the ‘imperial remains’ within CHW recruitment practices on the part of health agencies and INGOs. The research will secondly provide a historicized reading of (gendered) narratives regarding citizenship, public service and voluntarism in postcolonial Kenya. This research will then be brought into dialogue with detailed interviews with and ethnography of/by CHWs in Isiolo, northern Kenya, with implications for CHW policy but also for rethinking the desirability and justness of one of global health’s core assumptions.
|
| 19/01/2021 |
£175,664 |
|
UNIVERSITY OF MANCHESTER |
Novel social and cognitive science, approaching people and places as indivisible assemblages, challenges dementia research’s traditional humanism (people as exceptional entities) and neuroreductionism (brains as cognitive supercomputers). However, these traditional ideas permeate current "dementia-friendly" strategies, positing that agentic persons inhabit inactive spaces. Resulting initiatives assume that architectural refinement will maximise individuals’ intrinsic cognitive capacities, overlooking the complex distribution of cognition throughout evolving atmospheric spaces. They often lack user perspectives and sophisticated theoretical grounding. In response, I will combine cutting-edge scholarships to explore cognition-environment relations through a sensory ethnography of Manchester’s public transport, a target for dementia-friendly initiatives. I will accompany 25 passengers with dementia, documenting the journeys through interviewing, fieldnotes, photography and mapping. Participants will capture photographs and videos for an exhibition across the transport network. The exceptionally rich dataset, comprised of audio-visual media, sensory ethnographic data and maps, will be made available to future researchers. The project will challenge outdated assumptions in dementia research and policy, developing proposals for improving each. It aligns with policy priorities and will propose service improvements in collaboration with key stakeholders. It will generate an unprecedented open-access dataset for analysing dementia-friendliness and cognition-environment relations, and pioneer methods for inclusive ecological dementia research.
|
| 19/01/2021 |
£161,826 |
|
UNIVERSITY OF READING |
My project will investigate images (drawings, illustrations, and photographs) as central to scientific research into causes of the disease and the mechanisms of its spread in British India between 1890 and 1940. Despite Ronald Ross’ own emphasis that his experiments on malaria were visual revelations, visual representations of malaria have remained neglected in historiography so far. I intend to explore how images informed research on malaria and influenced future inquiries into the development of tropical medicine and the processes of their institutionalisation. This project enriches the scholarship on malaria in colonial India by bringing into focus the importance of visuality in knowledge-making. This will facilitate an exploration of the power of images in strengthening, as well as shaping resistance to British imperialism; and also how medical visual culture gave meaning to human-animal relationships within an imperial context. In so doing, beginning with scientific images produced in the laboratory, I move into the domains of British administration and that of the vernacular reception, translation, and appropriation of the malarial iconography. By examining the interactions between the fields of arts and medical science, this project will be a major contribution to the historiographies of British colonial medicine and modern South Asia.
|
| 19/01/2021 |
£154,510 |
|
UNIVERSITY OF WARWICK |
This project will produce a cultural and social history of speech therapy in twentieth-century Britain that is ambitious in seeking to account for the entwined relationship of speech therapy to stammering activism, not simply in a relationship of medical professional to patient. Municipalities employed speech therapists from c.1906 to ‘correct’ what (in contemporary language) were considered ‘defects’ of children’s speech. Early therapists were often female, trained in drama-school elocution and only later became medicalised. Consequently, they were as marginalised as the disabled subjects they sought to ‘treat’. Conversely, individuals who stammered long pointed towards the uniqueness of their position and voice to militate for improved therapy. In short, this project allows an ambitious study that cuts across normally polarised voices of ‘medical professional’ and ‘patient experience’ to explore the boundaries of what encompasses ‘the medical’ itself: both as practices (elocution therapeutics and activism) and as theories (what ‘stammering’ meant). ‘The Child’s Speech’ therefore offers a unique case study into the margins of disability studies which can point towards new frameworks for thinking about professionalisation; its relationship to competing, but also harmonising, forms of expertise, patient voice, experience and activism; and wider gender, race, class and disability dynamics within these.
|
| 19/01/2021 |
£210,087 |
|
UNIVERSITY OF LIVERPOOL |
The research project offers an in-depth analysis of the conflation between biomedical practice, care and antiblackness in the colonial wake. Using historical, geographic and ethnographic methods, it examines how the history of enslavement and colonialism is entangled with notions and practices of Western biomedical care and the spatial organisation of a postcolonial hospital. As a location for this study I have chosen Connaught Hospital in Freetown, Sierra Leone. Situated on Freetown's Northern coast between White Man's Bay and Susan's Bay, this was both the setting for mandatory quarantines for liberated slaves and the site of the British-built Colonial Hospital. Working with Sierra Leonean healthcare staff, I will examine the hold this violent past has on Sierra Leonean conceptions of care and trust in biomedicine. This allows me to 1) explore how biomedicine's conflation with antiblackness shapes biomedical encounters in postcolonial Sierra Leone and 2) examine how biomedical spaces and infrastructures perpetuate feelings of distrust and exclude other forms of care. In doing so I will 1) challenge the traditional geographical remit of Black Studies, 2) study how antiblackness weaves its way through medicine and care and 3) give Fanon's analyses of colonialism, racism and biomedicine a contemporary & geographic dimension.
|
| 19/01/2021 |
£246,365 |
|
KING'S COLLEGE LONDON |
Data-driven health research, and the technologies it produces (DHRTs), are increasingly driving the UK health sector. DHRTs, which rely on advanced computing sciences and ‘big data’, have the potential to make a profound impact on society, and the pace of development is staggering. Equally, the databases, infrastructures, and software supporting DHRTs have important environmental and health impacts: their heavy energy requirements lead to high carbon dioxide emissions, and the reliance on minerals to develop their technological components can lead to unsustainable and/or toxic mineral extraction and e-waste disposal. While the environmental footprint of DHRTs may be considered unproblematic because of improvements in energy efficiency and the move to renewable energy, the speed of innovation is set to outpace the world’s renewable energy sources, leading to increases in carbon emissions when other sectors are decreasing their energy use. Moreover, issues of unsustainable mineral extraction/e-waste disposal still remain. It is imperative that the environmental footprint of DHRTs is considered through responsible innovation that targets environmental sustainability. This project’s aim is to use a UK perspective, qualitative case-study approach, that builds an empirical knowledge base that identifies the ethical, social and regulatory issues associated with DHRT’s environmental impacts.
|
| 19/01/2021 |
£276,979 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
As people live longer, the coexistence of multiple conditions in one individual – ‘multimorbidity’ – becomes more common. Scholars across the biomedical sciences have expressed concern that research, training and care systems remain organised along single-disease and single-organ-system lines and that new ways of producing knowledge about multimorbidity are needed. Medical anthropologists, with well-established strengths in illuminating and unsettling dominant frameworks, are ideally equipped to collaborate with biomedical scientists to articulate and respond to the challenge posed by multimorbidity. Using the analytic frame of ‘epistemic infrastructures’, referring here to the fragmented global assemblages through which knowledge about (multi)morbidity is produced and legitimised, I will investigate how individuals in different settings and communities of practice understand and engage with multimorbidity. Further, I will co-produce with them a conceptual framework for responding to this complex bio-social phenomenon. To achieve this, I propose a collaborative multi-site ethnographic study in global health institutions in the UK and research, training and care institutions in Zimbabwe, involving participant-observation, in-depth interviews and participatory methods. These activities, culminating in a symposium, will iteratively build the proposed framework. By involving biomedical researchers throughout, my research will be uniquely positioned to open new pathways to influence research, policy and care.
|
| 19/01/2021 |
£177,775 |
|
UNIVERSITY OF LEICESTER |
This project will produce a history of grief and loss in late-Georgian Britain (c.1760-1830) that re-evaluates current perceptions of grief as unhealthy, and will redress the imbalance in historical and literary studies that have focused overwhelmingly on assessments of bereavement, mourning and mortuary rituals. It will recover the full range of Georgian experiences of grief to show how understandings of grief extended far beyond the immediate emotional upheaval associated with death, encompassing much wider definitions than those we attribute to grief today. Grief awarded meaning to interpersonal relationships, offerering avenues for self-reflection and providing comfort during periods of separation. This project will apply historical and literary research techniques to a linguistic and material culture analysis of grief, and engage with research in psychology, sociology and philosophy. It will interrogate grief across three main themes: Sadness and Separation; Bereavement; Loss and Abandonment – which are embedded within acts of resilience, remembrance and recovery. The main goals of this project are (1). to investigate what it meant to grieve in late-Georgian Britain (2). to examine the relationship between grief, loss, comfort and well-being, and to (3). assess to what extent experiences of grief were regulated by conventions and mediated through socio-cultural codes.
|
| 19/01/2021 |
£333,089 |
|
UNIVERSITY OF SHEFFIELD |
There is a growing recognition that Alzheimer’s-like dementias need to be understood in environmental, rather than simply genetic, terms. Head injury has been identified as one such environmental antecedent to dementia and a new class of dementias known as TReNDs – Traumatic brain injury Related NeuroDegenerative disorderS – has emerged. This recasting of Alzheimer’s-like dementias as environmental conditions has significant implications for professions, patients, and publics and potentially transforms the classification, diagnosis, treatment, and regulation of neurodegeneration.
This project is based around a multi-sited ethnography, undertaken with scientists in molecular neuroscience; neuropathology; and sports science. Sitting at the intersection of medical sociology and Science and Technology Studies, the project asks:
Q1: How does depicting Alzheimer’s-related dementias as environmentally-induced change understandings of the classification, cause, and diagnosis of neurodegenerative disease?
Q2: How is research into traumatic brain injury shaping novel therapeutic interventions for neurodegenerative diseases? What are the consequences for patients?
Q3: How are regulations embedded into research on environmentally-induced dementias? What are the envisaged risks, regulations, and wider policy implications of this biomedical research?
In asking these questions, this project is amongst the first to empirically explore the societal and scientific implications of these emerging sciences of dementia.
|
| 31/12/2020 |
£50,000,000 |
|
AMR ACTION FUND GP, LLC |
The AMR Action Fund aims to bridge the funding gaps and technical barriers that antibiotic developers face as they head into later-stage development and ensure new treatments for drug-resistant infections are available to the patients who need them the most. We aim to bring 2-4 new antibiotics to patients by 2030. We will work with partners to create market conditions that enable sustainable investment in the antibiotic pipeline. |
| 31/12/2020 |
£147,298 |
|
TASK FORCE FOR GLOBAL HEALTH |
Early 2019, a group of global health leaders with expertise in influenza, vaccinology and pandemic preparedness convened in London, for a Wellcome Trust-supported "Shaping Meeting to explore the value of a coordinated work plan for epidemic and pandemic influenza vaccine preparedness." Ready2Respond was formed as a global collaboration of partners committed to enhancing lower income countries’ readiness to respond against influenza and respiratory viral pandemics. With a Secretariat established at The Task Force for Global Health, Ready2Respond identified challenges and actionable solutions to promote pandemic preparedness. Though initially based on influenza preparedness, these priorities now include COVID-19.
Three Expert Working Groups will design and execute cross-collaborative projects within three strategic priorities.
Burden of Disease
Risk Communication and Community Engagement
Vaccine Access
Ready2Respond seeks an initial grant from the Wellcome Trust of US$ $196,650. This initial grant will allow to:
retain a Director, tasked with developing a comprehensive action plan with potential projects to start in 2021.
execute a mapping study of organizations and agencies working on global seasonal and/or pandemic vaccine preparedness to ensure the relevance of Ready2Respond’s mission and activities in the preparedness ecosystem.
support communication activities to secure funds for identified projects from potential partner organizations.
|
| 31/12/2020 |
£4,575,696 |
|
UNIVERSITY OF CAPE TOWN |
In the WHO AFRO, there is a need for sustainable mechanisms to provide scientific and technical EIDM support for vaccines and immunisation. We propose to establish a Regional Scientific Hub (RSH) to support NITAGs with EIDM. The RSH’s mission is to enable NITAGs in the WHO AFRO to strengthen EIDM with respect to vaccines and immunisation practices. The RSH will offer the EIDM support to NITAGs in close collaboration with the WHO. Public health professional members working within immunisation programmes, technical partners and other health groups will also be supported by the RSH. The support provided by RSH will strengthen the effectiveness of African NITAGs, resulting to an enhanced access to existing and new vaccines in the region.
Through the provision of the EIDM support, the RSH key goals are:
- Enhance access and use of EIDM resources and tools by members of NITAGs
- Empower NITAGs to produce timely and independent evidence-based recommendations that inform national decisions on vaccines
- Foster an increased national ownership of immunisation programmes in the region.
- Accelerate the strengthening of national immunisation programmes
Achieving these goals will result to increased immunisation rates and improved introduction of new vaccines in the WHO AFRO.
|
| 31/12/2020 |
£3,750,237 |
|
UNIVERSITY OF OXFORD |
The ACORN project will establish a network of hospitals and clinical laboratories in Asia and Africa to implement efficient patient-focused antimicrobial resistance (AMR) surveillance. Network data will be used to determine AMR disease burden, risk factors, and patient and economic impacts for key clinical syndromes and associated pathogens.
ACORN will address the need for better systems for linked clinical and microbiology data analysis to enable clinicians and ministries of health to understand and respond to the locally and nationally relevant AMR challenges and to engage meaningfully with international surveillance efforts. ACORN will provide simple to use data collection, visualisation, and analysis tools along with a framework for sites to improve clinician utilisation of diagnostic microbiology resources. Targeted clinical and outcome data collection will enable local use of pathogen and antimicrobial susceptibility data, for example by identification of high-risk patients and for development of empiric treatment guidelines.
Global AMR surveillance and mitigation endeavours are weakened as a result of limited active healthcare provider engagement via local data use. Project engagement efforts will focus on promotion of widespread adoption of ACORN, through collaborative links with key AMR stakeholders, to ensure that future global surveillance has meaning, from the ground up.
|
| 31/12/2020 |
£2,283,242 |
|
INTERNATIONAL VACCINE INSTITUTE |
The need for vaccines against invasive non-typhoidal salmonella (iNTS) is now increasingly being recognized, but there is no iNTS vaccine available for use in humans. Several potential candidate vaccines against iNTS are being developed. Vaccine development considerations include a bivalent iNTS vaccine (Typhimurium and Enteritidis) or possibly a trivalent vaccine (Typhi/iNTS). Such financial investments not only need public-private partnerships, but also demand economic and public health justification. The World Health Organization (WHO) and other global partners have recently highlighted the need to justify investments in vaccines from a multi-stakeholder perspective.
The overall objective of this project is to develop a Full Value of Vaccine Assessment (FVVA) to understand the value of investment in an iNTS vaccine from a multi-stakeholder perspective. The long-term goal of this proposal is to pave the way for the development of a safe and efficacious iNTS vaccine, in-country licensure (marketing authorization in the country of manufacture), any necessary policy recommendations from the WHO Strategic Advisory Group of Experts (SAGE) on Immunization, WHO prequalification (PQ), Gavi financing, UNICEF purchasing and national technical advisory groups recommendations for vaccine use. This will be achieved as a joint IVI/WHO leadership and collaboration through a consensus process in partnership with multiple stakeholders." |
| 31/12/2020 |
£1,418,660 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
In the next five years, the necessity for open science to solve global challenges will become increasingly apparent, and the need for Europe PMC as a critical piece of infrastructure will crystallise in the minds and usage patterns of researchers. The world of scientific publishing will undergo major changes, as routes for rapid and transparent publishing emerge, and efforts such as Plan S push towards universal open access. Europe PMC will support these goals by aggregating millions of articles and making them widely available. With a leading role in preprint aggregation and standards development, Europe PMC will be the go-to resource for searching life sciences literature from publication through review, revision, and citation. Publications at all stages need to be grounded in unambiguous links to supporting data, authors and reviewers, funding, and institutions, to build transparency and trust in the content; building these links will be a major direction for Europe PMC. Finally, transformative change in content search and retrieval will come from the development of AI methods that work on open access full text, encouraged by the Europe PMC platform for text and data mining, as well as the demonstration of machine learning benefits in user interfaces.
|
| 31/12/2020 |
£244,662 |
|
UNIVERSITY OF OXFORD |
Not available |
| 08/12/2020 |
£777,721 |
|
UNIVERSITY COLLEGE LONDON |
Despite successfully suppressing HIV infection with antiretroviral therapy (ART), cerebrovascular disease, including stroke and cognitive impairment, remains a dominant complication in this population. I have shown that HIV is a leading risk factor of stroke in the young and can contribute to 15-30% of overall stroke presentations in endemic regions. There is good evidence that atherogenesis is part of the mechanism. Chronic inflammation and antiretrovirals are amongst confounders that obscure delineating the exact pathway to atherogenesis. The Neurovascular Unit (NVU) which consists of the cerebrovascular endothelium supported by astrocytes and pericytes is pivotal to maintaining blood vessel function and impeding HIV to enter the brain. To date, scientific advancement has been limited by developing experimental systems that replicates the NVU in its normal environment. My fellowship proposes to use a powerful new in vitro multicellular 3D model of the NVU, with blood brain barrier (BBB) properties similar to those found in vivo, to investigate how HIV crosses the BBB, establishes NVU infection, and triggers endothelial dysfunction, a precursor for atherogenesis. Finally, I will exploit an established cohort of HIV patients with ART and phenotyped for cerebrovascular disease in Malawi, to verify the mechanistic insights from my in vitro findings.
|
| 08/12/2020 |
£1,194,434 |
|
UNIVERSITY OF OXFORD |
Entrapment neuropathies are the most common conditions causing nerve-related pain. Even though Physiotherapy is the recommended treatment, research suggests only modest benefits. A major road-block is the lack of adequate patient stratification. My fellowship will address this by investigating the role of neuroinflammation in precision physiotherapy. The key goals are to 1) characterise human neuroinflammation, 2) validate magnetic resonance neurography (MRN) as a non-invasive marker and 3) determine whether physiotherapeutic exercises (neurodynamics) can reduce neuroinflammation. I will use longitudinal cohorts of patients with carpal tunnel syndrome (CTS) and Morton’s neuroma undergoing surgery as model systems with unparalleled access to injured tissues (e.g., nerve, skin, tenosynovium, blood). I will characterise neuroinflammation and its relationship to symptoms in these samples using gene/protein expression and histological analyses. By directly comparing MRN with histological findings, I will determine its validity as a non-invasive marker for neuroinflammation. I will then perform a mechanistic trial to investigate whether neurodynamic exercises reduce neuroinflammation by measuring MRN before and after exercises or control interventions in CTS patients. My project will provide novel biological insights into neuroinflammation, and may revolutionise its clinical detection. The development of precision physiotherapy has high potential to reduce patients’ suffering and decrease healthcare costs.
|
| 08/12/2020 |
£658,017 |
|
IMPERIAL COLLEGE LONDON |
Antibodies are fundamental to defence against a wide range of infectious agents and yet antibody responses vary markedly from individual to individual. Although the reasons for this remain unclear, there is strong reason to suspect a role for immunoglobulin gene regions, not least because these are amongst the most variable in the human genome. In earlier work, I linked the immunoglobulin heavy chain (IGH) locus to susceptibility to the most serious diseases caused by Streptococcus pyogenes, a major global health concern, and I now wish to determine the biological basis for this association. This proposal therefore aims to test my hypothesis that common genetic variation in this locus impacts antibody-mediated immunity to S.pyogenes in a manner that alters disease susceptibility. To do this, using an innovative high-throughput long-read sequencing approach, I will establish the extent and nature of germline IGH variation in children and adults with and without severe infection. I will then assess the relationship between IGH variation and antibody-mediated immunity as well as susceptibility to severe infection. Moving forward, I plan to use this approach to identify and prioritise antigens for rationale design of highly targeted vaccines and antibody-based therapeutics to combat a range of infectious diseases.
|
| 08/12/2020 |
£1,155,073 |
|
UNIVERSITY OF LIVERPOOL |
Worldwide many women require drug treatment during breastfeeding, but data surrounding transfer of drug from mother to breastfed infant are scarce and of very low quality. This fellowship will provide robust pharmacological data to inform evidence-based decision-making, through collaboration between University of Liverpool, UK; Infectious Diseases Institute, Makerere University, Uganda (IDI); and University of Cape Town, South Africa (UCT).
The drug exposure of infants of breastfeeding mothers requiring treatment for TB (drug-sensitive or drug-resistant), malaria and peri-partum infection, identified as local priorities, will be described. Intensive pharmacokinetic sampling of maternal plasma, breastmilk and infant blood will be undertaken. Bioanalysis will be done in the country of study, with capacity building at IDI supported by Liverpool and UCT. Consolidation of an integrated clinical and modelling approach for clinical pharmacology at IDI will ensure the generation of high-quality, robust data, and a sustainable group generating fresh ideas and proposals alongside the fellowship.
South-north knowledge transfer will help define research priorities for the UK and build expertise in lactation pharmacology in Liverpool. Public engagement activities in both the UK and Uganda will communicate about study activities and harness the views and concerns of community members and healthcare workers about medication use in breastfeeding.
|
| 08/12/2020 |
£1,148,941 |
|
NEWCASTLE UNIVERSITY |
Generative models of perception, such as predictive coding, are mainstays of contemporary neuroscience. Whilst there is abundant evidence and theory concerning what is predicted and when it is expected, little is known about how predictive models influence how strongly sensations are received (i.e. their intensity, or its perceptual counterparts such as loudness).
This proposal builds upon the handful of studies demonstrating the existence of predictive processing of intensity, and on my own published work demonstrating that pathological states of perception (i.e. tinnitus) can be understood, and objectified, as pervasive states of aberrant sensory predictions. Its goal is a clear picture of the function and neurobiological basis of predictive intensity processing, which might subsequently lead to diagnostic and therapeutic avenues for clinical disorders such as tinnitus, chronic pain and fibromyalgia.
The investigative approach is multifaceted, examining a range of hierarchical levels through a progression of paradigm complexity, and using complementary neuroimaging modalities, including electroencephalography (EEG), magnetoencephalography (MEG), electrocorticography (ECoG) and functional MRI. The predominant focus is auditory intensity (and loudness) in normal-hearing controls, with a subset of successful paradigms being run in clinical populations (to demonstrate the practical relevance of measures obtained), and in the somatosensory system (to demonstrate modality-independent commonalities).
|
| 08/12/2020 |
£811,808 |
|
UNIVERSITY OF CAMBRIDGE |
I recently discovered the function of a previously uncharacterised gene, FAMIN, that is linked to Crohn’s disease, leprosy and arthritis. A multifunctional purine enzyme, FAMIN is the pacesetter for purine recycling and hence determines cellular redox status, pH balance and energy production. Altogether, these control macrophage functions, such as bacterial killing and cytokine production. Importantly, my work has established this therapeutically targetable purine pathway as a direct driver of human inflammatory disease. However, further investigation of this pathway is currently limited by the inability to directly visualise and study purine metabolites in-situ, in real-time, and at single-cell resolution. Thus, the spatiotemporal dynamics of purine metabolism are mostly unknown. Assessing these dynamics will be crucial in understanding how purine dysfunction emerges in individual cells and can influence disease pathogenesis, for example through affecting redox state. Samie Jaffrey has pioneered technology that could overcome this hurdle. His group has generated programmable RNA-biosensors capable of live-imaging metabolites in single cells. I intend to learn these techniques and will engineer bespoke sensors for purine metabolites. I shall use these biosensors to dynamically track purine metabolism, and interrogate how environmental triggers can cause the purine dysfunction seen in numerous pathological contexts including chronic inflammatory diseases.
|
| 08/12/2020 |
£1,588,250 |
|
KING'S COLLEGE LONDON |
The sex chromosomes underscore basic differences between males and females, and the X and Y chromosomes have specialized functions in the gonad and germ cells. Sex chromosome aneuploidies, i.e. Klinefelter (XXY), Turner (XO) and double-Y (XYY) syndromes), form the largest group of chromosomal abnormalities and are associated with infertility. While recent studies have defined the mechanisms for germ cell loss in XO and XYY mice, Klinefelter syndrome (KS) infertility remains poorly understood. KS males experience an early spermatogonial block and germ cell loss initiates in utero. The early loss of gonadal function has significant long-term consequences.
Gametogenesis in males occurs throughout their lifespan and relies on germline (spermatogonial) stem cells (SSCs), differing with females. Recent work from our group has identified the concerted activity of gene networks in driving spermatogenesis, and unique regulation of X-linked genes during this process. We observe that a number of X-genes express specifically in SSCs. However, regulation of SSCs self-renewal vs. differentiation dynamics, and the functional importance of X-linked genes in this process, remain poorly understood. We aim to understand physiological gene regulatory networks functional in SSCs using a combination of single-cell methods, to explain how perturbation in X-gene dosage in SSCs may cause infertility.
|
| 08/12/2020 |
£611,636 |
|
QUEEN MARY UNIVERSITY OF LONDON |
My proposal is focused on understanding the genetic basis, and consequently the pathophysiology, underpinning disordered human puberty.
Pubertal disorders are common, but associated with severe comorbidities. Delayed puberty presents a diagnostic challenge in adolescence, as conditions of gonadotropin deficiency and isolated delayed puberty display the same clinical and biochemical phenotype. However, correct management is vital because the former is associated with infertility and requires intensive reproductive therapy, whereas the latter is self-limiting but associated with a shortened reproductive lifespan. The biological mechanisms of precocious puberty, a condition associated with increased long-term cardiovascular and cancer risk and thus with significant impact on public health, remain similarly opaque.
The identification of causal genetic defects in disordered puberty allows interrogation of the key regulators of human puberty.
I will use whole genome sequencing, comparative transcriptomics and methylomics studies in my large human cohort with disordered puberty, to define shared exonic and regulatory mutations resulting in delayed and precocious puberty. I aim to characterise the biological mechanisms underlying pubertal disorders through functional characterisation of novel genomic defects using cellular assays and animal models. These findings will ultimately translate to improved diagnostics, tailored therapeutic management and improved long-term outcomes for patients with disorders of puberty.
|
| 08/12/2020 |
£807,333 |
|
UNIVERSITY OF LEEDS |
Patients with type 2 diabetes(T2D) are ‘cardiac energy-deficient’ and this deficiency contributes to their excess heart failure(HF) risk. The key mechanisms for cardiac energy deficiency are reduced myocardial blood flow, loss of metabolic flexibility over the choice of energy fuels and mitochondrial dysfunction. The contribution of these changes to the development of HF has not been systematically studied.Recent studies have highlighted the potential role of ketone bodies as a significant fuel source, and suggested an association between mild ketosis and improved clinical outcome in T2D.
Two work packages will be performed. Work-package1 aims to:
Elucidate the mechanisms of the energy-starved state of the heart in diabetes;
Determine how alterations of cardiac energy metabolism differ between prediabetes, T2D, and concomitant T2D and HF;
Determine if ketones induce a differential response in mitochondrial respiration and whether this differential response varies along the continuum of diabetic heart disease.
Data will be acquired from patients undergoing aortic valve surgery for comprehensive assessments including: cardiovascular magnetic resonance imaging and spectroscopy; coronary sinus sampling studies; high resolution respirometry and liquid chromatography-triple quadrupole-mass spectrometry metabolomics from heart samples.
Work-package 2 will explore the impact of ketone infusion on cardiac energy generation and contractile function in T2D patients.
|
| 08/12/2020 |
£321,092 |
|
UNIVERSITY COLLEGE LONDON |
Congenital athymia causes life-threatening T-cell immunodeficiency. The only definitive treatment is thymus transplantation (TT). Despite lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus, repopulated by recipient bone marrow-derived lymphoid progenitors, supports functional T-cell development restricted to host MHC alleles. Though lifesaving, TT results in subnormal circulating T-cell numbers and frequent autoimmune complications. I aim to dissect the cellular and molecular mechanisms of lympho-stromal crosstalk and thymopoiesis in the context of MHC-mismatched TT by using single-cell and spatial genomics on pre-transplantation cultured thymic tissue and post-transplantation graft biopsies. Donor thymocytes, possibly including long-lasting lymphoid progenitors, remaining at the time of transplantation despite lympho-depleting preparatory culture, may contribute to this crosstalk and assist thymic epithelial cell (TEC) homeostasis. Other recipient-derived haematopoietic cells may migrate into the graft to replace direct interactions between developing host thymocytes and TECs. Alternatively host TECs may develop in the transplanted thymus. I hypothesise that partial MHC-matching improves crosstalk signalling, achieving better immunoreconstitution and less autoimmunity. Optimising in vitro differentiation and maturation of TECs derived from pluripotent stem cells will make the in-depth investigation of MHC-TCR interactions and downstream signalling possible. New insights into TEC biology will advance alternative approaches to thymus replacement therapy.
|
| 08/12/2020 |
£99,012 |
|
WELLCOME SANGER INSTITUTE |
Congenital athymia causes life-threatening T-cell immunodeficiency. The only definitive treatment is thymus transplantation (TT). Despite lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus, repopulated by recipient bone marrow-derived lymphoid progenitors, supports functional T-cell development restricted to host MHC alleles. Though lifesaving, TT results in subnormal circulating T-cell numbers and frequent autoimmune complications. I aim to dissect the cellular and molecular mechanisms of lympho-stromal crosstalk and thymopoiesis in the context of MHC-mismatched TT by using single-cell and spatial genomics on pre-transplantation cultured thymic tissue and post-transplantation graft biopsies. Donor thymocytes, possibly including long-lasting lymphoid progenitors, remaining at the time of transplantation despite lympho-depleting preparatory culture, may contribute to this crosstalk and assist thymic epithelial cell (TEC) homeostasis. Other recipient-derived haematopoietic cells may migrate into the graft to replace direct interactions between developing host thymocytes and TECs. Alternatively host TECs may develop in the transplanted thymus. I hypothesise that partial MHC-matching improves crosstalk signalling, achieving better immunoreconstitution and less autoimmunity. Optimising in vitro differentiation and maturation of TECs derived from pluripotent stem cells will make the in-depth investigation of MHC-TCR interactions and downstream signalling possible. New insights into TEC biology will advance alternative approaches to thymus replacement therapy.
|
| 01/12/2020 |
£2,387,230 |
|
UNIVERSITY COLLEGE LONDON |
The vast majority of DNA is non-coding, repetitive, encompasses a significant proportion of disease risk and is divergent across populations. Major bottlenecks in the past restricted our understanding of this genomic region, including limited analysis techniques, inability to sequence large repetitive, homologous regions and the paucity of population control datasets. These restrictions have largely been overcome, and through early translation we have highlighted the importance of non-coding genomic factors with the identification of pathogenic recessive repeat expansions, homologous replicated regions and gene amplification events as major causes of neurological disease.
The overarching theme of this proposal is to investigate four large diverse neurology cohorts, where genome sequencing has explained less than one-third of cases. Initially, we will examine non-coding, short-read genome sequencing data using optimised and newly developed algorithms. Next, to overcome the limitations of short-read sequencing, we will apply and integrate long-read Oxford Nanopore genome sequencing and optical genome mapping to a range of neurological disease trios and paired brain and blood samples. Finally, we will comprehensively interpret and validate data, reannotate against diverse control genomes, compare disease-relevant transcriptome builds, interrogate collaborator cohorts and use transcriptome sequencing to inform on pathogenicity, identify mechanisms and pathways impacted by genetic vulnerability.
|
| 01/12/2020 |
£2,298,141 |
|
UNIVERSITY OF GLASGOW |
Leishmania parasites cause a neglected disease on the WHO priority list. During their life cycle, these single-celled parasites must migrate through the sandfly (promastigotes), pre-adapt for mammalian infectivity (metacyclic promastigotes) and proliferate inside macrophages (amastigotes) while withstanding host immune defences. Adaptation to these radically different environments involves many changes, including metabolic and cell structure specialisations, ensuring survival and transmission. However, current understanding of these processes is disjointed and biased towards predicted/expected pathways. Half of Leishmania’s protein-coding genes, including most unique to Leishmania, have no known or predicted function, (the "dark genome"), leaving potentially exploitable parasite biochemistry untapped in the search for new therapeutics. We aim to identify all major parasite pathogenicity factors. We will determine a) the subcellular localisation of all proteins with poorly predicted function (~50% of the genome) and b) the fitness cost of gene deletion in each life cycle stage (100% of the genome). Integrative analysis of this deep dataset will identify key pathways in 1) organelle adaptation for an intracellular parasitic lifestyle and 2) host interaction, which we will then functionally dissect. This will identify virulence factors on a genome scale, determine the most important pathways required for parasitism and illuminate the ‘dark genome’.
|
| 01/12/2020 |
£2,010,416 |
|
KING'S COLLEGE LONDON |
Depression and anxiety are leading contributors to the burden of disease among adolescents in low- and middle-income countries (LMIC), and they disproportionally affect adolescents living in poverty. Yet, the evidence base for interventions that effectively prevent depression and anxiety among adolescents living in poverty is weak. One major shortcoming is that interventions often fail to address poverty-related social determinants of mental health and neuropsychological consequences of poverty (such as impaired self-regulation). The aim of this study is to develop and pilot-test an intervention that equips adolescents with skills to escape poverty and strengthens self-regulation, thus preventing adolescent depression and anxiety in urban LMIC settings.The study objectives are to: (1) develop a theoretical model of the causal mechanisms linking poverty, self-regulation, and depression and anxiety among adolescents (age 10-19 years); (2) collaboratively develop a multi-component selective prevention intervention targeting self-regulation and skills for academic and employment success among adolescents at high risk of developing depression or anxiety living in urban poverty in Colombia, Nepal and South Africa; (3) adapt and validate key instruments to measure eligibility, implementation, mediators, and outcomes of the intervention; and (4) undertake a 4-arm pilot randomized controlled trial of the selective prevention intervention in each site.
|
| 01/12/2020 |
£2,946,454 |
|
UNIVERSITY OF SUSSEX |
How does a circuit of neurons process sensory information? And how is processing adjusted in relation to changes in the sensory environment or internal state of the animal? These questions will be investigated in larval zebrafish, where visual circuits and the behaviours they drive are altered in the context of
i) changes in the visual environment, such as luminance or contrast,
ii) information arriving through chemical and mechanical senses,
iii) the internal state, such as arousal or satiety, and
iv) circadian mechanisms.
To investigate how visual processing is adjusted under these different conditions we will use larval zebrafish to image neural activity through the retina and brain of the behaving animal. Zebrafish generate distinct motor responses to stimuli of different contrasts, size and speed, allowing us to investigate the plasticity of computations directly linked to behaviour.
Our guiding hypothesis is that the plasticity of visual circuits reflects use-dependent changes in synaptic strength and the actions of neuromodulators that reconfigure signal flow. A comparison of computations carried out in different circuits will be key to identifying general mechanisms by which the brain adjusts sensory processing to the sensory environment and/or internal state of the animal.
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| 01/12/2020 |
£2,367,251 |
|
UNIVERSITY COLLEGE LONDON |
Cognitive decline represents a significant and debilitating co-morbidity for patients with epilepsy which is poorly understood with an urgent clinical need for diagnostic, preventative and treatment strategies. Large epilepsy MRI datasets confirm progressive cortical atrophy and white matter abnormalities ; age-accelerated Tau protein accumulation has been reported in surgical resections, correlating with cognitive decline. We propose a comprehensive evaluation of mixed neurodegenerative processes integrating cross-sectional and longitudinal MRI, DWI, DCE-MRI and Tau-PETimaging with quantitative neuropathology measurements of cortical, white mater atrophy and vascular pathology and pTau in resected surgical specimens in the context of cognitive impairment and genetic risk. We aim to characterise tau forms in surgical and post-mortem cohorts compared to Alzheimer's disease and other tauopathies. In prospective surgical cohorts, Tau-PET will be correlated with CSF markers, tissue levels using autoradiography and extent of cortical atrophy with high resolution in-vivo 7T and ex-vivo 9.4T MRI. In addition, cellular drivers for tau accumulation, as MTOR and seizure activity, will be explored through human slice culture experiments with gene-expression analysis and the kinetics of tau incorporation through SILK studies and mass spectroscopy of tissues. These studies will elucidate pathomechanims of cognitive impairment, identify early disease-stage biomarkers enabling prediction and preventative strategies.
|
| 01/12/2020 |
£1,212,397 |
|
UNIVERSITY OF OXFORD |
In vivo methods for mapping brain connections are increasingly used in systems neuroscience but are yet to have significant clinical impact. We propose to develop new computational approaches that bridge information from precise but invasive methods in animals to enhance in vivo methods in humans. We translate this framework into clinical care in surgical patients:
In Aim 1, we will leverage a unique resource of macaque tracers currently being digitised. We will use state-of-the-art machine learning to automate quantification, and image processing for mapping histology to MRI, to produce a unique resource of macaque ground truth connectivity.
In Aim 2, we will develop computational approaches to enable macaque anatomical tracers, alongside multimodal MRI in macaques and humans, to be used to improve the accuracy of methods developed in humans.
In Aim 3, we will build end-to-end approaches for connectivity-based functional localisation, and deploy this as a tool to aid pre-surgical planning for localisation of subcortical targets in deep brain stimulation and for localisation of eloquent cortex in tumour surgery.
|
| 01/12/2020 |
£1,969,785 |
|
UNIVERSITY OF OXFORD |
Plasmids are responsible for virulence and antimicrobial resistance in many bacteria. We will dissect fundamental mechanisms of plasmid maintenance in the obligate human pathogens, Shigella spp. and Neisseria gonorrhoeae, declared as high priority organisms by WHO/CDC. Toxin:antitoxin (TA) systems (addiction systems) are important for plasmid maintenance by eliminating bacteria failing to inherit a plasmid after cell division. For example, the VapBC TA system is essential for maintaining the 210kb Shigella virulence plasmid. Additionally, TA systems (including VapBC) are increasingly recognised for their role in antibiotic tolerance, often a precursor to resistance. Despite this, little is known of how plasmid maintenance is integrated with the bacterial host, and how TA systems are activated after plasmid loss/during tolerance. Combining our understanding of variation in VapBC and the VapC toxin target tRNAfMet with multidisciplinary approaches (mutagenesis/structural:function studies/single cell analysis), we will define mechanisms of TA system activation and the temporal dynamics of events following plasmid loss that culminate in cell death. We will examine the acquisition and maintenance of resistance plasmids in Shigella and N. gonorrhoeae, and the interactions between plasmids and their contribtion to tolerance and horizontal transfer.
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| 01/12/2020 |
£1,465,345 |
|
UNIVERSITY COLLEGE LONDON |
This project uses computational modelling, machine learning, and big-data analysis to address key unknowns on the biology of neurodegenerative disease: when and where it starts; how it spreads over the brain ("propagates"); how it varies among diseases, subtypes, and individuals; how risk factors influence mechanisms. Current models linking imaging and other clinical data to propagation mechanisms are crude, and evaluation remains largely qualitative. The project introduces a powerful Bayesian inference framework, accounting for uncertainties throughout the data-processing pipeline, to enable robust evidence quantification of new and detailed computational models of disease propagation. The approach demands a rethink of contributing technologies. First, we unravel patient heterogeneity, which confounds propagation-model evaluation, through a new generation of data-driven disease progression models that identify fine-grained disease subtypes characterised by temporal trajectory of multi-modal biomarkers. Second, propagation models use brain connectome estimates and are confounded by high connection-error rates. We establish a new probabilistic connectomics paradigm that quantifies likelihoods of false positive and negative connections enabling models to mitigate their inevitable presence. We use the framework to provide the first truly quantitative evaluation of propagation models against state-of-the-art data sets leading to fundamental new insights on the mechanisms of pathology propagation in neurodegenerative diseases.
|
| 01/12/2020 |
£1,661,908 |
|
UNIVERSITY OF DUNDEE |
IL-33 is a critical cytokine in allergy, obesity, helminth infection, sepsis, and respiratory viral infection. Blockade of IL-33 (or its receptor, ST2) is currently being trialled in a range of allergic and inflammatory conditions, including Covid-19. The cytokine has a short half-life on release, but conversely has effects at distal sites and over long periods. Furthermore, innate immune cells in the intestine are poorly responsive to IL-33, but susceptibility to intestinal helminths is strongly controlled by IL-33.
This project will investigate:
1) How, at a protein structural level, parasite proteins effectively block IL-33 responses. Determination of the effects on the parasite and host of blocking parasite modulation of the IL-33 pathway.
2) What are the roles and targets of IL-33 released from the intestinal epithelium, both locally (in parasite infection) and systemically (in diet-induced obesity).
3) The role of soluble IL-33 receptor in stabilisation of IL-33, and its effects at distal sites.
To achieve these aims will we will use structural biology, in vivo models of IL-33-dependent responses, creation of cell-specific ST2-deficient mouse strains, and generation of a soluble ST2-deficient mouse. Finally we will use human blood samples and three-dimensional culture methods to ensure translation of these findings to humans.
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| 01/12/2020 |
£1,509,343 |
|
KING'S COLLEGE LONDON |
Asthma is an airway inflammatory disease, defined by bronchoconstrictive attacks that can be life-threatening. The two essential tissue components of the bronchioles are the airway epithelium and the underlying smooth muscle. In asthma, the smooth muscle is remodelled and becomes hyper-responsive, leading to excessive contractility. We have shown that epithelia are exquisitely sensitive to mechanical forces. Cell crowding triggers cell extrusion, while stretching triggers cell division. We recently discovered that the asthmatic bronchoconstrictive attack, causes excess airway epithelial extrusion and damage, compromising the barrier function, leading to inflammation. We propose that in healthy lungs, epithelia and smooth muscle communicate with each other to ensure sufficient epithelial cells numbers, essential to a tight barrier. However, in asthma, excess epithelial extrusion signals smooth muscle remodeling, actuating further rounds of more intense bronchoconstriction. This feed-forward cycle could perpetuate asthma attacks. We believe that our mechanochemical and cell biological insight into asthma will reveal novel ways to prevent it. We will investigate this hypothesis by addressing the following questions:
1) How are airways remodelled to cause an attack?
2) Do epithelia regulate constriction?
3) Does extrusion shed rhinovirus, yet trigger asthma attack
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| 01/12/2020 |
£1,906,940 |
|
UNIVERSITY OF CAMBRIDGE |
Before mitosis, cells must make two accurate and complete copies of their genome, to ensure genetic stability across cellular generations. This challenging biochemical task requires complex molecular systems that duplicate chromosomal DNA and repair lesions that stall DNA synthesis. Sporadic or inherited defects in the cellular apparatus of genomic duplication cause genetic instability, which is responsible for developmental and degenerative pathologies and for cancer predisposition.
Our knowledge of the molecular basis of eukaryotic DNA replication and related repair processes is incomplete, and this is especially true of genomic duplication in human cells, the most relevant to our health. Our proposal aims to provide a high-resolution view of the molecular mechanisms of DNA replication, using state-of-the-art biochemical and biophysical approaches. We will focus on components of the human replisome, the multi-protein assembly responsible for DNA synthesis in our cells.
There is intense medical interest in the molecular mechanisms responsible for genomic integrity and the rationale for the consequences of their occasional failure. In this respect, the work of our proposal is highly significant as it aims to deliver a comprehensive description in atomic detail of the complex and dynamic processes of DNA replication, when our genome is at its most vulnerable.
|
| 01/12/2020 |
£1,551,260 |
|
UNIVERSITY OF LEICESTER |
Recent chromosome capture experiments have revealed a hierarchical 3D organisation of the genome ranging from Topologically Associating Domains (TADs) to larger-scale active, euchromatic and inactive, heterochromatic compartments. TADs arise through chromatin loop extrusion by cohesin/CTCF while compartments arise through epigenetic modification of the chromatin polymer. It has long been known that dynamic histone acetylation switches between repressive and permissive chromatin, a key event in transcriptional activation. We aim to capture cohesin in different structural states to understand how it is regulated and catalyses large-scale chromatin transactions. We also aim to understand the molecular mechanism behind acetylation-dependent activation of chromatin a reaction that is critical for the establishment of active euchromatin and may contribute to genome compartmentalisation and enhancer-promoter interaction. This proposal has the potential to transform our understanding the molecular mechanism behind two key reactions that contribute short- and long-range 3D genome architecture. It is possible that both mechanisms are interconnected and provide unifying principles to explain gene regulation with broad implications for health and disease.
|
| 01/12/2020 |
£2,107,440 |
|
UNIVERSITY OF CAMBRIDGE |
Lungs possess a remarkable regenerative capacity by dynamic multicellular responses following injury. However, chronic damage makes these responses persistent, leading to fibrosis. We will define the mechanisms by which productive regeneration programmes are diverted to disease remodelling, with the ultimate goal of uncovering therapeutic strategies that can treat or prevent lung fibrosis.
We recently identified Damage-Associated Transient Progenitors (DATPs), a functional mediator of alveolar stem cell differentiation, emerging during lung regeneration. Notably, chronic inflammation leads to accumulation of DATPs displaying defective differentiation, resulting in impaired alveolar regeneration. We aim to identify strategies to target DATPs in chronic injury by dissecting changes in them and their niche environments. Specifically, we will define (1) key DATP-niche interactions during different phases of regeneration, and how to these evolve during disease progression utilising a novel niche-labelling system; (2) transcriptional and epigenetic changes mediating damage-associated reprogramming following injury at single-cell resolutions, and key signalling modules conferring lineage flexibility of stem/niche cells; (3) conserved regenerative programmes and potential therapeutic targets in preclinical 3D human lung disease models we have developed. Our work will provide fundamental insights into defining the cellular and molecular basis of lung regeneration as well as identifying selective therapeutic targets in lung diseases.
|
| 01/12/2020 |
£2,064,491 |
|
UNIVERSITY OF CAMBRIDGE |
The goal of this proposal is to transform our understanding of the molecular mechanisms that control early human development. The mechanisms that regulate early cell fate decisions in human development remain poorly understood, despite their fundamental biological importance and wide-reaching clinical implications for understanding infertility, miscarriages, developmental disorders and therapeutic applications of stem cells. We seek to uncover when and how human embryonic epiblast cells are established and maintained, and to understand the molecular mechanisms that distinguish these pluripotent cells from extra-embryonic cells during embryogenesis. We will further develop pioneering methods to investigate gene function during human embryogenesis using CRISPR-Cas9-mediated genome editing, TRIM-Away protein depletion, constitutively active and kinase dead variants of proteins and small molecule inhibitors and activators. These approaches will enable us to directly test the function of genes involved in Hippo and TGFb signalling, and key transcription factors downstream of these pathways, which we hypothesize are involved in the first and second cell fate decisions, respectively. Altogether, we expect this program to make significant advances in our understanding of the molecular programs that shape early human embryogenesis, which has the potential to provide fundamental insights and to drive clinical translation.
|
| 01/12/2020 |
£4,161,648 |
|
UNIVERSITY COLLEGE LONDON |
The overarching goal of this collaborative project is to make a step change in knowledge of dementia biomarkers by focusing on plasma proteome. We hypothesize that plasma is biologically informative due to the presence of protein signals: imprints of subclinical dementia progression that can be identified via repeated proteomic profiling decades before clinical symptoms, providing novel candidate targets for preventative treatments.
We will use the largest plasma proteome platform currently available, with three aims, to (1) prospectively examine 4,993 plasma proteins in relation to subsequent accelerated cognitive decline and clinical dementia across multiple cohort studies; (2) determine whether the protein hits identified in aim 1 have a causal association with dementia, whether modifiable and druggable, using analysis stratified by time between protein measurement and dementia onset and Mendelian Randomization framework in relation to novel genome-wide, and druggable-genome arrays; and (3) examine whether proteins predicting dementia risk are imprints of risk factors for dementia.
The expected new outcomes include protein targets for drug development; improved identification of potentially modifiable lifestyle risks; dementia trials surrogate outcomes; improved diagnostic markers, plus data resource for future in-depth research on the multisystem aetiology of dementias and proteomics of a range of major diseases beyond dementia
|
| 01/12/2020 |
£1,181,059 |
|
UNIVERSITY COLLEGE LONDON |
Depression is amongst the most burdensome disorders world-wide because it is a common disorder with frequent relapses. Relapse risk is increased by maladaptive thinking patterns such as rumination and helplessness, and by antidepressant discontinuation, which in turn increases maladaptive thinking patterns.
Maladaptive thinking patterns shape emotions and are influenced by emotions. However, we do not know the neurobiological mechanisms underlying these interactions. First, I propose to study this by measuring maladaptive thinking patterns directly using a decoding approach to magnetoencephalography (MEG). MEG decoding reveals fast sequences of stimulus representations during tasks. These sequences can then be compared to computational models to understand the algorithms the brain uses to prioritize information processing.
Maladaptive thinking patterns are targeted by psychotherapeutic interventions and are sensitive to serotonergic manipulations. I will examine how psychotherapeutic interventions influence the interaction between thoughts and emotions, and how an acute reduction in serotonin through tryptophan depletion affects them. The latter study will be performed in remitted depression and allow us to test whether the mechanisms are involved in subsequent relapses.
Overall, I aim to provide a comprehensive account of how objectively-measured thought processes relate to emotions and to the prevention of depression relapses.
|
| 01/12/2020 |
£1,973,118 |
|
KING'S COLLEGE LONDON |
TDP-43 is a conserved RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 normally autoregulates its expression by binding to the 3’UTR of its cognate transcript. We have linked disrupted TDP-43 autoregulation to disease, showing that disease-linked TDP-43 missense mutations disturb TDP-43 autoregulation causing a gain of function, finding that ALS patients harbour non-coding variants in the 5’ and 3’UTRs of TDP-43 that could disturb TDP-43 expression and observing that TDP-43 misregulation in mice causes selective brain atrophy reminiscent of human ALS-FTD. We will follow these leads to understand the causes and consequences of TDP-43 misregulation and elucidate therapeutic targets and biomarkers for ALS-FTD. Specifically, we will dissect the TDP-43 autoregulation protein interactome in wild-type and TDP-43 missense mutant cells by performing in-cell protein-RNA interaction studies and native mass spectrometry. To determine the significance of ALS-linked UTR variants in regulating TDP-43 expression we will perform an in-vitro CRISPR/Cas9 mutagenesis screen with parallel genomic and transcriptomic sequencing. To understand how TDP-43 misregulation causes regional and cell type-specific neurodegeneration we will use in situ sequencing of mouse brain sections to obtain transcriptomic information with single cell resolution.
|
| 01/12/2020 |
£1,490,731 |
|
KING'S COLLEGE LONDON |
The overarching goal of this proposal is to elucidate the functional diversity of the pancreatic mesenchymal lineage. In embryonic tissues, epithelial progenitors receive paracrine signals from the surrounding mesenchymal niche, which can modulate their ability to proliferate and differentiate. The pancreas consists of a variety of specialized epithelial cells, including endocrine and acinar cells, surrounded by a poorly defined heterogeneous mesenchyme. We hypothesise that different mesenchymal lineages define local instructive microenvironments, including cell–cell crosstalk, ECM and signalling molecules, which eventually trigger distinct differentiation programmes from pancreatic progenitors. Sc-RNA-sequencing has generated a transcriptional map of the pancreatic mesenchyme in the mouse embryo. Here, we will unravel the spatial architecture of the identified mesenchymal cell states, linking their position to emerging pancreatic cell identities. Next, we will assess if mesenchymal lineages with a distinct spatial address underlie unique niche regulatory functions, promoting acinar or beta-cell differentiation. Finally, we will study the organisation and function of the identified niche microenvironment(s) in human tissue and pluripotent stem cells. The proposed programme will yield novel insight into pancreas biology and will set the stage for manipulating combinatorial pancreatic niches - an important step towards engineering functional beta-cells for regenerative medicine applications.
|
| 01/12/2020 |
£1,904,154 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Invasive pneumococcal disease causes over a million deaths per year worldwide, particularly in sub-Saharan Africa. Streptococcus pneumoniae strains vary considerably in virulence, but the reasons for this are unclear. Capsular serotype 1 strains are particularly invasive and cause a major proportion of severe infections, including meningitis, but are poorly studied, partly because they have been genetically intractable. We want to understand why serotype 1 strains are highly invasive, and to identify mechanisms that distinguish aggressive S. pneumoniae strains from less aggressive variants. Furthermore, a low-cost serotype 1 vaccine is urgently needed, especially in sub-Saharan Africa. In this project, we will combine and exploit (i) recently-developed in vitro and in vivo infection models, (ii) bacterial RNAseq data (including our data obtained from cerebral spinal fluid from Malawian meningitis patients) and (iii) our methodologies for mutating serotype 1 strains, to identify and characterise the roles of multiple novel genetic determinants important for the pathogenesis of invasive S. pneumoniae infections. We will also characterise in detail the zwitterionic capsular polysaccharide that defines serotype 1 strains and assess its role in pathogenesis. Finally, we will exploit Protein Glycan Coupling Technology (pioneered by the applicants) to produce a much-needed and affordable glycoconjugate serotype 1 vaccine.
|
| 01/12/2020 |
£2,188,451 |
|
UNIVERSITY OF OXFORD |
The overarching goal of my research is to understand the relationship between membrane proteins and their lipid surroundings. This is important since many membrane proteins are unable to retain their structure and function when extracted from their native environment and reconstituted into a membrane mimetic. Dynamic proteins, for example G-protein coupled receptors, solute carriers and sigma receptors, are intimately connected to their membrane environments and prone to loss of function and activity in detergent micelles. To overcome this disconnect we will develop and apply our mass spectrometry approaches to examine dynamic drug targets within their membrane context. Our key goals will be to challenge these receptors and transporters with agonists, antagonists, inhibitors and lipids effectively in situ. Examples include solute carriers which during tumour progression respond to the need for an altered metabolism by increasing expression. Analogous methods will be used to uncover the targets of mitochondrial and lysosomal therapies. Many of our research themes converge on consequences of the COVID-19 pandemic. While this remains an area of intense scientific scrutiny we will focus on the less-studied receptors and ‘infection enhancers’, and contribute to understanding the roles of lipids in the endocytosis and viral recognition pathways.
|
| 01/12/2020 |
£2,336,909 |
|
UNIVERSITY OF OXFORD |
The overarching aim is to understand the neural mechanisms of learning, decision-making, and motivation in humans. We will examine how they emerge from distributed patterns of activity across networks of subcortical nuclei such as the basal forebrain and dorsal raphe nucleus. While we know about such subcortical areas from animal studies, they have been under-investigated in humans. New imaging and uni- and multivariate analysis methods now make it possible to examine the distributed patterns of activity that arise in these areas. We have recently shown that we can record from these areas of the human brain using ultra high field magnetic resonance imaging. In addition, we know that these nuclei interact with cortical areas, especially in orbitofrontal, anterior cingulate, and insula cortex (regions that are especially prominent in humans and other primates). We aim to record from both cortical and subcortical areas and to understand how they interact during learning, decision making, and motivation. The final aim is to assess whether new ultrasound stimulation tools that make it possible to alter neural activity in a minimally invasive manner even in brain areas far from the surface can be used to manipulate brain activity in these circuits in humans.
|
| 01/12/2020 |
£1,492,837 |
|
UNIVERSITY OF GLASGOW |
Cell migration is essential to processes throughout biology, especially embryonic development and immune function. Migration must be steered to be physiologically effective. Steering cues are not well understood; we know a lot about how cells interpret them, but relatively little about how they are generated.
The basic premise of this work is that the cells often generate their own cues, by breaking down attractants that are widely present (and thus initially give no steering information) into local gradients. Attractant breakdown and migration happen simultaneously. This mechanism - chemotaxis up self-generated gradients (SGGs) - is hard to dissect because it is complex, and based on positive feedback loops. We therefore propose a four-pronged, iterative approach, in which we combine less challenging components to create an understanding of the underlying biology.
Key goals are:
(1) explore possible mechanisms and new extensions using computational models;
(2) test outcomes using chemotactic Dictyostelium in custom microfluidic devices;
(3) verify these data by establishing cultured T cells chemotaxing to CCL19 as a model SGG;
(4) combine findings from parts 1-3 to make a 3D, SGG-based model of a lymph node.
Together they will illuminate chemotactic steering in general, by focussing on one physiologically important system.
|
| 01/12/2020 |
£2,059,266 |
|
UNIVERSITY OF OXFORD |
Central obesity is a leading contributing cause of illness and death across the world. Currently available strategies for prevention and treatment of this condition are manifestly inadequate. The research proposed here aims to identify fundamental processes involved in the development of central obesity. I plan to harness the power of human genetics, fused with deep molecular characterisation of the adipocytes to generate novel insights into the biology of central obesity. This ‘multi-omics’ approach will provide the basis for more effective preventative and therapeutic approaches that reduce the burden of central obesity and associated disease.
|
| 01/12/2020 |
£1,271,158 |
|
JOHN INNES CENTRE |
ATP and GTP switches are extensively used to control conformations and functions of proteins in a wide range of biological processes. However, CTP switches have rarely been found in biology. Recent work from our laboratory and others has shown that ParB is a founding member of a CTPase protein family that uses a CTP switch to regulate bacterial chromosome segregation. We hypothesize that CTP switches are currently unappreciated and may be widespread. In the proposed work we will exploit the tripartite ParABS system from Caulobacter crescentus to elucidate the structure, function, and mechanism of the CTP switch that ensures faithful chromosome segregation. Next, we will investigate how other CTP switches regulate membrane association and gene expression by employing Noc and KorB (proteins crucial for chromosome integrity and plasmid transmission, respectively) as models. Lastly, we will identify and characterize other CTP switch proteins in C.crescentus and systematically discover putative CTP-binding/CTPase proteins across all sequenced bacterial genomes. Altogether, this work will provide fundamental knowledge on the mechanism and evolution of CTP switches and open new and unexpected horizons in numerous fields beyond bacterial chromosome segregation. Moreover, our immediate research on plasmid/chromosome segregation and transmission may inform strategies to combat plasmid-borne antibiotic resistance.
|
| 01/12/2020 |
£4,079,159 |
|
UNIVERSITY OF CAMBRIDGE |
The clinical manifestations of placental dysfunction include pre-eclampsia, gestational hypertension and fetal growth restriction. Women who experience placental dysfunction have a two-fold risk of cardiovascular disease (CVD) and diabetes in later life compared to women with uncomplicated pregnancies. However, it is unclear whether placental syndromes have a direct adverse effect on cardiometabolic health, whether a healthy pregnancy is protective, or whether women who experience a placental syndrome simply had poorer cardiometabolic health prior to pregnancy. If placental syndromes do lead to CVD and diabetes independently of established cardiometabolic risk factors (e.g. by causing end organ damage), a focus on CVD/diabetes prevention in this high-risk group of women is likely to reduce the burden of these diseases. Conversely, if pre-pregnancy factors are more important, improving cardiometabolic health in young women prior to conception is key and could reduce the incidence of placental syndromes. We plan to assess cardiometabolic risk factors and validated intermediate phenotypes of CVD/diabetes before conception, during pregnancy, and post-partum to determine whether placental syndromes affect post-partum maternal cardiometabolic health independently of pre-conception cardiometabolic health. This will help to determine the optimal timing and nature of prevention strategies to reduce the burden of diabetes/CVD in women, in future trials.
|
| 01/12/2020 |
£1,947,704 |
|
KING'S COLLEGE LONDON |
Progressive hearing loss is very common but there are no medical treatments to slow down or reverse it. Histopathological reports suggest three main sites of lesion in the cochlea can be involved: sensory hair cells; synapses of hair cells with cochlear neurons; and the stria vascularis which produces a potassium-rich fluid with an endocochlear potential of +100mV that is essential for hair cell sensitivity. This research has three goals that will provide the scientific underpinning for development of new treatments for hearing loss. Firstly, we will investigate whether hearing loss in each of the three pathological categories can be reversed and hearing improved. Secondly, the research will determine what the limiting factors to reversal of hearing loss are and how these define the critical period for intervention. Thirdly, we will develop new diagnostic tools to distinguish the three sites of lesion using objective measures of auditory responses, to establish the underlying pathological contributions to hearing loss in an individual, and hence determine the optimum treatment. To achieve these goals, we will use mouse mutants with well-characterised cochlear pathology as examples of each site of lesion, and a new approach to reactivating a mutant gene after the onset of hearing loss.
|
| 01/12/2020 |
£1,793,281 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Bluetongue virus (BTV), a complex non-enveloped virus with a genome of ten double-stranded RNA segments, is an important pathogen and model for many similar large non-enveloped viruses (including the medically important rotaviruses). Previous studies have provided a well-understood replication cycle, a large range of research reagents and many novel assay systems, all complemented by high resolution atomic structures of many viral proteins. Notably, the recent structure of the viral polymerase in situ, a critical point of replication, has provided a unique opportunity to investigate many details involved in the virus life cycle. To achieve this we will will use state-of-the-art techniques such as cryoEM, cryo-ET, FCS and FRET in addition to our established in vitro and in vivo assays to determine how BTV entry to the cell causes the polymerase to initiate genome transcription from the 10 genomic dsRNAs and how this process differs from the later process of genome replication which follows the packaging of RNA during assembly. We will define how these processes link to the maturation of newly assembled virus particles and their exit from the cell. Our findings will have the potential to develop laboratory data to translational applications in future design of antiviral and vaccines.
|
| 01/12/2020 |
£1,827,981 |
|
UNIVERSITY OF EDINBURGH |
The type I interferon (IFN) response is the major antiviral pathway in mammals but needs to be tightly regulated to ensure effective defence against viruses whilst avoiding the negative consequences of their overproduction, resulting in autoimmune and autoinflammatory diseases.
I have recently demonstrated a central role for microRNAs (miRNAs) in maintaining optimal IFN levels, and conversely, that IFNs are important regulators of miRNA expression. These results led me to hypothesise that there is a tight interaction between the IFN and miRNA pathways, which contributes to specific traits of human diseases where one component of this interaction is altered.
Supporting this hypothesis, our unpublished results show that diseases characterised by altered miRNA expression, such as 22q11.2DS, exhibit a dysregulated IFN response. Vice versa, diseases characterised by an abnormal IFN response, such as systemic lupus erythematosus, display altered miRNA levels. I aim to identify the mechanisms by which the miRNA biogenesis and IFN pathways interact and study the role of this interaction in diseases where the IFN or miRNA biogenesis pathways are altered. These results will provide a mechanistic perspective to some of the common but unexplained traits presented in these diseases and provide novel targets for intervention strategies.
|
| 01/12/2020 |
£2,051,884 |
|
UNIVERSITY OF BIRMINGHAM |
gammadelta T-cells have been retained in vertebrates for ~500million years, and are of increasing therapeutic interest, but their mode of ligand recognition and immunological niche has remained largely mysterious. Here we build on the emergence of parallel innate-like and adaptive human gammadelta T-cell paradigms to address unresolved ‘keystone’ questions in gammadelta T-cell biology. Firstly, we will exploit multidisciplinary approaches to explore the diversity of innate-like and adaptive gammadelta biology in different tissues, their coordination with other immune responses, and how these change in disease states such as inflammation and cancer. Secondly, we will identify molecular targets of gammadelta-TCRs from innate-like subsets and structurally characterise their TCR/ligand interactions and cellular/molecular recognition mechanisms, focussing significantly on the strong emergence of Butyrophilin family molecules as critical TCR-ligands for such populations. Thirdly we will exploit cytomegalovirus infection as a unique human model to identify novel ligands for antigen-experienced adaptive-like gammadelta T-cell subsets. Finally, we will develop and apply new methodology to image and phenotype distinct human gammadelta T-cell subsets in solid tissues, using multispectral immunofluorescence and digital spatial profiling. This programme should help revolutionise our understanding of gammadelta T-cells, and provide a solid foundation for ongoing efforts to therapeutically harness the gammadelta T-cell compartment.
|
| 01/12/2020 |
£2,488,909 |
|
UNIVERSITY OF EDINBURGH |
Trypanosomes undergo development in both their mammalian host and in the tsetse fly to optimise their disease spread. In mammals, the parasites use quorum sensing (QS) to control their virulence and prepare for tsetse uptake through the generation of arrested stumpy forms, which are found in Trypanosoma brucei but not other African trypanosome species (namely, Trypanosoma congolense or Trypanosoma vivax). We recently discovered that oligopeptide signals can drive QS in Trypanosoma brucei, this activating a signal transduction cascade, some components of which we have already identified. We will now explore how the external signal connects to the identified signalling cascade to drive the differentiation response and how this is disrupted in laboratory-selected and naturally occurring trypanosomes that show reduced QS (so-called 'monomorphs'). We will also compare the distinct mechanisms used by different trypanosome species to prepare for transmission to tsetse flies. This will include characterisation of a cryptic 'stumpy like' stage in T. congolense and its developmental loss of the adherence phenotype characteristic of that species. Our research questions are:
How do trypanosomes generate, detect and transduce external QS signals?
How is QS lost in laboratory and natural parasite populations?
How do different trypanosome species prepare for transmission?
|
| 01/12/2020 |
£1,964,639 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Neutrophils contribute to the killing and clearance of pathogens as well as initiate inflammation resolution and tissue repair processes. Furthermore, the established phenotypic and functional diversity of neutrophils have markedly extended the physiological and pathological roles of these myeloid cells. Building on the developing concept of neutrophil heterogeneity in disease settings, and significant mechanistic and pathophysiological data from the applicant, the present project aims to acquire an in-depth understanding of one population of disease-inducing neutrophils, namely neutrophils that have exhibited reverse transendothelial cells migration (rTEM). This phenomenon describes cells that initiate diapedesis, engage with endothelial cell (EC) junctions but then exhibit retrograde motility and re-enter the vascular lumen. Crucially, we have ample evidence that rTEM bestows an activation state on neutrophils in vivo, and that rTEM neutrophils are aligned with remote organ damage. Thus, exploiting recent technological advancements and capabilities, the current proposal aims to gain an in-depth understanding of the prevalence, molecular signature and pathogenic role of this "subset" of neutrophils, most notably in ageing. Furthermore, hypothesizing that the activation state of rTEM neutrophils maybe beneficial for the host, the project will for the first time explore the potential protective, and thus physiological, role of rTEM neutrophils against pathogens.
|
| 01/12/2020 |
£4,031,379 |
|
UNIVERSITY OF OXFORD |
Sensory systems are typically viewed as being organized hierarchically, with stimulus features being progressively extracted as information flows from the sense organs to the neocortex. However, the responses of sensory neurons at each level are continually shaped by a vast network of poorly-understood descending projections. These ascending and descending circuits have largely been studied in isolation and little is known about how they interact to produce the remarkable neuronal adaptability crucial for auditory perception.
We will use coordinated computational and experimental approaches, involving cutting-edge methods for measuring, decoding and manipulating neural activity, to investigate sensory processing during active listening and learning. We will focus on the recurrent neural circuits that enable the brain to adapt to long- and short-term changes in auditory inputs and to integrate other sensory and motor signals. Our goal is to understand three aspects of these circuits: the computational principles behind their representational transformations, the dynamic interplay of bottom-up and top-down signals that enables neurons to adapt to changing auditory and behavioural demands, and the neural and behavioural consequences of hearing-loss related plasticity. Together, this work will transform our understanding of the recurrent, dynamic nature of auditory circuits and how they are affected by hearing loss.
|
| 30/11/2020 |
£249,100 |
|
NATURAL HISTORY MUSEUM |
Not available |
| 30/11/2020 |
£1,786,326 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
The WHO Global Ethics Unit is part of the newly formed Science Division and would like to capitalize on the potential of the division and the global leadership shown by the team during the current COVID-19 pandemic, to truly embed ethics at the heart of decision-making at WHO.
This proposal focuses on adding value to our current work programme. Additional technical and coordinating capacity will allow us to better leverage our vast bioethics networks and collaborative partnership with bioethics groups around the world to: support regional and in-country bioethics capacity needs; further develop a community of ethics experts; develop the global ethics agenda and focus on key areas of unmet or continuing need, including health emergency preparedness and response. Additional resource will also allow us to be more responsive to demand set by the WHO and global research and health communities.
|
| 30/11/2020 |
£44,838 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/11/2020 |
£45,045 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/11/2020 |
£43,573 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 30/11/2020 |
£45,043 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/11/2020 |
£100,000 |
|
CANNON AND MORLEY PRODUCTIONS LTD |
Typist Artist Pirate King is an innovative and accessible dramatic feature film drawn from the extensive archives of art, diaries and letters held at Wellcome of artist and mental health survivor, Audrey Amiss. The film is a first person account and offers a rich insight into how Amiss saw and experienced the world.
Amiss described herself as someone who people crossed the road to avoid. The film does not ‘other’ her, and, for those who did cross the road to avoid her, creates the opportunity to identify with her. The film is a powerful contribution to conversations about mental health stigma and plays an important role in creating representation that can help erase stigma.
For the many people who define themselves as mental health patients/ clients/ users/ former users/ survivors, the film is actively speaking to them. It does not merely address a so called "neuro-normal" audience but represents how ways of thinking, experiencing and seeing the world are diverse and urgently deserve to be represented in their complexity for all to see and engage with.
We anticipate a significant international release of the film, followed later by it being used as valuable study material within academia.
|
| 30/11/2020 |
£4,178,641 |
|
IMPERIAL COLLEGE LONDON |
In the current COVID-19 emergency, a controlled SARS-COV-2 human infection model (CHIM) has the potential to accelerate the understanding of pathogenesis, induction of immunity and immune mechanisms of resistance to disease, as well as a means to test novel diagnostics and treatments, especially between waves of the pandemic, when occurrence of natural disease is relatively uncommon. A large number of SARS-COV-2 vaccine candidates are at various stages of development internationally including those which have recently entered mid-late stage clinical testing in field studies. In order to make the greatest public health impact, there is an urgent need to select the most promising vaccines in the shortest possible timeframe. In addition, human infection challenge can contribute to the identification of correlates and mechanisms of protection against infection and shedding of virus in vaccinated volunteers. Finally, the model may be useful in the determination of the durability of protection in seropositive individuals with documented prior wild type infection. This proposal is a dose titration study to generate two GMP challenge agents and establish the safety of a wild-type SARS-COV-2 controlled infection in the upper respiratory tract of young healthy volunteers that will allow swift and robust assessment of vaccine efficacy.
|
| 30/11/2020 |
£2,134,694 |
|
UNIVERSITY OF OXFORD |
The Phase 3 RECOVERY platform has been a success, recruiting over 13,500 patients and producing 3 clear, world practice-changing results in the first 100 days of recruitment. The RECOVERY team has been approached by clinical investigators from various LMICs who wish to participate in RECOVERY. As it becomes clear that this pandemic will continue at various locations and paces over the next 24 months, there is an opportunity to increase the impact of the RECOVERY trial by expanding internationally. Expansion has the potential to speed up the assessment of novel treatments, increase the global relevance of the trial results, build capacity, and reduce wasted efforts on small uninformative studies. The key goal is to establish RECOVERY internationally, initially in Indonesia, Nepal and Vietnam, with a view to opening sites also in Africa.
|
| 30/11/2020 |
£1,120,861 |
|
UNIVERSITY OF OXFORD |
Understanding the nature, effectiveness and durability of the human immune response to SARS CoV2 is crucial for vaccine development and effective public health management. We are beginning to understand the pattern and kinetics of the humoral response to natural infection but are less certain about other aspects of the response. We are unable to establish with certainty whether an individual with a particular titre of antibody, or a particular T cell response, is likely to be protected from reinfection and, if so, for how long. These are central questions for the development of an effective vaccine. A controlled human infection model will provide a more detailed understanding of the protective immune response. It will provide the opportunity to interrogate the full extent of the immune response at the time of exposure and will also allow the evaluation of the durability of immune responses of all kinds and how they correlate with protection.
Key goals:
To establish an MHRA-approved SARS CoV2 viral stock for use in a controlled human infection model
To determine a challenge dose which is safe and allows virus to be recoverable from infected subjects
|
| 30/11/2020 |
£1,911,840 |
|
SCIENCE MUSEUM |
Not available |
| 30/11/2020 |
£350,000 |
|
UK RESEARCH AND INNOVATION |
Renewal of funding for Centre for Macaques (CfM) to August 2022
|
| 30/11/2020 |
£928,074 |
|
HEALTHY BRAINS GLOBAL INITIATIVE |
Healthy Brains Global Initiative (HBGI) is a collaboration of global leaders in neuroscience, policy, and financing working to improve the lives of those living with mental and neurological disorders and bend the unsustainable US$3 trillion global cost curve borne today by all countries. HBGI is developing an umbrella set of financing mechanisms to leverage billions in financing and fuel an unprecedented increase in brain science breakthroughs. We are currently in the mobilisation stage with a view to a formal launch in 2021.
The Co-Founders and Co-Chairs of the Board are Victor Dzau (National Academy of Medicine) and Garen Staglin (One Mind), and Brad Herbert is the interim CEO. The Wellcome Trust is involved in multiple ways. Ed Whiting is a member of HBGI’s Interim Board, and Miranda Wolpert is Co-Chair of the Use of Proceeds Working Group and Andrew Welchman is also part of the group.
We value the expertise that the Wellcome Trust is providing to us and are requesting US$1.2 million to contribute to HBGI's running costs for the start-up phase. This will fund us to design and launch a governance structure, determine the optimal use of proceeds, confirm metrics for ROI, and design and launch financing mechanisms.
|
| 30/11/2020 |
£505,090 |
|
INTERNATIONAL DEVELOPMENT RESEARCH CENTRE, CANADA |
Wellcome Trust and IDRC will be supporting the building of an agenda for action on the transition to a zero-carbon food system in Latin America. This work will be conducted in parallel to the work conducted by the Rockefeller Foundation and IDRC in East Africa, which aims to "improve the health and wellbeing of low-income and vulnerable populations who face the double burden of malnutrition and environmental threats like climate change" (see annexed document for more information). The work conducted in both regions are part of a growing initiative entitled "Catalysing change for healthy and sustainable food systems", launched by the three institutions. The initiative will provide research grants to leading evidence builders in low- and middle-income countries (LMICs), with the aim of strengthening the contribution and engagement of LMIC research and civil society institutions in regional and global discussions about healthy and sustainable food systems.
|
| 26/11/2020 |
£150,445 |
|
UNIVERSITY OF MELBOURNE |
We propose to address two key areas of research enrichment and public engagement related to our current Wellcome funding (establishing an Australia-wide clinical registry and clinical trials and translation network for early psychosis, the Australian Early Psychosis Collaborative Consortium, AEPCC). The first is co-design a comprehensive and world leading infrastructure for the meaningful involvement of young people and carers with lived experience of psychosis to support the national network of research trials, including necessary training and support. Secondly, utilising this infrastructure for lived experience engagement we will co-design at least two community engagement projects aimed to increase community knowledge and research uptake in young people experiencing a first episode of a psychotic disorder. At the end of the activity we will have developed a co-designed approach of embedding and prioritising the lived experience of young people and carers in the projects that will be prioritised by the AEPCC. We will also have crystallised our ideas as to how and where people with lived experience would like to be involved in promotion and leadership of the AEPCC. Both these outcomes involve scoping training needs and delivering long-term training and support for young people and carers to perform their roles. By the end of the activity we will have achieved a truly collaborative approach within the network to embed the voice of young people and carers with lived experience or early psychosis that will be able to continue and evolve as the AEPCC continues beyond the initial Wellcome grant period.
|
| 26/11/2020 |
£75,710 |
|
UNIVERSITY OF DERBY |
We will develop a collaborative relationship between the Addressing Health enrichment project and the public to improve access to archives and enhance understanding of the history of workplace health. This will be achieved through a programme of online and face-to-face outreach activities on a variety of project topics, with regular evaluation touchpoints to capture learning and improve processes. These activities will support and enhance the Zooniverse project, which will transcribe c. 30,000 postal pension records.
There are three key aims:
to develop archival and content creation skills for our growing community of citizen-scholars.
to enrich public knowledge about histories of workplace health through public-driven research.
to make our data and findings freely accessible through resources including a database of Post Office pensioners 1858-1908, interactive data visualisations, and other co-produced content.
Our project will develop a significant community of citizen-scholars with an understanding of histories of workplace health. These citizen-scholars will engage with the project in different ways: as data explorers using freely available data visualisation resources; by attending seminars, workshops, museum events, and conversation cafés, and through active participation as transcribers and volunteers. We will work with these citizen-scholars to develop research skills, frame new research questions, and co-create content such as blogs and podcasts. By taking our project ‘on the road’, we will also foster stronger links between TPM, local museums, past and present postal workers and citizen-scholars. Through our activities, the project will help facilitate new forms of collaborative research on histories of workplace health.
|
| 26/11/2020 |
£245,520 |
|
UNIVERSITY OF GLASGOW |
Supported by public engagement experts, local organisations and creatives, MEIRU researchers will co-design and deliver three core public engagement activities (PEA) mapped to key research themes of the HLM and GM programmes.
PEA1: Primary school engagement on early origins of long-term conditions
Students will create dramatic, musical, oral and poster presentations exploring the role of their parents’ health and childhood environment on future health and wellbeing for sharing with their communities, District Management Teams and researchers to start community conversations about their influence on health.
Y1 Creation, Y2/3 Presentation
Partners: School Health and Nutrition programme, Schools, UNICEF.
PEA2: Sharing voices of women and families affected by maternal mental health conditions
Creation of a resource (audio and video vignettes) to make women’s narratives of maternal mental health visible in communities, policy discussions (presenting to the Reproductive Health Unit and Mental Health Technical Working Group) and international meetings to agenda set and impact policy.
Y2 Creation, Y3/4 Dissemination
Partners: African Alliance for Maternal Mental Health (AAMMH), St John of God Mental Health Services
PEA3: Documenting family journeys and infant development in birth cohort families.
Documentary style interviews, observations with families on repeat occasions during cohort follow-up, to include filming of cohort procedures and interviews about cohort membership as well as footage of child development and family aspirations, to give context and meaning to statistics on child and family health in Malawi.
Y1 Recruitment, Y2-4 Filming, editing and dissemination
Partners: Art and Global Health Centre Africa (www.artgloafrica.org), UNICEF, film makers
|
| 26/11/2020 |
£63,053 |
|
UNIVERSITY OF YORK |
The Covid-19 pandemic has generated widespread interest in viruses. This public engagement initiative is an opportunity for members of the general public to explore the science underpinning viruses and showcase the opportunities for antiviral therapy generated by Wellcome Trust funded research. Viano - a fusion of the words "virus" and "piano" - is a virtual instrument for playing viral genome data-generated music in concert with 3D virus visuals. Its aim is to communicate the concepts of mutation and selective pressures in viral evolution, the challenges they pose for antiviral intervention, and the opportunities for therapy arising from our discovery of genetically robust features in viral genomes. Viano will be offered as a gallery exhibit and for home use as an app. In the Lowry Museum gallery, Viano will work on a large scale: the main virus 3D image will be projected on the wall (7m x 7m) and users will have access to a large projected musical keyboard on the floor with over 29,000 keys representing the virus’ genomic sequence. Both image and keyboard will be operated via body movement in a Covid secure manner, and a musical genome keyboard on the screen will also be accessible via an Android/Apple mobile and tablet app. Viano will come with a full programme of workshops and debates and will give the public the ability to save and share their musical viral compositions online.
|
| 25/11/2020 |
£611,008 |
|
UNIVERSITY OF OXFORD |
Control of HIV and hepatitis C virus (HCV) requires multi-pronged approaches, including development of curative treatment and effective vaccines, identifying drivers of epidemics, and optimal deployment of interventions. Mathematical modeling and evolutionary analysis of viral genetic data is an important component in achieving these goals, by identifying the drivers of viral spread and evolution.
Chronic viruses evolve rapidly within individuals, meaning transmitted viruses are different from the strain(s) that initiate infections. HIV is arguably the most studied pathogen in history, yet key unknowns remain, including the drivers of within-host evolution, and which viruses are transmitted. Less is known about HCV, which is further complicated by its complex within-host structure. Nevertheless, methodologies developed for HIV can be immediately employed for HCV, fast-tracking the analysis of this virus
A major obstacle has been the short-read nature of viral deep-sequencing, limiting the power of analyses. I will refine and use new long-read deep-sequencing approaches we have developed to sequence and analyse viral populations from an unprecedented number of longitudinally sampled individuals. I will determine the drivers of within-host evolution, with a view to characterise transmitted viruses, develop better methods to infer viral spread and predict evolution in populations, enabling better targeting of interventions.
|
| 25/11/2020 |
£711,213 |
|
UNIVERSITY OF MANCHESTER |
The mucosal immune system is critical for human health; mediating both immunity against pathogens and maintaining mutualism with the microbiota. In contrast, dysregulation of mucosal immune function and homeostatic host-commensal interactions results in chronic inflammatory and metabolic disease e.g. Inflammatory Bowel Disease, obesity and liver disease. Within the intestinal tract, Immunoglobulin A (IgA) is secreted in huge quantities by tissue-resident Plasma Cells to ensure a mutualistic balance of commensal microbial species, which metabolise dietary nutrients to the benefit of the host.
We demonstrate the magnitude of intestinal IgA secretion is entrained by signals associated with feeding, which imprint circadian rhythms onto Plasma Cells that act to align metabolically demanding immune surveillance with times of waking activity. In turn, circadian IgA secretion imprint daily oscillations in commensal microbial species. Despite our findings, the mechanistic basis and physiological relevance of this complex dialogue remain poorly understood. Here we will comprehensively define the molecular pathways that dictate IgA rhythmicity, and determine the consequences of this cross-regulation for host-microbial interactions, immunity and disease. Together this study will provide a step change in our understanding of how the diet, microbiota and mucosal immune system engage in complex temporal crosstalk to ensure metabolic and immune health.
|
| 24/11/2020 |
£120,000 |
|
KILIMANJARO CLINICAL RESEARCH INSTITUTE |
The primary aim of this study is to use next generation sequencing to investigate the T and B cell receptor repertoire in the conjunctival tissue in those susceptible to repeated ocular infection with Ct and those resistant despite similar exposures.
RNA samples selected from archived conjunctival swab samples from a 4-year longitudinal study of children with progressing trachomatous scarring and non-progressing will be used. Sequences will be aligned to their germline V-, D-, and J-genes and assigned according to the IMGT/GENE-DB reference directory. The average length of CDR3 regions, as well as the frequency of shared CDR3s will be compared. The usage of specific V genes, families and their frequency will also be compared. Initial analysis will be conducted on 25 progressors and 25 non-progressors at the final time points. Based on the results of the data obtained, a sufficient number of samples will be selected for further analysis from earlier timepoints in the cohort.
The project has the potential to contribute toward the evaluation and progression of current and future human clinical trials of Ct vaccines.
|
| 24/11/2020 |
£97,200 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Enteric pathogens are a major cause of hospitalisation among children and are associated with diarrhoea, enteric dysfunction, dysbiosis, and increased risk of mortality and readmission especially in low- and middle-income countries. When admitted to hospital, treatment failure may occur despite following guidelines. Furthermore, carriage of pathogens or disturbance in the intestinal microbiome may be hospital-acquired and/or resistant to first-line antimicrobials potentially increasing the risk of readmission. I aim to determine whether molecular evidence of enteric pathogens and gut dysbiosis at hospital discharge, when children were judged as clinically well, is associated with readmission post-discharge among children across the nutritional stratum. This case-control study is nested within the completed CHAIN cohort study (six countries) that aims to characterise demographic, clinical, and social risk factors for mortality among children
|
| 24/11/2020 |
£22,800 |
|
WELLCOME TRUST SANGER INSTITUTE |
Enteric pathogens are a major cause of hospitalisation among children and are associated with diarrhoea, enteric dysfunction, dysbiosis, and increased risk of mortality and readmission especially in low- and middle-income countries. When admitted to hospital, treatment failure may occur despite following guidelines. Furthermore, carriage of pathogens or disturbance in the intestinal microbiome may be hospital-acquired and/or resistant to first-line antimicrobials potentially increasing the risk of readmission. I aim to determine whether molecular evidence of enteric pathogens and gut dysbiosis at hospital discharge, when children were judged as clinically well, is associated with readmission post-discharge among children across the nutritional stratum. This case-control study is nested within the completed CHAIN cohort study (six countries) that aims to characterise demographic, clinical, and social risk factors for mortality among children
|
| 24/11/2020 |
£120,000 |
|
UNIVERSITY OF OXFORD |
There are an estimated 100-400 million cases of dengue worldwide per year with the highest burden of disease in Asia. The virus (DENV) is a positive-sense single stranded RNA virus belonging to the genus Flavivirus. There are four serotypes: DENV1 to DENV4. Dengue virus RNA dependent RNA polymerase has no proof-reading activity, resulting in accumulation of mutations at each replication cycle.
Therefore, within an infected individual, there is diversification of the DENV genome sequence leading to the presence of intra-host genetic variants (quasispecies), which may then lead, under selective pressure, to the emergence of a new strain of higher virulence. Previous findings suggested that immune pressure drives intra-host diversity.
My research will explore whether serotype-specific past immunity influences intra-host DENV genetic diversity during acute infection.
Objectives:
To describe intra host DENV genetic diversity in patients with primary and secondary infections
To compare quasispecies profiles between primary and secondary infections
To compare quasispecies profiles in secondary infections between two patient groups previously exposed to a different serotype.
Impact :
We expect the findings of this project would permit a better understanding of processes leading to viral genetic variation, and could eventually be useful for improving viral surveillance systems and epidemic forecasting.
|
| 24/11/2020 |
£580,378 |
|
UNIVERSITY OF CAPE TOWN |
While prevention of mother-to-child transmission (PMTCT) success has resulted in the decline in paediatric HIV infection, the number of HIV-exposed uninfected (HEU) infants has rapidly risen. In 2018, the population of HEU children in sub-Saharan Africa was estimated to be 13.2 million. In utero exposure to HIV may exert detrimental influences on the intricate neurodevelopmental processes during the first five years of life, with long-lasting effects on cognitive performance and behaviour. Our understanding of the pathophysiological mechanisms that are involved in conferring risk for neurodevelopmental deficits due to HIV exposure remains limited.
Altered neuroimmune regulation during pregnancy and early life may negatively affect neurodevelopment in children and in the context of maternal HIV infection may, in part, explain the delayed neurodevelopment observed in HEU children. However, the temporal regulation of neuroimmune markers during the critical period of the developing brain in HEU children remains unexplored. Importantly, it is also unknown at which stage (from in utero through to five years of age) the developing brain in children with HEU is affected. This study proposes to investigate longitudinally the association between maternal and infant neuroimmune function and brain development and neurodevelopmental outcomes in South African HEU children.
|
| 24/11/2020 |
£149,986 |
|
CENTRE NATIONAL DE RECHERCHE ET DE FORMATION SUR LE PALUDISME |
Long-Lasting Insecticide-Treated Nets (ITNs) are the most successful method for malaria vector control in Africa. Growing evidence indicates changes in mosquito vector biting and resting behaviours in several African settings where high ITN coverage has been achieved. These combined with growing resistance to pyrethroids, the insecticide class used in all nets, can reduce intervention success. This is the case in Burkina Faso where high outdoor biting and pyrethroid resistance is reducing the efficacy of standard ITNs. In response to this Burkina Faso, adopted the newly developed ‘Next Generation Nets’ in its 2019 mass distribution campaign, becoming the first country to deploy Interceptor G2 (IG2), a net combining a pyrethroid with chlorfenapyr, an insecticide that should be effective against pyrethroid-resistant vectors. However, my initial results from laboratory and semi-field studies on mosquitoes from the Cascades Region of Burkina Faso indicate much lower moralities with IG2 nets than expected from earlier trials raising concerns that local vectors may have already developed resistance to this insecticide class.
Combining field and laboratory works in the Cascades Region I will assess for chlorfenapyr-resistance, its potential mechanisms and the impact of IG2 on Anopheles gambiae s.l. demography, behaviours (resting and biting) and malaria transmission potential.
|
| 24/11/2020 |
£157,795 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
The World Health Organisation recommends use of sulphadoxine-pyrimethamine (SP), administered with routine immunisation, for intermittent preventive treatment of malaria in infancy (IPTi) in areas of moderate to high transmission in sub-Saharan Africa. However, there is limited uptake of this recommendation and increasing resistance of malaria parasites to SP. Fortunately, another antimalarial drug, dihydroartemisinin-piperaquine (DP), has shown higher protective efficacy than SP. However, there is paucity of evidence to guide its optimal dosing in infants. Additionally, IPTi is usually given to infants born to women who received SP or DP for intermittent preventive treatment of malaria in pregnancy (IPTp). The impact of using DP for IPTp on subsequent metabolism and efficacy of DP in infancy is not well understood.
In this Fellowship, I will develop optimised dosing regimens of DP for IPTi by applying population pharmacokinetic-pharmacodynamic modelling techniques on data obtained from:
Evaluating the pharmacokinetics, efficacy and safety of DP for IPTi, in a randomised-controlled trial, in infants born to Malawian women who received DP compared to SP for malaria prevention in pregnancy.
Understanding age-related changes in piperaquine pharmacokinetics during infancy.
This work will provide the much-needed evidence to inform DP dosing for IPTi, when administered with routine immunisation.
|
| 24/11/2020 |
£152,610 |
|
UNIVERSITY OF THE WITWATERSRAND |
The persistence of under- and over-nutrition, in conjunction with poor adherence to movement guidelines and lack of stimulation evident among South African children, is indicative of a generation being raised in an environment that is not conducive to optimum early childhood development. This perpetuates an intergenerational cycle of health inequality.
Nurturing care is essential for early childhood development, and relies on responsive and sensitive interactions between caregivers and infants. Considering the importance of caregiver-infant interaction, as well as of infant movement behaviours, I hypothesise that encouraging interactive play could improve childhood growth and developmental through both the biological pathways linked to infant movement, and nurturing care pathways that promote attachment and emotional development.
This study proposes to test this hypothesis by designing, implementing and testing the efficacy of an intervention that encourages interactive play during infancy. This study uses a novel objective assessments of interactive play, as well as rapid participant feedback tools and an adaptive intervention design to enhance behaviour change and therefore intervention adherence.
|
| 24/11/2020 |
£574,957 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Sickle cell disease (SCD) is the most important genetic disorder in sub-Saharan Africa, where over 280,000 affected children are born every year. Although children with SCD represent only 1-2% of all births within the region, they receive between 10 and 25% of all the blood transfusions administered to children
My fellowship has two main aims. First, I will describe the prevalence and consequences of alloimmunization among children attending the SCD clinic at Kilifi County Hospital in Kenya. Second, I will explore potential risk factors for the development of alloimmunization, including levels of inflammation within transfusion recipients and red blood cell genetic diversity in both donors and recipients. By identifying risk factors that contribute to alloimmunization, I will contribute to the development of better strategies that reduce the chance of development of alloimmunization for the transfusion management of patients with SCD in Africa.
|
| 24/11/2020 |
£347,486 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Globally, acute malnutrition affects 8.5 million infants under 6 months of age (u6m). Malnourished infants u6m are at elevated risk of death during admission and after discharge from hospital and of subsequent neurodevelopmental impairment. WHO nutritional rehabilitation guidelines for u6m focus on re-establishing exclusive breastfeeding (EBF) with discharge when consistent weight gain ( > 5g/kg/day) is achieved on breastmilk alone. My pilot study examined breastfeeding peer supporters to facilitate guideline implementation among hospitalised malnourished infants. We achieved 81% exclusive breastfeeding by discharge with 67% attaining the WHO recommended growth velocity on breastmilk alone. However, criteria for full nutritional recovery were generally not met 6 weeks after discharge. I now hypothesise that providing support during transition to home will improve nutritional recovery. In Phase 1 I will develop and pilot a breastfeeding support intervention among 30 recovering infants u6m. In Phase 2 I will apply a randomised controlled trial to evaluate effectiveness of the finalised intervention compared with standard care among 250 malnourished infants (4-12 weeks old) recovering from an illness. The primary outcome is growth (weight gain) assessed at age 6 months, with follow up to 12 months. Results will inform efforts to improve post-discharge management of recovering vulnerable infants u6m.
|
| 24/11/2020 |
£211,407 |
|
UNIVERSITY OF CAPE TOWN |
Approximately 30% of pregnant women in South Africa are HIV-infected resulting in over 300 000 infants exposed to HIV in utero every year. Rates of infectious mortality are reportedly higher among HIV-exposed uninfected infants (iHEU) compared to HIV-unexposed uninfected infants (iHUU). Studies evaluating the effects of maternal HIV infection on vaccine responses in their respective infants show that iHEU have similar antibody titres as those elicited in iHUU. These results imply efficacious vaccination in iHEU which contradicts the observed higher morbidity and mortality rates in iHEU. Therefore, I hypothesise that exposure to HIV in utero may impact the maturation of B cells leading to production of antibodies with poor Fc functions. Our preliminary analysis revealed altered B cell phenotypes across age in iHEU compared to iHUU. Therefore, in this study I aim to characterise B cell properties such as reduced somatic hypermutation for affinity maturation among iHEU using RNA-sequencing. Furthermore, I will analyse IgG Fc glycosylation that is associated with Fc-FcR affinity and Fc effector functions. Subsequently, I will develop in vitro models to measure antibody dependent cellular phagocytosis (ADCP) and cytotoxicity (ADCC) specific to early childhood vaccines.
|
| 24/11/2020 |
£467,629 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Context:
There are 2.2 billion visually impaired people globally. About 90% of these live in low-and-middle- income countries, 80% have avoidable conditions, which are amenable to well-established cost- effective interventions. WHO is promoting Universal Eye Health through integration of Primary Eye Care (PEC) into Primary Health Care (PHC). However, there is little evidence how and what interventions work to effectively and sustainably integrate PEC services into PHC in low-income settings.
Proposed Research:
The following studies will be conducted in Ethiopia in four phases:
Phase 1: Population-based cross-sectional studies to assess eye care need, inequalities, eye health-seeking behaviour and capabilities.
Phase 2: Health System Preparedness Evaluation Study to assess the health system's capacity and gaps to deliver integrated PEC interventions.
Phase 3: Intervention Development, informed by Phase 1 & 2, through Participatory Action Research (PAR) to develop contextually appropriate, feasible, community owned-and-led integrated & sustainable PEC services.
Phase 4: Iterated testing and piloting of the identified PEC interventions both individually and as integrated package at community, health facility, and healthcare organisation level to identify a working PEC intervention that will inform scaled-up delivery of equitably accessible, quality, and sustainable PEC services integrated with PHC.
|
| 24/11/2020 |
£1,535,040 |
|
UNIVERSITY COLLEGE LONDON |
Generation of functional HSC from pluripotent cells and robust HSC expansion in culture are limited by our incomplete understanding of the self-renewal process. My goal is to unveil the regulatory pathways that sustain HSC self-renewal, based on modulation of gene expression at pre- (chromatin modification) and co-transcriptional (transcriptional elongation and RNA polymerase II pausing) levels and as directed by the metabolic state of the cell. I will carry out my scientific goals with the following aims:
Determine the regulation of HSC self-renewal though modulation of transcriptional rate and RNA polymerase II activity.
Understand the role of HSC metabolism and nutrient availability in the regulation of the HSC self-renewal gene regulation machinery.
Modulate HSC transcriptional regulation to achieve successful HSC generation in culture.
These research avenues will lead to a better understanding of the molecular basis of self-renewal and will provide a foundation to improve the generation and expansion of engraftable human HSCs in culture, in order to fully exploit their potential for clinical applications. This work will expand our current knowledge of the HSC self-renewal process and provide new insights into the molecular features of stemness, with implications for other tissue stem cells and the cancer field.
|
| 24/11/2020 |
£1,185,742 |
|
UNIVERSITY OF GLASGOW |
Landscape changes disrupt infectious disease dynamics, requiring new approaches to characterise risks and prevent outbreaks. Focusing on emerging (Chikungunya, Zika) and epidemic (malaria, dengue) zoonotic and vector-borne diseases in Malaysia and the Philippines, I aim to design and evaluate enhanced surveillance systems linking health and environmental data to detect and prevent pathogen spillover and transmission. By developing novel models relating social and ecological processes across spatial and temporal scales, I will bridge critical gaps linking environmental change with human behaviour and health systems. Fine-scale studies of human mobility, behaviour and infection risks will be integrated within a large-scale experiment on tropical forest modification to understand how landscape change both interacts with and alters environmental factors (e.g. seasonality, biodiversity) and socioeconomic and biological factors (e.g. demography, mobility, immunity) to determine disease dynamics. Statistical and mathematical models will be used to explore factors across ecological settings, integrating routine surveillance data, population-based serological surveys and multitemporal Earth Observation data to reconstruct historical disease transmission over major environmental shifts. Predictive models will be designed to identify how future land use can reduce disease risks and how control programmes can use environmental data from new sources of real-time Earth Observation data to improve disease surveillance.
|
| 24/11/2020 |
£886,561 |
|
UNIVERSITY OF EDINBURGH |
Ageing-related cognitive decline carries a huge personal, societal, and financial cost. Understanding its underlying mechanisms with a view to ameliorating age-related cognitive decline is a huge challenge. It is essential to identify biomarkers of cognitive ageing and their potential determinants. Brain structural imaging markers in older age, their correspondence with proteomic and other biomarkers, and their potential determinants, are poorly characterised. Our understanding is informed by cross-sectional studies (which cannot fully reflect the dynamic within-person processes of ageing) and mainly univariate longitudinal data (i.e. describing how brain regions individually decline over time): most aspects of brain structure decline, on average.
However, these approaches do not tell us whether there are important patterns of coordinated change, nor are they well-aligned with other levels of biological explanation. Such information could potentially aid stratification of risk and identification of important clusters of determinants of brain and cognitive ageing.
I will apply cutting-edge factor-analytic methods to large longitudinal datasets to detect and validate patterns of correlated biological changes (brain structure, serum proteomic and DNA transcriptomic). I will test how these dimensions of ageing are associated with each other and with cognitive ageing, and use several techniques to ascertain their lifestyle, genetic and epigenetic predictors.
|
| 24/11/2020 |
£1,320,618 |
|
JOHN INNES CENTRE |
The project aims to investigate the mechanism of peptide transformations carried out by YcaO enzymes and to use this knowledge to create novel antimicrobials.
Bacterial YcaO proteins are essential for the biosynthesis of multiple classes of peptide natural products through their ability to introduce important structural modifications including heterocycles, macrocycles, and thioamides. YcaO repurposing and swapping between different pathways offers exciting possibilities to create novel artificial peptides bearing such modifications. Despite much recent progress, we still do not really understand how these proteins work, and how their activities are coordinated within multisubunit enzyme complexes. I will use cryo-EM in combination with X-ray crystallography to solve the structures of YcaOs within their native complex assemblies trapped at different catalytic stages. In parallel, I will discover and characterise new YcaO proteins to further expand their known catalytic repertoire.
Finally, the promiscuity of YcaOs allows for the production of large genetically encoded peptide antibiotic libraries. I will generate these by co-expressing randomised precursor genes along with modification systems. A high-throughput fluorescence-based version of a Waksman platform will be used for screening, where nano-sized "Petri dishes" (hydrogel beads) will be inoculated with both producer and reporter strains and sorted by FACS.
|
| 24/11/2020 |
£1,334,770 |
|
UNIVERSITY OF OXFORD |
Many RNA viruses (e.g. SARS-CoV-2, HIV-1) have evolved ways of reprogramming translation to expand the coding capacity of their small genomes. ‘Recoding’ events such as -1 frameshifting, stop codon read-through and StopGo peptide release are necessary for viral replication, producing viral proteins in optimal ratios for efficient assembly. Recoding is regulated by a complex interplay between the elongating ribosome, cis-acting elements in the mRNA or nascent peptide, and trans-acting protein factors. Elucidating the structural basis of recoding is essential to understand viral pathogenesis. However, classical biochemical approaches cannot accurately capture kinetics or per-ribosome heterogeneity, making it difficult to define a window of opportunity for structure determination. Recent technological advances allow single-molecule fluorescent imaging of translation in real-time. I will apply these methods to study recoding in vitro and in live cells, starting with -1 frameshifting in SARS-CoV-2, HIV-1 and EMCV, which utilise topologically-distinct stimulatory elements. I will determine the structure of key ribosomal states by time-resolved cryo-EM, and investigate the structure and stability of stimulatory elements using crystallography, single molecule FRET and optical tweezers. Longer-term, this approach will be applied to investigate other recoding events, thus revealing universal and case-specific mechanistic principles, and highlighting new avenues for therapeutic intervention.
|
| 24/11/2020 |
£1,110,044 |
|
BABRAHAM INSTITUTE |
Wnt and Hedgehog signalling regulate intestinal stem cell dynamics to ensure intestinal renewal, function and integrity is maintained. The activation of these two pathways involves crosstalk and communication between the mesenchymal and epithelial layers of the intestine. However, a puzzling conundrum is that both Wnt and Hedgehog carry hydrophobic lipid moieties that are required for receptor binding and signalling but that also hinder their solubility and diffusion and hence ability to move between intestinal cells. In Drosophila, the glypican Dally-like protein (Dlp), which possess a lipid binding pocket, binds and shields the lipid moiety of Wnts to aid transport. Dlp is also essential for initiating Hedgehog signalling but its precise mechanism of action is unknown. I will determine if Dlp also binds the lipid moieties of Hedgehog and what such binding means for Hedgehog solubility, transport and receptor engagement. I will determine if mammalian homologues of Dlp also bind the lipid moieties of Wnt and Hedgehog to regulate their activity and whether they are required in the mouse intestine for Wnt and Hedgehog signalling to orchestrate stem cell dynamics. A deep understanding of how glypicans modulate Wnt and Hedgehog signalling will answer major questions in developmental and stem cell biology.
|
| 24/11/2020 |
£993,004 |
|
UNIVERSITY OF OXFORD |
Altered cardiac metabolism is now recognized as an important component of many cardiovascular diseases, including heart failure. Accurate assessment of cellular energetics promises significantly better disease staging and treatment monitoring in such conditions. Current non-invasive techniques based on magnetic resonance spectroscopy (MRS) are not precise enough to reliably define cardiac energetics in individual patients.
In this fellowship, I will develop new highly-sensitive MRS techniques for complete cardiac energetics assessment at 7T. The main goals of this research are:
To establish a robust, patient-specific platform for cardiac energetics quantification, by developing novel approaches to overcome a range of technical challenges associated with 31P-MRS;
To develop advanced methods that will allow for complete assessment of cardiac energetics, including quantification of Gibbs free energy of adenosine-triphosphate (ATP) hydrolysis (deltaG), and of complete myocardial ATP fluxes;
To demonstrate the sensitivity of these novel methods to measure impairments in total cardiac ATP dynamics in patients with type II diabetes and to detect changes in cellular energetics that accompany the transition to heart failure.
These new measures will help provide unique insight into the pathophysiology of the failing heart and will be applicable in future studies monitoring novel metabolic therapies in cardiovascular disorders.
|
| 24/11/2020 |
£1,091,843 |
|
UNIVERSITY OF BRISTOL |
The distinct activities of polytopic channels, transporters and receptors are essential for cell signalling in response to external stimuli, and their dysfunction is frequently associated with disease. My research has revealed that these plasma membrane proteins undergo Conformational Surveillance by intramembrane proteases: their distinct conformations are recognised and subsequently downregulated by transmembrane domain cleavage. Substrates have never been identified for many intramembrane proteases; I propose this is largely due to a previous lack of systematic screening approaches, and that proteins with more than one transmembrane domain have not been fully explored as substrates.
The overarching aim in this fellowship is to discover the mechanisms that underpin Conformational Surveillance, and to reveal its full repertoire of functions.
My four main goals are:
1) to explore newly identified examples of Conformational Surveillance;
2) to examine whether intramembrane proteases of different families share this molecular activity;
3) to understand the mechanistic coupling of intramembrane proteolysis and lysosomal degradation;
4) to investigate Conformational Surveillance in neurons, where many intramembrane proteases are highly expressed.
Overall, this research programme will shed light on a potentially widespread yet overlooked branch of cell surface proteostasis.
|
| 24/11/2020 |
£1,121,260 |
|
UNIVERSITY OF OXFORD |
Meiotic recombination is essential for creation of haploid gametes. Errors in this process cause miscarriage, infertility, and developmental disorders. Recombination proceeds via repair of programmed DNA breaks; however, the molecular mechanisms ensuring their repair are not well understood. My work reveals that these breaks are a significant mutagenic force, leading to de novo mutations (DNMs) in 1 in 3 sperm and 1 in 13 eggs. My proposed research will harness cutting-edge experiments in genetically-engineered mouse models to generate novel data and will further leverage existing population-scale human genetic and phenotypic data. I will integrate these data through sophisticated statistical analyses to answer the following questions:
What are the properties, causes and impacts of recombination-associated mutations on human health? I will characterize these mutations comprehensively in humans and infer their molecular causes. I will investigate their impact on common and rare diseases.
What is the mechanism of break repair in recombination? I will build on my recent work and interrogate meiotic break repair through specialised experimental assays on key proteins in genetically-engineered mice.
What is the mechanism of mutagenesis? I will characterize the impact of pathways that are identified above as causal by disrupting them in genetically-engineered mice.
|
| 24/11/2020 |
£1,136,115 |
|
NEWCASTLE UNIVERSITY |
Necrotising enterocolitis (NEC) is a leading cause of death in babies born extremely preterm. NEC infants generally have increased gram-negative bacteria compared to matched controls, potentially resulting in an LPS-stimulated increase in TLR4 and inflammatory cytokines in the intestinal epithelium, ultimately leading to the breakdown of epithelial integrity and necrosis. My recent work has shown that human milk oligosaccharides (HMOs) promote the establishment of a protective microbiome in the infant gut, which is associated with reduced risk of NEC.
This project will identify specific HMOs and bacteria that promote gut health and reduce NEC in preterm infants. The project will take advantage of a host-microbe model system I have recently developed. This will provide new insights into NEC pathogenesis, potentially leading to the development or refinement of therapeutics. I will achieve this by answering four critical questions:
1. What specific HMOs and microbial species are associated with NEC or gut health?
2. Do HMOs directly influence the epithelial integrity and inflammation observed in NEC?
3. How do specific bacterial species interact with the preterm intestinal epithelium?
4. Can a combination of HMO (prebiotic) and bacteria (probiotic) promote gut health and protect against NEC?
|
| 24/11/2020 |
£667,750 |
|
INTERNATIONAL CENTRE OF INSECT PHYSIOLOGY AND ECOLOGY |
Malaria remains a major human burden in Africa despite the scale-up of control interventions. Factors driving the persistent transmission remain poorly characterised. In Kenya, the mosquito Anopheles funestus has gained prominence in malaria transmission, and we have documented genetic subdivision in the species locally with varied Plasmodium infection rates. Potentially, the discrete populations possess unique genetic variants conferring fitness advantage coupled with greater transmission role in specific ecologies. Moreover, the populations may present different adaptation to insecticide-based control interventions such as LLINs impacting local malaria epidemiology and control outcome. The proposed 5-year project will address these knowledge gaps by elucidating the underlying biological and ecological drivers influencing the vectorial role of An. funestus in persistent malaria transmission and impact of insecticide-based interventions. Field-based evidence will be generated to inform decisions on how to overcome major barriers in malaria control towards elimination. The project will be implemented under the guidance of a strong interdisciplinary team of scientists from the UK (Prof. Charles Wondji, vector biology, Liverpool School of Tropical Medicine), Greece (Prof John Vontas, vector biology, IMBB-FORTH) Africa (Prof. Baldwyn Torto, vector ecology; Dr Henri Tonnang, disease modeling; icipe), Dr. Luna Kamau (vector biology, KEMRI), and Dr Cyrille Ndo (CRID, Cameroon).
|
| 24/11/2020 |
£131,673 |
|
TRANSCULTURAL PSYCHOSOCIAL ORGANIZATION (TPO) NEPAL |
Depression is a highly prevalent mental health condition which has enormous emotional and financial burden on individuals, families, and society as a whole. Despite the availability of effective treatment, a large number of people needing depression care do not receive treatment. Individual often delay or avoid seeking help for depression due to various reasons including stigma and negative attitude towards services. The aim of this study is to develop and test the feasibility, acceptability, and appropriateness of a social contact-based community psychosocial intervention in order to improve help-seeking behavior of people with depression in Nepal. The objectives of the study are to; (1) systematically review the interventions that have shown effectiveness to improve help-seeking attitude, intension, and behavior among people with depression in LMICs; (2) assess the perceptions of people with depression, their family members and key community stakeholders about barriers for seeking depression care and potential strategy to address those barriers; (3) develop a social contact-based community psychosocial intervention in order to improve negative attitude and intention towards seeking depression care; and (4) test the feasibility, acceptability, and appropriateness of the social contact-based community psychosocial intervention through a pilot cluster randomized controlled trial in Jhapa district of Nepal.
|
| 24/11/2020 |
£339,911 |
|
ACADEMIA NACIONAL DE MEDICINA |
Dry eye is a highly prevalent ocular surface disorder in which a localized CD4+ T cell response and corneal nerve dysfunction are core pathophysiological mechanisms. Both aspects of the disease develop concomitantly in murine models but their connection is unclear. Our preliminary data suggests that the pathogenic immune response is linked to corneal nerve damage and that transient receptor potential vanilloid 1 (TRPV1) signaling promotes nerve-initiated (neurogenic) inflammation. Neurodegeneration is induced by TRPV1 overactivation and leads to neurogenic inflammation in other settings. Therefore, we hypothesize that 1) CD4+ T cells damage corneal nerves in dry eye; and that 2) increased TRPV1 activation promotes nerve damage and neurogenic inflammation, thus worsening the disease (vicious cycle). We will explore the first possibility by using T cell-deficient mice and adoptive transfer of T cells; and the second, with TRPV1-deficient mice and a unilateral surgical model of dry eye in which neurogenic inflammation manifests in the opposite eye. We will explore corneal nerve morphology and function, the possible autoimmune origin of neural changes, and the accompanying T cell response in these models. These findings could serve to develop a dry eye treatment that addresses corneal nerve damage and its associated neuropathic pain.
|
| 16/11/2020 |
£6,504 |
|
UNIVERSITY OF BRISTOL |
Although science prides itself on objectivity, in reality scientists harbor biases (conscious or otherwise), which inevitably influence their research. Consequently, UK (and arguably Global North) biomedical science has become pregnant with non-inclusive research practices. Practices such as the majority of cancer cell lines being derived from patients of European descent, an historic exclusion of female animals from biological research and heterosexist attitudes in study design(3) mean the majority of biomedical research is based on White, heterosexual men.
The Inclusive Research Collective (IRC) aims to educate staff and students on non-inclusive research practices and to challenge these methodologies within University of Bristol biomedical research. It is our aim that the IRC brings together the University of Bristol’s research community, amplifying the voices and experiences of individuals who are often side-lined in the academic sphere while creating a culture of awareness and accountability. We will create a repository of resources produced for future University of Bristol researchers to access, and we hope that this work will form a template for other institutions to deliver their own inclusive research series.
Truly inclusive research requires more than just an awareness of exclusionary practices and the tools to challenge and change them. It requires an inclusive and diverse academic environment, where under-represented individuals are supported fully. It is our aim that the IRC brings together the University of Bristol’s research community, amplifying the voices and experiences of individuals who are often side-lined in the academic sphere, while creating a supportive culture of awareness and accountability.
|
| 16/11/2020 |
£19,450 |
|
KING'S COLLEGE LONDON |
'Visible Skins' will deliver a collaborative programme of workshops and events addressing the presence of Black skin in Renaissance European art and culture, aimed at overcoming issues of underrepresentation at two critical junctures: first the absence of BME voices in scholarly conversation, and second the relative absence of Black identities in the study of the Renaissance.
Visible Skins takes the subject matter of Black skin in the Renaissance and uses it as a focal point to provide more inclusive scholarship, showcase underrepresented voices and reflect on the implications of a more diverse Renaissance.
Through a series of workshops, we will collaborate with BME academics such as Nick Jones of Bucknell University, and BME artists such as artist-practitioner and performer Peter Braithwaite. Inspired by Peter’s online Rediscovering Black Portraiture series, Visible Skins will create new narratives, placing the lives and stories of diverse ethnicities, center stage. Accompanying events will include an exhibition to promote the works of the artists, a panel discussion in conjunction with an academic workshop, and artist Q & A’s – all to be made available online.
By enabling a dialogue driven by artist-led practice rather than academic sources, we will broaden and strengthen our project’s engagement with material culture, better incorporating BME viewpoints into our own understandings. Outputs will expand perceptions of what is too often an elite, white, male canon. By showing that the population of Renaissance Europe was more diverse, we will contribute to awareness of the construction of racial norms and ideas in later periods.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF GLASGOW |
Apicomplexan parasites, which include Toxoplasma and Plasmodium, cause deadly human diseases, such as toxoplasmosis and malaria. Understanding their divergent cell biology could inform strategies to combat them. The apicomplexan mitochondrial electron transport chain (mETC) is essential for their survival and transmission, and highly divergent from the human mETC. Cytochrome bc1 is an mETC protein-complex that is essential, and a key target for drugs, like atovaquone. Yet its composition is unknown, and the mechanism of function and inhibition poorly understood. I propose to investigate how the cytochrome bc1 complex functions and interacts with inhibitors.
Using Toxoplasma as a model, I will uncover the role of my newly discovered apicomplexan cytochrome bc1 subunits, and decipher the role of respiratory super-complex formation, in parasite energy metabolism and survival. Using cryo-EM technology I will solve this complex’s structure to elucidate its mechanism of action, highlighting key differences with the human complex, and understand the way inhibitors disrupt the electron flow essential for energy conversion.
These studies will provide a mechanistic understanding of the essential apicomplexan cytochrome bc1 complex and how inhibitors stop its function. This work will fill a critical gap in our knowledge of fundamental parasite cell biology, and likely inform drug discovery.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF LEICESTER |
COVID-19 is an infectious respiratory disease with a global devastating health impact. Genetic and environmental factors influence COVID-19 susceptibility and outcomes, including the development of acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. These lung pathologies have a high mortality and there are no specific treatment options or effective prognostic methods for patients. Therefore, there is an urgent need to identify effective biomarkers of disease prognosis. The aim of this research is to perform a genomic epidemiology study of ARDS and pulmonary fibrosis in patients with COVID-19. For that purpose, we will perform genetic overlap studies that will include genetic correlation analyses, polygenic risk score approaches, and assessments of overlap of individual genetic variants, followed by fine mapping studies, bioinformatic approaches to identify the likely causal genes, and further experiments to evaluate their role in disease and their potential as drug targets. Results of these analyses will allow us to identify novel genetic risk factors and to develop risk prediction models, which could enhance COVID-19 patient stratification for those at increased risk of lung sequela. Furthermore, the project will reveal novel therapeutic strategies, which would translate into improved and more personalised clinical care for patients at risk of lung fibrosis.
|
| 11/11/2020 |
£458,214 |
|
NEWCASTLE UNIVERSITY |
Critically ill patients with pneumonia often have impaired neutrophil function and disruption of alveolar-capillary barrier integrity. During inflammation, excessive polycation generation activates the calcium-sensing receptor (CaSR), which can potentially compromise neutrophil function and barrier integrity. My over-arching hypothesis is that, during critical illness, CaSR, activated by polycations, mediates impairment of neutrophil, alveolar epithelial and pulmonary endothelial function, leading to reduced bacterial clearance and disruption of alveolar-capillary barrier.
To test the hypothesis, I shall use a range of complementary methods to (a) assess the effect of positive and negative allosteric CaSR modulators and polycations on a range of functions in neutrophils and monocytes from critically ill patients at high risk of developing nosocomial infection; (b) isolate human primary alveolar epithelial cells and culture primary human pulmonary microvascular endothelial cells, and assess the effect of CaSR modulators on barrier function, inflammatory signatures, and antimicrobial functions; (c) perform the first temporal assessment of CaSR expression (and effect of CaSR inhibition) in extravasated neutrophils and alveolar macrophages from human healthy volunteers receiving inhaled lipopolysaccharide (LPS) or control; and (d) create neutrophil-specific CaSR knockout mice, assessing the influence of neutrophil CaSR on the natural history of acute pulmonary infection, inflammation, and alveolar-capillary barrier disruption.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
The cerebellar cortex is thought to form predictive associations between sensory inputs and motor commands: animals leverage these associations to coordinate and adapt movements to contextual changes in the environment. This sensory-motor control depends on Purkinje neurons, each of which receives sensory, motor and cognitive signals from one climbing fibre as well as thousands of parallel fibres, the axons of granule cells. Despite years of anatomical work, cerebellar sensory-motor representations have not been mapped at the cellular scale; similarly, the functional circuit connectivity underlying sensory-motor integration remains unexplored.
To reveal the functional architecture of the mouse cerebellar cortex, I propose to use rabies monosynaptic tracing to map and functionally characterise the presynaptic ensemble of individual Purkinje neurons. I will validate my functional connectomics strategy with electron microscopy and elucidate whether the anatomical organisation of presynaptic circuits converging on Purkinje neurons is modular or random (Aim1). Then, I will harness functional imaging and optogenetics to map the topography of cortico-cerebellar representations, and discover whether Purkinje neurons pool inputs from related sensory-motor presynaptic modules (Aim2). Finally I will train mice in a sensory-guided forelimb task, and ascertain how these circuits are engaged by sensory-motor events, and their timing, during adaptive behaviour (Aim3).
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF MANCHESTER |
Polymicrobial infections consisting of Aspergillus fumigatus and Pseudomonas aeruginosa are associated with poorer patient outcomes and are often much harder to treat. There are a very limited number of drugs available to treat fungal infections, and both bacterial and fungal resistance is rapidly spreading in environmental and clinical settings. Determining the effect of inter-kingdom interactions between these pathogens upon the evolution of antimicrobial resistance is vital for the treatment of polymicrobial infections.
Multispecies biofilms caused by coinfection of these two key respiratory pathogens create a physical barrier preventing drug penetration leading to protection from antimicrobial treatment. However, we understand very little about how competitive interactions within such communities can alter the mutational drivers of resistance or how coexistence changes the pleiotropic fitness costs associated with resistance. The aim of the project is to understand how coexistence and competition between A. fumigatus and P. aeruginosa alters the rate of resistance evolution in the presence and absence of antimicrobial treatment and how interactions change the fitness landscape of resistant mutants within both species.
Understanding the drivers of resistance in polymicrobial communities may increase our ability to predict resistance evolution and aid the design therapeutic of strategies that limit the emergence of resistance.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to provide a reinforcement signal that is essential for learning. Despite recent advances, how VTA-DA neurons coordinate and modulate communication and synaptic plasticity across brain regions to drive behavior is still an open question. We hypothesise that 1) DA enhances communication of behaviorally relevant information across cortex and striatum and 2) the content of the information varies across corticostriatal regions. To test this model, we propose an ambitious research program in mice, using state-of-the-art in vivo electrophysiology, optogenetics, neuropharmacology and computational techniques. First, we will use high density in vivo electrophysiology (Neuropixels) to record neural activity across different corticostriatal regions, while optogenetically manipulating VTA-DA neurons in mice performing a visuospatial decision-making task. We will then use advanced computational methods to examine how and what information is communicated across corticostriatal regions, and how this process is modulated by DA. Finally, we will causally evaluate how DA mediated changes in cross-region communication depend on the receptor, synapses and the neuronal populations involved. In conclusion, we propose a comprehensive study of how DA modulates cross-region communication to drive behavior, providing a needed bridge between our systems and synaptic level understanding of VTA-DA.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Steroid hormone dysregulation has been linked to nearly all leading causes of death, notably cardio-metabolic diseases. Despite this, the aetiological contribution of steroid hormones to such disease is poorly understood and its potential as a therapeutic target remains largely unexplored. To fill this gap, I seek to pioneer a new aetiological understanding of steroid hormone dysregulation and its health consequences through multiple complementary data-driven approaches. I will do the following:
Identify the genomic basis of steroid regulation through large-scale genetic studies of steroid hormones, steroidogenic enzymes, and regulating peptides.
Pinpoint the tissues, genes and biological mechanisms involved in steroid dysregulation in men and women, through the vertical integration of genetics with tissue-specific molecular trait data. As part of this, I will set up an omics atlas of the adrenal gland and the ovary.
Map out the metabolic and regulatory relationships between steroid hormones and related traits through the identification of genetically determined multi-dimensional steroid traits.
Conduct a genomics-driven identification of new therapeutic pathways and protein targets to correct disease-causing steroid imbalances.
In short, this research agenda will not only uncover the aetiological pathways linking the steroid endocrine system to cardio-metabolic disease, but also instigate novel treatment strategies.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF BIRMINGHAM |
Cardiac arrhythmias are a common pathway for multiple cardiovascular diseases, the leading cause of death in the world. Ablation of cardiac arrhythmias is a recommended and common treatment option for arrhythmia patients, but success rates are poor. Cardiac electroanatomical mapping systems (EAMs) are used to identify ablation targets. EAMs generate a wealth of raw data that is ideal for developing algorithms to tailor treatments to an individual patients’ pathophysiology and improve treatment options. However, no platform exists for developing and testing algorithms.
Specific groups have developed closed-source software to identify ablation targets however, these results have not been widely reproducible. There is an acute need for an open-source and cross-vendor EAM analysis software to facilitate sharing methods, increase rigor and transparency and increase access to advanced processing tools.
I will develop expandable open-source software for analysis of EAM data. I will incorporate established and novel analysis methodologies, including machine learning approaches. Algorithms will be robustly validated using clinical, pre-clinical and in silico datasets. The software I will develop will enable myself and others to utilise routinely collected clinical data, to better treat cardiac arrhythmia. I will apply these approaches to identify mechanistic drives of atrial fibrillation as an exemplar application.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF EDINBURGH |
Despite new developments in treatment, cancer remains the second leading cause of death worldwide. Breast cancer is the most common cancer within the UK, with death generally caused by the formation of metastasis. I intend to investigate the hypothesis that immune responses at the metastatic site determine the long-term outcome of therapy.
I will compare immune responses at the primary and metastatic sites upon administration of checkpoint inhibitors that have different clinical success rates. Flow cytometry and t-SNE analysis will provide insight into the affected cell populations and timings. I will then utilise newly developed intravital imaging technologies to visualise immune responses in vivo at multiple cancer sites. I will measure cytotoxic cell activity and tumour cell death as indicators for anti-cancer response. Further, I will examine the ability of a combination of checkpoint inhibitor and focal adhesion kinase inhibitor to fully eradicate tumour cells. An inhibitor will be fluorescently tagged to study its access to tissue and interaction with immune cells dependent on combination therapy.
The proposed research will help to elucidate the role of immunotherapy on the metastatic foci and will provide the first insights into the benefit and limitations of combination therapy on secondary site immune responses.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY OF GLASGOW |
Sleep/wake cycles are arguably the most important circadian behavioural output controlling many aspects of animal physiology. However, some infections induce disruptions to these cycles, leading to pathology. Sleeping sickness is an infection caused by the African trypanosome Trypanosoma brucei. One of the most puzzling symptoms of this disease is the profound alteration in sleep patterns, which is now recognised as circadian disorder. This disease provides an ideal framework to study how pathogens disrupt host circadian behaviour.
I will use single-cell transcriptomics to profile the responses of key hypothalamic nuclei controlling circadian behaviour during infection. I will also characterise the population of parasites residing in the brain compared to bloodstream parasites to identify mechanisms of glial activation, neuroinflammation, and parasite survival in the CNS. These outputs will provide novel and unprecedented insights into the host-pathogen interactions in the hypothalamus that lead to disruptions of sleeping patterns.
My ultimate aim is to understand how pathogens interfere with the function of the central nervous system leading to changes in physiology and behaviour. The outcomes of my fellowship will provide a new understanding of infection-induced circadian disorders and will reveal factors that can be exploited for intervention and treatment of infections affecting the brain.
|
| 11/11/2020 |
£300,000 |
|
KING'S COLLEGE LONDON |
Individuals at the early stages of psychosis already suffer from neuroanatomical, neurofunctional and neurocognitive alterations. However, it is not clear how these alterations interact with each other and, more importantly, how this interaction may help predict who will become unwell. The aim of the proposed study is to uncover previously hidden relationships between brain anatomy, function and cognition that can improve our understanding of the first signs of the illness and help predict illness trajectory at the individual level. This will be achieved by triangulating, for the first time, data fusion, machine learning and a unique longitudinal dataset of individuals at the prodromal stage or with a recent first episode of psychosis. This combination of methods will allow me to address three main objectives: 1) identify previously unknown relationships between anatomy, function and cognition in healthy individuals; 2) develop a model that captures the normative pattern of these hidden relationships and determine by how much each patient deviates from this pattern; 3) use these deviations to predict each patient’s longitudinal clinical outcomes. I will also develop an open access tool that allows non-expert researchers to perform data fusion on their own data. Keywords: psychosis, data fusion, machine learning, outcome prediction.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
The gut-brain axis is at the heart of Parkinson’s disease (PD) etiology. Pathological alpha-synuclein accumulates early in the gut, potentially affecting the enteric nervous system (ENS) and spreads to the brain. However, we lack insights into how pathological alpha-synuclein affects ENS integrity and cellular mediators underlying their spread. Here, I propose to study the role of a unique subset of gut macrophages (gMacs), the ENS-gMacs, that coordinate neuronal function in their unique ENS niche. I hypothesize that ENS-gMacs critically dependent on LRRK2 for alpha-synuclein clearance. LRRK2 is a risk factor for PD, regulates alpha-synuclein clearance in macrophages and is highly enriched in ENS-gMacs compared to microglia and neurons. First, using state-of-the-art single cell RNA and in-situ sequencing techniques I will examine how ENS-gMacs and microglia become dysfunctional in PD mouse models. Second, using in vivo and in vitro tools, I will dissect whether mutant LRRK2 signaling in ENS-gMacs affects neuronal function and survival upon PD patient-derived pathological alpha-synuclein. Finally, I will investigate how ENS-gMacs contribute to alpha-synuclein pathology and spread. Insights obtained will create new avenues to study neuroimmune pathways along gut-brain axis for the future, as well as novel targets for early therapeutic interventions in PD.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Children develop and interact in complex, multimodal environments. I will investigate how deaf children with cochlear implant (CIs) integrate visual information from the talker’s face to supplement sound.
This is important because CIs provide a degraded sound that lacks pitch and much affective information, placing high cognitive demand on the developing brain and increasing reliance on visual information and audio-visual integration.
I will conduct experiments comparing adolescents with early-onset deafness and bilateral CIs to hearing controls. Eye tracking will be used to understand allocation of visual attention during word and emotion perception and the interaction between these processes. Visual evoked potentials will be measured using electroencephalography to understand the efficiency of cortical processing during visual perception. Psychophysics and pupillometry will be combined to estimate the benefit gained from audio-visual speech integration and the impact on cognitive effort. Functional near-infrared spectroscopy will enable cortical imaging of CI users without interference from CI-generated artefacts. Correlations between activity in temporal and occipital cortices will be examined to understand audio-visual cortical connectivity and to specify mechanisms of audio-visual integration.
This work will enable us to better understand the role for visual cues in augmenting current auditory-only rehabilitative interventions to help deaf children communicate effectively.
|
| 11/11/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease targeting motoneurons, leading to paresis and death. Changes in spinal microcircuits have been suggested to be part of an early homeostatic response to preserve motor output, possibly involving substantial alterations at the level of premotor synapses. Supported by solid preliminary data, I hypothesize that changes in these circuits precede motoneuron degeneration, and thus propose to address these aims: (1) define early disruptions in connectivity to motoneurons in ALS and (2) determine the genetic profile of these abnormalities. I will characterize well-known spinal synaptic pathways such as Ia excitation, disynaptic reciprocal inhibition and pre-synaptic inhibition in wildtype mice and 2 different models of ALS (SOD1G93A and TDP-43-A315T). I will do this both in vitro, by using a novel isolated mature mouse spinal cord preparation, and in vivo by performing intracellular recordings of motoneurons and EMG recordings with chronically implanted multielectrode arrays. These experiments will be complemented with transcriptomic analysis using single-cell patch seq and laser capture microscopy to reveal if changes in specific spinal microcircuits are accompanied by changes in expression profile of motoneurons and interneurons. This project will reveal if early degeneration in ALS results in generalized circuit impairment.
|
| 11/11/2020 |
£300,000 |
|
BEATSON INSTITUTE FOR CANCER RESEARCH |
Pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are leading causes of cancer-related deaths. Despite knowing these cancers’ driver mutations, there are no effective therapies. A universal yet understudied feature of both PDAC and HCC is their aberrant glycosylation. Glycosylated serum proteins act as clinical biomarkers, but it is unknown how altered glycosylation – driven by gene expression changes and mutations of glycosyltransferases/glycosidases – contributes to disease progression.
First, I propose to establish a new HCC mouse model combining genetic alterations with chronic alcohol consumption, a major risk factor. Second, I will systematically uncover the glycosylation changes in primary cells of this new HCC model and established PDAC models using unbiased mass spectrometry-based glycomics and lectin microarrays. By applying glycobiological techniques to this setting, I will bring together two hitherto disparate research fields. Third, based on these data, I will manipulate the glycosyltransferases/glycosidases most likely responsible for the glycosylation changes and examine disease progression, yielding new targetable oncogenes. In parallel, based on preliminary data, I will investigate the tumour suppressive mechanism of the fucosidase FUCA1 in mouse models of PDAC and HCC, using glycomics as a starting point. Finally, I will validate my findings in human PDAC and HCC samples.
|
| 11/11/2020 |
£630,613 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Diabetic cardiomyopathy (dbCM) is a complication of type II diabetes (T2D), characterised by systemic inflammation, impaired cardiac function and disrupted metabolism. However, the impact of systemic inflammation on the development of the myocardial inflammation and cardiac metabolic derangement that lead to dbCM remain unknown. This study will address how chronic adaptive inflammation driven by systemic metabolic stress in T2D causes cardiac dysfunction. Specifically, I hypothesise that it is caused by inflammation due to T-cell infiltration and not by direct metabolic perturbations that can lead to impaired energetics (reduced PCr/ATP ratio). Specifically, the aim is to use integrated experimental approach combining metabolic analysis with T-cell phenotypic profiling in murine and human T2D to address three research challenges:
A. Does infiltration of cardiotropic T-cells impair cardiac substrate plasticity and energetics in dbCM?
B. Do myocardial succinate efflux and signalling via SUCNR1 promote cardiac Teff and/or Treg activation by modifying T-cell metabolism and do they enhance pro-inflammatory T-cell differentiation?
C. Does stimulation of GCK-mediated glycolysis increase regulatory T-cell migration to the heart causing a switch in the nature of immune response from pro-inflammatory to immunosuppressive? Does the resultant reduction in myocardial exposure to pro-inflammatory cytokines improve cardiac function and mitochondrial performance?
|
| 28/10/2020 |
£149,995 |
|
RESTLESS DEVELOPMENT |
Restless Development will identify, train and empower 20 Young Leaders (18-24) in Zimbabwe, working in pairs across 10 rural and urban communities in 2 districts, to develop evidence based solutions to address the impacts of global heating on health. These Young Leaders will bring unique perspectives from the communities in which they live and work, first using a youth-led research methodology to develop evidence on current levels of young people and their community’s knowledge and understanding of global heating and health as interconnected issues, then using that evidence to conduct global heating and health advocacy work to develop community-based solutions. Acting as agents of change, Young Leaders will translate knowledge and research to their communities in order to improve the knowledge of the global heating and health related issues. By the end of the 12 month initiative, the project will have investigated and tested different methods young people can use to increase the understanding of the links between global heating and health, the subsequent impact on their communities, and identified local solutions to identified challenges.
|
| 28/10/2020 |
£193,379 |
|
CLIMATEWORKS FOUNDATION |
Healthy Food, Healthy Planet (Europe) (hereafter HFHP) is a collaboration of philanthropic and civil society organizations. Our goal is to support the formation of a movement across Europe advocating for a global food system compatible with climate, health, biodiversity, animal welfare, and just transition goals.
To execute a scoping strategy and facilitate scoping phase grantmaking of HFHP, ClimateWorks Foundation will establish a pooled fund with an option for aligned funding. The HFHP Fund has a target size of approximately USD $1 million, and will be managed by ClimateWorks.
The project will have two phases. The first phase will run from June to October 2020. It will culminate in an investment prospectus indicating opportunities for donors to support a European food movement. The second phase will run from October 2020 to July 2021 and will culminate in a strategic framework describing tactics for the movement.
The activities of both phases of HFHP will be overseen by a Project Lead who will design and execute consultative processes, work to ensure that research deployed and the materials produced reflect priorities of civil society, and incorporate learning from the research and consultative processes in the investment prospectus and the strategic framework.
|
| 19/10/2020 |
£1,382,640 |
|
KING'S COLLEGE LONDON |
Through SCOPE, we will produce high quality, contextual evidence and use it to design
innovations in detection and treatment, to improve the lives of people living with
psychosis in a low-income country.
Our key goals are to:
1. determine the rate of new cases of psychosis in rural and urban settings in
Ethiopia; identify possible risk factors for onset; and characterise the needs of
people with psychosis and the factors that affect early course and outcome.
2. use this evidence to co-develop innovations to improve early detection and
optimise the recovery of people with psychosis. The innovations will be
applicable to rural, urban and homeless populations in Ethiopia, with potential
generalisability to other low- and middle-income countries.
We will pilot test interventions, develop strategies to overcome implementation
challenges and identify key intervention components to inform adaptation for other
contexts. |
| 06/10/2020 |
£1,197,348 |
|
INSTITUT PASTEUR DE TUNIS |
We propose a different approach to antivenoms, based on recombinant nanobodies (Nbs), targeting the lethal cobra toxins, to reduce morbidity and mortality. Nbs have a high affinity for selected epitopes, allowing rapid recognition of antigens even if bound to cholinergic receptors, combined with a capacity to dislocate neurotoxin from the receptor.
This COBRA-NGaV project brings together research teams with extensive experience in venomics and antivenomics to provide the proof-of-concept (PoC) for cobra toxin-specific Nb candidates as a novel generation of antivenoms and to address the dual obstacle to neutralise cobra toxins: weak immunogenicity and fast diffusion.
Preliminary results have been obtained so far: i) strong and specific responses were elicited in dromedaries immunised against the toxic fractions of N. legionis, N. haje and N. oxiana; ii) phage display screenings were adopted to rescue strong Nb binders specific towards relevant N. l., N. h. and N. o. toxins; iii) several clusters of Nb sequences specifically binding cobra toxins have been identified.
Herein, Nb selections and combinations for optimal synergic effects and best cross-species performances will be generated. Best-in-class candidates will be tested in a pre-clinical study in mice and sheep according to GMP rules. Cost effectiveness will be established.
|
| 06/10/2020 |
£2,621,953 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Small molecule toxin inhibitors offer great potential to rapidly deliver inexpensive, safe and efficacious oral interventions in the community soon after a snakebite, prior to subsequent admission to a healthcare facility. Despite such promise, only a handful of toxin inhibitors have been robustly explored to date. We redress this here by expanding the chemical space available for snakebite treatments by employing a comprehensive drug discovery approach. Using toxin-specific assays, we will screen diverse compound libraries ( > 50,000 molecules), including using the Human Pharmacopoeia and Phase-1 approved molecules in a repurposing approach, for hits that demonstrate broad toxin family neutralisation. Thereafter, we will rationally identify lead series by defining the toxin-specificity, kinetics, phenotypic potency and medicinal chemistry characteristics of hits, before performing murine preclinical efficacy and pharmacokinetic experiments to rationally define oral dosage regimens of lead candidates capable of achieving systemic inhibitory concentrations throughout a snakebite treatment period. Finally, we will evaluate therapeutic combinations of lead candidates by performing dose optimisation via PK/PD modelling, and preclinical efficacy and drug-drug interactions studies. This comprehensive drug discovery pipeline will deliver a portfolio of lead candidates (and numerous backups) ready for translation into clinical studies to assess their tolerability and efficacy as next-generation snakebite therapeutics.
|
| 06/10/2020 |
£1,194,565 |
|
KATHOLIEKE UNIVERSITEIT LEUVEN |
One of the most common lethal snakebite pathologies is neurotoxicity, which is the result of neurotoxins blocking nerve transmission, commonly via interaction with nicotinic acetylcholine receptors (nAChRs). Here we will use molecules that mimic the structural components of nAChRs that are important for toxin binding to generically inhibit the functional activity of venom neurotoxins. Our pilot data demonstrates that such ‘decoy receptors’ offer great potential to generically neutralise venom neurotoxins irrespective of snake species (unlike antivenom).
We will use structural and informatic guided approaches to rationally design a panel of acetylcholine receptor binding proteins, nAChR ligand binding domains, and peptide mimotopes, before measuring their binding affinity to venom neurotoxins. We will then identify the toxins they capture using analytical approaches, before demonstrating that they effectively prevent binding to nAChRs. Thereafter, we will use in vivo efficacy studies to robustly assess whether mixtures of lead decoy receptors protect mice from venom lethality, as either solo or adjunct therapies.
We anticipate that our inhibitory mixtures will exhibit superiority over antivenom by neutralising neurotoxins irrespective of the snake species and at lower therapeutic doses. This project therefore has the potential to generate a single, generic, eminently translatable therapy for treating neurotoxic snakebites worldwide.
|
| 06/10/2020 |
£3,032,561 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
400,000 tropical snakebite victims require, every year, life-saving surgical debridement/amputation because there is no medicine to treat the disabling, income-depleting effects of snake venom-induced necrosis. A new therapy is urgently needed to prevent the severe health and socioeconomic consequences upon already-impoverished victims and health facilities.
Our evidence-underpinned hypothesis is that rationally-selected recombinant, humanised camelid VHH targeting necrosis-inducing venom toxins (NITs) will possess the efficacy, rapid in-tissue distribution, safety, thermostability, affordability and large scale production characteristics appropriate for future development of a community-dispensed therapy – a paradigm shift in the clinical management of venom-induced necrosis to reduce morbidity.
To achieve this for Africa and India, our partners bring new approaches, platforms and all required resources to select candidate recombinant NIT-specific monoclonal VHH from (i) B cells of NIT-immunised camels and (ii) a synthetic VHH library - complementary approaches maximising likely success.
Deploying sequential in vitro, ex vivo human skin and mouse in vivo assays of venom-induced necrosis enables down-selection of the most efficacious, thermostable recombinant VHH. ‘Humanising’ the latter donates the key safety criterion. E.coli expression enables inexpensive and large-scale production of humanised VHH. These therapy-characteristics and the vast panAfrica/India need, provide economy-of-scale production incentives for future manufacturing partners.
|
| 06/10/2020 |
£2,734,121 |
|
INTERNATIONAL AIDS VACCINE INITIATIVE |
This proposal aims to ultimately reduce global levels of morbidity and mortality from snakebite envenoming by discovering and developing antibodies that can neutralize the low molecular weight snake venom toxins – key contributors to the disease. These non-immunogenic toxins are poorly neutralized by currently available antivenoms produced by animal derived immunizations. This proposed project will discover neutralizing antibodies through immunization experiments using rationally designed immunogens and select for high-affinity antibodies via synthetic libraries using recombinant toxins.
|
| 06/10/2020 |
£3,081,450 |
|
TECHNICAL UNIVERSITY OF DENMARK |
Sub-Saharan Africa (sSA) is heavily burdened by snakebite envenoming. Existing antivenoms are scarce and many have suboptimal therapeutic properties. To improve snakebite envenoming therapy, the application of carefully designed mixtures of fully human monoclonal immunoglobulin G (IgG) antibodies for systemic and nanobodies for locally acting toxins poses as not only a therapeutically promising, but also scientifically feasible solution. Therefore, taking advantage of our well-established discovery pipelines and expertise in working with oligoclonal and broadly-neutralizing antibodies against toxins, we will develop a broad-spectrum (polyvalent) recombinant antivenom for sSA. The project will focus on the following technical goals that we believe have a potential to deliver measurable societal and humanitarian health impact: 1) The identification and isolation of all medically relevant snake venom toxins that need to be neutralized by a recombinant antivenom for sSA and 2) the discovery of a well-characterized panel of broadly-neutralizing IgGs and nanobodies that can neutralize all medically relevant systemically-acting and deep tissue penetrating toxins found in the 24 medically most relevant snake species from this region. Combined, these efforts will create a substantial shift in snakebite envenoming therapy and will enable the clinical development of improved, low-cost, and quality-assured snakebite therapeutics for victims in sSA.
|
| 06/10/2020 |
£1,768,776 |
|
UNIVERSITY OF CAMBRIDGE |
The main therapeutic intervention for snakebite envenomation relies on the century-old approach of injecting victims with animal-derived polyclonal antiserum. Animal immunisation generates high affinity antibodies and undoubtedly saves lives but the use of immune antiserum has a number of limitations around consistency, redundancy and immunogenicity. Recombinant antibody technology will allow the capture, sequencing and characterisation of the monoclonal antibody repertoire arising from immunisation. Furthermore, the resulting high affinity antibodies will be made more human-like by fusing animal-derived variable domains with human constant domains (chimeric antibodies).
This project will generate phage display libraries from horses and llamas immunised with venoms of 4 sub-saharan African snakes represented in the co-applicants antivenom EchiTab-Plus_ICP. We will generate antibody panels by phage selection, screening and sequencing. This resolution of the immune repertoire to a complex venom into its monoclonal components essentially transforms the problem into one of deconvolution. Affinity capture-mass spectrometry will be used to identify the target of thousands of individual antibodies based on their distinct mass-defined target. Following triage based on binding profiles, antibodies to individual targets will be expressed as chimeric antibodies and validated using in vitro and in vivo animal models of envenomation towards generation of life-saving, chimeric antibody cocktails.
|
| 05/10/2020 |
£709,662 |
|
UNIVERSITY OF EDINBURGH |
The application of next generation sequencing to bile duct cancers (cholangiocarcinoma) has revealed a subgroup with mutations in the Isocitrate Dehydrogenase (IDH1, IDH2) genes, which appear non-overlapping with other drivers including TP53 and KRAS and which are associated with relatively favourable, but still poor, clinical prognosis. IDH1/2 mutations result in neomorphic production of the oncometabolite 2-hydroxyglutarate (2HG), which causes cell toxicity, DNA hypermethylation, and repression of cellular differentiation. This project tests two hypotheses. First, it seeks to determine whether 2HG production can metabolically reprogramme liver cell identity, triggering a cell fate change from a hepatocyte to a biliary phenotype, thereby promoting the formation of cholangiocarcinoma. I will seek to define the cell populations in the liver in which IDH1 mutations occur in disease and use lineage tracing techniques to establish whether IDH1 mutation results in an increase in hepatic progenitor or ductal cells in vivo, as well as which cell types give rise to these ductular reactions. Second, I shall examine whether 2HG causes non-cell-autonomous local toxicity or inflammation, and determine whether this contributes to tumorigenesis. My results will elucidate fundamental mechanisms of biliary carcinogenesis and suggest the likely efficacy of targeted 2HG inhibition or, indeed, 2HG overexpression.
|
| 05/10/2020 |
£788,449 |
|
UNIVERSITY OF EDINBURGH |
The accumulation of intestinal macrophages (iMphis) and presence of a distinct mononuclear phagocyte gene-expression profile, predict treatment failure and adverse clinical outcomes in Crohn's disease (CD). Preliminary scRNA-seq data demonstrates that a transcriptionally distinct iMphi subtype (CD-MPhi) accumulates in human and murine colitis, which I have prospectively validated. Unbiased CD-MPhi-epithelium, ligand-receptor interaction analyses reveals CD-MPhi derived activin signals to cognate receptors on colonic epithelium. CD-MPhis are the exclusive iMphi source of activin in mouse and humans, a TGF-beta superfamily member with cell-specific cytokine, growth and hormone effects. Activin administration to human colonic epithelium inhibits proliferation with a dose-dependent effect on cytokine, chemokine and pattern recognition gene expression.
Aims
Define iMphi heterogeneity and dynamics in CD
Interrogate the functional role of a novel pathogenic subset (CD-MPhi) in regulating intestinal inflammation
Investigate CD-MPhi driven activin signalling as a therapeutic target for intestinal inflammation
Methods
Using a novel, human, biopsy-based sampling approach, I will perform scRNA-seq of iMphis in newly diagnosed, treatment naive CD patients, with longitudinal, flow cytometry-based intestinal characterisation to reveal iMphi dynamics over time. Lastly, I will manipulate cell-specific activin-signalling in transgenic animals and primary human epithelium co-culture models to probe the mechanisms of activin-mediated epithelium dysfunction in CD.
|
| 05/10/2020 |
£446,707 |
|
UNIVERSITY OF CAMBRIDGE |
People with progressive multiple sclerosis (P-MS) have substantial unmet clinical needs. While current therapies for MS are focused on manipulating the activity of the adaptive immune system, they have limited applicability for P-MS where a switch towards the chronic activation of innate immune cells, such as mononuclear phagocytes (MPs), occurs.
MITO_META aims to test the hypothesis that the detrimental activation of MPs in P-MS is dependent on their mitochondrial metabolism and that targeting mitochondrial complex I (CI) activity in MPs will lead to novel therapeutic approaches for P-MS.
To achieve this aim, I will adopt a combination of animal models and post-mortem biological samples obtained from MS patients. I will initially use the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to study the effect of removing Complex I from MPs during neuroinflammation (Aim 1). I will then analyse how the metabolism of MPs changes during neuroinflammation, and compare these findings to those obtained from post-mortem analysis of people with progressive MS (Aim 2).
Elucidating the role of mitochondrial function in MPs during chronic neuroinflammation will advance our understanding of P-MS and lead to new therapies to interfere with the progression of disability.
|
| 05/10/2020 |
£534,185 |
|
UNIVERSITY OF OXFORD |
Understanding the mechanisms that underlie epileptogenesis is crucial for the development of new treatments. Recent evidence has implicated astrocytes as a key cell population in the aetiology of focal epilepsy. Astrocytic gap-junction networks perform vital functions in supporting neural activity, including the shuttling of essential metabolic fuels and the regulation of the extracellular ionic environment for neurons. The objective of this project is to understand the relationship between neuronal activity and astrocytic gap-junction coupling, and how this relationship may break down in epilepsy. This will build upon preliminary evidence that astrocytic gap-junctions can show rapid, activity-dependent changes, in a manner related to levels of neuronal activity. The work will use surgically-resected human brain tissue and mouse models in which it is possible to selectively manipulate defined cell types. There are three parallel research aims. First, glioma-associated brain tissue will be used as a test case to relate functional astrocytic gap-junction coupling and neuronal hyperexcitability in a human context. Second, in vivo optical studies in mouse will examine how epileptiform network activity influences dynamic astrocytic gap-junction coupling. And third, optogenetic and pharmacological strategies will be used to dissect the cellular mechanisms that mediate activity-dependent changes in astrocytic coupling.
|
| 05/10/2020 |
£717,907 |
|
UNIVERSITY OF EAST ANGLIA |
Heart failure with preserved ejection fraction (HFpEF) is prevalent, increasing and has a poor prognosis. Left ventricular (LV) haemodynamic assessment is needed to diagnose and manage patients with HFpEF. The reference method for it is an invasive study and is rarely done due to costs and risks. Doppler-derived velocity is used as a surrogate for LV pressure. However, because it is based on a number of assumptions, Doppler remains unreliable for detecting increased LV end-diastolic pressure (LVEDP). I have validated a four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) acquisition which addresses issues with Doppler. I have further developed an accurate quantification method, which uniquely, measures intra-ventricular blood flow in 4D. Other advantages are that it does not require any additional hardware and has demonstrated superior associated with LVEDP. In this Fellowship, I will develop 4D flow techniques for an accurate assessment of LVEDP and pressure-volume loop in HFpEF. In addition, I will learn from and collaborate with the world-renowned clinicians, software/hardware engineers and modelling experts in academia and industry, to improve the method’s accuracy and applicability. I will validate the method’s accuracy and generate clinical data to support future clinical trials, clinical translation and patient benefit.
|
| 05/10/2020 |
£1,271,351 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
I will improve understanding of key determinants and the incidence of cardiovascular disease in low-income sub-Saharan-Africa, capitalising on my expertise in stroke epidemiology in rural and urban Malawi and the research infrastructure across seven sub-Saharan-Africa population cohorts.
Information on the age- and sex-specific incidences of priority cardiovascular diseases is essential for health service planning in sub-Saharan-Africa. "Traditional" risk-factors (hypertension, type-2 diabetes and obesity) are highly prevalent and increasing in incidence and some, particular to low-income settings, such as chronic-infections, are not declining. The performance of diagnostic tools and risk prediction scores for cardiovascular disease developed in high-income settings need to be tested and adapted for use in low-income sub-Saharan-Africa.
I will build on the urban/rural cohort in Malawi, extending community and clinic surveillance with population-level questionnaire-screening (followed by a diagnostic pathway in those with "possible cardiovascular disease") to estimate the true incidence of various cardiovascular diseases. I will also extend the follow-up for our seven African cohorts and use this harmonised dataset to estimate the relative contributions of key drivers of cardiovascular disease and assess the performance of existing cardiovascular disease risk prediction scores.
This work will inform the planning of evidence-based, health-systems responses and context-relevant, individual, and population-level interventions.
|
| 05/10/2020 |
£1,304,625 |
|
UNIVERSITY OF OXFORD |
Viral fusion proteins are important targets for vaccine-induced neutralising antibody. Structure-guided design of such antigens in pre-fusion conformation has created leading vaccine candidates against viruses with Class I and II fusion proteins, such as respiratory syncytial virus and dengue virus. Use of pre-fusion stabilised Class III proteins for vaccination has not yet been reported, but these too are major vaccine targets for rabies virus and the herpesviruses (the gB proteins).
I propose to build upon preliminary data demonstrating pre-fusion stabilisation of rabies glycoprotein. I will evaluate pre-fusion-stabilised immunogens for vaccines against rabies and a chosen herpesvirus, Epstein Barr virus (EBV). By isolating monoclonal antibodies against EBV gB, I will ascertain whether herpesvirus gB proteins contain pre-fusion-specific neutralising epitopes. In healthy EBV carriers, I will explore whether salivary EBV shedding can be used as a marker of immune control of virus reactivation, to dissect mechanisms of natural immunity, and to rapidly detect efficacy in future early-phase vaccine trials.
A low-cost single-dose vaccine based on stabilised rabies glycoprotein could help reduce the 60,000 deaths due to rabies each year. An effective EBV vaccine could reduce the > 100,000 deaths per year due to EBV-driven cancers and, many believe, could also prevent multiple sclerosis.
|
| 05/10/2020 |
£590,676 |
|
UNIVERSITY OF OXFORD |
Kidney stones, which are a major clinical and economic health burden, are commonly recurrent, and current stone prevention strategies are relatively ineffective. The renal tubular mechanisms underlying this disease are poorly understood, thereby limiting opportunities to develop novel therapies. Via a genome-wide association study (GWAS) we identified twenty genetic loci linked to kidney stone formation. However, the genes influenced by these loci remain to be elucidated. My goals are to: identify additional stone-associated loci by X chromosome and sex-specific GWAS studies; define biologically relevant renal cell types by identifying areas of accessible chromatin at relevant loci through single cell assays for transposase accessible chromatin (ATAC)-sequencing in renal tissue; determine causal GWAS-associated SNPs by examining local epigenetic modifications in relevant cell types via chromatin immunoprecipitation (ChIP)-sequencing; link causal SNPs to effector genes by determining the 3-dimensional chromatin landscape in relevant cell types through Next Generation Chromatin Conformation Capture; validate predicted genotype-phenotype associations in relevant cohorts; and elucidate the roles of effector genes in cellular function via in vitro studies. This research will provide new insights into tubular function and the molecular pathophysiology of renal stone disease and reveal new therapeutic targets for the prevention of kidney stone recurrence.
|
| 05/10/2020 |
£698,120 |
|
KING'S COLLEGE LONDON |
Gamma-delta T-cells are critical for protecting against carcinogenesis in mice but clinical associations have been equivocal and human trials of gamma-delta T-cell therapy have been disappointing. Previous studies have been limited by unavailable technologies to describe these cells with sufficient granularity whilst clinical trials have largely focussed on the more numerous V-delta-2 subtype. Using contemporary methods such as TCR-sequencing and ex vivo culture systems to extract gamma-delta T-cells from human tissues, we recently demonstrated that only certain subtypes of these cells, namely the V-delta-1 subtype, are associated with survival in triple-negative breast cancers.
This proposal aims to extend our previous findings to a pan-cancer setting by mapping, with greater and necessary detail, these cells in melanoma, breast, lung and other cancers with a particular focus on V-delta subtyping, differential effector functions and cell regulatory axes. Importantly, we will also map gamma-delta T-cell interactions with alpha-beta T-cells as these cells have been established as being critical to cancer immunosurveillance. We will stratify our findings to clinical outcomes to build a novel reference human tumour gamma-delta T-cell atlas to guide ongoing translational efforts in adoptive gamma-delta T-cell therapy. Hence, this proposal may lead to rapid translation into clinical benefit.
|
| 05/10/2020 |
£844,510 |
|
UNIVERSITY OF EDINBURGH |
Our vision is to create a Centre that combines novel, integrative humanities and social science (HSS) research with innovative approaches to collaboration, stakeholder and public engagement. This vision is anchored through key themes, each a site of socio-technical transformation: Beyond Bodies, Beyond Disease, Beyond Global, Beyond Legal and Beyond Engagement. Each theme is evolving rich theoretical and empirical research that cross cuts substantive and disciplinary boundaries. We are building new collaborations and partnerships and increasingly appreciate the work involved in building such relationships for long term benefit. We strive to create a mutually respectful relationship with biomedicine and public health that embeds HSS ‘upstream’. In the proposed extension period, we aim to deepen our research and engagement, enabling new ideas to flourish; this includes a expanding work on ‘Beyond Data’ and an emergent programme of work on sex and reproduction ‘ Beyond Sex’. Our research and engagement are underpinned by an inclusive research environment where we strive to adopt a feminist approach to leadership. Supporting Early Career Researchers is key to this. In this next phase we will deepen our research across and within themes and support scholars in developing interdisciplinary skills and expertise and continue to engage widely.
|
| 05/10/2020 |
£975,813 |
|
UNIVERSITY OF DURHAM |
In 2017, we set out a vision to develop ‘a nexus for world class medical humanities research that aims to improve human health through an enhanced understanding of human experience’. As the newly formed Institute for Medical Humanities (IMH), we have refined this original vision to focus on human experience that is variously marginalised, difficult, unspeakable, unacknowledged, invisible and hidden. This focus has developed from successful research on the experience of breathlessness, voice-hearing and collective wellbeing, and through developing work on dreams, memory, drug use, interoceptive sensation and the menopause.
The extension grant will enable IMH to take forward a substantial programme of work, ‘Researching Hidden Experience’; to expand our team and embed new permanent academic staff; to develop further our capacity to influence health research policy and expertise in public engagement; and to extend our global influence. The current background of increasingly complex, intersecting, and socially embedded health problems, including the experience of inequality in its various forms, requires a fundamental questioning of structures, models and assumptions that perpetuate hidden health problems. Such research is only possible within a culture that is aware of its own hidden inequities. We address this through a ten-year strategy for diversifying medical humanities.
|
| 05/10/2020 |
£1,048,732 |
|
UNIVERSITY OF OXFORD |
In this proposal we seek an 18-month extension to the Wellcome Centre for Ethics and Humanities (WEH). The WEH is a vibrant and dynamic ethics and humanities research centre located at the University of Oxford’s Big Data Institute. It provides a flexible multidisciplinary research platform capable of engaging with the profoundly difficult ethical and social challenges presented by the scale, scope and societal implications of emerging research in the biosciences at a time of rapid social change. At the heart of our work is a commitment to rethinking concepts, theories, and the nature of scholarship in ethics and the humanities to enable them to be adequate to the task of engaging meaningfully with these profound developments. This focus on ‘rethinking ethics and the humanities’ has proven to be a highly productive framing for the Centre’s research collaborations, and engagement activities. In this application we seek to build on these foundations to undertake new research programmes on, ‘infection and history’, ‘rethinking ethics and history’, ‘rethinking justice and discrimination’, and ‘ethical applications and potentials of collective minds’. This research will be underpinned by a centre-wide programme on ‘rethinking research cultures’ and complemented by an ambitious programme of public engagement initiatives and events.
|
| 05/10/2020 |
£1,428,973 |
|
UNIVERSITY OF EXETER |
During the Centre's first three years, we have focused on establishing transformative research and engagement programmes, developing partnerships with policy-makers and creative organisations, building an open research culture, and recruiting doctoral students, early career researchers, and senior staff. Committed to engaged research that enables health and well-being, our projects have brought researchers, public partners, and health organisations together to address key health challenges, including: the health impacts of loneliness and social isolation; the value of different forms of evidence in health policy; the impact of relationships on children's health; and community access to - and involvement in - research and data governance.
Additional funding will allow us to address further the health impacts of social and environmental inequalities, specifically through projects on health across the life course, ageing and dying, co-creating healthy cities, and recovering from - or living with - the social and cultural impacts of COVID-19. These research programmes - as well as an innovative Masters course in transformative health research and practice - will enable us to fully embed engagement and impact in our work locally, nationally and internationally, build training and career pathways in transdisciplinary research, and strengthen our commitment to an inclusive research culture.
|
| 01/10/2020 |
£12,883 |
|
UNIVERSITY OF DURHAM |
Not available |
| 01/10/2020 |
£16,190 |
|
BABRAHAM INSTITUTE |
Not available |
| 01/10/2020 |
£13,151 |
|
THE PIRBRIGHT INSTITUTE |
Not available |
| 01/10/2020 |
£99,635 |
|
THE FRANCIS CRICK INSTITUTE |
Not available |
| 01/10/2020 |
£18,877 |
|
UNIVERSITY OF EAST ANGLIA |
Not available |
| 01/10/2020 |
£35,181 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 01/10/2020 |
£25,084 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 01/10/2020 |
£68,783 |
|
UNIVERSITY OF OXFORD |
Not available |
| 01/10/2020 |
£75,506 |
|
UNIVERSITY OF OXFORD |
Not available |
| 01/10/2020 |
£109,200 |
|
UNIVERSITY OF OXFORD |
Not available |
| 01/10/2020 |
£23,592 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 01/10/2020 |
£29,873 |
|
UNIVERSITY OF SOUTHAMPTON |
Not available |
| 01/10/2020 |
£50,751 |
|
UNIVERSITY OF LEEDS |
Not available |
| 01/10/2020 |
£202,536 |
|
UNIVERSITY OF DUNDEE |
Not available |
| 01/10/2020 |
£44,293 |
|
UNIVERSITY OF EXETER |
Not available |
| 01/10/2020 |
£10,849 |
|
UNIVERSITY OF ST ANDREWS |
Not available |
| 01/10/2020 |
£10,925 |
|
UNIVERSITY OF STRATHCLYDE |
Not available |
| 01/10/2020 |
£13,297 |
|
KEELE UNIVERSITY |
Not available |
| 01/10/2020 |
£15,762 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 01/10/2020 |
£28,684 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 01/10/2020 |
£31,761 |
|
BIRKBECK UNIVERSITY OF LONDON |
Not available |
| 01/10/2020 |
£38,763 |
|
UNIVERSITY OF YORK |
Not available |
| 01/10/2020 |
£41,401 |
|
UNIVERSITY OF WARWICK |
Not available |
| 01/10/2020 |
£41,779 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 01/10/2020 |
£49,187 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 01/10/2020 |
£53,493 |
|
INSTITUTE OF CANCER RESEARCH |
Not available |
| 01/10/2020 |
£60,404 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 01/10/2020 |
£64,793 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Not available |
| 01/10/2020 |
£68,557 |
|
CARDIFF UNIVERSITY |
Not available |
| 01/10/2020 |
£80,459 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 01/10/2020 |
£80,561 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 01/10/2020 |
£94,276 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 01/10/2020 |
£111,364 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 01/10/2020 |
£139,146 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 01/10/2020 |
£171,317 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 01/10/2020 |
£183,060 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 01/10/2020 |
£204,330 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 01/10/2020 |
£345,206 |
|
KING'S COLLEGE LONDON |
Not available |
| 01/10/2020 |
£370,755 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 01/10/2020 |
£404,392 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 01/10/2020 |
£763,249 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 01/10/2020 |
£787,552 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 01/10/2020 |
£1,043,556 |
|
UNIVERSITY OF OXFORD |
Not available |
| 01/10/2020 |
£486,720 |
|
INVISIBLE FLOCK CO |
A two year exploration of Solastalgia - mental distress specifically caused by environmental change, defined as a land disease of "place-based lived experience".
Our team is a global collective of artists, researchers, designers, conservationists, technologists and activists from fields including psychology, arts, sustainability, sociology, design and medicine. Through the Hub we will place lived experiences at the forefront of understanding Solastalgia. We will use human centred design, storytelling and creative media arts to deeply explore human experiences and relationships with the natural world as an alternative to the current dominant, data-driven discourses.
Through a network of global field stations, sited in critical landscapes, we will work closely with local and indegnous communities to understand and communicate their connection to land and their lived experiences of climate change. Looking at Solastalgia through the lens of these communities we will together explore the complex, fragile relationship of psyche and land.
Through the Hub we will open up this urgent and timely discussion to multiple audiences. Incorporating diverse knowledge and perspectives, lived experiences that are complex and layered through storytelling and artistic approaches we will identify context-specific pathways towards a sustainable future.
|
| 30/09/2020 |
£6,920,135 |
|
UNIVERSITY OF OXFORD |
There is no proven treatment, chemoprophylaxis or vaccine for COVID-19. This is the most serious pandemic emergency for 100 years. Healthcare workers are being affected disproportionately in the continuing epidemic threatening an imminent breakdown of health services. Chloroquine and hydroxychloroquine are safe and well-tolerated medications which can be taken for years without adverse effects.Both have significant antiviral activity against SARS-CoV-2 and there is emerging evidence from China and Europe of efficacy in treatment. Unfortunately there is also premature recommendation from countries such as India which now recommends low dose hydroxychloroquine for prophylaxis in health care workers.
We propose conducting a multi-centre, multi-country randomised, double blind, placebo controlled assessment of the prophylactic efficacy of chloroquine (Asia) or hydroxychloroquine (Europe) in preventing COVID-19 illness in at-risk healthcare workers and other frontline staff. At least 40,000 participants in Asia and Europe will be randomised 1:1 to receive chloroquine or hydroxychloroquine or a matched film coated placebo as daily prophylaxis for three months. The study’s objectives are the prevention of symptomatic coronavirus disease (COVID-19) and the attenuation of the clinical severity.
|
| 30/09/2020 |
£224,392 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2020 |
£823,390 |
|
NATIONAL UNIVERSITY OF SINGAPORE |
We propose a prospective serological study to investigate the incidence of SARS-CoV-2 infection in the general population in three Asian settings: Singapore, Hong Kong and Thailand. The study will aim to measure the age-specific seroprevalence and incidence of SARS-CoV-2 infection at 3 time points, each 6 months apart. Age-specific incidence estimates will be applied to the census population to obtain numbers of infections in the population at each time point. These estimates will be compared with external data on COVID-19 hospitalisations and deaths in each setting, to calculate age-specific infection-hospitalisation and infection-fatality ratios. SARS-CoV-2 antibody kinetics will be defined by studying changes in antibody titres over time. Risk factors for infection will be studied by comparing SARS-CoV-2 seroconverters and non-seroconverters with respect to epidemiological exposures. This study will provide crucial information regarding population exposure and SARS-CoV-2 transmission dynamics, and will provide a complete picture of the relationship between clinically apparent and asymptomatic infections.
|
| 30/09/2020 |
£1,416,424 |
|
KWAME NKRUMAH UNIVERSITY OF SCIENCE AND TECHNOLOGY |
As part of the response to the emergence of COVID-19, the World Health Organization Africa Regional Office is organizing various Infection Prevention and Control (IPC) and critical care training activities targeted at Low and Middle-Income countries (LMICs) in Africa. While the initiatives taken by WHO/AFRO are critical, training for research into the disease also needs to be targeted at the same LMICs, because being an Emerging Infectious Disease, we need to "learn-as-we-go". Clinical research on COVID-19 will have to be closely integrated with the IPC, clinical care, and epidemiological training activities, including use of the WHO First Few X (FFX) Cases and contact investigation protocol for COVID-19. ALERRT proposes to work closely with the WHO/AFRO and Africa CDC and existing networks and structures across Africa and globally to provide the fore-mentioned clinical research training and support. ALERRT is a member of the Global Federation - ISARIC, which has developed a Clinical Characterization protocol for COVID-19. This protocol been endorsed by the WHO and is currently being used in China and across the UK and Europe.Being already established and conducting activities in sub-Sahara Africa, the ALERRT network has the capacity to effectively implement the proposed project.
|
| 30/09/2020 |
£2,003,681 |
|
WITS HEALTH CONSORTIUM (PTY) LTD |
Factors prevalent in Africa such as malnutrition, HIV, tuberculosis and limited access to healthcare, among others, may impact both transmission dynamics and disease progression associated with SARS-CoV-2 infection as well as the burden on the healthcare system and society.We aim to characterize key transmissibility and clinical features of and the antibody response to SARS-CoV-2 as well as to enhance surveillance for COVID-19, identify groups at increased risk of severe illness, estimate the disease burden of medically- and non-medically attended mild, severe-non-fatal and fatal illness and forecast the impact of the outbreak on the healthcare system and the society in South Africa. Particular emphasis will be given to HIV-infected individuals. The aims will be achieved through the implementation of shedding and household transmission studies, collection of sequential serum samples, enhanced facility-based (hospitals and clinics) surveillance among patients with mild and severerespiratory illness in well-established population-based surveillance sites where incidence can be calculated, and healthcare utilization and serological surveys in selected communities. In addition, digital surveillance (based on Google searches) will be used to complement virological surveillance and nowcasting and short-term forecasting (up to 4 weeks) will be implemented over the duration of the epidemic.
|
| 30/09/2020 |
£1,217,834 |
|
UNIVERSITY OF OXFORD |
Background; It is unknown how prior exposure to commonly circulating human coronaviruses (HCoV) impacts immunity against highly-pathogenic species (SARS, SARS-CoV-2 & MERS). There are limited data, across Europe, Asia and Africa, on the prevalence of infection and seroconversion against widely circulating and mildly symptomatic HCoVs (229E, NL63, OC43, and HKU1). There is a current supposition that antibody-dependent-enhancement (ADE) may play a role in the pathophysiology of COVID-19. ADE occurs when non-neutralizing antiviral proteins facilitate virus entry into host cells, leading to increased infectivity in the cells. In such cases, higher viremia has been measured and the clinical course of disease can be more severe. In preclinical animal models, immunopathology was observed after challenge following vaccination with some SARS vaccines. Therefore, concerns have been raised regarding the impact of immunopathology and ADE on prophylactic vaccination against SARS and possibly SARS-CoV-2.
Goals: to perform detailed systems serology of pre-existing immunity, in children and adults, from the UK and Africa, towards novel and commonly circulating coronaviruses.
Impact: These studies highlight the limited knowledge in the field and a need for a systematic approach to investigate cross-reactive humoral immunity against HCoV to inform the immunopathology and pathophysiology of COVID-19.
|
| 30/09/2020 |
£1,030,349 |
|
UNIVERSITY OF WARWICK |
COVID-19 is a global threat to health, with many countries reporting extended outbreaks. To date 9 countries in Africa have recorded infection and it seems imminent that East Africa will have introductions and onward transmission. The SARS-CoV-2 virus (the aetiological agent of COVID-19) spreads rapidly (R0~2, serial interval about 1 week), and hence control will be difficult. National plans for dealing with this public health emergency will benefit from predictions of the expected rate, distribution and extent of spread in countries throughout the region, and on the likely impact and feasibility of isolation and contact tracing interventions. We will support the emergency preparations through bespoke modelling, incorporating known demographic population structure, age-related contact patterns and existing mobile phone population movement data. In Uganda and Kenya we will collect epidemiological, genomic and behavioural data through health facility surveillance, household follow-up and contact studies to quantify uncertainties of SARS-CoV-2 virus epidemiology and contact patterns in well and unwell individuals. Results from the study will be rapidly communicated to the relevant authorities, and modelling code and analysis, and data including sequences, placed in the public domain in near real-time. This project could have lasting impact on the role of research in policy decisions.
|
| 30/09/2020 |
£864,564 |
|
IMPERIAL COLLEGE LONDON |
Since December 2019 the emergence of severe acute respiratory infections (COVID-19) in China, caused by the new coronavirus SARS-CoV-2, has posed a huge threat to global health with fatality rates up to 10% in elderly patients. Almost 100% of patients showed bilateral patchy shadows or ground glass opacity in their lungs by chest CT scans indicating acute lung injury (ALI). Therefore, understanding the underlying mechanism(s) of ALI induced by SARS-CoV-2 is very important to inform vaccine safety and immunotherapeutic strategies. In this proposal, we will investigate the host immune responses and their association with severity of ALI in patient samples and animal models. We will bring together a team of experts with complementary expertise including immunopathology in coronavirus infections, up-to-date lab technologies, and know-how to ensure the feasibility of this study with the following goals:
1) defining SARS-CoV-2 specific serum profiles (epitopes) using yeast display antigen library
2) determining antibody functions including antibody-dependent enhancement (ADE) vs neutralizing activities in vitro assays
3) studying T cell (CD4 and CD8) responses to whole SARS-CoV-2 genome
4) evaluating ALI in response to live SARS-CoV-2 infection with or without passive immunity (antibody or T cells) generated from vaccine candidates in a humanized mice model.
|
| 30/09/2020 |
£646,963 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Our project, AFRICO19, will enhance capacity to understand SARS-CoV-2/hCoV-19 infection in three regions of Africa and globally. Building on existing infrastructures and collaborations we will create a network to share knowledge on next generation sequencing (NGS), including Oxford Nanopore Technology (MinION), coronavirus biology and COVID-19 disease control. Our consortium links three African sites combined with genomics and informatics support from the University of Glasgow to achieve the following key goals:
1. Support East and West African capacities for rapid diagnosis and sequencing of SARS-CoV-2 to help with contact tracing and quarantine measures. Novel diagnostic tools optimized for this virus will be deployed. An African COVID-19 case definition will be refined using machine learning for identification of SARS-CoV-2 infections.
2. Surveillance of SARS-CoV-2 will be performed in one cohort at each African site. This will use established cohorts to ensure that sampling begins quickly. A sampling plan optimized to detect initial moderate and severe cases followed by household contact tracing will be employed to obtain both mild to severe COVID-19 cases.
3. Provide improved understanding of SARS-CoV-2 biology/evolution using machine learning and novel bioinformatics analyses. Our results will be shared via a real-time analysis platform using the newly developed CoV-GLUE resource.
|
| 30/09/2020 |
£782,901 |
|
WELLCOME LEAP INC. |
In early February 2020 Wellcome’s BoG approved the appointment of Regina Dugan as CEO of the Wellcome Leap Fund (WLF), the relocation of the WLF’s primary place of business to the U.S. and the creation of a U.S. not-for-profit entity within the Wellcome group (Leap US). This grant is a mobilisation fund to support the initial activities required for Leap US’ set up and strategy development, prior to the awarding of full grant which will be administered upon BoG approving the CEO’s strategy and business plan for the WLF. |
| 30/09/2020 |
£50,000 |
|
GENETIC ALLIANCE UK |
Not available |
| 30/09/2020 |
£888,104 |
|
MOLOGIC LTD |
Rapid diagnostics have been identified by the WHO R & D Blueprint as a critical unmet need for the control of COVID-19 - particularly in the absence of a vaccine and proven antiviral agents. Our primary objective is to develop a low cost, high performance rapid test for the detection and exclusion of SARS-CoV-2, the causative virus of coronavirus disease 2019 (COVID-19).
The technology will be made available in line with the Global Access Policy for Gavi-eligible countries that are most vulnerable to onward transmission of COVID-19 and of limited detection due to insufficient laboratory capacity. The RDT will be appropriate for assembly and manufacture with multiple quality-assured partners to meet demand.
|
| 30/09/2020 |
£249,926 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Malawi is at high risk of COVID-19 epidemic spread, the healthcare system is fragile and the population vulnerable to severe disease. This application proposes Malawi Liverpool Wellcome Trust Clinical Research Programme preparedness activities for epidemic COVID-19 disease. These are split into three work packages: 1) Diagnostic capacity and genomics surveillance; 2) Secondary care; 3) Epidemiology and control. Strategically, we have designed our activities to develop a platform for MLW to rapidly pivot into response mode to both support the healthcare system and deliver excellent research for current and future epidemic disease threats.
Key goals for this proposal are:
Provide diagnostic capability in Malawi for the COVID-19 epidemic
Develop clinical and epidemiological tools to manage epidemic disease in Malawi
|
| 30/09/2020 |
£79,890 |
|
SCHWARZKOPF STIFTUNG JUNGES EUROPA |
The European Youth Parliament (EYP) is based on the idea that the great challenges of our time cannot be tackled on a national level alone, but need to be addressed multilaterally. Moreover, the EYP leverages a new generation of young changemakers to be part of the solution.
As the umbrella organisation of the EYP, the Schwarzkopf Foundation Young Europe is proposing a project that will bring various interconnections between "Health" and "Politics" to the forefront of debate among young people across Europe. The project will bring together young people from across Europe with decision-makers and experts, to debate today’s pressing topics in the field of health, and to develop positions that will be shared with decision-makers and the public. Discussions will take place in a variety of formats and settings, constituting a broad consultation process that will aggregate "young opinions" from across Europe, which are then to be shared in close-up debates with decision-makers (especially in the context of Germany’s EU Council presidency) - as well as with young peers, and the broader public.
|
| 30/09/2020 |
£6,275 |
|
GREATER MANCHESTER COALITION OF DISABLED PEOPLE |
GMCDP’s archive collection reveals the changing perspectives, language and attitudes towards disabled people that have occurred over recent decades. It highlights changes in medical practices, discussions and debates around bio-ethics and end of life issues, campaigns for independent living, the self-organisation of disabled people, development of disability culture, and the significant impact of wider health determinants.
Following on from feedback on a previous application to Wellcome Trust, GMCDP recognises the need to have a more detailed, specialist assessment of our collection in order to be able to move forwarded to the next stage. GMCDP are therefore seeking to carry out an archivist assessment and collections appraisal of our archives, and will commission Janice Tullock Associates (archivist) and Sharon Oldale (conservator) to provide the following outcomes:
Survey the collection to assess its needs.
Assess the level of cataloguing the collection requires.
Develop a statement of the significance of the collection.
Provide a detailed report on findings, with recommendations.
Develop a project plan for the cataloguing of the archive.
Assess the level of archivist and specialist input required throughout the duration of the project.
Conservation assessment and recommendations.
|
| 30/09/2020 |
£176,431 |
|
SHEFFIELD HALLAM UNIVERSITY |
Not available |
| 30/09/2020 |
£30,000 |
|
KNIGHT HALL AGENCY LIMITED |
This is a prize for a Screenwriting Fellowship, awarded in collaboration with the BFI and Film4 in 2019 |
| 30/09/2020 |
£50,000 |
|
ARTS & HEALTH SOUTH WEST |
Contribution to the establishment of a national Centre for Creative Health as recommended by the APPG report into Creative Health: Arts , Health and Wellbeing (2017). |
| 30/09/2020 |
£125,000 |
|
BUREAU OF INVESTIGATIVE JOURNALISM |
This 12-month pilot project would test how we can use our innovative journalistic approach to find more effective, scalable ways to engage diverse audiences around health issues and research. The opportunity for collaboration with Wellcome will bring together our expertise in local engagement and community-led investigations across the UK with our global health track record of fact-based reporting and expert, external networks. A new Bureau Local health team will explore and test issues that impact nationally and globally with local communities to find connections.
If successful, an immediate outcome would be that we’d improved relevance and relatability around a critical health topic (and research around it) for affected communities and the wider public across the UK. For the longer term, our project would strengthen understanding of how engaged journalism can support a two-way flow of communication from and to affected communities. We would hope the findings from this project could support a collaborative framework for journalists, communities and researchers to use local investigative journalism to connect and engage people more effectively with health issues.
|
| 30/09/2020 |
£49,836 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Background Information:
The research and development (R & D) Blueprint is a global strategy and preparedness plan to address highly infectious diseases and strengthen the emergency response by bringing medical technologies to patients during epidemics. For each of these priority diseases, WHO is coordinating the elaboration of R & D roadmaps, to serve as collaborative frameworks underpinning strategic goals and research priority areas to accelerate the development of diagnostics, therapeutics and vaccines to prevent and control severe emerging diseases. R & D roadmaps have been developed for 4 priority diseases with epidemic potential: Crimean-Congo hemorrhagic fever and Ebola/Marburg virus diseases, Lassa Fever and Nipah virus disease.
Key Goals:
Effective publication and dissemination of these roadmaps, together with communication and advocacy, will help to achieve the R & D blueprint and roadmaps goals.
How the funds will be used:
To support the publishing costs of 4 of the Research and Development (R & D) Blueprint Roadmaps. |
| 30/09/2020 |
£120,000 |
|
ASSOCIATION OF RESEARCH MANAGERS AND ADMINISTRATORS |
This project is based on an invitation by the African Academy of Sciences (AAS) to the Association of Research Managers and Administrators (ARMA) in the UK, to contribute to their ongoing ReMPro programme. Drawing on their expertise and strengths as an association of research managers and administrators, ARMA will support ReMPro's strand on developing individual capacity of research management staff through various activities like, needs analysis and mapping workshops and implementation of an International Research Management Staff Development programme. ARMA is seeking funding to reinforce existing support to the project, specifically towards the International Research Management Staff Development Programme and personnel costs for the second phase.
1. International Research Management Staff Development Programme - aimed at strengthening capacity of research management staff in Africa, this will be an exchange programme between African and UK institutions. Participants will be drawn from diverse institutions through a competitive application process.
2. Personnel costs - to implement and oversee the activities, ARMA has employed a programme manager with a projected budget covering 12 months. However, their is a clear need to develop and implement outcomes from the mapping workshops. This will be carried out in the second phase of the programme.
|
| 30/09/2020 |
£75,000 |
|
UNDERSTANDING ANIMAL RESEARCH |
Support for UAR activities as per uploaded document
|
| 30/09/2020 |
£96,402 |
|
UNIVERSITY OF CAMBRIDGE |
This application is for support to develop a proposal for The Cambridge History of Medicine in six volumes. As General Editor, I will meet with a team of a dozen volume editors at a series of workshops to ask fundamental questions about what the history of medicine is, what it should be, and how best to represent it in these books.
|
| 30/09/2020 |
£200,000 |
|
EAT FOUNDATION |
With the support from Wellcome Trust during the years 2016-2019, EAT achieved important results. The EAT SFF is globally recognized as a meeting place for stakeholders to shape the future of food. The EAT-Lancet Commission changed the debate around food, environmental sustainability and health, and the scientific targets set by the Commission for healthy diets within safe planetary boundaries are guiding action by a wide range of actors across policy, business and civil society. EAT is catalyzing action through a number of collaborations, such as with C40, influencing food system policy agendas in 50 cities around the world. The GBP200,000 contribution from Wellcome Trust for 2019 will secure EAT’s ability to continue its efforts and avoid delay or disruption of its work, while working with Wellcome Trust ito develop a Phase 2 program.
EATrecognizes that there is an urgent need to undertake a proactive and strategic organizational review. This review will guide EAT in addressing weaknesses in its financial, operational, fundraising and reporting functions that have exposed risks that must be mitigated prior to the end of 2019 The review will provide a clear pathway to ensure financial and operational sustainability whilst supporting EAT’s agility within focused and strategic structures.
|
| 30/09/2020 |
£97,058 |
|
STEM LEARNING LIMITED |
The collaboration between Education Development Trust (EdDevTrust) and the National STEM Learning Centre (STEM Learning) will enable 60 highly trained and competent science teachers to access a unique approach (‘Test and Learn’) and set of tools to guide and support them to carry out their own rigorous classroom-based research. Teachers will test the evidence-based theories, approaches, pedagogies and policies introduced to them through STEM Learning’s CPD programme using randomised controlled trials, applying scientific method to explore science pedagogy.
|
| 30/09/2020 |
£269,680 |
|
ROEHAMPTON UNIVERSITY |
Spoke with Ruba Aljarf today (9 November 2019) and she said to simply upload the attachment.
|
| 30/09/2020 |
£76,800 |
|
COLLEGE OF TEACHING LTD |
Our project will support science teachers to engage with research through a ‘teacher journal club’ (TJC) approach, building on work in both education and in the medical sciences, where journal clubs are a well-established approach to CPD. As well as providing cost- and time-efficient CPD that adheres to the principles of effective learning for teachers, journal clubs are by their nature focused on helping teachers to engage effectively with research evidence. This project proposes to apply the principles of successful journal clubs from medicine to education. The journal clubs will exclusively be online and journal clubs facilitators and participants will receive online training before their first TJC. This online training will cover the background of TJCs and how it relates to effective teacher CPD, research appraisal and journal club facilitation skills. The project will take a 'fading scaffolding' approach where the support for TJC facilitators will fade over time with the goal for them to run TJC independently by the end of the project.
|
| 30/09/2020 |
£109,026 |
|
BEHAVIOURAL INSIGHTS TEAM |
Our project aims to increase teachers’ engagement with and use of research through the provision of teaching resources – a comprehensive program of work, including adaptable lesson plans – and training in their use. The lesson plans will be designed based on research evidence and will also contain annotated summaries of relevant research evidence with links to the underlying research. The training will help teachers understand how and why to engage with research evidence by using the lesson plans, and will be participatory in nature. Training will occur three times throughout delivery to remind teachers to engage with evidence. The intervention will pertain to a particular unit of year 8/9 physics e.g. forces. We will recruit physics teachers at a diverse mix of UK state-funded schools to test our resources.
In our approach, engaging with research and learning how to embed it in practice will be made extremely easy for teachers, which is the most effective way to increase the prevalence of desired behaviour (and is especially important in the context of an already overburdened workforce). In particular, this approach will address potential intention-action gaps between teachers engaging with research evidence and actually applying it in their teaching practice.
|
| 30/09/2020 |
£757,562 |
|
BRITISH ACADEMY |
The British Academy is submitting a funding proposal to the Wellcome Trust which will provide support for researchers in the humanities and social sciences working in areas related to health and wellbeing. Taking a broad definition of health, the proposal will provide a portfolio of support for academics, at all stages of their careers, working in the humanities and social sciences by providing funding for Small Research Grants, academic conferences and policy workshops. The proposal follows discussions with the Trust over a number of months and is valued at £3.97 million including: funding of £2.76 million for Small Research grants; £1.12 million for conferences; and £84,000 for policy workshops (over 3 years). Funding is proposed to begin in early 2020 and to finish in 2026. The collaboration is designed to demonstrate the relevance of humanities and social science research in relation to health and wellbeing through the scale and breadth of funding options for researchers and the potential for long term impact.
|
| 30/09/2020 |
£6,525 |
|
SHEFFIELD HALLAM UNIVERSITY |
This grant will support both Sheffield Hallam University and the National Foundation for Educational Research (NFER) to work with the four grantees of the Teacher Research Scoping Grants and to undertake the writing and costing of the proposal for the research and evaluation study of this programme. |
| 30/09/2020 |
£72,206 |
|
INTERNATIONAL AIDS VACCINE INITIATIVE |
Through this project, IAVI and WHO Immunizations, Vaccines, and Biologicals (IVB) will harness input from a broad network of stakeholders to produce a Preferred Product Characteristics (PPC) technical document for forthcoming monoclonal antibodies (mAbs) for HIV prevention. Created early in clinical development and with attentiveness to end-user and health systems perspectives, this PPC document will provide strategic guidance as to preferences for new HIV preventative antibodies to inform clinical development and support eventual integration into WHO policy. While the focus of this effort will be on articulating optimal product attributes for antibodies for HIV prophylaxis, it is anticipated that acceptability, suitability and feasibility criteria identified through this process can inform product design, clinical development, and access considerations for a broader array of antibody-based products for infectious and neglected diseases in the pipeline. |
| 30/09/2020 |
£510,000 |
|
UNIVERSITY OF OXFORD |
lvermectin is a very safe and beneficial drug which is used for the treatment of more than a
dozen different neglected tropical diseases (NTDs), many of which are associated with
important public health problems. Current label indications for ivermectin prevent use in
small children weighing less than 15kg, due to limited safety data in this group. Many of the
NTD treatment options for small children rely on compounds that are less safe and/or
efficacious compared to oral ivermectin. Our proposal will establish the safety and
pharmacokinetics of escalating doses of ivermectin to treat scabies infected children weighing less than 15kg. The safety assessment will provide crucial evidence on the use of
ivermectin for numerous diseases in children weighing less than 15kg. The information from
measuring drug concentrations in the patients will inform the optimal dosing of this drug in
small children. Assessment of the efficacy of ivermectin, compared to permethrin cream, for
the treatment of scabies in small children can provide an important alternative treatment for
this widespread disease. |
| 30/09/2020 |
£201,914 |
|
UNIVERSITY OF OXFORD |
Do political institutions influence the health of populations? Political institutions once seemed fixed and stable, but now appear to be flexible and open to change. This project seeks to uncover whether changing political institutions could affect health. Political institutions are the rules that govern who participates and how they participate in decision-making processes within societies; for example, they dictate who gets to vote and how votes are counted. Political institutions potentially affect health because they make governments more (less) responsive to what citizens want. However, this straightforward view of how political institutions affect health overlooks how democracies can privilege some voices over others (e.g., party donors may matter more than voters) and so universal suffrage may not necessarily deliver better health. This project will shed light on these questions through a series of empirical case studies. For example, I propose to examine whether political incorporation improves the health of formerly excluded groups, and whether their influence on policy decisions is weaker in majoritarian political systems than proportional representation systems because votes are counted differently. This project speaks to the sustainable development agenda by illuminating whether inclusive and representative decision-making institutions may accelerate progress toward ensuring healthy lives for all.
|
| 30/09/2020 |
£1,961,880 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
There is strong evidence that climate change presents severe health risks, while addressing the drivers of climate change can bring large health gains. Nationally Determined Contributions (NDCs) reflect countries' self-defined efforts to reduce greenhouse gas emissions, and adapt to climate change impacts, to meet the goals of the 2015 Paris Climate Agreement. They are renewed every five years, beginning in 2020. The first round of submitted NDCs are neither sufficient to limit warming below the global goal of 2C (aiming at 1.5C) nor to adequately strengthen resilience to climate risks. While 65% cite health, less than 25% include health cobenefits of mitigation, only 3% of proposed NDC actions connect to health, and only 50% of surveyed countries have a health adaptation strategy or plan.
The project will address barriers that currently hinder governments in systematically considering health in NDC design and implementation. It will provide national health and development actors with evidence, analytical and capacity building tools to support them in integrating health risks, and the health co-benefits of climate change mitigation, into NDCs. It will thereby contribute to protecting and promoting health, and to a more coherent and synergistic approach to climate action, health and sustainable development.
|
| 30/09/2020 |
£4,502,682 |
|
BRITISH SCIENCE ASSOCIATION |
The British Science Association is proposing a new funding scheme to support public engagement with health in the UK. This new fund will: take a more outcomes-focussed and targeted approach to working with applicants; support and foster innovation; and encourage the sector to diversify its approaches and audiences.
We are proposing a three in one scheme: an ‘Incubator Fund’ will provide smaller grants to support innovation and diversity, the ‘Main Fund’ will establish and expand proven links and approaches, while a ‘Discretionary Fund’ will allow us to invest in organisations or approaches that show particular promise.
As a result, the public engagement with health sector will benefit from a grants scheme that’s more flexible and easier to navigate. This will help support and diversify the applicant pool, and hence benefit the public who will be more empowered to engage in research and better equipped to interact with health researchers, or people in allied careers, on topics they’re interested in. Ultimately more people in the UK will be engaged with - and trusting of - health research, and be able to access its benefits.
|
| 30/09/2020 |
£542,290 |
|
INSTITUT PASTEUR DE DAKAR |
Ebola virus disease has been declared a Public Health Emergency of International Concern in Democratic Republic of the Congo.
In the short term, our consortium plans to optimise, manufacture, and validate a novel Ebola rapid diagnostic test (RDT) for deployment at the point of need — that is low cost and high performance. A simple, 5 minute, high performance test, that complements complex laboratory tools, is urgently needed to ensure earliest possible detection of Ebola in the heart of communities experiencing an outbreak.
Successful deployment will lead to an optimised and evaluated device for manufacture to support the current outbreak in DRC, surveillance in neighbouring regions, and in time post-DRC outbreak surveillance.
In the long term, we envision substantial impact generated by establishing a new model for sustainable delivery of high performance outbreak diagnostics, deployed at the point of need. Accordingly, diaTropix - a new manufacturing facility dedicated to epidemics and neglected diseases in Dakar, Senegal - will be set up with the capability, expertise, and reagents to produce rapid diagnostics responsively to evolving outbreaks — with Ebola demonstrating proof of concept and feasibility, and a portfolio of rapid diagnostics in the pipeline for dengue, yellow fever, measles, and malaria.
|
| 30/09/2020 |
£49,804 |
|
UNIVERSITY OF EXETER |
The project will bring to light the forgotten satiric traditions that accompanied the rise of experimental medicine in early modern Spain. Focusing on previously untapped archival and printed sources of Spain, the research will recover literary satires on diverse aspects of medical experimentation, including pharmacological trials, blood transfusions, and surgical experiments. These novel experiments prompted questions regarding the choice of patients, which frequently came from the dispossessed social groups, such as prisoners, soldiers, foreigners, servants, the poor, hospital patients, and asylum in-mates. Satire is inextricable from its public function and can therefore provide a valuable contribution to the understanding of the early modern medical experimental practices. The project aims to answer the following questions: How did satirists react to the choice of experimental bodies? What were their main concerns and how did they express them via the available satiric models? In what ways did physicians themselves use satire to discredit their rivals’ methods? Apart from yielding self-standing results in the form of two research articles and an online database, the research in Spain will prepare the ground for the investigation of satires of experimental medicine in Germany and the Netherlands.
|
| 30/09/2020 |
£20,000 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2020 |
£50,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2020 |
£85,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2020 |
£200,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2020 |
£255,939 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
Strengthening research ethics systems in Latin America and the Caribbean
This proposal of the Regional Program on Bioethics of the Pan American Health Organization (PAHO) aims at significantly improving the regional research ethics landscape and, specifically, at strengthening research ethics systems and enhancing ethics preparedness to conduct research during emergencies. In response to a 2018 explicit request from the countries in the Americas to advance research ethics with a systemic approach, PAHO’s Regional Program on Bioethics developed indicators and a strategy to address the regional challenges. While this action has already triggered progress rapidly in few countries (e.g. Peru), PAHO’s resources to scale up these efforts as requested by the countries are very limited. This grant would allow PAHO to (a) assess the current situation using indicators, (b) advance change in several countries in Latin America and the Caribbean using national research ethics policies as a strategy, (c) support the implementation of such policies through an online tool for ethics review, and (d) share this model so it can be replicated by other regions. PAHO is uniquely positioned to achieve these outcomes due to its ongoing work supporting national health authorities on bioethics.
|
| 30/09/2020 |
£56,936 |
|
UNIVERSITY OF YORK |
Not available |
| 30/09/2020 |
£101,427 |
|
UNIVERSITY OF SOUTHAMPTON |
Not available |
| 30/09/2020 |
£51,295 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 30/09/2020 |
£187,697 |
|
UNIVERSITY OF DUNDEE |
Not available |
| 30/09/2020 |
£4,970 |
|
ROYAL VETERINARY COLLEGE |
Not available |
| 30/09/2020 |
£5,851 |
|
UNIVERSITY OF BATH |
Not available |
| 30/09/2020 |
£33,735 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2020 |
£51,368 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/09/2020 |
£813,243 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2020 |
£62,339 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 30/09/2020 |
£23,319 |
|
UNIVERSITY OF STRATHCLYDE |
Not available |
| 30/09/2020 |
£13,694 |
|
ST GEORGE'S UNIVERSITY OF LONDON |
Not available |
| 30/09/2020 |
£16,582 |
|
UNIVERSITY OF ST ANDREWS |
Not available |
| 30/09/2020 |
£82,190 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2020 |
£53,976 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 30/09/2020 |
£170,540 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Not available |
| 30/09/2020 |
£1,157,238 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2020 |
£51,844 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 30/09/2020 |
£154,673 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 30/09/2020 |
£292,856 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 30/09/2020 |
£150,329 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 30/09/2020 |
£77,795 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2020 |
£120,337 |
|
UNIVERSITY OF LEEDS |
Not available |
| 30/09/2020 |
£341,763 |
|
KING'S COLLEGE LONDON |
Not available |
| 30/09/2020 |
£20,964 |
|
KEELE UNIVERSITY |
Not available |
| 30/09/2020 |
£220,862 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2020 |
£34,749 |
|
UNIVERSITY OF EXETER |
Not available |
| 30/09/2020 |
£449,124 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 30/09/2020 |
£297,213 |
|
INSTITUTE OF CANCER RESEARCH |
Not available |
| 30/09/2020 |
£457,088 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2020 |
£112,683 |
|
CARDIFF UNIVERSITY |
Not available |
| 30/09/2020 |
£33,015 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 30/09/2020 |
£1,029,579 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2020 |
£174,907 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 30/09/2020 |
£192,922 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 30/09/2020 |
£23,303 |
|
BIRKBECK UNIVERSITY OF LONDON |
Not available |
| 30/09/2020 |
£46,123 |
|
UNIVERSITY OF WARWICK |
For much of the twentieth century, children in Britain interacted with speech therapists in hospitals, private practice and the local school medical services. Emerging from the end of the eighteenth century and forming a recognised College in 1945, speech therapists became a medically-allied profession over the course of the period between 1900 and 2000. To date, however, there has been no dedicated historiographical study of speech therapy provision – either from the perspective of the therapists or their young patients. The proposed research undertaken during this grant will provide an opportunity to scope a variety of manuscript, published and oral history sources that may be used to tell the story of this profession and those who used it. By allowing a preliminary engagement with the evidence base, this initial scoping will also contribute to the development of a sound theoretical and analytic framework for a project that has the capacity to speak to on-going debates across several historiographies as well as concerns within the medical humanities - addressing the nature of children’s experiences (as ‘patients’ or recipients of therapy), the socio-cultural construction of disability, and the porous boundaries between medicine and the world of arts and theatre.
|
| 30/09/2020 |
£27,020 |
|
CENTRE FOR INFECTIOUS DISEASE RESEARCH IN ZAMBIA |
We aim to contribute to strengthening capacity of ethical and regulatory bodies in governing Human Infection Studies (HIS) and developing an ethical and regulatory framework applicable to Zambia and other low middle income countries (LMICs). Being new to Zambia, there is no ethical/regulatory precedence to guide conduct of HIS which are in the pipeline. Recent introduction to other LMICs have highlighted ethical dilemmas related to HIS implementation. Hence, we propose an engagement workshop to: 1) understand views, expectations, and experiences of ethical and regulatory bodies, and other stakeholders involved in HIS, 2) identify core ethical issues and their implications for HIS implementation in Zambia drawn from other LMICs' experience, and 3) develop modalities to address these and other issues as encapsulated in consultation reports from Malawi (Gordon SB et al (2017) Wellcome Open Research) and the World Health Organization (Jamrozik E & Selgelid MJ.) to be used in Zambia and the region. Through the work described in this proposal, we aim to inform ethical guidance to build a national platform for the conduct of current and future HIS at CIDRZ, Zambia and the wider region. This will accelerate development of next generation vaccines that can end preventable deaths globally.
|
| 30/09/2020 |
£1,544,321 |
|
HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH |
The Planetary Health Alliance (PHA) is a consortium of over 160 universities, NGOs, and other partners from 40 countries all committed to supporting the rapid growth of a robust, global field of planetary health. The PHA has become a nerve center for the international planetary health community, forging a network that bridges the culture and language of the expansive disciplines, organizations, and individuals involved in the field. The PHA’s strength lies in its leadership in addressing the global needs to advance the field as identified by the broader planetary health community, as well as its role of raising up and supporting the needs of its individual members. The PHA’s coalition of members has identified a common vision for the next critical needs to advance the planetary health field: 1) a global community of practice with strong regional leadership that supports robust interdisciplinary research, education, and policy translation efforts; 2) transformative planetary health education at every level; and 3) broad public outreach to mainstream planetary health messages. Support from the Wellcome Trust would allow the Planetary Health Alliance to continue driving forward its work in these three crucial areas to ensure the health of our most vulnerable populations and future generations.
|
| 30/09/2020 |
£56,842 |
|
UNIVERSITY OF KWAZULU NATAL |
This application requests funds from the Wellcome Trust to support the refinement of a research proposal that formed part of a recent fellowship application. In response to recommendations levelled by the panel, one year of activities will undertaken towards strengthening the proposal. Three activities will feed into this objective, namely round table discussions with local health system actors in South Africa, interviews with key academics, and interviews with policymakers and researchers in global health. Round table discussions will be held in the cities of Pretoria, Cape Town and Durban, with participants from different sectors. The revised proposal will be discussed with academic experts from different disciplines and geographical regions. Participants will be targeted from different disciplines, geographies, and levels of expertise in relevant theory and research. Revisions will be discussed with participants attending the 6th Global Symposium on Health Systems Research. The revised research proposal will be discussed with the proposed study supervisor and study sponsor, during meetings at Stellenbosch University. Following this work plan will no doubt result in a more focused, coherent research project that will yield important scholarship in an increasingly important area of work.
|
| 30/09/2020 |
£29,938 |
|
UNIVERSITY OF DURHAM |
What might be gained by ‘doing’ medical humanities through objects and images? This grant will support an innovative programme of activities designed to stimulate interdisciplinary dialogue around the holdings of the Wellcome Collection. By bringing together ECRs and other professional participants, including creative practitioners and museums/archives staff, the Collection will be activated to appeal to a range of stakeholders beyond those who usually carry out archival work. By approaching selected objects in the Collection as ‘provocations to thought’ and ‘companions to our emotional lives’ (Turkle, 2011), the proposed activities will investigate how thinking and feeling ‘through things’ can generate new understandings of health.
Activities will centre around two workshops, the first at the Wellcome Collection, and the second at Leeds/Durham. Outputs will include a series of linked podcasts, essays and interviews, showcasing the project’s findings; a Working Knowledge Project Short outlining best practice for ‘doing’ medical humanities with objects; and a sustainable network of collaborators for further projects. Additionally, the programme will support ECRs in acquiring the necessary skills for working with objects for research and engagement purposes, and will enable ECRs to form professional connections outside of the academy, laying the groundwork for future research, outreach, and engagement activities.
|
| 30/09/2020 |
£344,340 |
|
UNIVERSITY OF HONG KONG |
AMR has long been of concern to scientists and health professionals because of its adverse implications for healthcare, but many others including countries initially paid little attention. In essence, AMR-related policies across many governments and non-health sectors (in particular), are developing slower than desirable because many groups within non-health sectors do not believe they are contributing to the development of AMR. In this context, many groups are reluctant to commit to taking responsibility or actions because of this uncertainty. ACES aims squarely to reduce this uncertainty as a barrier to better policies. Normally, scientific findings are published and they may, or may not, come to the attention of policy makers. ACES plans, by contrast to use a more direct, guided and multi-pronged approach to influence policy directions from the start.
Under the following aims, ACES is intended to confirm that multiple sectors (health and non-health) contribute towards the development of AMR affecting people.
Aim#1: Determine what proportion of human AMR bacterial infections are attributable to antibiotic related practices, conditions or outcomes in human, plants, food-producing animals, food and the environment.
Aim#2: Determine the main pathways and mechanisms by which such practices, conditions or outcomes result in human AMR bacterial infections.
|
| 30/09/2020 |
£1,955,607 |
|
OPHIREX |
Ophirex seeks funding from the Wellcome Trust to cover a portion of costs associated with developing U.S. FDA approved and W.H.O pre-certified oral and IV broad-spectrum antidotes to snakebite.
The program will advance affordable, time-of-bite, heat-stable, easy-to-use, broad-spectrum treatments for snakebite based upon Ophirex’s privately developed toxin-targeting portfolio.
This new treatment strategy will provide superior care, rescue life and limb, and be easily administered in any environment. Not only will this antidote be easily used in unsupported environments in an oral form, it will also be effective in an IV formulation when needed, such as in pediatric care, rapid infusion for rescue/emergency treatment, and traditional intensive care.
Key attributes of this First-In-Class antidote are:
1) Broad spectrum efficacy for first-line treatment of snakebite
2) Excellent safety profile
3) Ease of use, easily administered anywhere
4) shelf-stability in Zone IV conditions with at least one-year shelf life.
All tasks support submission for FDA licensure and file transfers to other regulatory authorities (such as WHO precertification). Key goals include:
Goal 1: Complete GMP API manufacturing and begin stability testing of oral and IV formulations for use in clinical trials.
Goal 2: Support Clinical Trial for registration submission for FDA and WHO precertification.
|
| 30/09/2020 |
£1,179,736 |
|
RADBOUD UNIVERSITY MEDICAL CENTRE |
Resistance to commonly used antibiotics for common bacterial infections is a major health threat for the 21st century. The problem is particularly pressing in low- and middle-income countries (LMICs). This proposal builds on the work from a previous program (ABACUS I) that studied the access to and use of antibiotics in the communities of 3 African and 3 Asian countries. We propose to build the case for an international system that harmonizes the appearance and thus improves identification of oral solid formulations of antibiotics both for consumers and providers. We will consider the potential negative effects as well. We have formulated the following key goals:
Assess the potential impact of and obstacles to standardising the physical appearance of commonly used oral antibiotics on formal and informal suppliers as well as consumers in six LMICs.
Design, with key stakeholders and experts, an approach and prototypes that improves (for both suppliers and consumers) the appropriate identification of oral antibiotics
Perform a health economics analysis related to inappropriate identification of oral antibiotics and the potential impact of introducing the standardized designs
Assess the proportion of substandard and falsified oral antibiotics among three commonly sold antibiotics in four LMICs (Mozambique, Bangladesh, Ghana, Vietnam
|
| 30/09/2020 |
£2,063,517 |
|
INSTITUTE OF DEVELOPMENT STUDIES |
With the world facing repeated threats from disease outbreaks and with significant health and humanitarian crises engulfing regions, there is increasing recognition from humanitarian agencies of the value of social science knowledge and perspectives in contributing to operational preparedness and response efforts. In addition, there is a growing need for social scientists to assist with critical reflection on past responses and contribute to future learning, across all pillars of the emergency response. More targeted engagement with both agency staff involved in on-the-ground responses, as well as advocacy directed towards social scientists in order to improve their capacity to translate knowledge into actionable recommendations, could assist in mobilising a diverse and engaged community of practice. IDS, in collaboration with Anthrologica, has been a leader in such activities through the work of the Social Science in Humanitarian Action Platform, which has received acclaim for advocacy efforts and the production of synthesis briefings, such as for the current DRC Ebola outbreak. We are seeking funding to expand the work of the Platform in order to respond to an increasing demand for written and verbal briefings, for round table events in relation to crises, and for a fellowship scheme for practitioners and social scientists.
|
| 30/09/2020 |
£7,441,507 |
|
AFRICAN ACADEMY OF SCIENCES |
The African Academy of Sciences (AAS) established the AESA platform in 2015 in partnership with the Africa Union Development Agency (AUDA, formerly NEPAD Agency), the Wellcome Trust, the Bill and Melinda Gates Foundation (BMGF), and the UK Department for International Development (DFID).
The initial phase has been characterized by a growing portfolio of programme activities, aligned to the AAS STI strategies, and focused on achieving the four goals outlined in the AESA Partners’ Group - approved AESA Business Plan to develop scientific excellence, leadership, innovation and improve the research landscape in Africa.
The existence of the CORE grant has been an enabler to AAS with many benefits including:
Ability to receive and disburse complex grant funds after investing in world class financial and grants management systems and policies.
Ability to flexibly recruit and retain a high calibre multinational African team.
Ability to develop and deliver robust evaluation and risk management mechanisms
Resources to renovate and refurbish the AAS offices to provide more space and better work environment
Resources for team building and leadership coaching interventions
Ability to conduct internal audits and other due diligence exercises
Improved AAS competitiveness in the employment market in terms of staff benefits and welfare
|
| 30/09/2020 |
£52,480,377 |
|
AFRICAN ACADEMY OF SCIENCES |
The African Academy of Sciences (AAS) is submitting this application for renewal of the Developing Excellence in Leadership Training and Science in Africa (DELTAS) Africa programme in line with Wellcome’s strategy to strengthen Africa’s research outputs and capacity developments. The first 5-year funding cycle of DELTAS Africa I concludes in 2020 and has successfully laid a firm foundation on which to accelerate health research excellence and productivity. DELTAS Africa I has been successful in achieving its core objectives of scientific productivity and quality, building a critical mass in leadership through training and mentorship, gender parity particularly in onboarding more women in science and scientific impact including policy influence. Further, DELTAS Africa I has been vital in strengthening R & D infrastructure and providing significant investment for key disease priority areas. The DELTAS Africa programme requires a new cycle of funding as building a critical mass in research leadership for scientific impact is inherently long term. This application requests for an additional DELTAS Africa II 5-year grant (2021-2025) to build and expand on DELTAS Africa I with a deeper focus on scientific priorities, governance and impact measurement. The AAS is therefore requesting Wellcome to fund DELTAS Africa II to the level of £64,264,417.
|
| 30/09/2020 |
£38,701 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
The proposed project is a joint effort put forth by eleven comprehensive universities across China (including Hong Kong) and three regional partners in Japan, Korea and Vietnam, and supported by government agencies at local, national and regional levels. Following the World Health Organisation (WHO) "Operationalizing Emergency Preparedness" cycle, the proposed project aims to systematically engage researchers from various fields of social science to (a) build a mechanism that informs evidence-based response, (b) strengthen the social science research capacities in infectious disease emergency, and (c) create a strong network of social scientists for timely and effective deployment for outbreak response. A three-phase Scoping-Development-Evaluation working framework will be followed to match response needs with critical data derived through social science methods. We will review and synthesize successful strategies throughout different regions of East Asia and create a database with case studies. The ultimate product of this proposed project will be a protocol and associated tools (including training materials), and a strong regional research network that will effectively integrate social science research in the responses to local, national and multinational outbreaks. This newfound network will be better able to inform the preparedness partners on the social and behavioral determinants of effective epidemic control.
|
| 30/09/2020 |
£113,733 |
|
UNIVERSITY COLLEGE LONDON |
Sex education can positively impact upon sexual behaviour and reduce the likelihood of adverse sexual health outcomes, but the quality of provision and coverage of topics is variable. There is a need for evidence-based ways to improve knowledge of sex and relationships that speak to people across the lifecourse and from all walks-of-life. Uniting internationally-recognised scientists in sexology, epidemiology, and education, with the UK’s leading charities (Brook and the Sex Education Forum) promoting young people’s sexual health and the delivery of quality life-long relationship and sex education (RSE), we will use creative arts and online technologies to produce innovative resources that meet this need.
Evidence from Britain’s nationally-representative sexual health survey (the National Survey of Sexual Attitudes and Lifestyles, ‘Natsal’) and our previous public engagement will be used:
(i) to create a free-to-use interactive online resource for the general public, allowing exploration as to what is ‘normal’, the factors that shape sexual lifestyles, and the underpinning scientific research;
(ii) as a catalyst to facilitate dialogue with and between young people on issues around sex that matter to them. This young people-centred learning will be translated into resources to better equip teachers to deliver RSE, crucially coinciding with the introduction of mandatory RSE in schools in England (2020) and Wales (2022).
These evidence-based tools will empower people of all ages to improve their knowledge of sex and relationships, their sexual health and wellbeing. They will also demonstrate proof-of-concept around novel mechanisms for engaging the public with Natsal and science more broadly.
|
| 30/09/2020 |
£5,730,747 |
|
MERCK SHARP & DOHME |
Malaria is one of the world's most devastating diseases of humans and results
in over 400,000 deaths annually. Novel therapies are urgently required to
populate the antimalarial clinical portfolio, as the current therapeutics that treat
this disease are becoming less effective due to emerging resistance.
A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA
(known as MSD outside the US and Canada) and Professor Alan Cowman from
the Walter and Eliza Hall Institute (WEHI}, has demonstrated that malaria
aspartyl protease enzymes are attractive drug targets, as they perform
essential functions for survival in liver, blood, and sexual stages of the parasite
life cycle.
Through screening aspartyl protease inhibitor libraries, the collaboration has
identified novel drugwfike hit compounds that are potently active against the
malaria parasite. The proposed lead optimization research aims to increase
potency against the parasite whilst maintaining selectivity, progressing to a Iab development stage clinical candidate. |
| 30/09/2020 |
£931,685 |
|
WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH |
Malaria is one of the world's most devastating diseases of humans and results
in over 400,000 deaths annually. Novel therapies are urgently required to
populate the antimalarial clinical portfolio, as the current therapeutics that treat
this disease are becoming less effective due to emerging resistance.
A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA
(known as MSD outside the US and Canada) and Professor Alan Cowman from
the Walter and Eliza Hall Institute (WEHI}, has demonstrated that malaria
aspartyl protease enzymes are attractive drug targets, as they perform
essential functions for survival in liver, blood, and sexual stages of the parasite
life cycle.
Through screening aspartyl protease inhibitor libraries, the collaboration has
identified novel drugwfike hit compounds that are potently active against the
malaria parasite. The proposed lead optimization research aims to increase
potency against the parasite whilst maintaining selectivity, progressing to a I
development stage clinical candidate. |
| 30/09/2020 |
£248,509 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2020 |
£245,788 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2020 |
£243,492 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2020 |
£833,400 |
|
UNIVERSITY OF MANCHESTER |
The enzyme lysyl oxidase (LOX) regulates cross-linking of structural proteins in the extracellular matrix.
LOX also plays a role in stimulating the metastatic spread of cancer through the body. Its expression is increased in hypoxic cancers and is correlated with tumour metastasis and decreased patient survival. In model systems its inhibition significantly decreases cancer metastasis and increases survival. Since metastasis is responsible for over 90 per cent of cancer deaths these data validate LOX as an important therapeutic target in cancer.
Professor Caroline Springer and Professor Richard Marais from the Institute of Cancer Research have been awarded Seeding Drug Discovery funding to develop drugs that target LOX. They are applying a medicinal chemistry drug discovery approach underpinned by a strong programme in LOX biology with the aim of producing orally available, small molecular weight drugs that inhibit LOX activity for cancer treatment. |
| 30/09/2020 |
£100,000 |
|
INSTITUTE OF CANCER RESEARCH |
While effective treatments for many forms of cancer exist, therapies that are tailored for patients with niche forms of the disease, such as triple negative breast cancer are currently unavailable. The Trust has awarded £3.9 million over three years to Prof. Alan Ashworth, FRS, Dr. Christopher Lord, Prof. Caroline Springer and Prof. Laurence Pearl, FRS, for the development of orally available small molecules that could target specific cancer subtypes. Researchers led by Prof Alan Ashworth and Dr Christopher Lord have pioneered the exploitation of novel therapeutic approaches such as synthetic lethality and the use of PARP inhibitors in cancer treatment. PARP (Poly ADP-Ribose Polymerase) enzymes modify proteins and control cell function by catalyzing the addition of poly (ADP-ribose) polymers onto substrates. With funding from the Trust, Ashworth, Lord, Springer and Pearl, in collaboration with Domainex, will develop novel small molecule inhibitors that target additional PARP superfamily members. These inhibitors will be assessed in specific tumour models and then progressed into clinical candidates that could be ultimately assessed in drug trials that target cancer subtypes for which there is significant unmet clinical need. |
| 30/09/2020 |
£1,444,200 |
|
SAVE THE CHILDREN |
Not available |
| 30/09/2020 |
£555,800 |
|
SAVE THE CHILDREN |
Not available |
| 30/09/2020 |
£143,272 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
The project supports activities in the Immunization, Vaccines and biologicals
department of the WHO that aim to advance the product development and use of
monoclonal antibodies (mAbs) for infectious diseases, with a focus on meeting the
needs of Low and Middle Income Countries (LMICs). Three specific activities will be
carried out. First, a stakeholder consultation on monoclonal antibody technologies will
be held to discuss which would best support affordability and accessibility in LMICs.
Second, an application to establish rabies mAbs on the WHO model list of essential
medicines (EML) would set the precedent for inclusion of additional infectious diseases
mAbs in the future. Thirdly, an assessment of diphtheria immunoglobulin supply and
potential demand for mAb-based products will be carried out which could serve as a
methodology to be used to assess other mAb based products." |
| 30/09/2020 |
£50,000 |
|
UNIVERSITY COLLEGE LONDON |
We are launching a Lancet Commission on Gender and Global Health that intends to ensure that global health take gender into consideration. A continued failure to consider and act on gender in public health policies, programmes and practices results in lost opportunities to improve health outcomes across society, equitably and sustainably.
We have drawn together a cross- and inter-disciplinary Commission that benefits from the expertise and experience of around 20 Commissioners from different backgrounds, geographical settings and genders. The Commission will be guided by Dr Richard Horton and Dr Jocalyn Clark from The Lancet, and will be co-Chaired by Professor Pascale Allotey from UNU-IIGH, Professor Sarah Hawkes from UCL and Mr Elhadj As Sy, Chair of the Board of the Kofi Annan Foundation.
We plan to launch the Commission in October 2020 after the Berlin World Health Summit (WHS). We will organise a 2-day meeting bringing Commissioners together for the first time, to discuss the direction and content of the Commission and establish a workplan covering the next 2-3 years. Funding is required to host the launch in Berlin, and to follow up with post-launch co-ordination and communication activities.
|
| 30/09/2020 |
£240,730 |
|
GLOBAL POLICY REPORTING |
Reliable, evidence-based media remains a key means of advancing public health literacy and bringing news, views and opinions from diverse regions of the world into the corridors of power. The vision driving Health Policy Watch, launched in 2019 as an open-access, non-profit health news service, is to create a new "network paradigm" that connects the dots between policy trends and realities in the global North and South. We provide coverage across 5 key themes, including: infectious diseases; non-communicable diseases; antimicrobial resistance; climate and environmental health; and health emergencies.
The key objective of this proposal is to foster a more balanced- and "solutions"-oriented approach to health policy dialogue around issues and choices that are critical to effective response to the COVID-19 pandemic - and to the broader global health agenda in light of COVID-19 realities.
Institutional sustainability is a second key objective. To realize its public service mission, Health Policy Watch is committed to ensuring that all potential readers can access our content free of charge. As we work, with modest resources, to build a diverse array of donors and collaborations to advance that mission, Wellcome Trust support would empower us to develop a more sustainable and robust funding portfolio.
|
| 30/09/2020 |
£250,000 |
|
UNIVERSITY OF OXFORD |
In low-income countries there remains a lack of internationally competitive research leaders. The Global Health Network has analysed the barriers and enablers to health research and show that typical approaches to capability building have not delivered long-term capabilities that foster internationally competitive teams. The Network has built a novel mechanism to address this which works across all types of study, disease areas and organisations to share know-how and deliver training, guidance and methods using a digital platform alongside local programmes. The success and impact that arise from this combination of cross-cutting knowledge exchange and research capability building together provide a strong research enabling platform. This active exchange of knowledge, tools and processes is increasing quality and driving efficiency in health research. The Network is driving better methods, new skills and supporting career development through the creation of active communities of practice. These capacity building, methodology research activities and delivery costs cannot be met by our project-specific funding for knowledge exchange, yet these elements deliver success and impact by bringing the research community together. This application is part of our long-term strategic development plan that sets out to further develop our unique and impactful approach for which we require consortia funding.
|
| 30/09/2020 |
£4,483,010 |
|
UKRI-MRC |
Not available |
| 30/09/2020 |
£230,048 |
|
WORLD HEALTH SUMMIT |
The most pressing global health challenges of our time require strong partnerships for multi-stakeholder exchange and appropriate policy responses. Against this background, the World Health Summit would like to strengthen its collaboration with expert organizations such as Wellcome Trust, to make a greater contribution to policy-making in the field of global health research and strengthen scientific and political activity in Berlin and beyond in the spirit of the sustainable development goals.
|
| 30/09/2020 |
£341,655 |
|
MUNICH SECURITY CONFERENCE |
Building on the expertise and support provided by the Wellcome Trust in recent years, the MSC wishes to create a direct continuation of existing work, sustainably strengthen its global health dimension and expand its reach with additional activities in response to COVID-19 and beyond.
During the MSC fiscal year 2020-2021 activities will include two follow-up Digital Conversations and various roundtables and side events within the scope of the 2021 Munich Security Conference, a 2021 Health Security Roundtable in Berlin and potentially a Health Security Roundtable on the sidelines of the MSC Core Group Meeting 2021 in Washington D.C.
Additionally, a Special Edition of the Munich Security Report, the "Stability Report" will address many current issues and challenges in global health security. As part of the grant proposal, the MSC will facilitate Wellcome Trust participation at the report launch and will give updates on report progress.
Events similar in number and design will take place in the fiscal years 2021-2022 and 2022-2023. Due to COVID-19, detailed plans will only be made at a later stage. The MSC will keep the Wellcome Trust up to date on its plans for new MSC health security activities as soon as they become available.
|
| 30/09/2020 |
£419,410 |
|
ACCESS TO MEDICINE FOUNDATION |
Equitable access is critical for maximising the impact of innovation and heavily depends on proactive actions by pharmaceutical companies, during and after the COVID-19 pandemic. In order to bring the pandemic to an end, achieve universal health coverage and protect the gains made on Sustainable Development Goal 3, the pharmaceutical industry will need to ensure that all scientific advancements benefit the maximum number of people, independent of the place they live or their ability to pay. The Access to Medicine Foundation (ATMF) has incentivised pharmaceutical company action to improve access to new innovations for more than a decade. By rewarding positive action, sharing best practices, and highlighting opportunities for change, the ATMF encourages companies to become willing partners to improve global access to their products. The ATMF will support Wellcome Trust’s approach to equitable access to healthcare interventions through a combination of research and policy initiatives that will (a) incentivise pharmaceutical company action on COVID-19, (b) support global efforts to mainstream access principles during product development and (c) untap the potential of generic medicine manufacturers in expanding access to innovations in low- and middle-income countries. The request from the ATMF is for €471,750 (£425,000) from October 2020 to September 2021.
|
| 30/09/2020 |
£2,277,389 |
|
UNIVERSITY OF OXFORD |
OpenSAFELY is a new secure analytics platform for electronic health records in the NHS, created to deliver urgent results during the global COVID-19 emergency. It is now successfully delivering analyses across more than 24 million patients’ full pseudonymised primary care NHS records, with more to follow shortly. All our analytic software is open for security review, scientific review, and re-use. OpenSAFELY uses a new model for enhanced security and timely access to data: we don’t transport large volumes of potentially disclosive pseudonymised patient data outside of the secure environments managed by the electronic health record software company; instead, trusted analysts can run large scale computation across live pseudonymised patient records inside the data centre of the electronic health records software company. This pragmatic and secure approach has allowed us to deliver our first analyses in just five weeks from project start.
|
| 30/09/2020 |
£2,758,611 |
|
OPENING KNOWLEDGE ACROSS RESEARCH AND ENTERTAINMENT (OKRE) |
The proposal outlines the request for funding to support the set-up, operation and activities of OKRE: Opening Knowledge across Research and Entertainment over five years.
OKRE is a high-profile strategic initiative for working with the entertainment industries that has been developed in partnership with UKRI. OKRE enables Wellcome to build on the work it has done so far, to scale its impact and create a more sustainable transformation in the engagement of research with mass media.
A gap was identified between research and entertainment sectors for a body akin to the Science Media Centre but designed to address the particular challenges of working with the entertainment industries. OKRE's business model has now been developed and the organisation has been registered with Companies House and the Charity Commission.
Wellcome is uniquely positioned to establish such a body. Funding enables OKRE to deliver core services in line with Wellcome's new strategic vision. OKRE's objects include promoting research, advancing education of the public and advancing the arts in social, scientific and health-related issues, as well as promoting the efficiency and effectiveness of charities. By sharing infrastructure costs with other funders, OKRE will enable Wellcome to scale the impact of its funding.
|
| 30/09/2020 |
£248,240,718 |
|
WELLCOME LEAP INC. |
Wellcome Leap Inc. has been established by Wellcome as a US, wholly owned not for profit entity with the aim of delivering breakthroughs in human health and demonstrate seemingly impossible results on seemingly impossible timescales. This will be achieved through the creation of a small portfolio of goal focused Programmes selected based upon their potential to improve health globally rather than by their potential financial or commercial return.
Wellcome provides initial funding of $306.9M to Leap to cover their first 10 years of operation (although further funding may be provided over this 10 years). This funding will support Leap’s operational costs and ‘Programmatic costs’ which will include (but not be limited to) the employment of Programme Directors to build and orchestrate large research programmes, subject matter advice and support to formulate a programme and the funding of sub-awardees to carry out research in pursuit of a programme goal.
Wellcome may provide further funding to Leap after 3 years of operation and it is anticipated that Leap will in time attract funding from third parties. |
| 30/09/2020 |
£1,800,000 |
|
UNIVERSITY OF BRISTOL |
This University of Bristol-Wellcome Trust Translational Partnership Award (TPA) will build on the successes and insights gained from the past three years of our partnership to deliver a sustained, impactful change in our translational research and culture. Our ambition is to turn University research into real world solutions which transform our society, economy and health. In this award we will continue to try new things, disrupt the status quo and advance the way we support and accelerate translation by taking a bespoke, personalised approach, driving culture change to maximise the impact of our research. We will use this funding to work with researchers at all stages of the career pathway (PhD to Professor) to develop and realise their ambitions to translate their research through: - A Translational Research Hub to enable straightforward access to expertise and funding and facilitate engagement with non-academic partners - Proof of Concept and Translation Accelerator project funding to meet gaps in the translational funding pathway - Early Career Translational Fellowships to provide bespoke support for the most promising individuals and projects - Developing Innovation Networks with partner organisations in priority modalities and areas - Exploiting the translational platforms developed from our cutting-edge synthetic biology and informatics technologies in TPA1 and 2 - Providing training to researchers that embeds learning into practice through follow-up support and individualised action plans |
| 30/09/2020 |
£2,250,000 |
|
UNIVERSITY OF CAMBRIDGE |
The University of Cambridge will use the TPA funding to bridge the gap between discovery science and early stage translation of projects. The aim is to encourage and support basic scientists to realise the translational potential of their research by providing integrated facilitation for training, expert advice, funding and projects through creation of a virtual Therapeutic Hub, which supports the TPA within CATS. Our objectives are:
- To provide a gateway for translation into the therapeutics sciences pipeline through the creation of a virtual therapeutic hub;
- To facilitate early stage drug discovery and translational research
- To develop a community of Translational Champions across the University who will provide opportunities for Departments/Institutes to develop their own translational strategies
- To deliver training in early translation for research scientists and early career academics. |
| 30/09/2020 |
£2,397,523 |
|
UNIVERSITY OF MANCHESTER |
The University of Manchester will use the three-year Wellcome Translational Partnership
Award (TPA) renewal to build on the successful initiatives launched and delivered through the
first TPA and continue to grow the translational research culture and develop the translational
ecosystem in Manchester. The TPA funding will be used to address four aims: 1) support
translational research; 2) connect across disciplines; 3) innovate with industry; and 4) change
the culture by embedding translational research across the University. The Translational
Research Facilitators will continue to bring together a network of support, facilities and
expertise to build better links between science, technology and innovation, by removing
barriers between disciplines to make the pathway to translation quicker and easier. The TPA
will support translational research across all the stages of the translational pathway through
pump-priming funding schemes, training (particularly informatics), symposiums and
workshops, with a particular emphasis on new initiatives to support early career researchers.
The Translation Manchester Research Network (TMRN), established under the initial TPA,
brings together groups and organisations that exist to facilitate translational research across
the One Manchester health innovation ecosystem, making it the ‘one-stop-shop’ for
translational research support. The TMRN will continue to play a key role in the delivery of the
initiatives set out in the TPA renewal. In addition, Innovation Labs will connect academics with
industry partners, and pump-prime new collaborations and innovation through seed corn
funding. The Research Connections Tool will enable researchers and clinicians to easily find
appropriate collaborators across the University and our partner NHS trusts. To support
delivery of these new initiatives a Translational Research Support Officer and a Translational
Research Bioinformatician will be recruited into the Translation Manchester team. |
| 30/09/2020 |
£2,401,000 |
|
UNIVERSITY OF EDINBURGH |
Since 2018, the University of Edinburgh has been in receipt of a Wellcome Institutional
Translation Partnership Award which has now been renewed for a further three years. The
ambition of the partnership is to engage Wellcome Trust funded researchers and all of those
working within the Wellcome Trust scientific remit, to identify and develop early stage
translational opportunities within their research. Edinburgh embedded its scheme within
Edinburgh Innovations building a small focused team, including two Entrepreneurs-in-
Residence with a successful commercial/translational background to nurture projects towards
translation through leveraging future funding, industry collaborations or commercialisation plus
a dedicated Project Manager. Since inception, the program has engaged with hundreds of
researchers, providing mentoring and support.
Renewal of the award will allow access to translational support and funding across the
University at scale. This will make beginning and navigating the translational journey for all
researchers easier and increase the diversity of the translational portfolio both in terms of
thematic area and forms of impact. |
| 30/09/2020 |
£32,419 |
|
CODE FOR SCIENCE AND SOCIETY |
The coronavirus pandemic has led to an unprecedented uptake of preprints, with researchers from all over the globe collaborating and sharing information at record speeds. The Wellcome Trust-funded open source platform Outbreak Science Rapid PREreview (https://outbreaksci.prereview.org) launched by our team on January 1, 2020, is well-positioned to help provide rapid feedback and a help filter the high number of COVID-19 preprints for quality and potential impact.
In just a few months, the platform has reached about 500 users, 80 rapid reviews, and more than 230 requests for reviews, the majority of which are for COVID-19-related preprints. These numbers grow every day, and so do opportunities for collaborations with third-party sites and efforts that can increase the discoverability of the content and accessibility to the tool.
To leverage our platform and aid in tackling this pandemic, our team asks for financial support for the following activities and positions:
Feature implementation and customization of our open API to make COVID-19-related content more discoverable via integration with third-party sites, such as preprint servers and research platforms;
A full-time project manager to lead and coordinate the work.
|
| 30/09/2020 |
£240,000 |
|
ZINC |
The early stages of health startups are science-rich environments that provide opportunities for the public to engage in health research and co-design new solutions. However, many user groups - especially those who are underserved by existing digital health solutions - are not empowered to engage with the research activities of startups. This is particularly evident for health issues considered ‘taboo’, such as incontinence, menopause, fertility, IBS, and mental ill-health. The result is a startup landscape that is overly focused on a narrow set of health issues and populations.
This project will launch a new programme of public engagement at Zinc, providing formal support and a structured programme to ~6 startups that are science-rich, dealing with taboo health issues, and committed to empowering underrepresented ‘expert users’. Working closely with specialist consultants, we will create opportunities for the public to contribute to, and learn about, health research and innovation. This work will advance the evidence-base for public engagement - in particular, our understanding of how founders and researchers can more effectively engage with publics underserved by digital health solutions. Longer-term, our aim is that this will lead to better integration of academic health research, public engagement, and commercial tech innovation.
|
| 30/09/2020 |
£27,393 |
|
UNIVERSITY OF LEIDEN |
Not available |
| 30/09/2020 |
£49,903 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
We will develop software building-blocks to facilitate the use of operational health data in Africa to aid the COVID-19 response. The main gap the new work addresses is the use and re-use of health data in the immediate operational response to COVID-19. The project will run under the umbrella of afrimapr, an existing Wellcome Open Research Fund project improving the use of health research data. The project philosophy is the same: firstly to develop open-source R components to assist African data scientists in creating tools to address local issues, secondly to develop training resources and thirdly to promote them within African data communities. We have already started assessing, and improving access to, open-data on African health facility locations. This extension will allow us to continue working with new collaborators; healthsites.io and OpenStreetMap communities that collate and crowdsource health facility data. We will reach out to African data communities through DFID advisers to African ministries, national statistics institutes through the Global Statistical Service, and our networks and social media. Components for working with African health zones will also be developed. Increasing the use of open-access health data has the co-benefit of incentivizing improvements to the availability of the data themselves.
|
| 30/09/2020 |
£249,544 |
|
UNIVERSITY OF GLASGOW |
General population serosurveillance in low-income Africa is fundamental to understanding the population exposure to SARS-CoV-2, to explain the observed epidemiology and to ensure that ongoing control measures in the region are proportionate and are not guided by observations from very different settings. Detailed longitudinal immunological studies of infected individuals will be key to determining the long-term strategy in managing COVID-19 in highly vulnerable African populations.
Utilising the longitudinal urban and rural cohorts established by the Malawi Epidemiology and Intervention Research Unit, and supported by international and national expertise, we will undertake population immunoepidemiological surveillance to understand the trends in exposure and transmission of SARS-CoV-2, risk factors for SARS-CoV-2 infection and severe disease, as well as the proportion of asymptomatic or pauci-symptomatic infection in the population to enable an accurate estimate of infection fatality rate. Furthermore, we will recruit individuals with evidence of past SARS-CoV-2 infection to a nested cohort with 3-monthly sampling, to explore the magnitude and duration of antibody response and protective immunity in the Malawian population, and at the same time creating a biorepository for further in-depth virological and immunological studies.
|
| 30/09/2020 |
£908,761 |
|
PATH |
Public Health Value Propositions, also called Full value Vaccine Assessments, are critical, evidence-based analyses conducted to ensure that efforts to develop new vaccines align with the needs, interests and capacity of intended beneficiaries. We are developing a Shigella vaccine Value Proposition (svvp) to assess and possible enhance the probability that appropriate vaccines targeted at the diarrhoea-causing bacterium Shigella will be developed, produced, financed, widely recommended and adapted in low-middle income countries (LMICs)where it is endemic. The SVVP will inform late stage development investments in Shigella vaccine candidates. We are assessing and synthesizing relevant epidemiological, economic, policy regulatory and manufacturing aspects to address five broad questions and inform the SVVP.
1. How strong is the evidence linking Shigella to stunting, and what would be the economic consequences of vaccine-induced reductions in stunting?
2. What would be the projected impact on and cost effectiveness of the prevention of Shigellosis by effective vaccines?
3. What is the potential demand for Shigella vaccines across different markets?
4. What would be the optimal pathogen composition of a Shigella-containing combination vaccine potentially available in the near- or medium-term?
5. From the perspectives of LMIC-level policy makers and other key stakeholder, what would be the perceived value of a shigella-containing vaccine? |
| 30/09/2020 |
£140,190 |
|
ALBERT B. SABIN VACCINE INSTITUTE, INC |
The COVID-19 pandemic underscores the urgency and importance of vaccines and immunization to global health. There are significant and pressing scientific, technical and policy solutions needed to tackle the enormous challenges we face in a world with COVID-19. Bold thinking across disciplines, actionable recommendations and strong advocacy are all urgently needed to advance innovative ideas, overcome these hurdles and inform future programmatic work, in particular in light of the COVID pandemic. The goal of this project is to virtually convene The Sabin-Aspen Vaccine Science & Policy Group (Vaccine Group) in September 2020 to explore how the effort to accelerate the development of COVID-19 vaccines through ACT Accelerator and other initiatives can be harnessed to bring about a "new normal" for vaccine/vaccination ecosystem and ensure that vaccines for diseases with epidemic potential or those affecting low income populations are developed. The Sabin Vaccine Institute and the Aspen Institute, co-conveners of the Vaccine Group, will draft and disseminate a meeting report on the convening with principal findings and recommendations to inform program and policy planning.
|
| 30/09/2020 |
£45,714 |
|
INDEXICAL FILMS LLC |
Declaring "war on disease" affects how we treat sick people, how we define the "public" in public health, and how we respond to real-world pandemics.. This was demonstrated vividly during the COVID-19 crisis, when these declarations of war initiated militarized states of emergency, prompted border lockdowns, and refreshed old fears about "foreign" pathogens. But why was this public health crisis being treated as a national security issue? What else does this metaphor do in the world? And what if it weren't a war?
To answer those questions, the feature-length documentary "Dis-Ease" retraces the origin and evolution of our "war on disease" through the history, philosophy, culture, and pop-cultural imaginaries of medicine. It is constructed around particular episodes in the history of human encounters with epidemic, endemic, and pandemic diseases, including plague, malaria, cholera, tuberculosis, influenza, HIV/AIDS, and COVID-19. By examining the cultural history that runs alongside the growing scientific understanding of these diseases over time, DIS-EASE looks to understand how pandemic preparedness became framed as biodefense, and how that has contributed to the present crisis. And it proposes alternatives for the future.
|
| 30/09/2020 |
£239,027 |
|
UNICEF UK |
Aligned with Wellcome’s commitment to leveraging public partnership – throughout the cycles of response, recovery and resilience/sustainable preparedness – to inform research, create trusted research, and increase the access and use of research more equitably across communities, this project will (1) Fill a current gap in children and young people (CYP) insights around Covid-19 and other issues of health and science related research, (2) Equip young people with participatory research and multi-media production skills, and (3) Develop a scaleable participatory model of research and communication for change.
To achieve this, UNICEF C4D, a leader in using communication strategies to empower CYP as critical actors in research and development, will partner with innovative multi-media platforms -- inclusive of video, community radio, and mobile-based platforms -- to facilitate CYP-led cross-country surveying, personal stories (via video), in-depth interviews (with/by CYP), and deliberative dialogues (via community radio, video and mobile-based platforms), that will uncover CYP needs, behaviours and experiences with COVID-19 and other priority health and science challenges. UNICEF and its partners will develop a replicable model and partnership base for CYP-led research and engagement to influence social and behaviour change to support future joint research engagement to inform policy and programmatic decision making.
|
| 30/09/2020 |
£149,993 |
|
UNIVERSITY OF MANCHESTER |
A 9-part digital comic for young adults (YA) aged 16-25 providing an alternative, character-based narrative about a pandemic. Co-created with young adults from across the globe, multidisciplinary researchers and experts, renowned comic writers and artists, PlanetDivoc91 offers audiences diverse perspectives on how to make sense of a pandemic. It connects and empowers YA - whose voices have been marginal in the COVID crisis - to be heard in current and future pandemic research and policy. This proposal builds on work already started in the UK and internationally, to extend in greater depth globally, particularly in India and South Africa (SA). |
| 30/09/2020 |
£1,999,436 |
|
UNIVERSITY OF OXFORD |
We seek to establish a research network and collaborative platform for rapidly identifying and analysing ethical and policy issues arising in infectious disease treatment, research, response, and preparedness, and engaging in research on the profound ethical challenges presented by infectious diseases across the globe. The platform and network will provide real-time ethics and policy support, create a mechanism for collaborative responsive research as well as forward-looking projects with longer timeframes and engaging with crucial stakeholders from across high-resource and LMICs, all focusing on the critically important area of infectious disease and global health bioethics. In addition to being responsive to the needs as identified by the network, we expect the platform and network to be available to respond to needs identified by the WHO Public Health Emergency Ethics Preparedness and Response (PHEEPR) Network and other global bioethics efforts. The Platform and Network will be structured into two related and overlapping sets of activities, which will complement and build on each other. These will comprise: an Infectious Disease Ethics Forum for discussion of emerging ethical issues, a Collaborative Network to identify important issues for policy response and research; and, a programme of global health ethics research focusing on infectious disease.
|
| 30/09/2020 |
£191,745 |
|
UNIVERSITY OF BRISTOL |
The project will establish an interdisciplinary network of researchers with the aim of investigating and bringing to light perspectives from the Black humanities on Black health and wellbeing. Led by the Centre for Black Humanities at the University of Bristol, the project will consist of a series of video conferenced online workshops, symposiums and events, which will: a) create a community of scholars whose research concerns how Black writers, intellectuals, artists, activists and theorists have creatively and critically addressed the psychological and physiological health of black people across the twentieth and twenty-first centuries; b) explore how research in Black humanities might intervene in the current racialized landscape of medicine and health; c) train and develop a new generation of ECR scholars in the theories and methods of Black studies and the medical humanities and in how they insect.
|
| 30/09/2020 |
£2,352,590 |
|
GATES MEDICAL RESEARCH INSTITUTE |
The aim of this proposal is to obtain co-funding from the Wellcome Trust for a Phase 2 safety and immunogenicity trial of the M72/AS01E investigational vaccine. This Phase 2 trial in people living with HIV (PLHIV) is conducted to support inclusion of PLHIV in a following pivotal Phase 3 VE trial and to thus enable public health use of the vaccine in PLHIV should the Phase 2 and Phase 3 data support its use. PLHIV are at high risk for TB disease and deaths, and an estimated 251,000 of 1,450,000 deaths from tuberculosis in 2018 occurred in PLHIV.
The key deliverables of the full program (Phase 2 and 3) are:
Advance technical and clinical development of the M72/AS01E candidate vaccine from Phase 2b through Phase 3 (including Mtb uninfected and HIV-positive populations) and prepare for licensure
Identify a marketing authorization holder willing and capable to file the licensure application(s) and manufacture global product supply and to ensure global access to the vaccine
Aim for initial registration in South Africa to enable Phase 4 impact studies (outside the scope of this proposal) that generate robust effectiveness data for the prevention of TB in children and adults
|
| 30/09/2020 |
£1,521,343 |
|
JOHNS HOPKINS UNIVERSITY |
In this study co-funded by Wellcome and Gavi, the aim is to study the impact of mass
cholera vaccination in Uvira, DR Congo through a multifaceted approach aimed at estimating
changes in clinical disease incidence, infection rates, and the type and frequency of
occurrence of toxigenic V. cholerae in the environment. Successful completion of this project
will provide critical insights into the impact that mass OCV campaigns can have on human
health while at the same time providing a new understanding of the epidemiology of cholera
in this hyper-endemic setting. Our specific objectives are:
Objective 1: To enhance the cholera surveillance system in Uvira, South Kivu, DR Congo in
order to estimate the impact of mass vaccination on lab-confirmed cholera incidence and
mortality.
Objective 2: To conduct serial cross-sectional serosurveys after vaccination to estimate the
seroincidence of V. cholerae infection in Uvira over time and contextualize the primary
results based on clinical cholera cases.
Objective 3: To use phenotypic and molecular methods to describe the changes in the V.
cholerae population after vaccination in both human and environmental samples in Uvira.
Objective 4: To use phenotypic and molecular methods to describe the changes in the V.
cholerae population after vaccination in both human and environmental samples in Uvira. |
| 30/09/2020 |
£232,758 |
|
CLEAN AIR FUND |
Air pollution is a global health emergency. Outdoor air pollution causes 4.2 million premature deaths every year and 90% of these deaths happen in low- and middle-income countries. Additionally, air pollution has significant overlaps with climate change, both being caused in large part by the combustion of fossil fuels. While the link between air pollution and climate change isn’t always straightforward, smart solutions can ensure a win-win.
A survey commissioned by the Clean Air Fund (CAF) found that health professionals are the most trusted spokespeople on air pollution in all countries.[1] Consequently, there is an important opportunity to encourage real change if the health sector could be engaged as spokespeople to reduce air pollution, which has been further strengthened by COVID-19.
In this application we propose research on communications strategies that spur action on air pollution by healthcare practitioners. CAF is already funding such work in UK, India and at a global level. Additional support would add Bangladesh, Mexico and Ethiopia. Outputs include strategic recommendations for communicating on air pollution in the respective countries, as well as a database with existing campaigns and their effectiveness.
[1] Research carried out in May 2020 in the UK, India, Poland, Bulgaria and Nigeria.
|
| 30/09/2020 |
£30,476 |
|
CODE FOR SCIENCE AND SOCIETY |
Over the next 12-18 months, leading structures relied on to conduct, publish and disseminate scholarly research are at risk of collapse.
One leading use case to illustrate the current reality as it unfolds, and how it will affect scholarly research communications is the impact on university and scholar led presses, and the risks that presents to the creation of scholarly monographs.
University presses are collectively facing unprecedented deficits and sales shortfalls for print books this year. Budget constraints at the library level may well directly affect the sale of scholarly monographs as well as subsidies and subventions.
To address this potential threat to scholarship, we are launching a cross-institutional research effort to address pending infrastructure consolidation and collapse across the ecosystem, identifying the opportunities, leverage points, costs and approaches that could be employed.
The project sets out to deliver the following:
Cost-benefit analyses to enable faster, more informed decision making in support of open scholarship;
Criteria for assessing solutions in service of the academy;
Actionable recommendations and guidance for budget owners;
Actionable recommendations and models for projects to operate sustainably;
Scenario planning for 6, 12, and 18+ months outlooks;
A collective model for stewardship, cost-sharing, and risk pooling.
|
| 30/09/2020 |
£52,264 |
|
GLOBAL HEALTHCARE INNOVATION ALLIANCE ACCELERATOR |
GHIAA started the process of transforming its ‘paper’ Master Alliance Provisions Guide (MAPGuide) into an online resource in autumn 2019. Using Wellcome’s funding, GHIAA has made significant progress towards developing an intuitive, user-friendly tool, and a robust online platform to support future growth.
The development process began with creating a prototype MAPGuide tool and conducting initial stakeholder consultations in January and February 2020. These consultations provided vital input on adjustments needed to improve the user experience with the online tool. Driven by that input, GHIAA has recently completed significant improvements to the beta version of the MAPGuide.
During additional consultations in June 2020, stakeholders provided encouraging and constructive feedback on the improvements to the features and functionality of the MAPGuide. The next step in the development process is a public launch, targeted for early August 2020.
GHIAA is seeking further funding from Wellcome to:
Conduct additional consultations for wider stakeholder groups over the rest of 2020
Make additional improvements based on feedback identified through consultations and user surveys after rollout
Conduct targeted workshops on potential future features and improvements
Conduct a consultative process to advance the Global Health Transactions Glossary
Develop additional content, features and supporting tools for the MAPGuide
|
| 30/09/2020 |
£503,102 |
|
CARDIFF UNIVERSITY |
After giving birth, some women have the rapid onset of a severe mental health condition, postpartum psychosis, with mood symptoms, hallucinations and delusions. Postpartum psychosis is a medical emergency due to the risk to both mother and child. During pregnancy there is an increase in circulating hormones called neurosteroids and these enter the brain and change the function of proteins called GABA-A receptors. In order to adapt, the brain reduces the amount of these proteins but following the rapid drop of neurosteroids after birth, the GABA-A receptors cannot recover to their pre-pregnancy levels quickly enough and therefore normal brain function is compromised, triggering postpartum psychosis. Our aim is to identify a synthetic neuroactive steroid that can compensate for the postpartum loss of natural neurosteroids and thereby reduce the symptoms in affected mothers and also prevent episodes in women at high risk. This will be of enormous benefit to women and their families. |
| 30/09/2020 |
£230,515 |
|
UNIVERSITY OF OXFORD |
To address the problem of antimicrobial resistance (AMR) in Thailand, the Thai government produced the "Thailand National Strategic Action Plan on Antimicrobial Resistance 2017-2021" (TNSAP). While public engagement sits at the heart of the TNSAP, Thai campaigns so far have predominantly focused on raising awareness through educational materials and events like the annual AMR Week, but less on patient and public involvement in shaping the national AMR response. In our project, we will bring together adult audiences (e.g. patients, consumers, young professionals), non-governmental organisation representatives, AMR researchers and national policy makers to co-create an AMR stakeholder map, an AMR engagement strategy, and context-specific solutions to reduce the burden of AMR. The project will be implemented over 18 months, employing Wellcome’s Responsive Dialogues approach to design and implement a combination of in-person regional Conversations and nation-wide virtual Conversations. Our main outcomes are (1) improved understanding and engagement with the issue of AMR among adult Thai communities (2) changes in the national AMR policy to include context-specific solutions and (3) improved understanding about the implementation of Wellcome’s ‘Responsive Dialogues’ toolkit in Thailand. Our project will be integrated into the activities implemented within the current TNSAP and inform the next TNSAP .
|
| 30/09/2020 |
£498,326 |
|
NEUROCENTRX PHARMA LTD |
Neurocentrx has developed oral capsule formulations of Ketamine, aiming to be new treatments for Depression. Ketamine is a synthetic drug created in the 1960’s. It is on the "essential medicine" list of the World Health Organisation (WHO), approved and licensed by health regulators worldwide as an injectable anaesthetic. More recently, and at sub-anaesthetic doses, clinical trials have shown that some patients with depression have a rapid response to injectable ketamine (hours or days). Most other anti-depressant medicines take many weeks to work. No oral ketamine products are currently available as a licensed medicine worldwide. Our project will assess oral capsules in healthy people in a clinical trial. We will assess absorption and excretion with increasing doses of drug and measure any side-effects. These data will be essential to accurately plan trials in depression patients where we will then look for benefits. Oral capsules could be used at home, and are hoped to be a cheaper treatment option, with fewer side-effects for patients. The summary above may be amended from time to time by mutual agreement of the Parties. For this clause agreement by email will be sufficient to render a valid amendment to the summary). |
| 30/09/2020 |
£398,043 |
|
THE BIOVAC INSTITUTE |
Group B Streptococcus (GBS) bacterial infection is a major health concern and a leading cause of sepsis and meningitis in infants, particularly in Africa. A promising prevention for GBS infection in newborns is maternal immunization with a GBS vaccine. Currently no vaccine for GBS is available. Several conjugate GBS vaccines using GBS surface-expressed polysaccharides linked to carrier proteins are under development. We are proposing a novel vaccine design using GBS polysaccharides conjugated to GBS conserved surface proteins which induce immune responses in infected individuals, making them potential candidates as carrier proteins for novel GBS vaccines. It combines two virulence factors of GBS with the potential to provide not only enhanced overall protection compared to traditional conjugate vaccines but also to potentially provide protection against those serotypes not included in the vaccine. It could lead to the development of an affordable and cost-effective vaccine that protects against all GBS serotypes. |
| 30/09/2020 |
£456,865 |
|
INTERNATIONAL VACCINE INSTITUTE |
Cholera is a disease of inequity that continues to disproportionately affect the world’s poorest and
most vulnerable people. An oral cholera vaccine (OCV) is available and in use around the world,
but it has lower efficacy in young children than in adults and a relatively short duration of protection
necessitating re-vaccination every few years. We are developing a new conjugate vaccine that
offers the promise of improved efficacy in all age groups, including those less than 5 years, and an
extended duration of protection, thus reducing the requirements for repetitive vaccination to sustain
population immunity. It can be implemented in place of OCV or as a complementary tool to prevent
or limit outbreaks in high risk settings, and build enduring population immunity that will costeffectively
control cholera over the decades required to build definitive public health capacities in at
risk countries. |
| 30/09/2020 |
£3,069,077 |
|
UNIVERSITY OF LIVERPOOL |
Conventional evaluation of new medicines is not fast enough for a pandemic. Our aim is to accelerate this process, rapidly identifying which drugs are safe and potentially effective treatments for COVID-19. AGILE is an innovative, multi-arm, multi-dose, multi-stage Phase I/IIa Bayesian adaptive platform protocol to evaluate experimental COVID-19 therapies, and to funnel plausible candidates into large Phase IIb/III trials such as RECOVERY and SOLIDARITY. We will efficiently eliminate candidates with little or no prospect of clinical success.
AGILE will recruit COVID-19 patients into very early phase clinical studies, including first-in-human. The innovative design allows us to move seamlessly from first-in-human use to finding the optimal dose for COVID-19 patients. The trial is pragmatic (requiring only small numbers of patients), adaptive (so that the right drug is tested in the right group of COVID-19 patients, either in the community or in hospital) and statistically efficient (so that several drugs can be tested in parallel, making best use of a small number of patients). Our primary focus is population-scalable antiviral drugs for early treatment of COVID-19, for which we will recruit primarily in the community. AGILE has full regulatory and ethics approvals in the UK.
|
| 30/09/2020 |
£402,298 |
|
UNIVERSITY OF DUNDEE |
The pathogenic bacterium Group A Streptococcus (GAS) causes a range of infections, ranging from mild tonsillitis to invasive necrotising fasciitis, sepsis and toxic shock syndrome. GAS also induces severe long-lasting autoimmune disease, including rheumatic heart disease. Annually, GAS infections kill > 500,000 people worldwide. While antibiotics are considered a reliable first line of defence against GAS infections, globally emerging antimicrobial resistance is an enormous threat. The WHO has included GAS in its vaccine priority list to finally reduce the high mortality and morbidity. We will use our developed novel modular system to produce the first dual-acting and lowcost GAS vaccine candidates targeting all > 150 GAS strains. Our approach provides the first robust and affordable solution to target and prevent GAS infections, urgently required for the global population and in particular the people in low-income countries. |
| 30/09/2020 |
£1,130,853 |
|
UNIVERSITY OF GOTHENBURG |
"The Project aims at completion of the preclinical development of a new, improved oral cholera vaccine (OCV), DuoChol. This is a proposed thermostable OCV consisting of a lyophilized mixture of formalin-killed V. cholerae O1 Ogawa and Inaba strain whole-cells and cholera toxin B-subunit (rCTB) formulated in an enterocoated capsule. The two strains are isogenic except for the single serotype determining wbeT gene, and this allows them to be co-cultured to high density, which together with inexpensive high-yield rCTB production ensures low-cost manufacturing. The Project will build a solid platform for the subsequent clinical development of DuoChol, whose affordable cost, practical formulation and higher efficacy compared with current OCVs will make this a very attractive OCV for use in national cholera control programs and ideal for use in cholera outbreaks where rapid deployment and maximal early efficacy is of the essence. |
| 30/09/2020 |
£347,602 |
|
KING'S COLLEGE LONDON |
Responses to psychological interventions for anxiety vary greatly. Clients and clinicians want better ways to predict outcomes. One contender is fear extinction, the process through which exposure, the "behavioural" part of Cognitive Behavioural Therapy (CBT) is thought to work. Whilst there are robust differences in fear extinction between individuals with anxiety disorders versus controls, evidence that extinction predicts CBT response is modest.
We first became interested in fear extinction as a mechanistic tool to help understand how CBT works. In order to build algorithms from numerous potential predictors, including fear extinction, we needed to undertake fear conditioning at a scale. We developed a smartphone App FLARe, that remotely delivers a fear conditioning paradigm. Our validation studies showed that fear extinction data from our App mirror that from gold-standard in-lab delivery.
We now want to test the extent to which App-delivered fear extinction data predicts CBT response. We will assess young adults with high anxiety using our App before enrolling them in CBT. We will test the strength of correlation between fear extinction and treatment outcome. We will also explore the extent to which this association is stronger in specific sub-groups (e.g. those who completed more exposure homework during treatment).
|
| 30/09/2020 |
£765,283 |
|
UNIVERSITY OF OXFORD |
This study aims to address the following questions through a global network of hospitals:
Is there evidence for a reduction in the total number or rates (per 1,000 inpatients) of blood cultures taken over twelve months?
Has there been changes in antimicrobial usage (quantitative and qualitative)?
Are there major changes in antibiotic resistance profiles from major pathogens?
Have there been changes in antimicrobial stewardship and why?
What is the overall change in the management of these patients?
What is the impact of COVID-19 on infection control practices during the pandemic?
Is there any evidence of reduction in nosocomial infections and bacterial outbreaks during the COVID-19 pandemic?
We will collect clinical (patient-based [severe pneumonia, ARDS, sepsis patients], hospital and microbiological data from 11 countries (UK, Switzerland, Italy, Brazil, Nigeria, Malawi, Turkey, Iran, India, Bangladesh and South Korea).
Our primary outcome will be to determine if there has been a reduction in blood cultures taken. Secondary outcomes include whether 1. changes in antimicrobial usage 2. major changes in antibiotic resistance profiles from major pathogens in hospitals during COVID-19 and correlate resistance profiles with antibiotic usage. 3. changes in infection control practices and other aspects of sepsis management behaviour during the COVID-19 pandemic.
|
| 30/09/2020 |
£48,135 |
|
ADDIS ABABA UNIVERSITY |
This proposal outlines the establishment of a pilot Unit for Health Evidence and Policy within CDT-Africa, a World Bank African Centre for Excellence based at Addis Ababa University, Ethiopia. Building on strong operational research into Neglected Tropical Diseases, and existing relationships within Ethiopia’s Ministry of Health, the Unit for Health Policy and Evidence will identify challenges to research uptake, pilot and evaluate an approach to improving research uptake, and produce a framework to guide future research uptake in this setting and possibly more broadly.
The pilot Unit for Health Policy and Evidence will be a 12-month project, divided into two Periods. Period 1 will comprise stakeholder consultation through two Theory of Change workshops and other interviews as necessary. During Period 2, research uptake in an NTD area defined in Period 1 will be evaluated using the Diversity Approach (see below). A Research Uptake Framework will be developed and a dissemination workshop held with key national and international stakeholders.
|
| 30/09/2020 |
£1,495,762 |
|
UNIVERSITY OF OXFORD |
While the first wave of COVID-19 is passing, we have yet to identify effective treatments. Most treatments have been used late in the illness. There is a pressing need to identify treatments delivered in community settings that avoid hospital admission. Novel immunomodulatory treatments have a well understood safety profile but are not suitable for studies such as Principle which rely on remote assessment. Hospital at home is a developing networ; teams of consultant physicians and nurses deliver high intensity care in community settings, commonly using point of care diagnostics. This provides a suitable framework for evaluation of novel therapies. This approach has parallels with healthcare systems employed in low and middle income countries and so the results will directly inform the delivery of interventions in these settings.
Multiple strands of evidence identify TNFa as an important mediator of the hyperinflammatory state that is associated with poor outcome. Early intervention with anti-TNF therapy has the potential to substantially mitigate its effects and improve outcomes. Adalimumab is an established subcutaneous anti-TNF therapy. We propose a randomised dose ranging study in community settings to establish whether it can mitigate progression to respiratory failure (requirement for oxygen, non invasive and invasive ventilation) or death.
|
| 30/09/2020 |
£120,585 |
|
UNIVERSITY OF BRISTOL |
Our objective is to provide an efficient coordinating body ("secretariat") for the continued development, deployment, collection and analysis of a shared COVID-19 questionnaire across UK cohorts.
The value of undertaking this in multiple longitudinal UK cohorts is that data can be collected in extremely well characterised members of the population across a wide demographic range who are already engaged in research, who have had data and biological samples collected on them, who have an established collection of record linked data already record linked and who sit behind supported infrastructure able to undertake novel data collection and research. Each of these cohorts is research active and collectively offers a depth or domain expertise not available within any one cohort, including that of UK Biobank. In this first coordination of COVID-19 research in deeply characterised UK cohorts, we identified the added value of a core questionnaire prospectively aligned to capture data pertinent to understanding COVID-19, as well as the direct and indirect consequences of the pandemic on health, wellbeing, social and economic outcomes.
|
| 30/09/2020 |
£504,745 |
|
UNIVERSITY OF OXFORD |
Ischaemic heart disease remains a major cause of disability and death world-wide. When a
major blood vessel in the heart suddenly becomes blocked, the muscle that it supplies dies
and is replaced with scar tissue. This is what happens in a heart attack. The scarred heart
no longer pumps blood properly and 40% of patients who develop heart failure die within 5
years. There is currently no treatment to help make new heart muscle after a heart attack.
We have identified a protein already present in the body, a single injection of which within a
few hours after injury can dramatically improve heart function by limiting damage and
promoting repair. We will now engineer this protein molecule to retain only the regenerative
properties, whilst eliminating potential unwanted effects. We anticipate the engineered
product to be safe, limit the damage after a heart attack and also promote regeneration of
heart muscle. |
| 30/09/2020 |
£498,656 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
As COVID-19 lacks a definitive treatment, critical care is the primary therapeutic means for
reducing mortality. How the world effectively scales up critical care will be a fundamental
determinant of the overall impact of the pandemic. Advanced critical care may be difficult or
impossible to scale-up in many settings and instead, essential, life-saving treatments should
be provided to all who need. Essential Emergency and Critical Care (EECC) is the basic,
low-cost care required by critically ill patients, such as oxygen and intravenous fluids, and
the system-wide requirements for their provision. The project will assess the costeffectiveness
of EECC and advanced critical care in Tanzania and Kenya, and analyse the
impact of the global and national response strategies to COVID-19 on critical care services.
The project aims to guide COVID-19 responses in LMICs towards scalable strategies with
the greatest potential for increased survival of critically ill patients, both in the pandemic and
beyond. |
| 30/09/2020 |
£248,385 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
The diminishing effectiveness of antimicrobials is a public health challenge of major global importance. In the Global South, where health systems are weaker and the burden of severe bacterial infection greater, the impact is already being acutely felt. In Malawi, a Ministerial AMR Unit has been established to coordinate Malawi’s response, culminating in a National Action Plan. However, the implementation of the Action Plan needs key stakeholders – including affected community members – to develop and implement interventions. This project will undertake facilitated dialogues with stakeholders in two different contexts: rural Chikwawa and urban Blantyre. Through four Responsive Dialogues events per area, participants from national, district and community levels will share their understandings, experiences and perspectives on AMR, leading to the co-creation of concrete policy asks and actions. Conversations will be carefully designed and facilitated to enable evidence about AMR to be shared, understood and used to generate ideas, as well as to inform policies governing how AMR is addressed. Through this approach the project will work closely with the AMR unit to cocreate local actions, that communities themselves can carry out to reduce the burden of AMR as well as policies and interventions that reflect people’s lived realities.
|
| 30/09/2020 |
£50,000 |
|
UNIVERSITY OF OXFORD |
There is a need to build capacity and improve evidence-informed decision-making concerning resource allocation and priority-setting in health in low- and middle-income countries, such as Laos. This kind of capacity building and institutional strengthening is all the more important in an era of aid transitions and uncertainty related to the current COVID-19 pandemic, to enable Laos to continue progressing towards Universal Health Coverage.
We propose the creation of a Unit for Health Evidence and Policy (UHEP) based in the University of Health Sciences in Vientiane, to enhance the use of research evidence to inform policy. UHEP will focus on health technology assessment (HTA) as a tool to enable priority-setting.
We aim to complete four main activities for this pilot project over one year.
Situational analysis of the Lao health policy context including stakeholder mapping
Training of Lao researchers and policy makers in HTA and on synthesis and use of research evidence (includes funding for one MSc student)
Development of a roadmap for institutionalisation of rational priority setting in health policy development in Laos
Selection and implementation of a pilot HTA project
At the end of this year UHEP will be established as a government technical partner for HTA in Laos
|
| 30/09/2020 |
£22,524 |
|
OPEN ACCESS SCHOLARLY PUBLISHERS ASSOCIATION (OASPA) |
Throughout 2020, a project is run to prepare for the OA Switchboard (a collaboratively developed and community run open source solution) to go live as an operational solution. The OA Switchboard provides essential infrastructure and back office services to facilitate the fulfilment of open access strategies across business models, policies and agreements via: 1. communication standards (‘metadata’); 2. technical solutions (‘hub’); 3. standardised real-time monitoring and reporting.
The essence of the problems it aims to address as a priority:
It is complicated/cumbersome to find out how to get the service charges for a certain OA publication settled, and to prepare for (enable) such financial settlement
It is a challenge to monitor funds and track spending in real time
In the current situation, enabling open access to scholarship has never been more pressing. Supporting the OA Switchboard is investing in open source infrastructure that will ensure that transformational change to open access can be achieved by all publishers, whilst reducing complexity for funders, institutions and researchers. It will also work alongside and strengthen other initiatives that the Wellcome Trust is supporting in this space, specifically in realising the synergies of interlinking the Journal Checker Tool and the OA Switchboard.
|
| 30/09/2020 |
£222,683 |
|
UNIVERSITY OF OXFORD |
Meat Your Persona will further the public’s understanding of the connection between their meat consumption and its environmental and health impacts and will empower them with accessible information and tools to make better informed choices about their consumption.
Building on the successful pilot (https://www.youtube.com/watch?v=QbHb4ap39nw), we propose a national tour, taking Meat Your Persona to audiences at urban and suburban shopping centres and community hubs. Our goal is to reach those with low science capital who are disconnected from the current conversation. In particular we will target Brexit-voting men outside London who are the most likely to eat the most meat and to not connect meat consumption with health and environmental impacts.
We will capitalise on renewed public interest in evidence, using creative design methods to convey key facts from the LEAP research so that people are able to make better informed choices. We will actively signpost people to a purpose-built website where they can receive evidence-based support to reduce their meat consumption. The project will be evaluated independently to see if we have achieved our three goals: to drive behaviour change, build public trust in science and inform research through advancing the public conversation.
|
| 30/09/2020 |
£800,000 |
|
GLOBAL POVERTY PROJECT INC |
Global Citizen and the European Commission ran a campaign, Global Goal: Unite for Our Future, with the aim of ensuring that everywhere in the world, those who need them have access to COVID-19 tests, treatments, and vaccines. The campaign also sought to lessen the impact of COVID-19 on the world’s most vulnerable people, ensuring they still have access to education, clean water, and more.
The campaign, launched under the patronage of European Commission President Ursula von der Leyen, focused on the development of tools to tackle COVID-19, and ensuring that these tools are available to all communities equally, as well as mitigating the impacts of COVID-19 on those living in poverty. |
| 30/09/2020 |
£283,840 |
|
UNIVERSITY OF OXFORD |
With this proposal we seek to establish a global community of bioethicists (to be known as 'Epidemics Ethics') combined with a range of online resources and activities together capable of providing real-time, contextually appropriate support to assist researchers, policy-makers, communities, and responders in identifying, analysing and addressing ethical issues arising in the context of global health emergencies. Epidemics Ethics will complement the newly established Public Health Emergency Preparedness and Response Ethics Network (PHEPREN) by providing: timely responses to ethical problems, access to networks of experts, an array of online resources including seminars, workshops, blogs, and ethics briefings on issues of current concern. A key aim of Epidemics Ethics will be to support the establishment of fair, collaborative partnerships to enable ethics research to be conducted by ethics scholars in low and middle-income countries in the context of broader supportive international collaborations. With this in mind, capacity building will be a key focus.
|
| 30/09/2020 |
£324,364 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
In this pandemic, researchers have responded by publishing results rapidly, often through preprints. In fact, about half of the publications in Europe PMC on COVID-19 are preprints rather than peer-reviewed journal articles. Currently, the full text of these preprints are scattered as PDFs on preprint servers, or, available as a non-standard set of documents for machine learning purposes. This proposal is about making the full text of COVID-19 preprints available on Europe PMC, a large and sustainable life sciences archive, for reading and reuse via a standard XML format, alongside peer-reviewed full text articles. Being able to easily search and read preprint full text on a site already frequented by millions of users a month, means that they will be significantly more discoverable by people, and will be able to make use of existing infrastructure to integrate into the typical ecosystem of publications - for example, linking to related data - as well as being more open to scrutiny. This will accelerate scientific research on COVID-19, provide an opportunity to build new open and rapid publication systems, and form a corpus for future history of science research.
|
| 30/09/2020 |
£198,817 |
|
JOHNS HOPKINS UNIVERSITY |
With the rapid development of candidate vaccines for COVID-19, this project will identify and provide guidance on a range ethical issues arising in the development and deployment of COVID-19 vaccines. Over the next six months, the COVER project will concentrate on the ethics of vaccine research and development—including phase 3 trial design and equitable inclusion of special populations in the research agenda, with a particular focus on pregnant women as well as population groups that have or likely will experience disproportionate burden from COVID-19. This project will also conduct formative landscaping work on the ethical challenges and tradeoffs in the allocation and deployment of vaccines, both globally and within nations. This work will lay the groundwork for normative guidance and mathematical models to best inform policymaking once efficacious vaccines become available for wider use, with explicit consideration and assessment of how various approaches will not only impact the trajectory of the COVID-19 pandemic overall, but also how the benefits of vaccination will be fairly distributed across different population subgroups. In addition, the COVER project will begin to address ethical issues of COVID-19 vaccine development and deployment specific to Africa, with a concentrated body of work in Nigeria.
|
| 30/09/2020 |
£233,652 |
|
C40 CITIES |
While prior national level and regional studies have evaluated the contribution of coal combustion on air quality-related health impacts at the national or regional level, a concrete understanding of how coal combustion impacts urban populations can make a strong case for the rapid phase-out of coal-fired electricity generation in cities around the world.
Project aims:
(1) demonstrate a strong urban case for a rapid-phase out of coal-fired electricity generation; and (2) utilise the research results for an effective advocacy and communications campaign at COP26. In the research project, C40 will estimate the contribution of coal combustion for C40 city electricity generation to global GHG emissions, to air quality-related health burdens in C40 cities, to COVID-19-related health impacts as well as analyse the economic benefits of different coal phase-out scenarios by looking at: (1) the economic value of improved health associated with reduced coal combustion for electricity generation in C40 cities; and (2) the number of net jobs that are generated with a switch from coal combustion to clean energy.
|
| 30/09/2020 |
£602,803 |
|
THE UNITED NATIONS FOUNDATION |
Global action to tackle AMR is insufficient because public engagement on AMR is limited[1]. CGD[2] can help close this gap and help communities and decision-makers take collective action on AMR.
This project will apply CGD methods in three Kenyan counties over 14 months to empower communities, health-workers, researchers and policymakers to generate and use data on AMR. A robust scoping phase will involve stakeholder consultations to tailor CGD methods and engagement mechanisms to the local contexts. The project will have three tracks:
Data to Empower: engaging citizens to better understand AMR related behavior and perceptions, and empowering citizens with objective and contextually relevant information
Data to Give Direction: using CGD to empower citizens to change behaviors, fill evidence gaps for the research community, and support health policy decision-making,
Advocacy on CGD: encouraging researchers and policymakers to incorporate CGD as an important source of evidence for more holistic AMR policies
[1] https://wellcome.ac.uk/reports/reframing-antimicrobial-resistance-antibiotic-resistance
[2] CGD is ‘data that people or their organisations produce to directly monitor, demand or drive change on issues that affect them. It is actively given by citizens, providing direct representations of their perspectives and an alternative to datasets collected by governments or international institutions’
|
| 30/09/2020 |
£245,691 |
|
UNIVERSITY OF OXFORD |
This project will undertake large scale data linkage between critical and primary care and
Public Health England to investigate the effects of routine medications and patient
comorbidities on the outcomes from COVID-19 disease.
Assessing the effects of routine medications on COVID-19 disease is important for two
reasons. Firstly, some medications have been suggested to make the disease worse. As a
result, patients and clinicians are unclear about whether they should be continued. Secondly,
some routine drugs may treat or lessen the effects of infection. Establishing whether peopleon particular drugs are less likely to get severe infection will help researchers find treatments
for the disease.
Identifying what types of patient are prone to get severe disease and how long term conditions
affect outcomes will help provide advice and target interventions to the right people.
Undertaking these objectives will allow us to develop a platform linking all the patients in the
primary care database to all the Public Health England COVID-19 tests undertaken and all the
patients admitted to an Intensive Care Unit. This platform will allow detailed assessment of the
course of patients during the COVID-19 outbreak, including assessment of the effects on health
for patients without COVID-19 disease.
This platform will also enable studies investigating health, medication and health resource use
before and after critical illness, accelerating development of a long term rich research resource. |
| 30/09/2020 |
£57,800 |
|
NHS CONFEDERATION |
Make a clear case for and facilitate UK involvement in the joint action with UK and EU stakeholders.
Act as a secretariat to support the UK partner in the joint action.
Prepare contingency plans for maintaining an influence in the absence of UK representation in the Joint Action.
Gather a body of evidence of NHS and UK expertise on data processing in the health sector to contribute to the European Code of Conduct
Maintain regular updates and briefings on the scope and objectives of the GPDR code of conduct, to maximise UK preparedness.
Follow progress of Europe’s data strategy, the European health data space and the development of a legislative proposal on Artificial Intelligence, using the same UK stakeholder group to feed in expertise where possible and provide intelligence and updates on possible implications for the health sector.
|
| 30/09/2020 |
£77,068 |
|
UNIVERSITY OF OXFORD |
This proposal will address the intersection of mental health and Equality, Diversity & Inclusion (EDI) within Oxford’s three Wellcome Centres. Mental health concerns permeate a broad range of challenges relevant to EDI, including social exclusion, chronic illness and disability, and minoritised populations (detailed below) that are disproportionately affected by mental ill-health.
By identifying specific mental health challenges that different groups face, we can improve equality. Through normalisation of discussions around mental health in the workplace, and building an appreciation for how these issues affect people differently, we foster inclusion. If we can recruit and retain a broader range of researchers further into their careers, we improve diversity, and therefore our science. An increasingly inclusive, fair and kind research culture will lower the risk of mental ill-health for all our team and staff members within the high-impact but high-pressure academic environment.
Our specific objectives are to:
(i) Conduct an in-depth, expert review of mental health as it relates to EDI within our Centre work environments.
(ii) Implement recommendations arising from this review relating to policies, communication and practices.
(iii) Build a broad, cross-Centre programme promoting positive research change around mental health and EDI.
|
| 30/09/2020 |
£155,243 |
|
REX LIFE SCIENCES LLC |
Starting February 2017, the insight from a significant amount of the Wellcome Trust-supported Expert-in-Residence work done by the applicant in support of the R & D efforts of the AMR community has been translated into a newsletter and a mirroring blogpost website. This content has come from attending key meetings (Dr. Rex is often asked to present, chair, and/or serve on program committees), authoring papers, and engagement (ad hoc email, TCs, and/or face-to-face meetings with key members of the developer community.
Wellcome Trust supported this work 2017-2019 through hourly billing and expense reimbursement. It is now proposed this support be converted to a fixed-term grant with consideration of the possibility of extensions of the grant if / as the DRI program progresses
The grant funds would be used to transformation and grow the project in 3 ways:
Website upgrade for improved analytics and visual quality.
Audience growth beyond R & D to the disciplines as finance, corporate leadership, and media relations, all of whom are key to success in this area.
Social media outreach by maintaining the core USP while making use of Twitter, Facebook, Instagram, and LinkedIn to reach more deeply into the audience of those working in antibiotic R & D.
|
| 30/09/2020 |
£327,745 |
|
INTERCHANGE RESEARCH LIMITED |
The Wellcome Trust 2019 PhD Programmes Call had two central criteria: scientific excellence and positive research culture. The call was unusual in the relative weight given to each of these criteria, and the open-ness to different understandings of research culture. It is important to understand the impacts of this intervention on the part of a major funder into research training. The aim of this study is to gain insights into the impact of this intervention, and into the development and implementation of measures to improve research culture. The study embraces the emergent nature of understandings of positive research that has distinguished this call from the outset. It adopts a dual approach: firstly it will support the formation of a community of practice, consisting of the funded programmes and the Wellcome Trust, as equal members; and secondly it will use the methods of participant action research to support iterative and reflective processes for understanding what positive research culture consists in, and what constitutes best practice. This dual approach serves as a framework for active observation, in which the lessons learned by the community of practice can be articulated and shared with other stakeholders, in the form of reports and publications.
|
| 30/09/2020 |
£207,999 |
|
YOUNG FOUNDATION |
This landmark research aims to understand in real time, and longitudinally, how Covid-19 is changing people’s experience of community and levels of social protection in society.
It will specifically focus on the ways in which:
Covid-19 is affecting and shaping the interactions between individuals in society and the effect on health, wellbeing, resilience, quality of life, and community
digital is playing a role in community responses to the virus
different measures to mitigate the virus changes the experience of community in a time of crisis
individuals and communities relate to science, research and its role with respect to Covid-19
The aim of this project is to collect real-time information to inform policy makers and practitioners about how communities are responding to the pandemic, public health measures and other mitigation measures. It will also generate early insight into the potential longer-term impacts on both individuals’ mental health and community wellbeing.
To understand how communities are experiencing Covid-19 across the UK, we will conduct a quantitative study with a nationally representative sample across the four nations. This will be supplemented by innovative digital ethnographic research which generates in-depth real time insight into the experiences of a diverse group of 100 adults.
|
| 30/09/2020 |
£955,118 |
|
UNIVERSITY OF MINNESOTA |
The CIDRAP Antimicrobial Stewardship Project (CIDRAP-ASP) was launched in July 2016 with the
goal of building an online international community focused on antimicrobial stewardship through
various platforms and with content and ASP tools applicable to high, middle and low income
countries. CIDRAP-ASP has offered freely available, high-quality information and educational
resources on antimicrobial stewardship practice, research, and policy. It features a dynamic,
content-rich website designed to engage a diverse, international audience. This project capitalizes
on CIDRAP’s existing internationally recognized expertise, infectious disease news and information
system, website infrastructure, and strong national and international audiences.
Through our partnerships with subject matter experts, we provide a wealth of diverse resources for
practitioners across the spectrum of human, animal, and environmental health to support their
ability to provide optimal care. CIDRAP-ASP generates deep, rich original content and aggregates
the most useful information from diverse perspectives and expertise.
CIDRAP-ASP occupies a unique niche in the ecosystem of projects addressing antimicrobial
resistance and stewardship because of the diversity of resources to which it provides access, and
the research and integrity with which it approaches nuanced and sometimes controversial topics.
|
| 30/09/2020 |
£142,915 |
|
UNIVERSITY OF OXFORD |
Findings from health research should be translated into recommendations that can be implemented within policy and practice if research is to deliver its maximum impact and ability to change health outcomes. Currently research ‘success’ typically concludes with the publishing of papers in high impact journals with less attention to how, and indeed whether, those findings are made visible and accessible to those tasked with decision making that should be changing their practice on the basis of these new findings. Compounding this is the current difficulty for these practice and policy decision-makers to easily be made aware, find, access and synthesise new research recommendations. The Global Health Network seeks to address this by bringing researchers and decision makers together to find new tools and mechanisms for researchers to present their outcomes as recommendations that can be readily discoverable and put into practice. This proposal will firstly, establish a community of practice for researchers and decision-makers to share knowledge and develop resources, processes and mechanisms that can support turning results into discoverable, practical and usable recommendations. Secondly, to deliver an advanced digital database which enables rapid synthesis of the available research recommendations to drive improvements in uptake.
|
| 30/09/2020 |
£349,617 |
|
SURGICAL SYSTEMS RESEARCH GROUP |
To respond to the COVID19 pandemic, we will be deploying community health workers, equipped with mobile technology, and accompanied by youth to visit households door to door to screen for symptoms of COVID19, isolate, test, and manage suspected cases of COVID19. The community health workers and youth will educate households about preventive measures including frequent handwashing and home management of mild cases. Simultaneously, we will work with nurses, doctors, and clinical officers, to test and treat more severe cases of COVID19 in health facilities. Our goals are to visit every household in Siaya county covering a population of close to 1 million, and to train and support health workers working in the 32 health facilities in Siaya." |
| 30/09/2020 |
£249,200 |
|
FIRST DRAFT |
This project will ensure as many people as possible have access to straightforward, clear information, that quickly responds to the questions and confusion people have about the coronavirus and the ways in which it is impacting their own lives and those they love. In order to reach millions of people around the world, the project will create high quality, embeddable content that newsrooms, platforms, health authorities, government bodies can all share with their audiences. It will also galvanise engaged citizens, who want to help, by creating an 'army' of 'Information Volunteers' who can take the same content and push it out to their own networks, whether that's via WhatsApp groups, Facebook communities, or family email chains. This crisis has demonstrated that there is no time or resource for duplication. By sharing efforts to monitor trending misinformation, collect real-time questions and areas of confusion from the public, and centralizing the output of shareable 'cards' that respond to these rumours and questions, it will help over-stretched newsrooms and communication departments, and provide concerned citizens with a role to play during a time where they want to help their communities.
|
| 30/09/2020 |
£411,826 |
|
UNIVERSITY COLLEGE LONDON |
This proposal is for the establishment of an international mental health research network for Covid-19 and the running of a UK mixed-methods mental health study.
The proposed network will have three core aims:
To support the establishment of high-quality longitudinal studies in countries internationally exploring the effects of Covid-19 on mental health
To enable international collaboration in longitudinal data analysis to understand cross-cultural differences in the mental health effects of Covid-19
To catalogue and disseminate other quantitative and qualitative mental health research on Covid-19
We will also lead a large-scale UK concurrent mixed methods study comprising a longitudinal study and a qualitative interview study to provide high quality, rigorous scientific data on the mental health impact of Covid-19 in the UK. This study is already underway and has 5 core aims:
To understand the psychological and social impact of Covid-19
To map how the psychosocial impact evolves over time as social isolation measures get stricter and once measures are relaxed
To ascertain which groups are at greatest risk of adverse effects on their mental health
To explore the interaction between psychosocial impact and adherence to healthy and protective behaviours
To identify activities during isolation that could buffer against adverse effects
|
| 30/09/2020 |
£1,000,000 |
|
INSTITUT PASTEUR DE DAKAR |
The African Union, Africa CDC, in collaboration with WHO on Febraury 22nd, 2020 convened an emergency meeting of all 55 ministers of health to discuss the COVID-19 pandemic. At the end of the meeting, they agreed on a continent-wide strategy for COVID-19 that will allow for greater coordination, collaboration, cooperation and communication. The strategy focuses on six major technical areas and is implemented through and endorsed Africa Coronavirus Task Force (AFCOR). As of 15 March 2020, over 26 countries have reported greater than 250 cases. In Africa, the primary strategy for COVID-19, therefore, is based on limiting transmission and minimizing harm. Delaying and diminishing the peak of outbreaks can help health systems better manage the surge of patients and communities better adapt to the disruption of social, cultural, and economic activities. In order to compliment WHO’s efforts to respond to COVID-19, Africa CDC is uniquely positioned to support Member States through its presence within the African Union, the highest political body in Africa, and its five Regional Collaborating Centers. The primary challenge now is executing these tactics in a continent that is large, diverse, and at high risk of social and economic disruption from a pandemic.
|
| 30/09/2020 |
£147,311 |
|
AFRICAN INSTITUTE FOR DEVELOPMENT POLICY |
Enhance DELTAS is a programme led by the African Institute for Development Policy (AFIDEP) to provide research uptake and policy engagement support to awardees of the Developing Excellence in Leadership, Training and Science (DELTAS) Africa initiative, led by the African Academy of Sciences. Enhance DELTAS will work with the first and second DELTAS Africa programmes to develop the capacity of individuals, support DELTAS institutions in creating enabling environments for policy engagement and research uptake, facilitate interaction between researchers and policymakers, and contribute to the field of Evidence Informed Decision-Making through peer reviewed publications. The programme will use face-to-face workshops, online self-learning materials including videos, interactive webinars, toolkits, and talks by policymakers. The programme will be underpinned by a robust monitoring, evaluation, and learning framework so that the programme can be continually improved, the changes as a result of the programme can be assessed, and the knowledge from implementing the programme can be shared with the EIDM community.
|
| 30/09/2020 |
£548,031 |
|
AFRICAN ACADEMY OF SCIENCES |
Success against the Covid-19 pandemic requires a transdisciplinary approach incorporating social sciences and humanities, economic research and health systems research. It also requires access to funding. The African Academy of Sciences (AAS), through its hosted AESA Platform, acts as Secretariat for this Fund for Covid-19 R & D priorities in Africa. This Fund is seeking proposals against identified priorities; coordinating a network of researchers working on Covid-19 R & D to build a clinical research and trials platform for Africa; and taking a longer-term view to address pandemic preparedness in research actions.
The Fund is open to multiple priority areas for research and development, including:
Epidemiological studies
Studies to define disease severity and susceptibility of particularly groups at high risk of severe infection; the role of different age groups in transmission; the impact of control and mitigation measures; and to predict the most effective interventions.
Clinical management
Studies to define the natural history of Covid-19 infection including the identification of prognostic factors for severe disease and the identification of vulnerable groups; and studies to improve the clinical outcome of Covid-19, including strategies to improve the processes of care.
Infection prevention and control
Studies to assess the effectiveness, in both healthcare and community settings, of movement control strategies in preventing secondary transmission and of personal protective equipment in reducing the risk of transmission.
Candidate vaccines, diagnostics and therapeutics
Clinical trials of potential treatments and preventative strategies, facilitated by the recent AESA programme launched as the Clinical Trials Community online platform.
Ethical considerations for research
Studies on culturally appropriate approaches to the ethical, social and legal issues prevalent in emergency situations, such as presented by Covid-19.
Social sciences in a pandemic response
Engagement to bring community voices to decision-making processes, to understand non-intended consequences of pandemic-control decisions and to understand contextual vulnerability; and studies to mitigate impacts of the socio-economic and political externalities of Covid-19. |
| 30/09/2020 |
£4,916,005 |
|
OXITEC LIMITED |
Human diseases that are transmitted by the Aedes genus of mosquitoes are
increasing rapidly, diseases such as Zika, dengue, chikungunya and yellow fever.
Recent estimates suggest that today around half the world’s population are at daily
risk of infection, the vast majority by a single mosquito species, Aedes aegypti.
Oxitec’s have developed a ground-breaking biological approach to control this vector
using safe, non-biting male mosquitoes ("OX5034-E"). Our male-only mosquitoes
carry a self-limiting gene, which means that when they mate with wild females,
offspring inherit a copy of this gene that prevents females from surviving to
adulthood. The genetic mechanism that prevents females from surviving also enables
deployment of our safe, non-toxic, non-biting male Aedes aegypti via egg packets in
small recyclable boxes filled with water.
This project will fund the final stages of tailoring Oxitec’s "just-add-water" vectorcontrol
device into a sustainable and scalable Aedes aegypti control solution. We
will be optimising the OX5034-E device and developing customised digital tools to
support the wide-spread deployment of this technology, particularly in low-income
communities that so often require it most.
The project’s three primary goals to accomplish this are:
- Developing new methods for scalable and rapid deployment of OX5034-E
devices in dengue-prone settings.
- Demonstrating OX5034-E’s ability to integrate with traditional Aedes aegypti
control programs used by resource-limited governments and communities.
- Completing the supporting online and mobile platform to help future end-users
manage the planning and deployment of OX5034-E.
We will provide immediate benefits by delivering a two-year Aedes control program
in a dengue-impacted city in Brazil, but importantly our project is destined to deliver
impact at a global scale. In the years to come we anticipate saving thousands of lives,
and positively impacting the livelihoods of many millions of people who currently live
under the near constant threat of this invasive and dangerous vector. |
| 30/09/2020 |
£1,001,596 |
|
EAT FOUNDATION |
Summary
EAT is pleased to submit this request for a continuation of Wellcome’s support for EAT knowledge engagement and communications activities. A critical assessment of the economics of food and land used systems was identified as a critical knowledge gap to further progress on transitions to healthy and sustainable food and land use system. In collaboration with SISTEMIQ, FOLU, and PIK, we are pleased to share our comprehensive proposal for the Food System Economics Commission building on the foundational work of the EAT-Lancet Commission, and FOLU’s Growing Better report.
Second, while EAT has had to cancel the 2020 version of the EAT Stockholm Food Forum, the Communications team has very rapidly pivoted and begun to develop an online version of the Forum, EAT at Home. This virtual forum is a multi-month digital food festival experience, designed to spotlight leading science, planetary health chefs, business solutions, dynamic dialogs and debates, cooking demos and more in an interactive and accessible format that will build and continue momentum on food transition, while greatly increasing the diversity of voices that EAT is able to feature and engage.
Third, EAT thanks Wellcome for its continued support, including to core institutional functions.
|
| 30/09/2020 |
£2,158,322 |
|
UNIVERSITY OF OXFORD |
This study will: assess the change of medium-term efficacy of the new Typhoid Conju-gate Vaccine (TCV) in children, by comparing the relative risk of typhoid in those initially vaccinated in 2017/2018 with later cohorts vaccinated in 2020 and 2021; assess the de-cline in individual-level immunity 3-5 years after vaccination; measure ongoing popula-tion-level impact against typhoid fever in the community. The data collected will help identify correlates of medium-term protection; inform the need for, timing of and potential cost-effectiveness of adding booster doses to vaccine schedules; permit the develop-ment of a mathematical model to predict future impact of typhoid vaccination in two en-demic settings. |
| 30/09/2020 |
£55,300 |
|
ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE |
For Wellcome Trust to contribute to the established RSTMH small grants programme to enable those early in their careers to conduct small research projects into the topic of snakebite. Our small grants are awards of up to £5,000 including VAT and available to those early in their careers who are working in a field relevant to tropical medicine or global health e.g. doctors, nurses, academic researchers, NGO workers, health economists, social scientists. These grants typically represent the very first time someone has received funding in their own name, the first application form they have written, and the first time they have managed their own project,including a budget and reporting. The grant process is designed to be as straightforward as possible, for many applicants English is not often their first language. The application is made through our online portal and 2 referees, including their supervisor, must be provided. Snakebite is a topic of great importance to RSTMH given its high levels of death and disability. Though funding has increased in the topic there is a need to encourage early career interest and we feel the small grants present a way to do this, which is easy for Wellcome to benefit from.
|
| 30/09/2020 |
£21,115 |
|
WELLCOME TRUST/DBT INDIA ALLIANCE |
The DBT/Wellcome Trust India Alliance will shortly be organizing the first Conference for Indian Research Managers and Administrators (RMAs), as part of the ongoing India Research Management Initiative (IRMI). IRMI activities represent the foundational steps towards strengthening research ecosystems in India. The IRMI Annual Conference series is intended as a platform for Indian RMAs to share their work and perspectives with peers, for institutional and funder representatives to engage with the possibilities of Research Management in India, and for Indian RMAs to work together as a community of professionals. Work has begun on creating a structure for the 2020 Conference, which will include 60-80 RMAs, researchers and funder representatives from India. As the current pool of RMAs in India is small and relatively inexperienced, it will be beneficial to additionally include a small group of international RMAs, for presentations and interactions at the Conference. This is a request to the Wellcome Trust for funding the costs of attendance of international experts at the IRMI Annual Conference 2020.
|
| 30/09/2020 |
£2,636,462 |
|
UNIVERSITY OF CAMBRIDGE |
We previously proposed to generate a complete connectome for the adult male Drosophila central nervous system (CNS), comprising both brain and nerve cord. Capitalising on that investment, this discretionary award would allow us to deliver a second, high-quality, female connectome just one year later, at a fraction of the cost.
This would be the first full CNS connectome, bilaterally complete and with sensorimotor circuits intact, of an adult female animal with complex behaviours. It would immediately allow comparisons of neuronal number, morphology, and connectivity across 1) hemispheres (this animal), 2) sexes (with the male CNS), and 3) three same-sex individuals (with partial datasets FAFB and the hemibrain) and global estimates of intra-individual, inter-sex, and inter-individual variation.
The PIs will use this joint resource to investigate circuitry underlying sexually dimorphic behaviours such as decision-making (e.g., mating receptivity and egg-laying), aggression, sensory integration and descending control of motor programmes, memory formation and recall, and sleep. We will make both datasets available with a range of analytic tools for use by the > 200 labs studying Drosophila neurobiology worldwide. Moreover, we expect the technology and pipelines developed for obtaining and comparing these connectomes to facilitate future studies in other organisms, ultimately including humans.
|
| 30/09/2020 |
£52,000 |
|
JISC |
The core aim of this proposal is to further increase the number of transformative open access agreements in place with Society and smaller publishers to ensure that Wellcome Trust funded authors have maximum opportunity and ability to publish in compliance with the 2021 Wellcome Trust Open Access policy.
The proposal seeks funding for a one year extension to the negotiation and licensing activity currently led by licensing manager, Kathryn Spiller. This role is dedicated to achieving agreements that meet the requirements of Wellcome Trust's policy and targets the society publishers that over the last 3 years have received the most revenue via Wellcome Trust funding grants.
|
| 30/09/2020 |
£1,412,289 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
We propose a global Commission to quantify evidence for national, regional and global actions that will be positive for health, the environment and the economy. It will draw on knowledge generated by other initiatives where relevant but will fill a major gap that is not currently addressed, namely the focus on human health as well as decarbonising economies. This will require identifying and assessing policies, technologies and interventions across a range of sectors including transport, food systems, cities, energy, industry and health systems. The Commission will fill a number of knowledge gaps that are impeding progress towards a healthy zero-carbon economy – namely which actions will have the largest multiple benefits for health, the environment and prosperity in particular contexts, and which implementation strategies should be employed for effective scale-up.
In addition to synthesising and grading the evidence, the Commission will generate a framework for action in the form of practical guidelines targeted towards national and city governments, NGOs, civil society and the private sector. These guidelines will indicate how to assess which actions should be prioritised in particular contexts. It will also include a comprehensive influence strategy to be developed with partner organisations and a leading creative agency.
|
| 30/09/2020 |
£91,887 |
|
JAMAL EDWARDS DELVE |
Through workshops with mental health researchers, at our youth centres, young people will deconstruct hip-hop lyrics understanding how to link them to wider mental health issues and research. The project will focus on empowering young people to investigate mental health experiences in the community and gather evidence on the mechanisms others have relied on to overcome their struggles with the aim of reinforcing young people’s resilience and discovering, through peer-led research, accessible prosocial tools to combat deterioration in mental health.
|
| 30/09/2020 |
£1,899,321 |
|
MRC LABORATORY OF MOLECULAR BIOLOGY |
The ability to make any human genome would transform hypothesis driven investigations in diverse areas of biology, genetic-archaeology and biotechnologies. However, there are currently no technologies for building human genomes. Moreover, there is a technological void between the state of the art in the creation of synthetic genomes and what will be required to enable the synthesis of human genomes. The current challenge is therefore to bridge this void. The goal of this proposal is to bridge the technological void between the state of the art, which has enabled the synthesis of Mbp-scale microbial genomes, and the technologies that will be required to build a human genome, which is 3 orders of magnitude larger than any synthetic genome that has been created to date. We will establish key technologies for human genome synthesis and exemplify these technologies through the synthesis of a recoded human chromosome.
|
| 30/09/2020 |
£599,245 |
|
UNIVERSITY OF LIVERPOOL |
Invasive non-typhoidal
Salmonella (iNTS) is estimated to cause 535,000 illnesses, 77,500 deaths, and the loss of
4,263,500 disability-adjusted life years (DALY’s) every year, with 86.7% of the global burden
falling in sub-Saharan Africa (sSA). The proposed SAiNTS study will work with the EU-funded
Vacc-iNTS consortium, and will complete a comprehensive rural community-based seroepidemiological
study in a malarial area, measuring age-stratified exposure, susceptibility and
natural immunity to NTS, and leveraging multiple additional cohort datasets, with the
overarching goals of:
- Accelerating the clinical development of 3 new iNTS vaccines in early clinical
development through phase 1 and phase 2a immunogenicity studies
- Providing a model contributing to realistic assessments of the impact of iNTS
vaccination in varying epidemiological settings across Africa.
The SAiNTS study, accordingly, has the following specific aims:
Aim 1: Develop a regression model for age-dependant, naturally acquired immunity against
iNTS disease (alphaLPS-IgG antibody and SBA) and compare to the age-stratified incidence of
Salmonella enteric infections (eNTS).
Aim 2: Estimate a Correlate of Protection for invasive NTS, based on naturally acquired
antibody levels and known age-stratified disease incidence.
Aim 3: Assess the effect of different iNTS risk factors on the age-dependent acquisition of
natural immunity, and how they might impact on estimated correlates of protection and iNTS
vaccine impact in different scenarios. |
| 30/09/2020 |
£876,884 |
|
NEWCASTLE UNIVERSITY |
We propose to generate an in-depth single cell and spatial atlas of embryos during late organogenesis, at 6/7 post conception weeks (PCW). This project will form a blueprint for a complete HCA development cell atlas, which will ultimately cover all accessible developmental stages week by week. We will leverage genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. This work will significantly extend our existing WSSS-funded Development Cell Atlas research programme, which is focused on organ-based profiling. Our reconstruction of a complete human embryo atlas will provide a blueprint for establishing high resolution molecular-based anatomical landmarks during human development, harmonizing developmental knowledge across species, and establishing a foundational resource with significant implications for developmental and childhood disorders, regenerative medicine and tissue engineering.
|
| 30/09/2020 |
£2,164,882 |
|
WELLCOME TRUST SANGER INSTITUTE |
We propose to generate an in-depth single cell and spatial atlas of embryos during late organogenesis, at 6/7 post conception weeks (PCW). This project will form a blueprint for a complete HCA development cell atlas, which will ultimately cover all accessible developmental stages week by week. We will leverage genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. This work will significantly extend our existing WSSS-funded Development Cell Atlas research programme, which is focused on organ-based profiling. Our reconstruction of a complete human embryo atlas will provide a blueprint for establishing high resolution molecular-based anatomical landmarks during human development, harmonizing developmental knowledge across species, and establishing a foundational resource with significant implications for developmental and childhood disorders, regenerative medicine and tissue engineering.
|
| 30/09/2020 |
£119,697 |
|
UNIVERSITY OF CAMBRIDGE |
We propose to generate an in-depth single cell and spatial atlas of embryos during late organogenesis, at 6/7 post conception weeks (PCW). This project will form a blueprint for a complete HCA development cell atlas, which will ultimately cover all accessible developmental stages week by week. We will leverage genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. This work will significantly extend our existing WSSS-funded Development Cell Atlas research programme, which is focused on organ-based profiling. Our reconstruction of a complete human embryo atlas will provide a blueprint for establishing high resolution molecular-based anatomical landmarks during human development, harmonizing developmental knowledge across species, and establishing a foundational resource with significant implications for developmental and childhood disorders, regenerative medicine and tissue engineering.
|
| 30/09/2020 |
£161,121 |
|
UNIVERSITY OF CAMBRIDGE |
We propose to generate an in-depth single cell and spatial atlas of embryos during late organogenesis, at 6/7 post conception weeks (PCW). This project will form a blueprint for a complete HCA development cell atlas, which will ultimately cover all accessible developmental stages week by week. We will leverage genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. This work will significantly extend our existing WSSS-funded Development Cell Atlas research programme, which is focused on organ-based profiling. Our reconstruction of a complete human embryo atlas will provide a blueprint for establishing high resolution molecular-based anatomical landmarks during human development, harmonizing developmental knowledge across species, and establishing a foundational resource with significant implications for developmental and childhood disorders, regenerative medicine and tissue engineering.
|
| 30/09/2020 |
£121,985 |
|
UNIVERSITY OF CAMBRIDGE |
We propose to generate an in-depth single cell and spatial atlas of embryos during late organogenesis, at 6/7 post conception weeks (PCW). This project will form a blueprint for a complete HCA development cell atlas, which will ultimately cover all accessible developmental stages week by week. We will leverage genomics technologies to profile single cells from dissociated tissues and within intact tissue sections, and deploy cutting-edge computational methods to reconstruct, in silico, a three-dimensional atlas of the whole human embryo. This work will significantly extend our existing WSSS-funded Development Cell Atlas research programme, which is focused on organ-based profiling. Our reconstruction of a complete human embryo atlas will provide a blueprint for establishing high resolution molecular-based anatomical landmarks during human development, harmonizing developmental knowledge across species, and establishing a foundational resource with significant implications for developmental and childhood disorders, regenerative medicine and tissue engineering.
|
| 30/09/2020 |
£399,144 |
|
GLOBAL GENOMIC MEDICINE COLLABORATIVE (G2MC) |
This proposal is for partial funding of the IHCC as it transitions from a nascent organization to a mature and sustainable one. The IHCC’s inaugural summit was funded by the Wellcome Trust, the NIH, and the Medical Research Council of the UK. Since, the NIH has provided support for both administration of the IHCC, its second and third summit and pilot work on the Atlas and scientific projects. The funding period from June 2020-2021 will be one of organizational maturing, strategic planning, demonstration of feasibility of prioritized cross cohort projects and the development of a business plan. Funding from new industry members and from HIROs is anticipated for growth and sustainability. The Wellcome Trusts’ investment will be highly levered with NIH’s investment and is key to allowing the IHCC to launch itself with a robust charter and organizational structure, a scientific plan an Atlas and data structure that will make the IHCC’s assets accessible. Deliverables from this funding will be a) a strategic plan, b) a 4th ICS, c) completion of 3-5 pilot cross- cohort demonstration projects, and d) a compendium of opportunities for research across the globe, and e) formal engagement of funders toward a sustainable funding model.
|
| 30/09/2020 |
£150,000 |
|
MQ TRANSFORMING MENTAL HEALTH |
This grant will enable MQ to deliver two key activities in 2020/21: the implementation of our income generation strategy, and the development and delivery of the MQ Annual Mental Health Science Meeting 2021.
MQ exists to ‘create a world where mental illness is understood, effectively treated and one-day prevented’. In 2019, MQ worked with the agency Open Creates to develop a new income generation strategy to deliver these ambitions - bringing the public and scientists together to fund ground-breaking mental health research, more quickly.
With the support of this grant, MQ will work with Open Creates to define and test priority research themes that align with the views of target audiences. Following identification of priority theme(s), MQ will then roll out activity to build public awareness, engage and grow a base of supporters, and raise funds for mental health research against a compelling research and organisational strategy.
This grant will also support MQ to work with the mental health science community and key supporters to develop and deliver a successful Mental Health Science Meeting in 2021, championing collaboration and knowledge sharing amongst researchers, and showcasing the potential of mental health science to excite and motivate our supporters and stakeholders.
|
| 30/09/2020 |
£1,499,800 |
|
GUY’S AND ST THOMAS’ CHARITY |
We are applying to Wellcome for a £1.5M investment as match towards an overall £3M+ programme that will test new ways of working to embed health research in our practice.
This will be split between two priority portfolio areas; Adolescent Mental Health (AMH) and Multiple Long-term Conditions (MLTCs)
We will explore 3 opportunity areas, these are:
1. New models for generating and using public insight in research
2. New models for creating impact through investment partnerships
3. Accelerating our evidence
The work will be supported by research partnerships, a network of public engagement expertise and a partnership advisory group. We already have an existing relationship with KCL, with whom we currently run a £1m+ MLTC research challenge fund in the MLTC programme, as well as our cornerstone investment into the Science Gallery London https://london.sciencegallery.com/. We would also like to deepen our relationships with other academic institutions as part of this work.
Please see Partnership Plan for details.
Please see Partnership Slide Deck
|
| 30/09/2020 |
£1,957,254 |
|
FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH |
Not Available |
| 30/09/2020 |
£3,914,507 |
|
FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH |
Not Available |
| 30/09/2020 |
£250,190 |
|
UNITED FOR GLOBAL MENTAL HEALTH |
This proposal aims to sustain lasting activity on mental health advocacy. The United GMH team will leverage support from Wellcome to mobilise partners, and the wider global mental health community, to maintain the momentum built since 2018 to raise mental health further up the global political agenda in 2020. We are requesting £250,000 from Wellcome to further this work.
This proposal plans activities covering four streams:
Sustaining the work of the BluePrint Group including delivery of the Kenya face to face meeting and a second meeting later in the year (TBC Sept/Oct)
Leading the BluePrint Group and the wider mental health community to design and undertake a comprehensive multi-stakeholder consultation and create and finalise an action plan to ensure the Global Mental Health Roadmap is delivered; starting with the engagement with key stakeholders at Davos and at the Speak Your Mind and BPG meetings in February
Working with WHO to develop the advocacy strategy, consultation process and finalisation of their WHO Mental Health Action Plan
Working to incorporate messaging around the need for more mental health research as part of UnitedGMH’s research on broader advocacy
|
| 30/09/2020 |
£100,546 |
|
UNIVERSITY OF OXFORD |
Blood culture (BC), the core sample for antimicrobial resistance surveillance, is recommended to be sampled from all sepsis patients prior to administration of antibiotics. However, BC sampling rates are lower than recommended in both high-income countries (HICs) and low and middle-income countries (LMICs). Various barriers and enablers have been identified that impeded the adoption of BC sampling recommendations using different theories; however, a systematic review on this topic is not currently available.
We propose to conduct a systematic review to identify known barriers and enablers to the adoption of local and international BC sampling recommendations. We will use the theoretical domain framework (TDF), which has been developed by refining a wide range of theories, as a framework for synthesizing evidence on barriers and enablers. Findings will be stratified by HICs and LMICs. We will then conduct a survey study among medical doctors using face-to-face interviews and electronic questionnaires to explore generalizability of systematic review findings among medical doctors in Thailand, Viet Nam and Indonesia. All questionnaires (in Thai, Vietnamese, Indonesian and English) will also be made available online, and open for public participation.
A systematic summary of the existing evidence can inform the development of interventions.
|
| 30/09/2020 |
£2,499,432 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
The decreasing cost of genomic sequencing will yield millions of samples in the coming years from both research and healthcare. To make the most use of these data, the community must agree on common methods for collecting, storing, transferring, accessing, and analyzing data.
This proposal will support the Global Alliance for Genomics and Health (GA4GH; www.ga4gh.org) as it develops the standards and policies necessary for effective and responsible data sharing. With more than 1,000 active contributors working across more than 30 countries in the areas of healthcare, research, patient advocacy, life science, and information technology, this diverse organization enables broad sharing that transcends the boundaries of any single institution or country.
We envision a future in which the full suite of GA4GH standards enables all clinicians, geneticists, and researchers to search across the world’s collective genomic data to reveal unanticipated gene-disease associations, make otherwise impossible drug-response predictions, and generally participate in genomics at a competitive pace—regardless of their means or location.
The promise of genomic medicine lies at a crossroads that depends on community harmonization and will significantly enhance human health and medicine if we succeed. We believe GA4GH is necessary to that success.
|
| 30/09/2020 |
£19,231,767 |
|
ROSALIND FRANKLIN INSTITUTE |
The ability to image life lies at the heart of biology and medicine. Imaging the molecules of life leads directly to discoveries since they can then be understood in atomic detail. For molecular imaging, electrons give more signal for less damage than X-rays, as demonstrated by the current success of single-particle electron cryomicroscopy. The key recent breakthrough underpinning this technology was the development of direct electron detectors for cryoEM, based on silicon computer chip technology from the 1990s. The promise of using electrons in structural biology more broadly is still held back by several technological hurdles. Here we propose a major cross disciplinary effort to develop new technologies that use electrons to revolutionise biology. There are three components: AMPLUS – using electrons to visualise proteins inside cells, (electron cryotomography) at unprecedented resolution, cryoEM100 – a ten-fold cheaper purpose-built cryomicroscope that will democratise single particle imaging, and HEXI – a project that will create a world-leading combined X-ray and electron beamline, enabling structure determination from crystals ranging from the smallest that exhibit Bragg diffraction up to those useable at a microfocus X-ray beamline.
|
| 30/09/2020 |
£1,783,532 |
|
UKRI-MRC |
The ability to image life lies at the heart of biology and medicine. Imaging the molecules of life leads directly to discoveries since they can then be understood in atomic detail. For molecular imaging, electrons give more signal for less damage than X-rays, as demonstrated by the current success of single-particle electron cryomicroscopy. The key recent breakthrough underpinning this technology was the development of direct electron detectors for cryoEM, based on silicon computer chip technology from the 1990s. The promise of using electrons in structural biology more broadly is still held back by several technological hurdles. Here we propose a major cross disciplinary effort to develop new technologies that use electrons to revolutionise biology. There are three components: AMPLUS – using electrons to visualise proteins inside cells, (electron cryotomography) at unprecedented resolution, cryoEM100 – a ten-fold cheaper purpose-built cryomicroscope that will democratise single particle imaging, and HEXI – a project that will create a world-leading combined X-ray and electron beamline, enabling structure determination from crystals ranging from the smallest that exhibit Bragg diffraction up to those useable at a microfocus X-ray beamline.
|
| 30/09/2020 |
£3,916,135 |
|
DIAMOND LIGHT SOURCE LTD |
The ability to image life lies at the heart of biology and medicine. Imaging the molecules of life leads directly to discoveries since they can then be understood in atomic detail. For molecular imaging, electrons give more signal for less damage than X-rays, as demonstrated by the current success of single-particle electron cryomicroscopy. The key recent breakthrough underpinning this technology was the development of direct electron detectors for cryoEM, based on silicon computer chip technology from the 1990s. The promise of using electrons in structural biology more broadly is still held back by several technological hurdles. Here we propose a major cross disciplinary effort to develop new technologies that use electrons to revolutionise biology. There are three components: AMPLUS – using electrons to visualise proteins inside cells, (electron cryotomography) at unprecedented resolution, cryoEM100 – a ten-fold cheaper purpose-built cryomicroscope that will democratise single particle imaging, and HEXI – a project that will create a world-leading combined X-ray and electron beamline, enabling structure determination from crystals ranging from the smallest that exhibit Bragg diffraction up to those useable at a microfocus X-ray beamline.
|
| 30/09/2020 |
£1,987,486 |
|
FUNDACIó UCR |
Animal-derived antivenoms are the mainstay in the therapy of snakebite envenoming. There is an urgent need to develop knowledge-based protocols for the immunization of horses, as this key aspect of production has lacked research and innovation. This project is aimed at developing protocols for the management of horses used for immunization with venoms in a pilot farm. The following aspects will be investigated: (1) Evaluation of feeding protocols; (2) veterinary care and management aimed at minimizing the deleterious effects of venoms; (3) selection of the most appropriate adjuvants for immunization and development of new immunization schemes for generating high antibody titers; (4) design of bleeding protocols providing a high yield of plasma while not affecting the overall condition of horses. The project is also aimed at selecting the best combination of venoms from African snakes in order to generate a polyspecific antivenom of wide neutralizing coverage, as well as to device ways to improve the antibody titers against poorly immunogenic low molecular mass neurotoxins from snake venoms. In order to apply the principle of 3Rs (Replacement, Reduction and Refinement) in the assessment of antivenom potency, in vitro tests will be evaluated for their correlation with in vivo toxicity assays.
|
| 30/09/2020 |
£500,971 |
|
CARDIFF UNIVERSITY |
Recent evidence suggests that a part of the brain called the hippocampus is responsible for
the increase in dopamine in a different part of the brain, the striatum, known to cause
psychosis. Our hypothesis is that by attenuating activity within the hippocampus, we will then
be able to reduce the increase in dopamine associated with psychosis. In order to do this,
we plan to target the GABA chemical signalling pathway which inhibits nerve cell excitability.
More specifically, we aim to increase the inhibitory actions of the so-called alpha5-GABAAR
protein, which is highly expressed within the hippocampus and is therefore ideally placed to
control overall hippocampal activity. In this proposal, we will identify molecules that
selectively enhance the function of GABA at alpha5-GABAARs and then test representative
compounds in an animal model of schizophrenia to see if they do indeed attenuate
increased dopamine activity. |
| 30/09/2020 |
£497,900 |
|
BRINK |
Over 30m days are lost to work-related ill health annually in the UK. Of all employers’ health-related investments, only 5.6% are being used by employees and under 15% are evidence-based.
Our aim?
Develop, test, and scale an ‘Evidence Accelerator’ that bridges the gap between science, research and the workplace. Using design methods to translate evidence into action, with employers as the bridge, it’ll provide ways marginalised employees can access, use and respond to scientific health research and improve their health.
We will
narrow in on key mission areas where under-utilised EVIDENCE shows most promise to positively impact marginalised workers’ health, (e.g. mental, musculoskeletal)
ENGAGE cohorts of employers across industries with marginalised workers most susceptible to those health issues
prototype and test a wide range of design-led and evidence-based workplace interventions to ACCELERATE the flow of evidence into the workplace
explore which offer demonstrable positive impact on workers and organisations as a result of their involvement, and which show most promise of a model that can SUSTAIN
Success means:
Marginalised workers are accessing, using, responding to health research and truly improving their health and wellbeing
More researchers and employers engaged in informing evidence-based, design-led workplace interventions
Sustainable operating and business model
|
| 30/09/2020 |
£388,023 |
|
THINKSONO LTD |
Deep vein thrombosis (DVT) is a condition where blood clots form in the veins
of the body, most frequently the leg. It is a serious condition and if left untreated
clots can move to the lungs, which can be fatal. Early diagnosis is vital. Normally
three steps are needed for a DVT diagnosis: a GP appointment; a hospital DVT
clinic appointment and a leg ultrasound scan. This process should take only 4
hours, but it often takes longer and therefore a precautionary anticoagulant
(blood-thinning) drug is given. Nearly 90% of people investigated for a DVT have
no clot. |
| 30/09/2020 |
£285,881 |
|
UNIVERSITY OF CAMBRIDGE |
Salmonella are bacteria that cause life-threatening infections in adults and children. These diseases co-exist in many geographical areas, especially in Low and Middle Income Countries. Therefore, a vaccine that can protect against all the major Salmonella infections would be highly desirable. The project will exploit the remarkable features of Outer Membrane Vesicles (mOMV) to deliver antigens from many species of Salmonella that cause disease in humans. mOMV are outer membrane blebs naturally shed by Gram-negative bacteria, including Salmonella. These bacteria can be genetically manipulated to increase mOMV production, to decrease adverse reactions and to include additional antigens. mOMV are easy and cheap to produce, strongly immunogenic and protective. The innovator award will therefore allow the development of a multivalent, easy to produce, low-cost, safe, effective Salmonella vaccine to be taken towards the end of preclinical experimentation. |
| 30/09/2020 |
£1,184,320 |
|
ROYAL COLLEGE OF SURGEONS IN IRELAND |
Mental disorders such as schizophrenia are among the most expensive disorders in
terms of quality of life and societal cost. Early identification and intervention is
associated with improved outcome and is facilitated by targeting those at clinical-highrisk-
for-psychosis (CHR) as up to 25-30% develop psychotic disorder (PD) at 6 year
follow-up. There is growing evidence for the involvement of the immune system and
inflammation in this disorder. We have added to this literature by demonstrating that
the complement pathway, the blood plasma component of the innate immune system is dysregulated in blood samples of individuals at age 11, many years before these
individuals report symptoms in keeping with psychotic disorder at age 17.
Based on our own plasma proteomic data and machine learning analyses, we now
have evidence for a set of biomarker proteins which can predict transition from the
CHR to PD with a high degree of accuracy. We now seek to refine and replicate these
findings.
Our study: Using state-of-the-art proteomic methods and machine learning approaches
we will replicate and refine this biomarker signature of transition from CHR to psychotic
disorder in three distinct international samples and one longitudinal cohort with a total
CHR sample size of over 1000 CHR subjects. We will also undertake functional assays
that measure plasma protein levels of the complement and coagulation pathway and
their activation fragments as indicators of complement and coagulation dysregulation.
Our study includes commercial diagnostic/prognostic biomarker expertise. |
| 30/09/2020 |
£2,000,000 |
|
UKRI-MRC |
N/A |
| 30/09/2020 |
£466,154 |
|
KING'S COLLEGE LONDON |
Brain-based disorders, including psychiatric and neurological illnesses, represent
10.4% of the global burden of disease. At present, there are no established imagingbased
tests for detecting these disorders, monitoring their progression over time and
optimising treatment. In a previous Wellcome Innovator Award, Prof Andrea Mechelli and team at KCL developed Neurofind - a user-friendly web-based tool, which usesdeep learning technology to quantify neuroanatomical abnormalities from structural Magnetic Resonance Imaging scans. This tool compares an individual scan against a
reference database and generates an individualised report that could support
diagnostic, prognostic and treatment decisions in individual patients. In this follow-on
award, the feasibility, acceptability, safety and clinical utility of Neurofind will now be
assessed in a real-world setting. Neurofind will be tested in patients with first episode
psychosis recruited from the South London and Maudsley NHS Foundation Trust.
The study aims to test if Neurofind is feasible, acceptable, safe and if the information
in the individualised patient reports it produces is predictive of clinical outcomes at 6-
months follow-up. If successful, the proposed trial will lead to the adoption of
Neurofind in real-world clinical services, with tangible benefits for patients, clinicians and service providers
|
| 30/09/2020 |
£501,929 |
|
KING'S COLLEGE LONDON |
In the UK and in many countries around the world, it is routine for women to undergo an
ultrasound (US) screening examination about halfway through pregnancy to check if their
fetus is developing normally. This is important as undiscovered fetal anomalies can have a
lifelong impact on the families affected, with huge cost to health services as well as
substantial wider societal impact. Currently, international screening detection rates are
highly variable, and are strongly dependent on the skill and experience of the sonographer
performing the examination.
This project builds on iFIND (www.ifindproject.com), a Wellcome Trust (WT) Innovative
Engineering in Health award, which has yielded powerful computerized technology that
uses artificial intelligence to simplify and enhance fetal US screening by automating many
routine tasks. This technology has been created by a fully integrated team of computer
scientists and clinicians working together using a close couple cycle of innovation and
clinical testing. It has the potential to have a significant impact on fetal screening, but to
achieve that it is necessary to transition from University developed prototype to healthcare
product. The usual strategy is to license to an existing player or spin-out a company.
However, in both cases the close coupling between technology innovation and clinical
testing that has proved so effective can get stressed or broken. We propose an innovative
approach in which the next stage of development is undertaken by an embedded team of
engineers working directly within a clinical environment. This will provide opportunities not
available by either of the conventional routes, providing an effective pathway to impact. |
| 30/09/2020 |
£120,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2020 |
£4,333,936 |
|
INTERNATIONAL AIDS VACCINE INITIATIVE |
Long-standing global health challenges like antimicrobial resistance (AMR) require
synergistic approaches to dramatically reduce global morbidity and mortality levels.
We think that the availability of antimicrobial monoclonal antibodies (mAbs), which can
be used as a complementary strategy for vaccines, holds great promise for
ameliorating the expansion of AMR. A major challenge for the uptake of such antibody
interventions by those most vulnerable to AMR in low- and middle-income countries
(LMICs) is the associated costs of mAbs. This proposal is focused on two major
themes. First, we are proposing a portfolio approach to Ab discovery and development
for enteric bacteria with a focus on cross-reactive mAbs that enable broad spectrum
use to obviate the need for an accompanying diagnostic. This portfolio approach
includes the optimization and development of an existing lead mAb as well as
screening cohorts to discover new antibodies for different enteric bacteria. The second
theme is to set up a pipeline for Ab optimization to improve antibody bactericidal
potency, cross-reactivity to different enteric bacteria, Ab half-life, and manufacturability
to reduce cost of goods associated with an Ab intervention. These approaches are
meant to, respectively, reduce dosage requirements, enable broad spectrum use,
reduce administration frequency, and increase the probability of success of advancing
lead Abs through manufacturing and process development. IAVI and partners think
that investing in these two themes will greatly expedite the likelihood of advancing an
effective Ab intervention to address AMR and the burden of diarrheal disease caused
by enteric bacteria. |
| 30/09/2020 |
£3,532,625 |
|
FONDAZIONE TOSCANA LIFE SCIENCES |
Shigella, a gram-negative bacterium with more than 50 different serotypes, is a
major global health problem in low income countries. A recent estimate reported
more than 93 million episodes of shigellosis associated with diarrhoea and 238,000
deaths per year, 92,700 of which are in children under 5. The problem is
exacerbated by widespread antimicrobial resistance (AMR) which makes the
bacterium increasingly difficult to treat. There are several vaccines in development,
however they face the challenging need to cover a vast number of serotypes and
the absence of correlates of protection. This project aims to accelerate the
development of an ultimate remedy for shigellosis. We will isolate human
monoclonal antibodies (mAbs) from B cells collected from people previously
exposed to Shigella or vaccinated with experimental vaccines with the overarching
goal to provide new therapeutic solutions to Shigella infections. Shigella-specific
mAbs will be selected and engineered to have high potency and low cost to make
them affordable to low- and middle-income countries. The project will attempt to
establish correlates of protection that will facilitate vaccine development and
licensure and the identification of antigens common to all or to most of the
serotypes to underpin the development of universal vaccines.?? |
| 30/09/2020 |
£9,238,794 |
|
NOVARTIS INSTITUTE FOR BIOMEDICAL RESEARCH |
Since its launch in 2003, the Novartis Institute for Tropical Diseases has become
a world-leading drug discovery center of transformative medicines for neglected
tropical diseases – delivering a robust pipeline of drug candidates to treat
malaria, visceral leishmaniasis, sleeping sickness and dengue. In this award, we
propose to strengthen the pipeline by targeting two of the most neglected tropical
diseases, Chagas disease and cryptosporidiosis.
An estimated 8 million people are infected by the Trypanosoma cruzi parasite,
the causative agent of Chagas disease. Current therapeutics are widely
considered to be poorly effective and toxic. We aim to deliver a portfolio of highly
effective and safe new chemical entities with proven sterilising activity in Chagas
disease animal models.
Cryptosporidiosis causes an estimated 200,000 deaths in children aged under 24
months each year. With support from the Bill & Melinda Gates Foundation, and
together with our partners, we have identified drug candidates with a remarkable
safety profile, novel mechanism of action and unprecedented efficacy in
cryptosporidiosis animal models. In this award, we aim to establish a
cryptosporidium controlled human infection model for a proof-of-concept trial with
healthy adult volunteers, followed by definitive trials in the vulnerable pediatric
population. |
| 30/09/2020 |
£25,000,000 |
|
UNIVERSITY COLLEGE LONDON |
The Sainsbury Wellcome Centre aims to understand how computation in neural circuits generates flexible behaviour—a complex, scientific challenge that cannot be tackled by any one laboratory. The Centre is in a unique position to reveal general principles that link behaviour to neural processes across scales, by relating algorithms to neural circuits, cells and synapses. We will determine how these neural elements give rise to computations contributing to innate and learned behaviours, and develop a theoretical framework that explains how flexible, adaptive behaviour arises from neural activity. We have assembled outstanding scientific talent in an exceptional environment, with access to shared resources and state-of-the-art facilities that deliver new technologies, empowering bold research. We will exploit new models of scientific collaboration by integrating experiment, theory, data science and engineering, in close partnership with colleagues at the Gatsby Computational Neuroscience Unit. Our multi-disciplinary collaborative approach extends to the training and support of early career researchers, enhancing their success within and beyond our walls. By sharing our resources, knowledge and research culture, and through initiatives with our UCL, UK and international partners, we will collectively advance global efforts to understand the neural underpinnings of behaviour.
|
| 30/09/2020 |
£755,414 |
|
IMPERIAL COLLEGE LONDON |
Rapid brain imaging is central to the diagnosis and treatment of acute neurological
conditions, but existing imaging methods require large, immobile, high-power instruments
that are near-impossible to deploy outside specialized environments. We will create a device
that can be simply and rapidly applied to any patient, any time, any place, exploiting
advances that have already revolutionised imaging in geophysics. We will image the brain
using sound waves, transmitted across the head, applying advanced computer modelling to
remove the distorting effects of the skull, thereby enabling high-resolution high-contrast
imaging of the brain unachievable by conventional ultrasound. Safe, fast, universally
applicable, deployable continuously, and above all portable by paramedics, our device will
revolutionise brain imaging, in health and disease. The technology has particular relevance
to stroke – globally the second-commonest cause of premature death and a major, growing
cause of adult disability – and to brain imaging in resource-limited and inaccessible
environments. |
| 30/09/2020 |
£445,279 |
|
QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE |
Dengue virus is an important mosquito-borne viral disease in humans. Dengue virus inflicts
390 million people annually in more than 100 countries. Currently, no specific anti-viral
treatment for dengue infection is available. This project will develop an innovative
therapeutic agent to treat dengue infection in patients. The approach is based on defective
interfering particles or DIPs, which are able to robustly inhibit dengue virus infections. DIPs
represent a novel approach for developing an anti-viral for dengue infection because they
are a specific, effective and non-toxic dengue inhibitor. DIPs are reported to co-evolve with
the infectious virus thereby potentially preventing development of viral escape mutants. This
study will evaluate the ability of DIPs to attenuate infection and disease by dengue virus in
vivo, it will determine if DIPs can block transmission of dengue virus between vertebrates
and mosquitoes and investigate co-evolution of dengue virus and DIPs. |
| 30/09/2020 |
£500,000 |
|
UNIVERSITY OF LEEDS |
Recent advances in cryo-electron microscopy/tomography (cryoEM/ET) are transforming structural biology, and thanks to recent investments in infrastructure the EM community has unprecedented access to high-end instrumentation. However, a severe lack of training opportunities means that the skills required to make the most of these instruments are in very short supply. This in turn is slowing progress on many existing projects within EM-focussed laboratories, and limiting access to EM by the mainstream structural and cell biology communities who are desperate to gain access to the cryoEM methodology. Effectively, there is a block on discovery, which is caused in large part by a deficit in knowledge, expertise, and training. To rectify this training shortfall, we propose a coordinated, multi-level programme of training, that complements those training opportunities that do exist, but expands upon them, significantly increasing the amount of ‘hands-on’ EM training available in the UK. This programme, which will encompass introductory "sample work up", intermediate "high resolution data collection" and advanced "Facility Placements" will provide a path for users with different expertise, and from different scientific backgrounds, to access the training they require, maximise the return on existing and new investments in EM, and drive forward new biological and biomedical discovery.
|
| 30/09/2020 |
£51,766 |
|
UKRI-MRC |
The UKPRP is an inter-disciplinary national initiative supported by an alliance of UK charities, Research Councils and the UK Health Departments, and established in recognition of the need for research into population-level strategies that will prevent non-communicable diseases (NCDs) and reduce inequalities in health. |
| 30/09/2020 |
£399,123 |
|
WELLCOME TRUST SANGER INSTITUTE |
The biodiversity of our living landscapes has never been more vital for the future health of our planet and humanity. A decade ago, Darwin 200 and the International Year of Biodiversity cast a public spotlight on evolution and biodiversity. In the subsequent decade biology has made huge advances, especially in the field of genomics where a radical new window to the natural world is being opened. The Darwin Tree of Life project is at the heart of this revolution, and will generate a library of the genomes of every complex species in Britain and Ireland, while playing a leading role in the ambitious Earth BioGenome Project - to sequence the genomes of all eukaryotic species on earth by 2030.
Just as new research questions will thrive on the new genomic datasets taking shape, the opportunities for public engagement will also evolve. Many communities passionate about nature and the environment will bring expertise to the scientific effort. Diverse themes, ranging from changing land use to pollution and climate change will resonate with particular groups. An opportunity exists to nurture a new generation of citizen genomicists, empowering people motivated by environmental challenges but new to the potential of understanding DNA and genomics.
|
| 30/09/2020 |
£499,579 |
|
UNIVERSITY OF GLASGOW |
High quality public engagement by Wellcome researchers will be enabled by open-call funding combined with responsive training and support - drawing on expertise and brokerage from institutional PEPs and the wider Scottish Public Engagement Network (ScotPEN). This application extends the successful collaborative ScotPEN Wellcome Enrichment Award (Phase 1) to allocate Wellcome Research Enrichment for Public Engagement funding in Scotland.
As well as increasing the quantity and quality of applications to the scheme, the activities, relationships, and resources generated across the two phases will strengthen the culture of engagement within and between Scottish institutions and extend relationships between researchers, PEPs, partner organisations, and communities within Scotland and beyond.
Building on the success of Phase 1, where 12 proposals were awarded funding of £463,670, we will:
(1) Add a new management post to support capacity building both for SWEA and ScotPEN development.
(2) Provide responsive pre- and post-award support tailored to the needs of awardees and prospective applicants.
(3) Strengthen Phase 1 partnership development with organisations including the Scottish science centres and community groups.
(4) Include Public Engagement Professionals (PEPs) more explicitly in our training offer – helping increase their visibility and capacity to progress culture change.
|
| 30/09/2020 |
£749,862 |
|
UNIVERSITY OF OXFORD |
This proposal is to extend the initial Oxford Enriching Engagement pilot scheme (Institutional Research Enrichment Fund award 217077/Z/19/Z, 2019-2020) for devolved Wellcome Research Enrichment: Public Engagement funding.
This extended pilot programme will build on, enhance and enrich the significant work that has already taken place to further increase the effectiveness and dynamism of this scheme to achieve the desired outcomes.
Enriching Engagement will continue to support a diverse range of Wellcome-funded researchers to apply for, and if funded deliver, high-quality PER activities that result in tangible positive changes and outcomes, drawing upon the expertise of Oxford's PE staff.
This extended pilot will also enable an increase in evidence to be gathered on outcomes, successes, challenges and lessons learnt from this approach across the whole pilot period (which, if this extension is funded, will be April 2019 - December 2021) and gather medium and longer term outcomes from the initial pilot phase.
This learning has the potential to shape future engagement funding mechanisms and inform other institutions and networks on running their own devolved funding schemes - the latter has the potential to significantly increase the effectiveness and efficiency of these institutions' plans from the get-go, therefore offering significant added-value.
|
| 30/09/2020 |
£622,407 |
|
WORLD ECONOMIC FORUM |
Strategic partnership with WEF, renewed annually. |
| 30/09/2020 |
£3,703,029 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
MARVELS 1
Respiratory infections are common, potentially vaccine-preventable causes of death. Despite dramatic progress in pneumococcal and influenza vaccination, much remains to be done, both to prevent mucosal disease from these pathogens and the complex effects of co-infections. As nasopharyngeal carriage provides the mode of transmission and the source of infection for pneumococcal disease, it is also an excellent point of intervention to prevent respiratory infections.
MARVELS 1 will establish respiratory infection models in the human nasopharynx in order to answer 3 main questions:
Which vaccines can prevent acquisition of pneumococcal carriage in Malawi?
Which vaccines are most effective in vulnerable populations in Malawi, particularly those with substantial exposure to household air pollution, HIV, malnutrition?
What are the critical mechanisms of respiratory tract defence that can be harnessed to develop an effective mucosal vaccine suitable for low and middle income country (LMIC) use?
This programme of work will transfer our established controlled human infection models (MRC UK Programme grant) to Malawi in order to test vaccines in populations at risk of disease, determine mucosal immune responses, including those in co-infection and in risk populations, in order to accelerate vaccine discovery.
|
| 30/09/2020 |
£1,900,000 |
|
WELLCOME TRUST SANGER INSTITUTE |
No Data Entered |
| 30/09/2020 |
£3,286,966 |
|
UNIVERSITY OF CAMBRIDGE |
Stem cell research is rich in fundamental questions and offers unparalleled translational prospects – stem cell dysfunction underlies many global health challenges and stem cell manipulations provide immense therapeutic opportunities. The Cambridge Stem Cell Institute (CSCI) is a world-leading centre for stem cell research with the largest critical mass of recognised stem cell researchers in any single institution in Europe. Its mission is to transform the prevention, diagnosis and treatment of disease through a deep understanding of the mechanisms regulating stem and progenitor cells, both normal and pathological.
In 2019 all CSCI research groups moved to the Jeffrey Cheah Biomedical Centre on the Cambridge Biomedical Campus adjacent to Addenbrookes and Royal Papworth Hospitals. The purpose-built laboratories with state-of-the-art core facilities constitute a superb setting for contemporary stem cell research. A key strategy is to embed biological, clinical and physical scientists operating across disparate tissues at multiple scales to foster cross-disciplinary innovation. A critical mass of clinician scientists facilitates synergistic interactions between basic and disease-focussed research, and a network of 35 affiliated PIs provide bridges to Departments and Institutes throughout Cambridge, placing CSCI at the heart of a vibrant stem cell community of > 700 scientists.
|
| 30/09/2020 |
£2,582,105 |
|
UNIVERSITY OF EDINBURGH |
The Wellcome Centre for Cell Biology (WCB) is internationally renowned for discovery of key cellular mechanisms. During the current quinquennium, WCB researchers made transformative advances, aligned with our vision of uncovering cellular epigenetic mechanisms and their impact in disease. Influential breakthroughs in fundamental genome organisation and expression, epigenetic inheritance in fungal resistance and the molecular basis of a neurological disorder provide exemplars of our accomplishments. From these exceptional foundations, we have evolved a new scientific vision for WCB: to understand transitions between cellular states in health and disease. We will determine how cells are developmentally re-programmed and respond to environmental and other stresses, how differentiation goes awry in disease, and how pathogens switch states to evade toxins. We have made recent strategic appointments aligned with these aims, in transcriptomics, cellular development, cell growth and structural epigenetics, and invested in mass spectrometry and Cryo-EM. Future appointments in epigenetic transcriptomics of infectious disease and early development will help deliver this vision. WCB will prioritise building inter-disciplinary connections and changing perceptions around translatable research. Scientific excellence will be underpinned by a strong commitment to growing an exemplary cultural environment. With this holistic vision, WCB is poised to deliver transformative scientific and cultural breakthroughs.
|
| 30/09/2020 |
£265,576 |
|
KING'S COLLEGE LONDON |
The Wellcome/EPSRC Centre for Medical Engineering has 3 clinical challenges: cancer, cardiovascular and neurological and psychiatric conditions. We seek to work with local partners and national charities relevant to our clinical challenges, to not just disseminate but also to engage with them to help support them and integrate into their policies. Since 2017, the Public Engagement programme has focused mainly on heart research. We have ongoing association with a local heart charity (ECHO) that we expect to lead to even stronger relationships working on newly identified, mutually beneficial priorities. Extra funding will allow us to further strengthen our partnership with ECHO and enable us to work more alongside patient groups with cancer and neurological and psychiatric conditions.
This new proposal will allow us to deliver a series of discreet projects as well as providing small seed funds for our researchers to lead on their own ideas. We hope to secure a secondment or local individual with experience of, and from, the local
community to work with us. We are approaching Wellcome for this funding, as no applicable grants are available from other funders.
|
| 30/09/2020 |
£3,732,109 |
|
UNIVERSITY COLLEGE LONDON |
Our overarching vision is to deliver clinically transformative applications of neuroimaging that catalyse the understanding and treatment of patients with neurological and psychiatric disorders. Cornerstone to this is the integration of paradigm-shifting neuroimaging technologies with neuronal and behavioural modelling to establish non-invasive, computationally-derived measures of neuronal function and structure. The resulting methodological innovations will be exploited to provide mechanistic explanations of how the human brain supports sensory, motor and cognitive functions in health, how these mechanisms are affected by disease, how they respond to therapeutic interventions, and how to deliver personalised prognoses.
A fundamental tenet of our vision is to conduct our science in a transparent and open manner, and to engage with stakeholders from patient groups and the wider community. Promoting this approach, in conjunction with an inclusive and positive research culture, will remain integral to our vision. Our supportive environment, highly-trained, multidisciplinary staff, innovative technological capacity, and embedded position within the Queen Square Institute of Neurology, creates a dynamic and cooperative critical mass with expertise in the use and development of computational approaches that make our neurobiological questions tractable. These factors provide the capacity to deliver our vision of clinically transformative applications of neuroimaging.
|
| 30/09/2020 |
£3,820,192 |
|
UNIVERSITY OF CAMBRIDGE |
Our vision is to understand the fundamental mechanisms of normal development, to determine how these mechanisms are subverted in cancer and other diseases, and to apply this knowledge to develop new therapies. Our research themes focus on: cell proliferation and genome maintenance; function and regulation of the genome and epigenome; mechanisms of cell fate determination, multipotency and plasticity; and the cell biology of organ development and function. We also emphasize two strategic directions: (i) human development and disease and (ii) quantitative analysis of cellular dynamics, to understand developmental and disease processes quantitatively at the molecular, cellular and tissue scales. We investigate both normal development and disease in a range of in vivo model systems, as well as primary human tissues, organoid systems, and patient-derived stem cells. Extension funding would allow us to further progress our overall scientific vision, our strategic areas of human development and quantitative approaches, our work on in vivo models of disease, and the translation of our research. It would also support our ambitious public engagement programme, enable continuation and development of our training activities, and underpin our efforts towards and commitment to a positive and inclusive research culture.
|
| 30/09/2020 |
£5,405,397 |
|
UNIVERSITY OF OXFORD |
We are a research community of basic and clinician scientists on an inter-disciplinary hospital campus with extensive outreach to Oxford’s tropical medicine units and global health challenges. Our vision is improving human health by maximising the informativeness of human genetics and disease mechanisms.
We commit to:
Responding to clinical need, making discoveries in biology to investigate genome function, translating them to molecular-cellular structures and mechanisms, and investigating impact of variation between individuals and cells, with disease and clinical outcomes.
Enabling through technology, using genetics/genomics, bioinformatics, structure determination, computing, and cell/mouse genome editing, underpinned by world-leading core facilities, to understand human physiology and pathology. Data, results, materials, software, and knowhow are made fully accessible.
Translating knowledge to the clinic and, where appropriate, filing patents and establishing partnerships, within the University and wider academic, technology, and biomedical sectors.
Promoting a positive research culture and building capacity in people and expertise, for all staff, including enabling early-career researchers to test ideas and flourish with essential support from our core facilities.
This extension will enable us to capitalize on, and extend, significant innovations since 2016, developing the next generation of innovative, game-changing technologies, approaches, and researchers, to meet still-existing and emerging threats to health.
|
| 30/09/2020 |
£3,101,188 |
|
UNIVERSITY OF OXFORD |
Understanding how interactions between neurons generate human behaviour, why individual brains vary from one another, or whether a patient is likely to develop a particular disease, requires explanations that span vast differences in scale. Yet such explanations are essential if insights from neuroscience are to make a meaningful impact on human health. Precise mechanisms discovered in animal models must be related to clinical phenotypes discovered through population studies; both must be combined to improve diagnosis and treatment in individual patients. Neuroimaging offers a powerful route to connect these different scales, providing measurements that are sensitive to cellular phenomena and that can be acquired in living humans.
The Wellcome Centre for Integrative Neuroimaging aims to enable novel insights into brain function that span levels of description, and therefore bridge the gap between laboratory neuroscience and human health. This requires fundamental discoveries concerning relationships between species and between scales, and major technological developments for mapping big-data discoveries onto neurobiological mechanisms. We bring together diverse investigators who can tackle different themes within this grand challenge. Within each theme, neuroimaging is used alongside complementary methodologies, ensuring that it takes inspiration from, and has impact on, areas beyond its typical reach.
|
| 30/09/2020 |
£185,420 |
|
UNIVERSITY OF CAPE TOWN |
The Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) at the University of Cape Town leads research programmes on high-burden infectious diseases, particularly HIV and tuberculosis. Through this enrichment grant, we will develop our researcher community as public engagement champions, improve our research through inolvement of our local communities and stakeholders, and raise awareness of our research to maximise health outcomes.
To develop our researcher community’s involvement in PE, we will create and implement a PE communication toolkit, which will become an embedded component of study conduct at CIDRI-Africa, and enable our researchers to confidently engage the wider public.
We will continue to engage the community with whom we conduct research through health research awareness activities, and establish a community advocacy programme to extend the work of CIDRI-Africa’s Community Advisory Group. Members of the advocacy programme will bridge research and non-research communities, providing input to both and effectively advocating tuberculosis and HIV research.
We will engage young people through our school’s engagement project, drawing on methods from a previous pilot. This will follow a workshop format, and improve understanding amongst school learners and the people they connect with of tuberculosis and HIV as well as research into these conditions.
|
| 30/09/2020 |
£1,471,193 |
|
UNIVERSITY OF CAPE TOWN |
The Centre
1. Fosters investigator-led approaches with the overarching scientific objective of combating infection, especially HIV-1 and tuberculosis, through epidemiological, clinical and laboratory research.
2. Supports research on the interaction between communicable and non-communicable diseases, especially where the latter impact susceptibility to infection, or arise as a consequence of infection.
3. Improves understanding and management of the challenges of antiretroviral therapy (ART) such as metabolic complications and antiretroviral drug resistance.
In its first 2.5 years the Centre has been strikingly successful, with Centre facilities and expertise contributing to multiple successful investigator and fellowship submissions that already exceed the value of the Centre award itself. The Centre is a cross-cutting, dendritic organisation promoting the values and mission of Wellcome via its meetings, investigator support, platforms and provision of core services. It is an integral part of Faculty and Institute life and has disproportionately high influence in research and engagement strategy and in the development of a healthy research culture. Its brand is highly positive and prestigious. A very strong commitment to individual investigator development, University and national transformation goals and to internationalisation, particularly within the context of African science and development, will remain core to the mission.
|
| 30/09/2020 |
£1,579,167 |
|
UNIVERSITY OF MANCHESTER |
Matrix accounts for two-thirds of total protein mass and provides the scaffolds necessary for cell function and tissue health. Consequently, matrix dysregulation is central to ageing and the pathogenesis of major human chronic diseases affecting all organ systems. Discoveries in the Centre have shown that synthesis and degradation of matrix is under circadian clock control, we have identified immunomodulatory pathogen proteins that tether to the matrix during gut infection, and have identified specialised adhesion complexes that mediate cell migration, division and attachment to matrix. We are learning how to regulate matrix synthesis, have unravelled the disease mechanism in a chondrodysplasia, and developed a biologic for the treatment of osteoarthritis and dry eye disease. These, and other Centre discoveries described below were only possible when researchers with complementary approaches worked together in a collaborative environment underpinned by exceptional core facilities. Importantly, we have learned the value of incorporating bioinformatics and mathematics into our research programmes. We are applying for a 2-year extension to our Core Award to implement predictive mathematical modelling, machine learning, and bioinformatics throughout the Centre, maintain our Core Facilities and make ground-breaking discoveries that underpin all of biomedical research and translation combined with a strong public involvement programme.
|
| 30/09/2020 |
£2,369,302 |
|
NEWCASTLE UNIVERSITY |
Our mission is to transform the lives of patients with mitochondrial disease.
The key aims of our Centre are to:
1. Understand the clinical course of patients with mitochondrial disease and how this relates to the underlying disease mechanisms
2. Delineate the molecular and genetic mechanisms causing mitochondrial disease
3. Develop techniques to prevent the transmission of mtDNA disease and improve treatment for patients with mitochondrial disease.
The training aims of our Centre are to:
1. Provide the optimum training opportunities for all postgraduate students including our MRes programme in Mitochondrial Biology
2. Ensure the continued professional development of all staff in the Wellcome Trust Centre for Mitochondrial Research.
The public and policy engagement aims of our Centre are to:
1. Engage with patients and their carers to ensure that research in the Centre is responsive to their needs
2. Engage with policy makers and clinicians ensuring our research discoveries that lead to improved care are made available for all patients with mitochondrial disease.
|
| 30/09/2020 |
£52,181 |
|
MERCK SHARP & DOHME |
Malaria is one of the world's most devastating diseases of humans and results in over 450,000 deaths annually. Novel therapies are urgently required to populate the antimalarial clinical portfolio, as the current therapeutics that treat this disease are becoming less effective due to emerging resistance. A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA (known as MSD outside the US and Canada) and Professor Alan Cowman from the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria aspartyl protease enzymes are an attractive drug target, as they perform essential functions for survival in blood, sexual and liver stages of the parasite life cycle. Through screening aspartyl protease inhibitor libraries, the collaboration has identified novel drug-/ike hit compounds that are potently active against the malaria parasite. The proposed research aims to increase potency against the parasite whilst maintaining selectivity, progressing to a lead optimisation stage discovery program. |
| 30/09/2020 |
£52,181 |
|
WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH |
Malaria is one of the world's most devastating diseases of humans and results in over 450,000 deaths annually. Novel therapies are urgently required to populate the antimalarial clinical portfolio, as the current therapeutics that treat this disease are becoming less effective due to emerging resistance. A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA (known as MSD outside the US and Canada) and Professor Alan Cowman from the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria aspartyl protease enzymes are an attractive drug target, as they perform essential functions for survival in blood, sexual and liver stages of the parasite life cycle. Through screening aspartyl protease inhibitor libraries, the collaboration has identified novel drug-/ike hit compounds that are potently active against the malaria parasite. The proposed research aims to increase potency against the parasite whilst maintaining selectivity, progressing to a lead optimisation stage discovery program. |
| 30/09/2020 |
£69,533 |
|
EXONATE LIMITED |
Exudative age-related macular degeneration (wAMD) and diabetic macular oedema (DME) are the leading causes of blindness in the Western world. wAMD affects 1.3 per cent of people over 50 years old with a global incidence of 1. 5 million. Diabetes affects 382 million people worldwide, expected to increase to 592 million by 2035 and is the leading cause of severe vision loss in working age adults. Diabetic macular oedema is the major cause of visual loss in diabetic patients. Approximately 14% of diabetes patients develop DME and the prevalence increases to 29% (696, 000) for patients using insulin for more than 20 years. Current treatment options for these conditions are limited. Anti-Vascular Endothelial Growth Factor (VEGF) agents improve vision in some patients and slow its deterioration in most, but they must be administered by regular intravitreal injections and non-specifically block both pro-angiogenic and antiangiogenic isoforms of VEGF. There is therefore an incentive to develop a non-invasive therapeutic modality with efficacious and safe agents. Exonate has developed small molecules that inhibit production of proangiogenic VEGF through selective inhibition of Serine/threonine-protein kinase 1 (SRPK1)-mediated VEGF splicing. These inhibitors have already demonstrated superior efficacy as topical agents in preclinical models of wAMD. Thanks to the support of the Wei/come Trust, Exonate will take several of these inhibitors into an optimisation programme culminating in the nomination of a preclinical candidate drug with optimal characteristics for clinical development. The funded project will also involve the assessment of the candidate in regulatory toxicology and safety pharmacology studies to support an application to the regulatory authorities for clinical evaluation at the end of the funding. Exonate expects to reach this milestone and enter the clinic in early 2020. |
| 30/09/2020 |
£209,348 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2020 |
£218,456 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2020 |
£196,434 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 30/09/2020 |
£161,237 |
|
CARDIFF UNIVERSITY |
Huntington's disease is a fatal genetic disease characterised by a movement disorder that is accompanied by a decline in cognitive function and changes in mood and behaviour. The decline in cognitive function may precede the movement disorder by a decade or more and is a very important component of the functional disability associated with the disease. There is, however, no effective treatment for enhancing cognitive performance in Huntington's. Professor John Atack at the University of Sussex aims to identify novel drugs that can enhance cognitive performance in subjects with Huntington's disease to address a large unmet medical need. |
| 30/09/2020 |
£232,800,000 |
|
WELLCOME TRUST SANGER INSTITUTE |
Not available |
| 30/09/2020 |
£1,813,110 |
|
UNIVERSITY OF GLASGOW |
The Wellcome Centre for Integrative Parasitology (WCIP) has evolved through Trust support since 1987 into a world-leading and cutting-edge research hub. We now propose a further transformation to take us and the field forward through the integration of disciplines, locations and scales, to tackle disease problems in disease endemic regions (DER). Our 2014 renewal broadened our portfolio of pathogens and technologies and grew the Centre at every level. Our PI complement increased from 9 to 15, including numerous Fellowship and Investigator Award holders (6F/5M). World-leading recruits from Harvard, Oxford and Edinburgh together with young emerging (female) PIs radically extended the Centre’s activities. We have new programmes on immunology, helminths and their population structures, single cell bioinformatics, and clinical pathology of parasitic diseases. Technologically, we have expanded with dedicated technologists in both imaging and metabolomics, while internationally, fruitful engagement with Malawi has embedded Centre members in key areas such as paediatric malaria, epidemiology and enhanced training opportunities. Our strategic growth reflects the evolution of our vision from the intense, largely laboratory-based investigation of parasite biology into the integrated pursuit of WCIP-generated knowledge-based therapies positioned by informed interactions with Global Health stakeholders in Glasgow and selected partners across Europe and particularly DER.
|
| 30/09/2020 |
£94,780 |
|
CARDIFF UNIVERSITY |
Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications.
However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problem-solving that result in a “brain fog”. These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, “normal” life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion.
Professor Simon Ward from the University of Sussex has received a Seeding Drug Discovery Award to identify and develop drug which is a selective modulator of the AMPA receptor which has the potential to provide an innovative new treatment for patients with schizophrenia. If successful the team expect to have a compound ready for clinical evaluation in just over three years time.
Nerve cells (neurons) communicate with each other by releasing chemicals known as neurotransmitters that interact with proteins called receptors on adjacent neurons. Levels of the neurotransmitter glutamate, which is crucial for normal cognitive function, are altered in schizophrenia. A specific subtype of glutamate receptor, the AMPA receptor, is thought to be associated with cognition and therefore increasing AMPA receptor function should improve cognitive performance in schizophrenia and thereby addressing an unmet need and revolutionizing the functional outcome of this patient population. |
| 30/09/2020 |
£149,640 |
|
UNIVERSITY OF MANCHESTER |
The enzyme lysyl oxidase (LOX) regulates cross-linking of structural proteins in the extracellular matrix.
LOX also plays a role in stimulating the metastatic spread of cancer through the body. Its expression is increased in hypoxic cancers and is correlated with tumour metastasis and decreased patient survival. In model systems its inhibition significantly decreases cancer metastasis and increases survival. Since metastasis is responsible for over 90 per cent of cancer deaths these data validate LOX as an important therapeutic target in cancer.
Professor Caroline Springer and Professor Richard Marais from the Institute of Cancer Research have been awarded Seeding Drug Discovery funding to develop drugs that target LOX. They are applying a medicinal chemistry drug discovery approach underpinned by a strong programme in LOX biology with the aim of producing orally available, small molecular weight drugs that inhibit LOX activity for cancer treatment. |
| 30/09/2020 |
£99,998 |
|
UNIVERSITY OF EDINBURGH |
Human African Trypanosomiasis (sleeping sickness) is a neglected disease which is transmitted by tsetse flies. Without treatment death is inevitable and current drugs are poorly effective.
Professor Malcolm Walkinshaw of the University of Edinburgh and colleagues are working on developing a new drug for sleeping sickness based on understanding the biology of the T. brucei parasite that causes the disease. T. brucei gets its energy from the breakdown of glucose (glycolysis) obtained from host blood for survival. The proteins used for this process (so-called glycolytic enzymes) provide the parasite with its only source of energy (ATP molecules).
The compounds already identified in this project have been shown to kill the parasite by specifically inhibiting glycolysis. High throughput screening against one of the glycolytic enzymes (PFK) identified three chemically different families of inhibitors each capable of killing T. brucei parasites. The objective of this project is to design and synthesise related compounds to improve potency so that very low (nanomolar) concentrations of compound are needed to kill parasites. |
| 30/09/2020 |
£53,847 |
|
MQ TRANSFORMING MENTAL HEALTH |
Interest payable to MQ |
| 30/09/2020 |
£10,000,000 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
Not available |
| 30/09/2020 |
£2,573,099 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2020 |
£8,780,116 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2020 |
£715,680 |
|
IMPERIAL COLLEGE LONDON |
Malaria kills half a million children each year. Despite decades of investment, there is still no efficacious vaccine. To date, the best protection achieved against malaria came from injecting volunteers with live parasites, attenuated so they don't cause disease. However, translation of this approach has performed poorly in field trials, largely because of the laborious nature of isolating pure parasites from mosquitoes, a process that requires skilled manual dissection. We have developed a revolutionary, dissection-independent process for malaria parasite isolation, extracting them from thousands of pulverised, infected mosquitoes. This scalable method produces pure, highly-infectious parasites that offer robust immune protection. Here we propose to advance this technology into a pipeline for parasite purification, vaccine formulation and vaccine production that has potential for good manufacturing production. By reducing costs and improving the effectiveness of whole-parasite vaccines we aim to reinvigorate malaria vaccinology providing a pathway for protecting children from disease. |
| 01/09/2020 |
£15,653,620 |
|
ACADEMY OF MEDICAL SCIENCES |
The Academy of Medical Sciences’ mission is to advance biomedical and health research and its translation into benefits for society. The vision set out in this proposal is central to our strategy to create a diverse workforce of researchers to advance scientific discovery and to generate and optimise improvements in health.
Drawing on our strengths of breadth, connectivity and unparalleled career support activities, over the next five years we will:
Support researchers’ transition to independence by enhancing our Starter Grants for Clinical Lecturers and Springboard for Biomedical Researchers schemes
Promote health innovation with new programmes that support greater cross-disciplinary and pan-sector connectivity and collaboration by researchers
This proposal will enable us deliver a platform of cohesive, innovative activities that enhance research career pathways and achieve wider positive impacts on diversity and research culture. Our proven track record in galvanising action across the sector and leveraging further funding will drive greater coordination and effort across the UK’s university, healthcare and industry sectors.
In five years’ time we will have created mechanisms and a regional infrastructure that will equip and support cohorts of excellent researchers and future leaders to work collaboratively and proactively in addressing societal health challenges.
|
| 30/07/2020 |
£1,560,998 |
|
UNIVERSITY OF EXETER |
The project pioneers a new history of global health that, for the first time, incorporates the socialist world - a constellation of countries in a fluctuating political, economic and military nexus distinct from the capitalist West. It identifies the particular health cultures produced by socialism (in all its variety) and explores the impact of socialist internationalism in co-producing global health in the 20th century. This project offers a radical new account that will not only transform our knowledge of historical processes, but will further our understanding of ideas, practices and processes that current global health structures have been built on.
Global health histories are framed mainly through American, colonial and liberal perspectives. The omission of socialist contexts, however, distorts our understanding of what global health is. Although there was not one socialist template, diverse framings of socialist medicine played major roles in shaping and contesting global practices.
A systematic analysis of socialist medicine and international health through global case studies integrates missing expert networks, political agendas, public health models and diplomatic agreements in global health history. This work, in turn, allows us to rethink concepts such as socialism, solidarity, development, socialist medical research and health provision.
|
| 30/07/2020 |
£599,638 |
|
UNIVERSITY OF EDINBURGH |
This study investigates the biosocial conditions that frame the persistence of rabies as a public health concern in India to rethink One Health approaches in post-anthropocentric directions. Dog-mediated rabies in Asia and Africa is a priority in transnational public health, and One Health approaches have scientific consensus as being key to its prevention (WHO 2019). India has the highest burden of human rabies globally despite long-standing initiatives, including One Health, on rabies elimination. Our project addresses this impasse.
Challenging the (post)colonial One Health conceptualisation of street dogs as out-of-place disease vectors, our analytical framework of multispecies cultures directs new inter-disciplinary attention to the lived experiences of human and nonhuman animal actors, and to multiple dimensions of people-street dog relations in urban and rural India. We will examine historical and contemporary transnational influences on dog-related public health agendas; public attitudes and knowledge; everyday interactions between people, dogs, and the biophysical environment; and institutional interventions to advance decolonial concepts and practices for healthy multispecies societies. Through this fresh approach to rabies, we will reframe how One Health is theorised and pursued, and reconfigure it to enable more equitable approaches to health in a world marked by multispecies risk and vulnerability.
|
| 30/07/2020 |
£238,110 |
|
UNIVERSITY OF TECHNOLOGY, SYDNEY |
This study investigates the biosocial conditions that frame the persistence of rabies as a public health concern in India to rethink One Health approaches in post-anthropocentric directions. Dog-mediated rabies in Asia and Africa is a priority in transnational public health, and One Health approaches have scientific consensus as being key to its prevention (WHO 2019). India has the highest burden of human rabies globally despite long-standing initiatives, including One Health, on rabies elimination. Our project addresses this impasse.
Challenging the (post)colonial One Health conceptualisation of street dogs as out-of-place disease vectors, our analytical framework of multispecies cultures directs new inter-disciplinary attention to the lived experiences of human and nonhuman animal actors, and to multiple dimensions of people-street dog relations in urban and rural India. We will examine historical and contemporary transnational influences on dog-related public health agendas; public attitudes and knowledge; everyday interactions between people, dogs, and the biophysical environment; and institutional interventions to advance decolonial concepts and practices for healthy multispecies societies. Through this fresh approach to rabies, we will reframe how One Health is theorised and pursued, and reconfigure it to enable more equitable approaches to health in a world marked by multispecies risk and vulnerability.
|
| 30/07/2020 |
£338,768 |
|
UNIVERSITY OF WESTERN AUSTRALIA |
This study investigates the biosocial conditions that frame the persistence of rabies as a public health concern in India to rethink One Health approaches in post-anthropocentric directions. Dog-mediated rabies in Asia and Africa is a priority in transnational public health, and One Health approaches have scientific consensus as being key to its prevention (WHO 2019). India has the highest burden of human rabies globally despite long-standing initiatives, including One Health, on rabies elimination. Our project addresses this impasse.
Challenging the (post)colonial One Health conceptualisation of street dogs as out-of-place disease vectors, our analytical framework of multispecies cultures directs new inter-disciplinary attention to the lived experiences of human and nonhuman animal actors, and to multiple dimensions of people-street dog relations in urban and rural India. We will examine historical and contemporary transnational influences on dog-related public health agendas; public attitudes and knowledge; everyday interactions between people, dogs, and the biophysical environment; and institutional interventions to advance decolonial concepts and practices for healthy multispecies societies. Through this fresh approach to rabies, we will reframe how One Health is theorised and pursued, and reconfigure it to enable more equitable approaches to health in a world marked by multispecies risk and vulnerability.
|
| 30/07/2020 |
£326,834 |
|
UNIVERSITY OF LIVERPOOL |
This study investigates the biosocial conditions that frame the persistence of rabies as a public health concern in India to rethink One Health approaches in post-anthropocentric directions. Dog-mediated rabies in Asia and Africa is a priority in transnational public health, and One Health approaches have scientific consensus as being key to its prevention (WHO 2019). India has the highest burden of human rabies globally despite long-standing initiatives, including One Health, on rabies elimination. Our project addresses this impasse.
Challenging the (post)colonial One Health conceptualisation of street dogs as out-of-place disease vectors, our analytical framework of multispecies cultures directs new inter-disciplinary attention to the lived experiences of human and nonhuman animal actors, and to multiple dimensions of people-street dog relations in urban and rural India. We will examine historical and contemporary transnational influences on dog-related public health agendas; public attitudes and knowledge; everyday interactions between people, dogs, and the biophysical environment; and institutional interventions to advance decolonial concepts and practices for healthy multispecies societies. Through this fresh approach to rabies, we will reframe how One Health is theorised and pursued, and reconfigure it to enable more equitable approaches to health in a world marked by multispecies risk and vulnerability.
|
| 30/07/2020 |
£398,900 |
|
UNIVERSITY OF WARWICK |
Around 1900 a new classificatory system appeared to eliminate puerperal insanity from the psychiatric canon. However, as this project will illuminate, far from disappearing from psychiatric practice, mental hospital admissions under this category actually increased, while maternal mental illness was frequently drawn on in constructing defence pleas in infanticide trials. Exploration of postnatal mental illness offers a superb opportunity to understand the relationship between psychiatric theory and practice across the twentieth century, how psychiatric categories were defined, understood and implemented, and how they both adapted to and helped create new service provisions and treatments. The project will also explore how broader social and cultural factors, including attitudes towards motherhood and women’s changing status, especially in relation to their alleged bodily and reproductive autonomy, was reflected in interpretations of postnatal mental illness. Existing at the ‘borderland’ of psychiatry and obstetrics, the project will investigate the energetic and on-going debates on causality, that became increasingly complex with the involvement of an expanding range of health professionals and campaign organisations in the second half of the century. Finally the project will explore how public and media responses and the experiences of sufferers can enhance our understanding of postnatal mental illness in the past.
|
| 30/07/2020 |
£701,588 |
|
UNIVERSITY OF OXFORD |
Despite policy changes and advocacy efforts to promote the inclusion of women as participants in research and to advance a global agenda of women’s sexual reproductive health over the past two decades, women remain significantly underrepresented in biomedical research and its translational outputs beyond reproductive health. In this empirical ethics project, we will investigate the reasons why structural barriers to women’s health improvements persist within the practices of research itself—in how research is designed, conducted, and translated. More deeply, we will interrogate the role that implicit and explicit moral attitudes, beliefs and arguments play in making the case for a focus on women’s and girl’s health needs, and in the reactions to these priority-setting appeals in academic, policy, and social media domains. Taken together this work aims to make a significant contribution to evidence-based advocacy within biomedical research practice, transforming how researchers think and do research with and for women and girls.
|
| 30/07/2020 |
£648,234 |
|
UNIVERSITY OF MANCHESTER |
In contemporary Kazakhstan, Kyrgyzstan and Tajikistan, involuntary childlessness is a source of immense social stigma, addressed through a heterogeneous therapeutic landscape including shrines and sacred sites, Soviet-era sanatoria, and newly-opened fertility clinics. Central Asian states are positioning themselves as international ‘reprohubs’ (Inhorn) offering fertility treatment within strict conjugal confines to growing Chinese, European and local markets for Assisted Reproductive Technologies (ARTs). This configuration has generated intense public debate about the ethics of medically assisted reproduction, specifically concerning the intensified movement of people, gametes and technologies across borders. Through a tripartite focus on sites of reproductive care, itineraries of reproductive assistance, and debates about the (bio)ethics of emergent reproductive technologies, this project will illuminate how different models and practices of reproductive care are debated and used by individuals and couples to address infertility in stratified and rapidly-marketizing medical landscapes. Immersive ethnographic fieldwork will reveal how biomedical interventions to address infertility are incorporated into wider repertoires of healing practices and will examine how ARTs appear as objects of policy intervention, legal regulation, and religious commentary in emerging reproductive markets. In so doing, it will advance our understanding of involuntary childlessness, therapeutic landscapes, and the social ramifications of both in the global South.
|
| 30/07/2020 |
£650,069 |
|
KING'S COLLEGE LONDON |
Epidemiological efforts to map cancer in sub-Saharan Africa have a long history, playing an important role in how the disease has been imagined in the region. In the late colonial and early postcolonial period, British and French doctors produced small-scale epidemiological maps to advance understandings of cancer aetiology and improve treatment strategies at home. More recently, global surveillance initiatives seeking to rationalise health policy and planning in Africa have generated political atlases of the continent with national cancer burdens.
This project carries out an archival and ethnographic study of these epidemiological efforts to chart malignancy in sub-Saharan Africa over the past 70 years. It takes these cartographies of diseases as its object of study, examining their scientific, political and material conditions of possibility and analysing their influence on cancer imaginaries and healthcare policies in Africa. In doing so, the project aims to draw attention to the crucial role that epidemiological maps have played in the postcolonial history of biomedicine in Africa, while developing an innovative approach to epidemiological surveillance that highlights its socio-technical infrastructure and performative power. At the same time, the project also purports to move Africa out of the margins of the global history of cancer.
|
| 30/07/2020 |
£913,683 |
|
NEWCASTLE UNIVERSITY |
North and South: Regional Health Inequalities in England
The ‘north-south health divide’ in England is longstanding and persistent, documented both before and after the epidemiological transition. In the mid-19th century, life expectancies in northern cities were four years lower than in southern cities, and today, there is still a two-year difference in average life expectancy between the northern and southern regions.
However, there has been no thorough academic study of regional health inequalities, so we know little about the temporality, aetiology, experience, representation or perception of the ‘north-south health divide’. This oversight is becoming even more pressing given emerging evidence that health inequalities are increasing and that the north is falling further behind.
Using a novel, mixed-method, intensive, multi-disciplinary approach, the North and South project will fill this gap by providing the definitive account of the ‘north-south health divide’ and regional inequalities in health in England – contextualised within the wider European experience.
By drawing on concepts, data and methods from geography, epidemiology, sociology, history, social policy and literary studies, the project will enhance our understanding of the ‘north-south health divide’; provide insights into how to close it; and advance the international health inequalities field empirically, methodologically, and conceptually.
|
| 21/07/2020 |
£378,655 |
|
UNIVERSITY OF MANCHESTER |
Prosthetic Embodiment investigates what it means to live – and live well – with prostheses. Adopting a historical approach, informed by critical medical humanities and disability studies, and focusing on artificial legs and their users, this globally sensitive project will be the first to consider how the experience of prosthetic embodiment has changed, from the 1970s through to the present. For people to use and live healthy lives with prosthetic legs, collaboration with those who make and fit them is vital. Through an innovative combination of historical approaches and visual anthropology, this study explores the agency and materiality of users, health professionals and technologies, following the relations between them in terms of prosthetic design, fitting, use, and recycling. A central question to be investigated is how practicalities of lives and bodily experiences are negotiated and renegotiated as users learn to live with new prostheses, and once again when devices are recycled through charitable organisations to new users in the global south. Exploring the diverse embodiment of people with limb difference will reveal important insights into how prostheses create both new possibilities and unexpected constraints on day-to-day living, and the experience of disability and medical technology more generally.
|
| 21/07/2020 |
£245,249 |
|
UNIVERSITY OF CAMBRIDGE |
High prices of new medicines have led most European countries to set up health technology assessment (HTA): evidence-based processes that evaluate whether a drug’s benefits outweigh its costs, before it receives public funding. Yet, increasingly, expensive new medicines bypass this scrutiny. Instead, they enter health systems through alternative access schemes: diverse provisions that provide patients with access to treatment that are not routinely funded – for example the English Cancer Drugs Fund or individual patient funding requests. As a result, some drugs, including notably expensive cancer medicines, are prescribed even though they never demonstrated their "value for money" in HTA, reaching up to 5% of pharmaceutical budgets in some countries. Despite evidence of their growing significance, there is little systematic research on alternative access schemes.
This project seeks to understand why alternative access schemes emerged, how decisions in these schemes are made, and what the policy implications are for patients and public finances. It systematises knowledge of this emerging phenomenon by providing an overview of alternative access schemes in Europe and a detailed analysis of their political economy in selected health systems. It will contribute to debates on affordability of new medicines.
|
| 21/07/2020 |
£174,702 |
|
UNIVERSITY OF OXFORD |
Patients’ 'best interests' are important in healthcare, but their use faces challenges:
Resource allocation: As well as aggregate measurements like population health, healthcare resource allocation should be sensitive to individual patients' claims. The idea of best interests provides limited guidance here, since resource constraints mean we cannot promote everyone's best interests.
Value disagreement: Caring for patients who cannot communicate preferences – including infants – often generates fundamental value disagreement between carers and medical professionals over their best interests.
My proposal explores whether a principle of sufficiency - the idea that it is particularly important to prevent people from being very badly off - can help. Sufficiency has received renewed attention in political philosophy; my research will build on recent theoretical advances, developing a theory that is responsive and applicable to practical challenges.
Goals
Systematically outline challenges to best interests and existing work on sufficiency;
Generate a novel sufficiency-based approach that can be used in healthcare decisions;
Consider challenges and develop recommendations for two related practical issues: resource allocation and the care of critically ill infants;
Publish 12 peer-reviewed journal articles;
Disseminate research findings via websites and public-engagement activity at Oxford;
Host a workshop on the role of sufficiency in healthcare.
|
| 21/07/2020 |
£236,313 |
|
UNIVERSITY COLLEGE LONDON |
A recent, unprecedented influx of migrants to Peru means that roughly 3% of the country’s population are now of Venezuelan origin, with an estimated 1,700+ living with HIV. The focus of this research will be the social, medical, and legal aspects of ‘belonging’ for migrants in situations of medical precarity. This will be achieved by exploring the processes whereby these refugees access HIV-related medical-care and legal-migratory status, integrate into the wider Peruvian community, and interact with a biomedical system troubled with intersections of race, racisms, and xenophobia at a transformative moment in the history of Peru with never-before-seen mass- immigration from a Caribbean to an Andean nation.
In order to address this focus, the key research goals will be to:
Investigate how HIV-positive Venezuelans negotiate ‘pharmaceutical citizenship’ (citizenship dependent on pharmaceutical compliance (Ecks,2005)) and receipt of Anti-retroviral therapy (ART).
Interrogate actual and potential integration into biosocial communities (social-kinship based upon shared bio-factors (Young,2016)) based upon HIV-positivity.
Query the intersections of racism and biomedicine when seeking HIV/AIDS-related health care for migrants.
Research for this project will involve 18-months ethnographic fieldwork in Lima, Peru with migrants and stakeholders, and will transform our understandings of migrant health, race, and ‘belonging’.
|
| 21/07/2020 |
£231,432 |
|
UNIVERSITY OF OXFORD |
New ‘pathogen sequencing technologies’, which have the power to identify and describe infectious disease transmission networks, are transforming public health practice. They also raise practically important ethical questions (for example regarding privacy protection), as-well-as conceptual and normative questions concerning responsibility for disease transmission, blame and the obligations of various actors.
This empirical bioethics study will combine qualitative research with normative ethical analysis to develop an account of ethical practice in the use of technologies that can identify and describe infectious disease transmission networks.
This will be achieved by answering the following research question:
What are expert and lay views on the potential social consequences and ethical risks of identifying transmission networks through the use of pathogen sequencing technologies?
What ethical norms concerning transmission of infectious disease underpin these views?
How do the concepts of personal responsibility, blame and obligation bear on the ethics of using pathogen technologies to identify and describe infectious disease transmission networks?
What contextual factors influence ethical norms and ethical practice in this area?
|
| 21/07/2020 |
£245,971 |
|
UNIVERSITY OF YORK |
This Fellowship will explore the intersection of contemporary marginality, ethnicity and mental health through an integrative mixed methods study of the prevalence, causes, and lived experience of food insecurity in the UK.
The goals are to:
understand variations in the prevalence and socio-demographic correlates of food insecurity, and its interaction with mental health, among UK ethnic groups
understand how different ethnic groups conceptualise ‘food insecurity’ and how this shapes its interaction with their mental health
understand ethnic variations in the lived experience of food insecurity, including food bank use, and its interaction with mental health
theorise the nexus of marginality, ethnicity and health in post-industrial Britain
provide a platform for mixed-methods, longitudinal analyses of food insecurity.
The Fellowship is composed of two interlinked studies, integrated within a new theoretical framework on contemporary marginality. Study 1 employs Qualitative Longitudinal Research methods (N=30) over two years to explore the experience of food insecurity, the contingent nature of ethnicity, and the interaction of food insecurity, ethnicity and mental health.
Study 2 will estimate the prevalence, socio-demographic correlates and mental health causes and consequences of food insecurity and food bank use among UK ethnic groups, using existing and commissioned national and local survey data.
|
| 14/07/2020 |
£4,000,000 |
|
UNIVERSITY OF EDINBURGH |
I propose to study how a set of key proteins (condensins I/II, cohesin, Kif4A, topo IIalpha) mold the chromatin fibre into its characteristic rod-shaped helix of loops in mitosis. Using a transformative system allowing us to obtain cultures entering mitosis with near-perfect synchrony we will adopt an interdisciplinary approach involving genomics (Hi-C, Capture-C, cut & run), proteomics, crosslinking, microscopy and molecular modelling to resolve changes in chromatin fibre and chromosomal protein organisation on a minute-by-minute basis during mitotic entry. Using non-toxic synchrony methods plus acute (and reversible) protein depletion with auxin degrons, we will determine when, where, how and with whom these proteins act to shape mitotic chromosomes. Access to the single copy chicken Z chromosome with its unique-sequence centromere allows us unprecedented mapping of the chromatin folding and protein distribution at a vertebrate centromere during this process. Following our discovery that RNAs mediate assembly of the mitotic chromosome periphery compartment (MCPC) downstream of Ki-67, we will initiate a new research direction identifying the proteins and RNAs involved, and determining their functional significance for chromosome segregation. Lastly, we will optimise methods for isolating human artificial chromosomes (HACs), avoiding unwanted DNA rearrangements that endanger future synthetic genome efforts.
|
| 14/07/2020 |
£3,640,891 |
|
UNIVERSITY OF CAMBRIDGE |
Programmed axon degeneration (or Wallerian degeneration; WD) is a preventable and druggable mechanism of axon loss. WD is well-characterised in animals and highly conserved. Blocking WD alleviates axon loss and symptoms in multiple disease models, suggesting a common, downstream mechanism. Human data are essential to confirm the role of WD in specific human diseases, ensuring drugs under development are tested in highly-relevant disorders and patients. We reported mutations in rare human axonopathies that aberrantly activate WD, and lifelong rescue of a related mouse model. Our programme determines the wider involvement of WD in rare and common human disorders, specifically peripheral neuropathies and ALS, where axon degeneration is important. We use online resources (100,000 Genomes, Project MinE, UK Biobank, etc.) and targeted sequencing of well-phenotyped cohorts and test roles of gene variants in causation, risk and severity. We determine their functional impact using complementary human iPSC and mouse modelling and develop specific biomarkers of WD for clinical samples. This project will provide insight into pathogenic mechanisms and a firm platform for developing and testing therapeutics. Our team, a world leader in Wallerian degeneration and leading neurogeneticists in rare and common neuropathies and human iPSC modelling, is uniquely placed to deliver this.
|
| 14/07/2020 |
£1,409,484 |
|
IMPERIAL COLLEGE LONDON |
The last decade has witnessed substantial declines in the global burden of malaria; however, in recent years progress has stalled. We aim to combine a mathematical modelling framework with economic analyses to gain insight into the optimal global, regional and country strategies to achieve the ultimate aim of malaria eradication. Specifically:
What is the optimal strategy to achieve malaria eradication? Should resources initially focus on high burden countries, elimination countries or a balance between these? How does this change as burden and transmission decline? How do competing aims in the short-term (e.g. the need to reduce morbidity and mortality) hamper achieving longer-term eradication aims?
What is the trade-off between country priorities and regional and global strategies? How do competing national priorities determine regional and global success? What degree of international cooperation is needed and at what scale? What are the economic benefits and costs of co-operation to countries?
How are strategies influenced by the wider political economy? How do competing priorities influencing national decision makers impact wider eradication efforts? How does weak governance and political constraints in national and international decision-making reduce the effectiveness of strategies?
|
| 14/07/2020 |
£1,555,838 |
|
UNIVERSITY COLLEGE LONDON |
The lymphatic vasculature is essential for health in vertebrates. Alongside roles in tissue fluid balance, cholesterol transport and immunomodulation, lymphatic vessels possess remarkable organotypicity, which underpins organ-specific lymphatic functions during embryonic development, health and disease.
Using the mammalian kidney as a model system, I will study two concepts responsible for the organotypicity of lymphatics: the cellular sources of lymphatic endothelial cells and molecular crosstalk between lymphatics and epithelia, a paradigm that may be applicable to other organs like lung and gut. I will focus on these processes in embryonic development, health and polycystic kidney disease (PKD); the most common genetic renal disorder, which features dysfunctional lymphatics. I will use several emerging technologies including high-resolution three-dimensional imaging, single-cell RNA sequencing, novel in vivo imaging modalities, targeted kidney delivery of therapeutics and computational modelling.
The insights arising from these experiments in this Investigator Award will enhance our understanding of lymphatic biology in kidney development, physiology and disease; areas in which the contribution of lymphatics is poorly understood. The findings will provide new directions and tools for understanding and manipulating lymphatic function in organogenesis, health and multiple disease processes.
|
| 14/07/2020 |
£2,276,736 |
|
UNIVERSITY OF OXFORD |
The goal of this proposal is to transform our understanding of both the molecular mechanisms and the pathophysiological roles of members of the rhomboid-like superfamily. At the mechanistic level, our long-term research into this group of polytopic membrane proteins has led us to the hypothesis that the core function of the rhomboid-like domain is specific TMD recognition of substrates (of the rhomboid intramembrane serine proteases) and clients (of the non-protease members of the clan). Using a structural and biochemical approach, we seek to understand the molecular details of how this specific recognition is achieved.
Biologically, rhomboid-like proteins have many functions, but we still have little understanding of their role in mammals, particularly of the rhomboid proteases. Building on our mechanistic aims, we plan to break this log-jam by pioneering systematic methods of substrate identification. We already know that iRhoms, catalytically inactive homologues of rhomboids, regulate inflammation, growth factor signalling and, as we have recently discovered, tumour growth. We plan to further elucidate these roles, both at the level of fundamental cell biology but also with a goal to reveal their potential medical significance. By the end of this work we expect to know which rhomboid-like proteins are useful therapeutic targets.
|
| 14/07/2020 |
£1,636,956 |
|
UNIVERSITY COLLEGE LONDON |
This proposal aims to understand how neural networks for memory emerge during post-natal development, both during normal development and following early-life brain damage.
Episodic memories (memories of events and their spatio-temporal context), and generalised learning such as semantic memories (factual world-knowledge) are supported by different brain networks. Episodic memories are thought to be encoded initially by the hippocampus, whilst general knowledge would be extracted by integrating across experiences via hippocampus-neocortical interactions.
However, the ontogenetic unfolding of memory runs counter to this framework. Early development is characterised by the rapid acquisition of general knowledge, despite amnesia for specific events. Furthermore, sustaining early-life hippocampal damage results in dense amnesia for specific episodes, but general learning is relatively preserved.
We aim to resolve this apparent paradox by studying neural circuit activity in vivo, in conjunction with behaviour, in developing rodents.
Our goals are to:
1) Understand the development of hippocampal mechanisms supporting the generation of memory traces of specific events;
2) Understand the neural mechanisms that enable the association of items with their spatio-temporal context (episodic memory processing);
3) Discover how neural coding for generalised knowledge emerges across cortical-hippocampal networks during normal development, and identify networks supporting preserved learning after early-life hippocampal damage.
|
| 14/07/2020 |
£654,391 |
|
IMPERIAL COLLEGE LONDON |
This proposal concerns the identification of genetic polymorphisms which alter the fitness of Human Immunodeficiency Virus (HIV-1), the robust estimation of virus fitness, and the characterization of how polymorphisms influence replicative fitness within hosts versus transmission to new hosts.
HIV evolves to evade the immune system, resist antiviral medications, and maximize its rate of replication within infected hosts. But at the epidemic level, natural selection promotes evolution of variants which are more transmissible. Natural selection within and between hosts can act in opposing directions, and evolutionary trends have been discerned from population based sampling of HIV such as a hypothetical transmission/virulence tradeoff. Because HIV evolves at multiple scales, the fitness of a particular polymorphism should be characterized along multiple dimensions including its impact on replication within hosts and transmission to new hosts. We will develop a framework for characterizing genetic fitness along multiple dimensions by building on theory developed for estimating state-dependent speciation rates. These methods will be applied to several large population-based samples of whole-genome deep sequencing (WGDS) of HIV. The outcome of this analysis will be an unprecedentedly detailed characterization of how particular genetic substitutions influence HIV pathogenesis and transmission at the epidemic level.
|
| 14/07/2020 |
£1,666,180 |
|
TECHNICAL UNIVERSITY OF MUNICH |
‘First contact’ between Bifidobacterium and their infant host represents a critical developmental window.
Our studies show that supplementation with Bifidobacterium isolates that metabolize breastmilk positively influences the preterm infant microbiota. We have also shown that: full-term infants have mini-bifidobacterial ecosystems that form dietary (breastmilk) cross-feeding networks; that geographically-separated infants harbour Bifidobacterium isolates with key differences in genomic content, and that particular Bifidobacterium genetic variants drive beneficial immune programming.
Building on our established findings and preliminary data, bringing together global maternal-infant cohort samples and using integrated multi-disciplinary approaches, we will:
Genetically characterise geographically distinct intra- and inter-infant Bifidobacterium populations
Profile geographically divergent maternal breastmilk samples, link them to genetic and phenotypic variation in Bifidobacterium, and define novel breastmilk metabolism pathways.
Determine how different Bifidobacterium communities influence immune responses, and how this relates to vaccine-related immunity.
We will significantly expand our fundamental knowledge by elucidating how Bifidobacterium species and genetic variants co-operate within an early-life diet (breastmilk) environment and define ‘signatures’ across different geographical regions. In a direct link to infant health, we will probe how these communities alter immune system development and vaccination responses. A fundamental understanding of these features will allow selection of Bifidobacterium-communities for next-stage translational projects.
|
| 14/07/2020 |
£2,258,810 |
|
UNIVERSITY OF EDINBURGH |
Atopic eczema is an itchy condition characterised by skin barrier dysfunction and inflammation. It frequently causes chronic morbidity, but a subset of cases enter long-term remission, demonstrating that resolution may be a tractable therapeutic aim.
Eczema is highly heritable. Null mutations in FLG are the strongest genetic risk and a locus on chr11q13.5, for which the nearest gene is EMSY, has a multiplicative effect. We have shown that EMSY is a transcriptional regulator in skin, controlling multiple aspect of barrier formation.
We will investigate molecular mechanisms at these two major risk loci: chr1q21.3 (FLG, FLG-AS1 and related genes) and chr11q13.5 (EMSY and LRRC32), aiming to define pathways contributing to eczema resolution. Findings will be tested in a well-characterised birth cohort (ALSPAC), to confirm clinical relevance.
Analyses of European cohorts (n > 25,000) show evidence of gene-environment interactions in eczema, but these findings require validation. We will use an optimised skin organoid model to investigate three environmental factors (tobacco smoke, wash-products and pet allergens) for which there is evidence of interaction with FLG genotype. Detailed functional and biochemical phenotyping will increase understanding of gene-environment interactions.
This work will inform eczema prevention strategies and characterise mechanisms contributing to eczema resolution, as future therapeutic targets.
|
| 14/07/2020 |
£1,374,681 |
|
KING'S COLLEGE LONDON |
We have identified bifurcation in human B cell development from shortly after bone marrow exit. B cells following one trajectory express high levels of IgM and have a gut-homing phenotype when in blood. They selectively migrate through gut and ultimately give rise to marginal zone B cells (MZB). The other branch expresses low levels of IgM and is systemic. All stages of the gut-homing branch are vastly depleted in the autoimmune disease lupus nephritis.
We will ask:
1. What drives the lineage split that commits a subset of developing B cells to migrate into GALT, and how does this fail in lupus nephritis?
2. What happens to MZB and their precursors in GALT?
3. Do MZB emergent from GALT enter spleen and respond to further tissue specific cues?
We will apply cutting-edge technologies to identify the epigenetic marks and transcriptomes that reflect the key events in vivo and use these to compare pseudotime developmental sequences. We will merge deep single cell phenotype in tissues with paired transcriptomes of single cells in suspension to create a multidimensional map of events in GALT, and track subsequent clone evolution across tissues.
This understudied area of basic immunology is fundamental to good human health.
|
| 14/07/2020 |
£1,776,461 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Malaria is predominantly a rural disease in Africa and whilst urbanisation is occurring rapidly it was thought unlikely to lead to substantial increases in malaria transmission because Africa lacks an urban-adapted malaria vector. However, Anopheles stephensi, a common and efficient urban malaria vector in South Asia and the Persian Gulf, has recently been found in the Horn of Africa, including Ethiopia and Sudan and is associated with a rise in malaria in Djibouti. This prompted the WHO to call for urgent action to control the spread of the vector. This proposal brings together biologists, epidemiologists, mathematical and geostatistical modellers and medical anthropologists with the aim of preventing the spread of An. stephensi in Ethiopia and Sudan. The research will: (i) investigate the distribution, routes of introduction/reintroduction and spread of An. stephensi; (ii) quantify the importance of An. stephensi for malaria transmission and iii) evaluate multi-sectoral vector control strategies. This incredibly timely research will quantify the threat posed by An. stephensi in Ethiopia and Sudan and identify control measures to reduce populations and combat further spread in Africa. Historic examples (e.g. An. gambiae in Brazil) demonstrate that without prompt action, invasive species can become established with massive impacts on morbidity/mortality.
|
| 14/07/2020 |
£1,395,744 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Hepatitis C infection can be cured by affordable drugs, leading to calls to expand treatment among the 70 million infected people worldwide. Many countries have initiated ‘test and treat’ programmes. e.g. India have reported treatment for ~40,000 patients in Punjab. However, 5-10% of infected people don’t respond and may develop viral resistance and go on to develop liver cancer. Salvage regimens are often unaffordable/unavailable.
We will address the remaining questions in hepatitis C therapy. We will work in Pakistan where hepatitis C is highly endemic (4.8% sero-prevalence) with regions reaching sero-prevalences of 10-20% (hot-spots). We will link with the government HCV programme to determine the most effective treatment for people who don’t respond to initial therapy. We will examine viral resistance in treatment failures to determine whether resistance dissemination is problematic and develop strategies to address it. We will determine whether some viruses are more oncogenic, allowing targeted surveillance. We will measure incident infection in the uninfected population (in hot-spot areas) and treated people, using modelling to determine what proportion of people must be cured to prevent disease recurrence. These data will inform the global elimination agenda and provide crucial data to develop optimised elimination programmes.
|
| 14/07/2020 |
£1,878,714 |
|
UNIVERSITY COLLEGE LONDON |
I propose a new overarching hypothesis that innate immune sensing of nucleic acids, cell cycle regulation, and a hitherto unappreciated function of endogenous viral elements, contribute to an integrated system of regulating inflammatory responses to infection. Encouraged by preliminary data we will investigate the relationship between cell cycle and innate immune sensing by manipulating cell cycle and measuring responses to infection and relating expression of endogenous viral elements to cell cycle and their activation of nucleic acid sensing. We will also study the mechanisms of lentiviral Vpx/Vpr proteins taking molecular genetic and structural approaches to examine their enhancement of viral expression, manipulation of endogenous element expression and inhibition of innate immune signaling. We will also investigate the role of G3BP1 stress granules and their role in coordinating nucleic acid sensing with regulation of translation by PKR, mediated through cyclophilins. Overall our approach is to manipulate cellular pathways, for example cell division, and test sensing responses or manipulate virus and measure activation of sensing or viral inhibition of sensing. We expect to reveal mechanisms of nucleic acid sensing that can be tractably inhibited therapeutically and provide new mechanistic knowledge of inflammatory pathways broadly relevant to infectious and inflammatory diseases.
|
| 14/07/2020 |
£1,690,786 |
|
KING'S COLLEGE LONDON |
In recent years, RNA dynamics in axons and dendrites have arisen as central to neuronal maturation and maintenance of healthy neuronal connectivity. However, the functional roles of transported mRNAs and their binding proteins are scarcely understood. Some of the proteins associated to local mRNAs are splicing factors and spliceosome proteins.
We recently demonstrated that their axonal role is complex, as, in developing neurons in vivo, the splicing factor SFPQ and the U1 spliceosome protein snRNP70 locally control axonal shape and connectivity, through modulation of the local transcriptome. These findings open two essential questions: how are these splicing proteins shaping the transcriptome landscape locally and what is the molecular nature of the axonal interactions between specific mRNAs and these two proteins?
Moreover, the recent findings of axonal and dendritic partially spliced mRNAs, retaining a single intron, open the additional question of the role(s) of intron-retaining transcripts in neurites and the possibility of direct functional interaction between retained introns and splicing proteins.
We propose to answer these essential questions, at cellular and molecular levels, using zebrafish developing neurons (in embryos and in culture) as experimental models.
|
| 14/07/2020 |
£2,530,384 |
|
UNIVERSITY OF EDINBURGH |
Despite major advances in our understanding of depression’s genetic architecture, there remain major gaps in our understanding of its environmental risk factors that impede prevention. Using studies of both related and unrelated individuals, I will identify the genetic changes and behaviours in those individuals that lead to depression in those individuals, as well as in their relatives. I will compare these changes with the genetic signatures of lifestyle factors (e.g. obesity) and behaviours, such as smoking and alcohol consumption, to identify if they are environmental risk factors for depression. In a complimentary approach, I will measure epigenetic changes in DNA methylation associated with depression and its risk factors. I will use optimise these epigenetic measures to improve the prediction of depression and the measurement of its risk factors. Finally, I will optimise the prediction of depression and its risk factors by applying these findings to prospective longitudinal dataset where depression and environmental risk factors have been measured on multiple occasions. These studies will be used to refine the accuracy of each predictor and estimate how it would behave in unseen samples of individuals, in whom it may be applied for prevention in future studies.
|
| 14/07/2020 |
£859,476 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Our discovery of Schistosoma haematobium hybrids co-infecting Malawian children exposes critical knowledge gaps in WHO’s preventive chemotherapy (PC) strategy for schistosomiasis. Our HUGS (hybridisation in urogenital schistosomiasis) study will generate robust evidence that best informs medical, veterinary and environmental sectors in schistosomiasis control and interruption of schistosome transmission. This 4-year multidisciplinary investigation will develop new molecular assays that quantify multihost transmission dynamics and zoonotic spill-overs. We will reveal which pre- or post-zygotic drivers facilitate saltatory hybrid evolution. HUGS is set out in four objectives [% allocation] that:
Obj-1 [25%]: Test if the proportion of hybrid co-infection is (non)uniform across two representative communities where S. haematobium-mattheei or S. haematobium-bovis occur, inclusive of household GPS mapping and identification of associated risk factors by questionnaire;
Obj-2 [45%]: Verify, in a 2-year longitudinal population follow-up study with annual PC, if the above proportions and spatial patterns of hybrid co-infection hold or alter in the two communities;
Obj-3 [15%]: Ascertain if there is any increased host morbidity (e.g. anaemia or urogenital disease) in hybrid co-infection(s) as measured by point-of-contact assays and portable ultrasonography;
Obj-4 [15%]: Reveal hybrid environmental transmission by malacological inspections, livestock tracking and abattoir surveillance, with advanced molecular typing of collected schistosome material.
|
| 14/07/2020 |
£1,628,077 |
|
UNIVERSITY OF CAMBRIDGE |
Protein synthesis is one of the most fundamental processes in all organisms. Due to the unique constraints under which RNA viruses evolve, non-canonical mechanisms are particularly prevalent in RNA virus gene expression. Thus, we are using viruses as a source for the discovery of novel gene expression strategies. We will leverage our expertise in computational biology to mine public transcriptomic datasets for 10000s of novel virus species, and use our expertise in virus comparative genomics and molecular biology to identify and characterize novel translational mechanisms. An important feature of the research strategy is close synergistic interaction between the bioinformaticians and experimentalists in my team, which allows us to efficiently investigate new discoveries.
Key goals are to:
Search ~120,000 RNA-Seq datasets for RNA virus-derived sequences from diverse host organisms from protists to mammals.
Use comparative genomics to predict novel cases of non-canonical gene expression.
Experimentally characterize the most interesting novel mechanisms.
Characterizing these exceptions to the rules of canonical translation will provide new insights into the mechanisms underlying protein synthesis, reveal new modes of cellular gene expression, and provide new tools for molecular biology research, biotechnology and synthetic biology. Thus the results will have broad applications in fundamental molecular biology.
|
| 14/07/2020 |
£1,882,059 |
|
THE FRANCIS CRICK INSTITUTE |
To maintain unlimited proliferative capacity, cancer cells must maintain their telomeres. ~85% of cancers achieve this by up-regulating telomerase, while the remaining ~15% of cancers employ the Alternative Lengthening of telomeres (ALT) pathway. Currently, there are no targeted treatments for ALT cancers, which have a poor prognosis and are universally aggressive. Insights into the mechanisms that promote/are essential for the ALT process may reveal vulnerabilities that could be exploited therapeutically. However, the lack of a cellular model that permits the induction of ALT has severely limited our ability to interrogate the underlying mechanisms. We have recently made a key discovery that Kaposi’s Sarcoma Herpes Virus (KSHV) infection triggers the stable acquisition of ALT. In this application, we will exploit KSHV to identify the host and virally encoded factors that are critical for ALT induction. Using PICh to interrogate the proteomic composition of telomeres, we have identified 703 proteins that are specifically enriched at ALT telomeres. We will perform a "703 ALT" CRISPR dropout screens to identify genes that modulate/are essential in ALT cancer cells but are dispensable in normal cells. Our proposal will expand our understanding of the ALT process and may identify critical vulnerabilities, which could be targeted therapeutically.
|
| 14/07/2020 |
£2,769,513 |
|
MRC LABORATORY OF MOLECULAR BIOLOGY |
Genetic code expansion enables the site-specific, incorporation of non-canonical amino acids (ncAAs) into proteins, and has enabled diverse biological discoveries. Most experiments incorporate ncAAs in response to amber stop codons. This strategy is limited to incorporating one type of ncAAs into a protein at a time, and there are no other natural blank codons that can be used for ncAA incorporation.
We synthesized a 4 Mb E. coli genome with a compressed genetic code, through the genome-wide substitution of three target codons by defined synonyms. The resulting cell, Syn61, uses 61 codons to encode the 20 canonical amino acids.
In Aim 1 we address the limitations of genetic code expansion by encoding multiple distinct ncAAs in response to blank codons in Syn61. This dramatically expands the applications of ncAA incorporation.
The recoding of Syn61 was based on the prior identification of a synonymous codon compression scheme (a rule that defines which codons to remove and which codons to replace them with). In Aim 2 and Aim 3 we systematically discover allowed synonymous codon compression schemes that we use to create deeply compressed synthetic genomes using accelerated genome synthesis methods. This creates more blank codons that may be reassigned to ncAAs.
|
| 14/07/2020 |
£1,104,076 |
|
UNIVERSITY OF BRISTOL |
The endocannabinoid system (ECS) acts as a negative feedback mechanism to suppress excitatory and inhibitory synaptic transmission. This is critically important for a wide range of brain functions including appetite, pain, and cognition. Moreover, ECS dysfunction is implicated in multiple neuropathologies, and there is increasing scientific and public interest in drugs that target the ECS, including medical marijuana.
The molecular organisation of the ECS is highly unusual because, in reverse to other neurotransmitter systems, endocannabinoids are released from the postsynaptic membrane to activate receptors at the presynaptic membrane. Despite its importance, remarkably little is known about how the enzymes and receptors essential for ECS ‘backwards’ transmission are targeted to, and retained at, opposing sides of the synapse.
Focusing on the primary cannabinoid receptor CB1R and the major endocannabinoid synthesising enzyme diacylglycerol lipase alpha (DAGLalpha) as prototypic examples, we will investigate the protein interactions and pathways that determine the architecture and organisation of the ECS.
Our goal is to define how the differentially polarised trafficking of ECS components to synapses is orchestrated.
This mechanistic knowledge of the ECS will advance understanding of neuronal protein polarisation and inform the design of future strategies to modulate ECS signalling for therapeutic benefit.
|
| 14/07/2020 |
£2,105,418 |
|
UNIVERSITY OF OXFORD |
Invasion of erythrocytes is one of the most critical steps in the life cycle of the malaria parasite. Prevent erythrocyte invasion, and we can prevent parasite growth, disease symptoms and transmission.
Essential for erythrocyte invasion is the PfRCR complex of Plasmodium falciparum, consisting of PfRH5, PfCyRPA and PfRIPR. This proposal will use structural insights to guide experiments to understand the function of PfRCR in erythrocyte invasion, and to guide development of future vaccines and therapeutic antibodies. Over the next five years, I will:
(i) Determine structures of PfRCR and PfRIPR and understand whether complex formation is necessary for invasion.
(ii) Understand molecular mechanisms of the most invasion-neutralising human antibodies targeting PfRH5, PfCyRPA and PfRIPR.
(iii) Determine how PfRH5 induces calcium flux in erythrocytes.
(iv) Use structural insights to design improved therapeutic monoclonal antibodies and vaccine immunogens targeting PfRCR.
These studies will deepen our understanding of this critical event in erythrocyte invasion. They will reveal the human antibody response to PfRCR vaccination and use this insight to guide design of the malaria therapeutics of the future.
|
| 14/07/2020 |
£1,201,563 |
|
IMPERIAL COLLEGE LONDON |
For 500 million years, vertebrates have retained three distinct lymphocyte lineages bearing rearranged receptors– alphabeta T-cells, B-cells, and gammadelta T-cells - suggesting that each compartment is critical to host immunity. We have a good understanding of classical alphabeta T-cells and B-cells but our knowledge of "unconventional" gammadelta T-cells lags far behind. There has been a recent explosion of interest in the gammadelta population and considerable excitement around their therapeutic potential. This is motivated by their unique recognition capabilities, their enrichment at sites of pathogen entry, and potent antimicrobial/antiviral/antitumour activities. Previously assumed to sit at the interface of innate and adaptive immunity, recent work has shown that gammadelta T-cells can be divided into functionally-distinct innate-like and adaptive-like subsets. A knowledge of the dynamics that critically underpin such diverse populations is lacking, hindering fundamental understanding and therapeutic exploitation. We will investigate gammadelta T-cell dynamics in humans including quantification of in vivo lifespans, maintenance mechanisms (de novo production versus self-renewal), and repertoire dynamics relative to canonical adaptive (CD8) and innate-like (MAIT) populations. We will establish benchmark in vivo dynamic measurements for "innate" and "adaptive" human gammadelta T-cell subsets, and generate the first quantitative models of the human gammadelta T-cell compartment.
|
| 14/07/2020 |
£1,813,347 |
|
KING'S COLLEGE LONDON |
Membrane function is fundamental to life. Deregulation of the membrane lipid repertoire has severe consequences for cellular and organismal fitness. Defining how lipid composition controls membrane organization and cellular physiology remains a major challenge in biology. Membrane lipid composition is subject to complex feedbacks and reflects the metabolic and regulatory capabilities of the specific experimental system. I propose to attack this problem by exploiting the natural divergence in membrane lipid composition between S. pombe and S. japonicus, two related genetically tractable fission yeasts with different lifestyles. I believe that our research program integrating comparative analyses and reverse engineering of cellular mechanisms with biophysics and systems approaches, provides an unmatched discovery platform capable of revealing the core principles that govern membrane organization and function. Our research will explain how changes in the architecture of glycerophospholipid fatty acyl tails affect membrane properties. It will provide insights into the organization and evolution of genetic networks regulating membrane homeostasis. Finally, it will test if acquisition of new lipid metabolic functionalities engenders diversification of cellular pathways and organismal physiology.
|
| 14/07/2020 |
£1,243,595 |
|
UNIVERSITY OF CAMBRIDGE |
Genetic and transcriptional studies have demonstrated that shared aetiology between immune-mediated diseases (IMD) is reflected in shared patterns in both data types, and suggested new targets for treatment. However, the huge number of variants and genes measured mean that only a minority of potential information in these data has been harnessed, and disease prognosis and treatment success remains variable and unpredictable. My goal is to overcome this dimensional challenge by developing genomic feature engineering which exploits these shared patterns, to extract new insight from jointly analysing over a hundred existing datasets.
I will generate summary features by tailoring dimension-reduction strategies and applying them to genetic and transcriptomic data from patients and cohorts with related traits measured. I will investigate how each feature contributes to rare and common IMD risk, and prognostic variability within diseases. I will correlate features with molecular measurements and clinical data to understand the gene products they represent, and the situations (cell type, disease state/subtype) in which they are relevant. Finally, through predictive modeling, I will explore the expected impact of targeting these gene products in different diseases and subtypes, to generate, and test, hypotheses about which targets might modify specific IMD activity or progression.
|
| 14/07/2020 |
£1,789,979 |
|
UNIVERSITY OF OXFORD |
Lymphocyte function underpins effective immunity to infection and cancer, and is adversely affected by age in a process called immune senescence, a major obstacle to having a healthy lifespan. The cellular basis of T cell senescence is largely unknown. Maintaining proteostasis, regulated by protein synthesis and degradation, in the face of intrinsic and environmental insults is a key determinant of cellular and organismal lifespan. We will address the hypothesis that modulating the conserved degradation and recycling process known as autophagy, can restore immune responses in lymphocytes in the elderly. We have shown that autophagy prevents immune aging, and demonstrated a decline in autophagic flux in lymphocytes with age, and a global age-related decline of protein translation. But it is uncertain which of the synthesized and degraded proteins are most important. It is clear, however, that the induction of specific repair pathways, including autophagy, extends life and health span. We have uncovered a novel pathway that rejuvenates lymphocyte function by regulating autophagy translationally, which we intend now to fully characterize. Our goal is to identify potential therapeutic strategies for restoring health span in the elderly. This work will also address fundamental gaps in our understanding of the aging process.
|
| 14/07/2020 |
£2,345,878 |
|
UNIVERSITY OF EDINBURGH |
Meiosis generates gametes with half the parental genome through two consecutive chromosome segregation events, meiosis I and meiosis II. Meiotic errors are prevalent in humans, accounting for frequent miscarriages, birth defects and infertility, yet the mechanistic origins of these errors are undefined. Our vision is to discover the molecular basis of the adaptations that sort chromosomes into gametes during meiosis. We will exploit the tractability of yeast meiosis to overcome the limitations of protracted meiosis and scarcity of material in other systems, to address three complementary aims. First, we will determine the mechanism by which kinetochores suppress crossover recombination near centromeres during meiotic prophase, and the significance of this suppression for chromosome segregation. Second, we will reveal how sister kinetochores are specifically fused, and the surveillance machinery re-wired, to permit sister chromatid co-segregation only during meiosis I. Third, we will identify the modified cell cycle controls that drive two consecutive chromosome segregation events during meiosis and determine how these controls couple chromosome morphogenesis to gametogenesis. The molecular pathways we discover will provide a framework for identifying potential sources of meiotic errors in humans.
|
| 14/07/2020 |
£1,567,546 |
|
UNIVERSITY OF OXFORD |
This proposal will investigate the mechanism of cell-to-cell transmission and spread of flaviviruses using Dengue and Zika as model systems. We will therefore address a longstanding debate on how they exit from infected cells, and preferentially spread into specific cell types. Dengue and Zika are the two most prevalent flaviviruses worldwide, sharing significant overlap in their genome architecture and biology. Dengue infects > 50 million people annually, causing severe pathologies. Zika too has emerged as a global threat with recent outbreaks linked to serious neuro-developmental complications in children and Guillain Barré syndrome in adults. No vaccines or therapeutics exist for these viruses, and our current understanding on mechanisms of their transmission and spread is severely limited.
Viral infections spread by overcoming multiple barriers to move from cell to cell. Viral progenies can move across extracellular space either as free particles via fluid phase diffusion, within vesicles, or by cell-cell contacts. To understand transmission, we will therefore address: (i) characteristics of the extracellular virus populations, (ii) whether multiple transmission routes exist (iii) whether the viral envelope is the primary determinant of transmissibility. This proposal builds on our previously published and ongoing studies on viral manipulation of autophagy for assembly and spread.
|
| 14/07/2020 |
£1,900,785 |
|
UNIVERSITY COLLEGE LONDON |
Productive communication between T cells and B cells is vital for protective immunity, however dysregulation of this process can trigger autoimmunity. Costimulatory checkpoints limit T cell help for B cells by controlling the differentiation of follicular helper T cells (Tfh), a cellular subset overrepresented in multiple autoimmune diseases. We have found that anti-CTLA-4 antibodies can trigger spontaneous Tfh differentiation in mice. Targeting CTLA-4 with checkpoint inhibitors in cancer patients may therefore induce Tfh, potentially relevant to the autoimmune side-effects seen with these treatments. Despite their escalating clinical burden, the cellular mechanisms underpinning checkpoint-inhibitor induced autoimmunity remain poorly understood.
In this proposal I will investigate the hypothesis that induction of Tfh responses is a general feature of autoimmunity, reflecting a loss of costimulatory (checkpoint) control. I will explore how CTLA-4 and PD-1 co-operate to regulate Tfh differentiation, and establish the consequence of a Tfh response for tissue autoimmunity. Insights will be drawn from autoimmune patients treated with CTLA-4-Ig, and cancer patients treated with CTLA-4 antibodies. Building on exciting preliminary data, I will determine whether Tfh populations have value in predicting outcomes in classical autoimmunity as well as in checkpoint-inhibitor induced disease.
|
| 14/07/2020 |
£64,000 |
|
WELLCOME TRUST SANGER INSTITUTE |
Productive communication between T cells and B cells is vital for protective immunity, however dysregulation of this process can trigger autoimmunity. Costimulatory checkpoints limit T cell help for B cells by controlling the differentiation of follicular helper T cells (Tfh), a cellular subset overrepresented in multiple autoimmune diseases. We have found that anti-CTLA-4 antibodies can trigger spontaneous Tfh differentiation in mice. Targeting CTLA-4 with checkpoint inhibitors in cancer patients may therefore induce Tfh, potentially relevant to the autoimmune side-effects seen with these treatments. Despite their escalating clinical burden, the cellular mechanisms underpinning checkpoint-inhibitor induced autoimmunity remain poorly understood.
In this proposal I will investigate the hypothesis that induction of Tfh responses is a general feature of autoimmunity, reflecting a loss of costimulatory (checkpoint) control. I will explore how CTLA-4 and PD-1 co-operate to regulate Tfh differentiation, and establish the consequence of a Tfh response for tissue autoimmunity. Insights will be drawn from autoimmune patients treated with CTLA-4-Ig, and cancer patients treated with CTLA-4 antibodies. Building on exciting preliminary data, I will determine whether Tfh populations have value in predicting outcomes in classical autoimmunity as well as in checkpoint-inhibitor induced disease.
|
| 14/07/2020 |
£2,388,796 |
|
IMPERIAL COLLEGE LONDON |
This proposal aims to understand:
1) What circuitries sense the inexorable drive to sleep when we are sleep-deprived? We will investigate if sleep need is sensed locally in the brain by a distributed circuit network that feeds into a central hub, the lateral hypothalamus, providing global restorative sleep. We have identified neurons in the mouse prefrontal cortex, preoptic hypothalamus, and ventral tegmental area (VTA) that sense sleep need and contribute to inducing sleep after sleep deprivation. Learning how responses to sleep deprivation are embedded in distributed sleep circuitry would explain how sleep homeostasis works at the circuit level.
2) Do sedative drugs promote these restorative sleep pathways? How do two important drugs, propofol and dexmedetomidine, intervene in the sleep-homeostasis circuitry? We will search for cells that respond to sedatives to induce restorative sleep without deleterious effects (hypothermia). Understanding this circuitry may identify new drug targets.
3) What is the significance of sleep-promoting circuitry we have discovered in the basal ganglia and midbrain (globus pallidus to lateral habenula to VTA to lateral hypothalamus), which overlaps with circuitry that responds to aversive outcomes and stress? We will investigate if this basal ganglia-triggered sleep helps offline processing of negative experience.
|
| 14/07/2020 |
£1,195,323 |
|
UNIVERSITY OF CAMBRIDGE |
Kidneys play a vital role in homeostasis. Chronic kidney disease (CKD) is characterised by kidney dysfunction and organ fibrosis, and affects millions of patients worldwide, but the underlying pathogenic mechanisms are poorly understood. Using single cell RNA sequencing, we have shown that the human kidney contains a network of tissue-resident immune cells, including macrophages and two subsets of natural killer (NK) cells. These NK subsets have distinct transcriptional signatures suggestive of differing interactions with macrophage subsets, and the potential to variably influence tissue repair/fibrosis by via production of the epidermal growth factor receptor ligand amphiregulin (AREG) and by regulating macrophage polarisation towards a wound-healing M2 phenotype.
My key goals are:
1. To determine the functional characteristics, cellular interactions, developmental relationships and lifespan of NK cell subsets in normal human kidney.
2. To understand how the global kidney immune landscape and NK cell phenotype/function/interactions change in CKD.
3. To determine if NK-cell depletion or NK cell-specific AREG-deficiency affects macrophage polarisation and kidney fibrosis in mouse models of kidney injury.
Answering these questions will provide critical information about tissue immunity in the kidney, delineate previously unappreciated aspects of NK cell biology, and will potentially identify new therapeutic targets for CKD.
|
| 09/07/2020 |
£997,614 |
|
IMPERIAL COLLEGE LONDON |
The Centre for Structural Biology at Imperial College London includes a heavily-used electron microscopy facility on the South Kensington campus that features four electron microscopes for single particle and tomographic analysis of biological samples. A large and rapidly-growing Imperial- and London-based user community spanning molecular biology, chemical biology, and drug development, uses these instruments for sample screening, optimisation, and data collection. These instruments, however, are all based on 20+ year-old archetype, resulting in rising maintenance costs and risk become irreparable any day due to inability to source replacement parts. These machines are also bottlenecks, incapable of providing high-throughput screening, optimisation, and data collection needed to feed high-resolution data collection instruments such as Titan Krioses accessible at various UK-based facilities. Our community is in urgent need of a contemporary electron microscope such as a Talos Arctica capable of both single particle and tomography cryoEM, equipped with technology for rapid screening and optimisation and compatibility with Krios sample handling. The instrument will be embedded and managed within the CSB EM facility and accessible by all CSB users on an hourly user rate basis to guarantee full cost recovery, a company-based service contract, and long-term sustainability.
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| 09/07/2020 |
£172,500 |
|
IMPERIAL COLLEGE LONDON |
Multiparameter analysis of nanoscale entities such as viruses, nanoparticles and extracellular vesicles is restricted by the limited resolution of standard flow cytometers. Both the nanoparticle and extracellular vesicle fields are rapidly growing in the academic and commercial setting.
We are applying for a state-of-the-art dual-laser Flow NanoAnalyzer (model U30) from NanoFCM, as well as five years discounted servicing and support. The Flow NanoAnalyzer (FNA) is an innovative flow cytometer which has been specifically engineered to surpass the nanoparticle detection limitations of current commercial flow cytometers. In particular, the FNA enables detection of nanomaterials, nano-drug delivery systems, bacteria, viruses, cell organelles (e.g. mitochondria) and extracellular vesicles (e.g. exosomes and microvesicles) within a size range of 7-1000nm. The FNA is equipped with one highly sensitive side scatter channel, a 488 nm laser, a 638 nm laser and three single-photon counting module (SPCM) detectors (525/40 nm, 580/40 nm and > 650 nm) to enable multi-colour/parameter experiments.
The FNA only recently launched in the UK (April 2019). Therefore, if funded, Imperial will become one of the first UK (and potentially European) universities to have this machine. This will attract significant interest from UK, as well as, international academic and industrial collaborators or users.
|
| 09/07/2020 |
£1,000,000 |
|
UNIVERSITY OF GLASGOW |
Magnetoencephalography (MEG) is an advanced technology using super-conducting quantum interference devices (SQUIDs) for measuring the tiny magnetic fields produced by the coherent electrical activity in groups of neurons. MEG is the only neuroimaging technology that enables non-invasive recordings with both excellent temporal and good anatomical resolutions. Such spatiotemporal accuracy is instrumental for discovering the mechanisms underlying mental functions and deficits in healthy and impaired brains.
We seek Wellcome Trust funding to replace our 12-year old MEG system with a state-of-the-art TRIUX-neo from MEGIN Ltd. The TRIUX-neo is an ultra-sensitive system based on new technology that combines MEG recordings with high-density EEG, online head-motion tracking and a helium recycling mechanism now essential with worldwide helium shortage.
With the TRIUX-neo, our multi-user MEG group (with significant Wellcome Trust funding, Investigator, Innovator, Seed and Sir Henry Wellcome Fellowship) will keep enhancing its cutting-edge, unique, cohesive and collaborative research and pioneer new methods and techniques across our extensive platform of in-house imaging facilities (i.e. EEG, MEG, NIRS, 3/7T fMRI).
Key MEG innovations will focus on understanding brain network dynamics and oscillations in health and disease, using information theory and advanced network analyses and unique data fusion of EEG and 3/7TfMRI and neurostimulation (TMS, tES).
|
| 09/07/2020 |
£232,273 |
|
BIRKBECK UNIVERSITY OF LONDON |
ISMB (Birkbeck/UCL) is renowned for its research in structural biology, successfully combining X-ray crystallography and electron microscopy and supporting users from a wider scientific community. The current set up for crystallisation includes a nanoliter liquid handler (Mosquito, SPT Labtech), an old Perkin-Elmer liquid handling robot for sample optimisation and an outdated Minstrel/Rigaku automated imaging suite. Recent crystallography beamline technological developments at high-end synchrotrons have pushed the boundaries of data collection and reduced the usable size of crystals down to a few microns. However, our current instrumentation does not allow us to take full advantage of these new technologies since refinement of crystallisation conditions, and monitoring of ‘microcrystals’ growth, cannot be managed by our outdated equipment. Moreover, two of the existing instruments are no longer supported by authorized services.
Therefore, we are requesting the purchase of a new state-of-the-art ‘imaging hotel’ (UVEXps, swissci) and liquid handler (Dragonfly, SPT Labtech). Specifically, we propose to purchase a microliter liquid handler for optimisation of crystallisation conditions and a high-resolution crystal imaging system for storage, monitoring, imaging and detection of protein crystals. The two instruments will complement the existing liquid handler (Mosquito), while offering more flexibility to all users by remote access.
|
| 09/07/2020 |
£162,283 |
|
UNIVERSITY OF LEEDS |
The Flow Cytometry & Imaging Facility, Leeds Institute of Medical Research, needs to expand capability and capacity for live cell and high content imaging (HCI) to serve the local and wider scientific community. We request part-funding of a LIPSI high content/multichannel live-cell imager with environmental control (Nikon Instruments UK Ltd). The acquisition of a state-of-the-art LIPSI will replace our obsolete Operetta and Incucyte instruments and will transform our Facility by allowing fully integrated, automated, high-throughput, and high-content/live-cell imaging. The system allows very rapid epifluorescence (six simultaneous fluorescence channels), chromogenic and DIC acquisitions whilst running multiple time-lapse assays with sampling rates up to 60fps. This allows imaging of long-term live-cell 2D/3D cell cultures, tissue sections, small model organisms or rapid HCI of fixed cells. For increased throughput, the LIPSI includes motorised stage, robotic handler and environmentally-controlled plate-holder. This enables streamlined automated processing of multiplexed long-term live cell functional assays, with complex imaging schedules in both hypoxic and normoxic environments for up to 20 plates. Standard acquisitions comprise multichannel, time-lapse, multiple-positions, z-stacks, large images and multidimensional imaging using standard plastic or glass SBS plate, dish and slide formats used within the Facility.
|
| 09/07/2020 |
£189,485 |
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UNIVERSITY OF LEEDS |
We request a 75% contribution to purchase two IncuCyte S3 Live-Cell Analysis Systems, together with archive data storage capacity (£189,485). These instruments are designed to acquire real-time growth, migration, morphology, phenotypic and gene expression data from virus-infected cells in microplates. They will be located in newly-opened Biological Safety Level 3 (BSL3) and BSL2 laboratories, transforming existing capacity for real-time analysis of virus-infected cells and enabling ambitious plans for expansion of virology research. The overall aims of the research supported by these instruments are: 1) to understand the molecular mechanisms by which viruses enter cells, replicate their genomes and assemble into infectious virions, and 2) to drive early-stage development of new anti-viral therapeutics (eg screening compound libraries). The IncuCyte instruments will facilitate both work streams. They will be housed in standard cell culture incubators and can be remote controlled allowing the analysis of cell parameters over time safely without disturbance. In order to effectively train users, provide technical advice, oversee usage and manage the instruments, we also request funding for 10% of the salary of the current BSL2/BSL3 laboratory manager, and 5% of the BioImaging facility support scientist over 5 years (£31,390).
|
| 09/07/2020 |
£271,222 |
|
UNIVERSITY COLLEGE LONDON |
This application is for the purchase of a BD Aria-Fusion fluorescence activated cell sorter. The instrument performs high-speed multi-parameter sorting, allowing isolation of rare cell subsets and supporting single-cell genetic and functional analyses. It will enable scientists at the UCL Institute of Immunity and Transplantation (IIT) to be at the forefront of studies of the patho-physiology of the human immune system and responses to disease treatments.
This state-of-the-art sorter is essential to allow us to maintain a cutting edge flow-cytometry core facility in the newly constructed Pears building, which will house the IIT from late 2020. The Pears building is a £61 million joint project between UCL and the Royal Free NHS Foundation Trust to create a world-leading centre for disease-focused immunology research. The building will accommodate some 20 research groups comprising approximately 200 scientists. The translational immunology programs of the IIT include mechanistic studies in animal models, genetic and functional analyses of the human immune system, high-dimensional analysis of clinical samples and the monitoring of patients participating in novel immunotherapy trials. The technical capability of the FACS-Aria-Fusion is therefore required to support a wide variety of cutting-edge research programs in infection and immunity.
|
| 09/07/2020 |
£1,000,000 |
|
UNIVERSITY OF LEEDS |
The Astbury Biostructure Laboratory, was established in 2015 with University of Leeds investment, and a Wellcome multi-user equipment award, allowing us to install two Titan Krios microscopes (2016). In just three years, we have established an international reputation for excellence in cryoEM, and a buoyant user base that means our facility is already operating at capacity. We request funds to upgrade our microscopes, aiming to increase data acquisition rates, whilst improving data quality, allowing us to shorten session lengths, increase sample throughput, and introduce new methodologies.
Upgrades will include:
1. A ThermoFisher Falcon-4EC camera on Krios#1
2. A Gatan Bioquantum K3 on Krios#2
3. Aberration-Free/Fringe Free Imaging Systems (both microscopes)
4. EPU-D software for electron diffraction (Krios#1)
5. Whole-system maintenance contract extensions to 5 years from installation.
We anticipate a 5-8x improvement in data acquisition, empowering users to drive more challenging biological and biomedical discovery. We will be able to determine new high-resolution structures and integrate them into their cellular/tissue context, helping us to understand the molecular basis of diseases such as infections, cardiovascular disease, degeneration and cancer.
We request £1m from Wellcome, with a University capital contribution of £325k, plus salary costs, Giving a total project cost of ~£2.13m.
|
| 09/07/2020 |
£517,128 |
|
IMPERIAL COLLEGE LONDON |
We propose the establishment of a dedicated facility for three-photon live imaging of deep tissue. This will comprise a dedicated multiphoton microscope (Scientifica Hyperscope or similar) with optical components anti-reflectance coated for long-wavelength light (up to 1700 nm) for three photon imaging, together with a suitable laser excitation source. Funding is requested for a high power ultrafast laser (Amplitude Systems Satsuma 40/40 or similar) producing up to 40W at 1030nm, pumping an Optical Parametric Amplifier (APE/Amplitude Mango SP or similar) to produce 1150-1700 nm light at a 2 MHz repetition rate, optimised for three photon excitation of both green and red fluorophores. The microscope will be mounted on a single large antivibration table. The three-photon microscope will be installed in a Home-Office designated small animal imaging suite. A dedicated facility manager (with substantial expertise of in vivo multiphoton imaging including biomedical optics), will run the facility, ensuring continued high imaging performance, and maximising effective and collaborative use of the facility. The imaging suite will provide a unique capability for deep tissue imaging by Wellcome Trust funded researchers across a range of biomedical application areas, including neuroscience, cardiology, stem cell biology and respiratory physiology.
|
| 09/07/2020 |
£674,756 |
|
UNIVERSITY COLLEGE LONDON |
The requested equipment is the ThermoFisher Orbitrap Eclipse Tribrid Mass Spectrometer with an Ultimate3000 LC system. This new instrument is designed for high-end proteomics, top-down protein characterisation, and crosslinking analysis and is equipped with the latest Orbitrap analyser, which offers higher resolution, sensitivity and acquisition rates compared to previous Orbitraps.
These features result in improvements to both limit of detection and quantification of peptides, ultimately leading to enhanced quantitative proteomics and crosslinking analysis.
Its atypical geometry allows multistage fragmentation of ions (MSn), which is necessary for multiplexed proteomics experiments and for advanced crosslinking analyses using cleavable crosslinkers. Combined with a novel in-built real-time search algorithm, fragment ions of interest e.g. crosslinked peptides can be preferentially selected, further increasing the depth of analysis. The Eclipse is also capable of top-down proteomics experiments which is an ideal method for the study of proteoforms and labile post-translational modifications.
We will use the Eclipse to study the biological processes underpinning viral secondary envelopment, type 2 diabetes, cell responses to protein misfolding and cell competition; these studies are challenging due to the low amounts of sample available. The sensitivity and robustness in protein quantitation provided by the requested instrument will be key for their success.
|
| 09/07/2020 |
£369,413 |
|
UNIVERSITY OF OXFORD |
Protein crystallisation continues to play a central role in structural biology as the foundation for determining the atomic structures of macromolecules, understanding disease mechanisms, vaccine design and drug discovery. Several challenges remain, including crystallisation of multiprotein complexes, membrane proteins and time-resolved studies from systems directly engaged in catalysis, cell signalling, and ion movement. Studying different levels of structural complexity and dynamics is essential to understand protein function in health and disease. Technical developments are contributing to progress in these areas, including X-Ray Free Electron Lasers (XFELs) and Serial Synchrotron (SFX) data collection, coupled with advances in crystal imaging, which enable researchers to identify microcrystals that were previously not detectable with older instrumentation. This proposal builds on these advances through the acquisition of cutting-edge instrumentation for protein crystallisation, including advanced UV and multi fluorescence imaging optics and lipid cubic phase fluorescence after photobleaching (LCP FRAP) systems, which will provide access to, and development of, novel methods to detect and grow protein crystals of challenging multiprotein systems. A new multiuser protein crystallisation facility, centred in Oxford Biochemistry, but incorporating several stakeholders from across the wider University research community, will provide access and training.
|
| 09/07/2020 |
£367,500 |
|
NEWCASTLE UNIVERSITY |
Multi-dimensional single cell analysis using cytometry technologies is one of the most significant contributors to our understanding of complex cellular compartments such as the immune system. In recent years we have seen an explosion of new technologies and methodologies that have expanded the number of parameters per cell such as scRNA-seq, but we have suffered from an inverse correlation with scalability and throughput due to significant associated costs. Our goal is to successfully introduce Spectral Flow Cytometry (SFC) as a new, sensitive, scalable and future proof multi-dimensional single cell phenotyping technology to the vibrant, multi-user core facility. We will use the immense capabilities of SFC to understand rare immune-deficiencies (Hambleton); decode the developing blood and immune system (Haniffa); dissect the role of macrophages in inflammatory disease through somatic mutation analysis (Collin); unravel molecular processes in host-pathogen interactions that dictate immune responses (Trost); understand more about Giant Cell Arteritis (Reynolds), anti-viral responses (Duncan), immune surveillance of liver cancer (Wilson) and the control/relapse of Rheumatoid Arthritis (Pratt). We will also address fundamental questions about the technology and methodology itself through expanding the parameter set using probes and label free measurements based on auto-fluorescence (Filby) as well as develop analytical tools (Rico).
|
| 09/07/2020 |
£1,560,990 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
Single Cell Expression Atlas (https://www.ebi.ac.uk/gxa/sc) is an open science resource that offers powerful searches for a gene expression data in different cell types, across tissues, species and conditions. Since its launch in May 2018, the Single Cell Expression Atlas has annotated and reanalysed 132 single cell RNA-Seq (scRNA-Seq) experiments across 12 different species that can be searched and visualised through its web interfaces. The SCEA is unique in that it reprocesses raw scRNA-Seq data in a standardised way. This proposal aims to keep up with the rapid technology development, expand the resource with new data modalities, continue expanding the species coverage and cross-species mapping and expand the functionality of the resource. In particular, we will integrate single cell data sets from spatial and in-situ transcriptomics technologies, as well as emerging single cell omics protocols. Additionally, we will expand the types of analyses performed to facilitate study integration, cell type discovery and annotation. Finally, we will develop anatomograms at the organ, tissue and cell type level to enable intuitive interpretation of the experimental results and easily integrate the different types of data on the user interface.
|
| 09/07/2020 |
£1,504,262 |
|
UNIVERSITY OF CAPE TOWN LUNG INSTITUTE |
We propose to create an African biorepository and linked comprehensive database to support cross-disciplinary research that advances child health. The biorepository will consolidate > 527,000 samples and data from three ongoing large population-based studies: (i) Drakenstein Child Health Study, a birth cohort with samples from parents, children and the environment collected antenatally through childhood; (ii) paediatric tuberculosis studies with samples longitudinally collected over 15 years; and (iii) Cape Town Adolescent Antiretroviral Cohort, a study of HIV-infected adolescents on antiretroviral-therapy and uninfected controls investigating development and determinants of chronic disease. Ongoing prospective data and sample collection for the next 5 years, in these and other child health studies, will substantially grow this facility ( > 732,000 samples). The facility will support several Wellcome Trust grantees and serve as a platform for cross-disciplinary research, linking metadata and samples to different databases (demographic, clinical, radiological, microbiological, genetic, transcriptomic, environmental, immunological, psychosocial). A key focus is on infectious exposures and development of non-communicable diseases, key priorities in African health. A web interface will be created for investigators to access samples or datasets. This resource will be invaluable for current and future collaborative research to advance child health and to provide African-specific data and samples.
|
| 09/07/2020 |
£1,476,141 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
The Electron Microscopy Public Image Archive (EMPIAR) was developed following consultations with the cryo-EM community highlighting the pressing need for public dissemination of image data underpinning cryo-EM structures. Since 2014, EMPIAR has quickly grown in volume (286 entries; 284 terabytes as of 01/04/2020) and established its role and value for the community ( > 180 EMPIAR citations). Its remit now includes micro-crystal electron diffraction (microED), soft-X-ray tomography (SXT), and volume-EM (including Focused Ion Beam and Serial Block-Face SEM) data. The main goals of this grant are to streamline and facilitate the deposition process (encouraging deposition and improving quality and quantity of deposited information) and to enhance and facilitate data reuse. All hardware and IT infrastructure will be provided by EMBL-EBI.
Specific aims:
Fully support deposition of volume-EM data;
Support handling large (tissue- and organism-level) 3D-volumes by pump-priming EMPIAR with flagship connectomics and non-connectomics datasets;
Enable efficient and interactive reuse of large 3D-volumes by supporting multiscale imaging formats;
Facilitate potential mandatory deposition by simplifying the deposition workflow and enhancing data reuse;
Improve support for correlative imaging data, working with stakeholder communities and the EMBL-EBI BioImage Archive;
Prepare for rapid growth of data volumes by evaluating and implementing data-compression methods.
|
| 09/07/2020 |
£1,132,223 |
|
NATURAL HISTORY MUSEUM |
Schistosomes, transmitted by freshwater snails, infect > 200 million people in low/middle-income countries, particularly sub-Saharan Africa. While substantial advances have been made in the control of human schistosomiasis, the diversity and complexity of schistosomes and their specific fresh-water snail hosts warrants fundamental research requiring lifecycles and live material. Without the availability of Schistosoma lifecycles, future research faces substantial obstacles; currently very few labs are able to maintain the parasites and/or the snail hosts and current long-term cultures lack the genetic heterogeneity observed in natural populations. Our proposal is for the creation of a Schistosome and Snail Resource (SSR), maintaining live material and lifecycles that are currently limited or that do not exist elsewhere. The SSR will provide access to 1) the "standard/model" Schistosoma and snail species; 2) key African Schistosoma species/strains; 3) cultures of diverse snail vectors, enhancing current research and capacity while enabling new research avenues. Our historical expertise in establishing and maintaining unique schistosome and snail isolates from different endemic settings, together with our state-of-the-art snail facility (NHM) and LSHTM rodent facility will facilitate the development of the resource. The SSR will add considerable value by facilitating priority research needed to support schistosomiasis control and elimination.
|
| 09/07/2020 |
£1,288,017 |
|
UNIVERSITY COLLEGE LONDON |
We are seeking to acquire the resources to develop a unique X-ray 3D nanoscope. We will need: custom-source, isolation, manipulators, custom-detector, radiation-safe enclosure, two PDRAs (hardware- and software-focussed) and 1year system engineer for the transition to the long-term maintenance/management of the instrument.
We plan to build a nano-resolution multi-contrast 3D scanner with transformative potential across diverse disciplines, including cellular structural biology, pathology, musculoskeletal and respiratory medicine, tissue engineering and child health.
This will create a multi-user tool, benefitting researchers across multiple specialties. The simultaneous attainment of nano-scale resolution, unprecedented scale range (six orders of magnitude,5cm/50nm), multi-contrasts and a wide energy range will make the X-ray nanoscope proposed here a unique non-destructive 3D imaging tool.
Its key advancements will be ultra-high-resolution zoom-ins on intact samples, whose entire structure is measured at a lower resolution, combined with multi-contrast modes arising from phase effects. A simple analogy of this new X-ray tomography paradigm is the way we navigate digital maps. We use coarse resolution at large scales, blowing-up in precise locations of interest. Both capabilities must be concurrently present: it would not be useful to navigate large areas at highest resolution (lost in space) and having only coarse resolution would lack invaluable insights.
|
| 09/07/2020 |
£845,715 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
We will establish a facility for the transmission of human malaria parasites to the mosquito vector and onwards to humanized mice that is open to all members of the research community. Owing to the difficulty in transmission of human malaria parasites in laboratory settings, only few facilities exist where this can be achieved consistently. The three UK facilities capable of this are not open facilities, and none have established the humanized mouse model for investigating the liver stage of the parasite. Notably, this facility will enable the investigation of transmission-blocking compounds, malaria vaccine development, basic research into the interaction of the parasite with the mosquito host and the mammalian liver using a humanized mouse model, the effect of insecticides on the transmission of parasites by insecticide-resistant mosquitoes, the trial of specific genetic modifications of mosquitoes, genetic crosses of malaria parasites and many other investigations. This will make available avenues of research that are currently out of reach for most members of the research community and support the acceleration of new and innovative interventions to halt the spread of malaria.
|
| 09/07/2020 |
£1,282,716 |
|
UNIVERSITY OF DUNDEE |
Bioimaging measures the structure, constitution and dynamics of molecules, cells, tissues and organisms in biological systems. Data are often GBytes or Tbytes in size, cover space, time and other dimensions, include complex metadata that describe experimental setups, acquisition parameters and analytic outputs and are stored in 100s of different proprietary file formats. The scale and complexity of these data are a consistent, unsolved block to researchers making their bioimaging data public and FAIR, despite the fact that open data sharing and publication are mandated by the Wellcome and many other funding agencies.
OME is a globally recognised, open source bioimage data specification and software project (https://www.openmicroscopy.org). Since 2002, OME's OME-TIFF file format and Bio-Formats file translation library have served as the global de facto standard for accessing bioimage data, but the capabilities of these tools will soon be surpassed by the growing volume and complexity of bioimaging datasets. We propose to build next generation bioimage file formats, flexible data models, data linkages and transfer tools to serve the needs of the rapidly evolving bioimaging community and feed new public data repositories and databases. The software will be liberally licensed to allow adoption across the research and industrial bioimaging communities.
|
| 09/07/2020 |
£635,056 |
|
UNIVERSITY OF SHEFFIELD |
AFM has unique capabilities for understanding life, and is able to image living systems in their native state under physiological conditions with molecular resolution. However, technologically, it is where EM was in the 1990s – far from delivering its theoretical potential when imaging biology. By understanding the physical principles of the technique and systematically optimising the instrumentation, the potential of EM has been unleashed in recent years. We aim to drive a similar "resolution revolution" in AFM, developing an instrument that can:
Image functioning biological molecules in intact systems, including living cells, without perturbing their function or structure.
Obtain these images with sufficient resolution to identify biomolecules by their topography.
Accurately measure the organisation of biological molecules in complex, native samples.
We will do this by targeting fundamental weaknesses in AFM technology:
Reducing the thermal noise of the cantilever by producing smaller and softer cantilevers, and a microscope that can use them, reducing the imaging force 10-100x compared to the current state-of-the-art.
Reducing positioning noise and drift by developing a hierarchical, interferometric closed-loop scanner that reduces noise by > 10x and drift by 100-1000x compared to the current state-of-the-art, providing traceably accurate measurements of size and position.
|
| 09/07/2020 |
£983,193 |
|
UNIVERSITY OF YORK |
A comprehensive understanding of communication in both healthy and diseased cells requires new tools to quantify the spatial distribution, onset and rate of protein secretion. To address this challenge, we will develop an in vitro technology that maps the three-dimensional (x, y, time) distribution of multiple cell-secreted molecules, such as chemokines, hormones, and cytokines, with single cell resolution. This technology allows to better characterise the heterogeneity of cell populations in response to stimuli and to define mechanisms of inter-cellular communication. Our innovation exploits the sensitivity of optical resonances to map the secretion of specific proteins without the need for a labelled antibody. Critically, and in contrast to competing technologies, such label-free approaches enable protein detection in real time. The photonic sensor can be fabricated at low-cost and can be integrated into standard commercial microscopes rendering the technology widely applicable. We have already demonstrated the technology and will now optimise its performance, develop its capability to detect at least 3 different types of proteins in parallel and work with a commercial partner to develop a system compatible with a laboratory-standard inverted microscope. We will engage with the community through exemplar projects that span infection and immunity, cancer, haematology and vaccinology.
|
| 09/07/2020 |
£851,128 |
|
UNIVERSITY COLLEGE LONDON |
We will significantly expand CATH, widely used by biomedical researchers, and enhance its value for disease analyses. Data on disease-associated genetic variations is vastly increasing but to fully exploit it we must understand how the resulting residue mutations impact protein functional sites and therefore functions. We will use CATH to predict the impact of variants on diseases and drug responses, enabling personalised medicine.
CATH-FunFams are functional sub-classifications of CATH evolutionary superfamilies and the only structural resource comprehensively linking variants, structure and vast sequence data for predicting functional sites accurately (FunSites). Close proximity of disease variants (residue mutations) to FunSites, in 3D, is a key indicator of pathogenicity.
Our expanded CATH-FunFams and FunSites will enhance machine learning methods to predict functional impacts and drug responses/side effects, including for different genders and ethnicities.
We will:-
1. Expand CATH-FunFams and FunSites > 5-fold by adding sequence data from metagenomes.
2. Expand CATH-FunSites further by integrating comprehensive data from PDBe-KB, PDBsum and VarSite.
3. Develop machine-learning tools that exploit data from (1) & (2) to predict impacts of genetic variations in different populations.
4. Integrate drug data into FunFams and develop tools to predict drug repurposing/side effects.
5. Develop intuitive webpages reporting functional impacts/drug repurposing/toxicity.
|
| 09/07/2020 |
£1,391,682 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
InterPro is a core protein data resource that amalgamates 13 protein family databases (including Pfam) to provide the definitive description and classification of protein domains and families. Various scientific communities rely on the range of annotations provided by InterPro and its member databases to acquire novel insights into the vast amounts of new DNA sequence data, enabling scientists to interpret experiments and design new ones based on annotations spanning complete genomes down to single residues. The past five years have witnessed a major increase in the scale of sequences, concomitant with the emergence of AI/ML approaches for unlocking the biological signals encoded within the data. This project will exploit these innovative approaches to enhance protein annotations and refine classifications through the incorporation of additional data types, along with the application of ML methods and organisation of the protein family data. We will integrate KOfams and AMRFinder into InterPro, while continuing to scale the InterPro/Pfam/HMMER resources to tackle billions of proteins. Cumulatively, these developments will accelerate biomedical research by facilitating scientists to decipher the effect of human mutations, understand drug interactions, combat antimicrobial resistance, and tackle emerging pathogens.
|
| 09/07/2020 |
£1,559,880 |
|
UNIVERSITY OF MANCHESTER |
Our goal is to enhance and accelerate the validation and translation of new drug targets identified by the UK academic biomedical research community. In order to achieve this we will establish a DNA-Encoded Library (DEL) screening resource that will provide cost-free and commitment-free access to high-throughput compound screening for academic research groups, by;
1) Designing and preparing DNA-encoded libraries containing 5-10 million diverse and drug-like compounds, representing a unique resource for academic researchers.
2) Utilising these libraries to undertake 40 target selections against novel protein targets for academic users, delivering validated hit compounds to > 20 research groups by 2025.
3) Developing a sustainable and expandable resource which will continue to deliver beyond the current funding period.
DELs are an established screening approach that are utilised by the majority of large pharmaceutical companies. The technology allows for the rapid identification of ligands for a target protein with a very simple protocol compared to other screening approaches. Active compounds are identified by affinity selection of protein-binding compounds from libraries containing millions of different compounds that are each linked to a unique DNA sequence. The DNA tag allows for rapid and high-throughput deconvolution of the active compounds by next-generation sequencing.
|
| 09/07/2020 |
£1,062,390 |
|
UNIVERSITY OF EDINBURGH |
Synapses are damaged in over 130 different brain diseases and yet thus far there are no reliable ways to measure synaptic structure or function in vivo in a preclinical or clinical setting. The recent discovery of promising Positron Emission Tomography (PET) radiotracers for imaging synapses, by targeting the synaptic vesicle glycoprotein 2A (SV2A), has the potential to transform clinical diagnosis, neuropathology, drug development and treatment of multiple brain diseases. Two major bottlenecks to deliver on this promise are: (1) the unavailability of high-yield and high-molar activity [18F]MNI1126, the lead SV2A PET radiotracer; and (2) the lack of a quantitatively accurate and validated SV2A brain PET atlas during normal aging in rodent models. This project will generate synthetic routes and radiochemistry methods for efficient production of [18F]MNI1126, it will develop detailed template resources for quantitative analysis of SV2A PET signal in different brain regions over the course of natural aging in the rat and mouse, and it will validate SV2A PET in vivo outcomes at unprecedented scale and resolution using synaptome mapping technology. The development of SV2A PET technology proposed in this award will catapult the use of quantitative SV2A PET in many brain diseases in humans and model organisms.
|
| 23/06/2020 |
£917,588 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
In sub-Saharan Africa, over 50 million people have chronic kidney disease (CKD) making Africa the continent with the highest burden of CKD in the world. With rapidly increasing urbanisation, trends towards unhealthy diets, obesity and increases in metabolic risk factors, the projected increase in the prevalence of CKD may be even greater in Africa than in other parts of the world.
Over the past decade, genome-wide association studies have uncovered numerous genetic determinants of CKD in European and Asian ancestry populations. These studies have led to numerous novel findings, which are helping improve our understanding of factors and pathways affecting both normal and pathologic kidney function. However, to date, there is no known published GWAS of CKD in any continental African population.
Key goals include
Conduct large-scale genomic studies of CKD in Africa which will potentially provide new opportunities to identify the biological determinants of CKD in individuals of African ancestry.
Leverage the low linkage disequilibrium between genetic markers in African populations to conduct fine-mapping of novel and previously identified signals in the trans-ethnic meta-analysis.
Develop a Polygenic Risk Score for CKD risk in Africa and assess whether cardiometabolic traits/diseases are causally related to the risk of CKD in Africans.
|
| 23/06/2020 |
£613,982 |
|
NOGUCHI MEMORIAL INSTITUTE FOR MEDICAL RESEARCH |
Some bacteria species in the mosquito midgut demonstrate anti-Plasmodial effect independent of the mosquito immune system. Understanding this mechanism could help propose bacteria-mediated strategies for targeting and blocking transmission without producing transgenic bacteria. This project proposes to identify mosquito midgut bacteria that secrete anti-parasitic factors and investigate their variations in natural Anopheles mosquito populations. Mosquito stages of P. falciparum will be exposed to spent culture media of midgut bacteria species through in vitro and in vivo (using axenic mosquitoes) assays and developmental and functional parasite effects assessed by immunofluorescence microscopy. The biological significance of the bacteria secreted products will be confirmed by comparing with parasite exposure to bacteria cells. The natural prevalence of effective bacteria will be investigated in blood-fed field-caught Anopheles malaria vector species from areas of high and low malaria transmission using 16S sequencing. In addition, bacterial metabolites will be identified by LC MS/MS for further investigations into their mechanisms of cell activity. It is expected that results from this study will increase our knowledge in the biological role of specific bacteria in natural variations of vector competence and reveal bacterial products from mosquito microbiome that can be further explored for parasite transmission-blocking in the mosquitoes.
|
| 23/06/2020 |
£695,284 |
|
CENTRE FOR RESEARCH IN INFECTIOUS DISEASES (CRID) |
Insecticide resistance is threatening effectiveness of insecticide-based interventions to control malaria across Africa. However, the impact of this resistance on malaria transmission remains a matter of debate. It is not yet well established whether insecticide resistance, particularly metabolic resistance, in addition to allow survival to insecticide exposure, positively or negatively affect capacity of vectors to develop and transmit malaria parasites. Taking advantage of the recent designs of the first simple DNA-based assays allowing to track cytochrome P450- and glutathione-S-transferase mediated metabolic resistance in the major malaria vector Anopheles funestus, this project aims at establishing the impact of metabolic resistance on malaria transmission in Africa, to improve resistance management. More specifically, I will: Aim1) Investigate the influence of metabolic resistance on the development of P. falciparum in An. funestus using GST and P450 markers; Aim2) Characterize the transcriptomic changes accompanying P. falciparum infection in metabolic insecticide resistant An. funestus using RNAseq; Aim3) Investigate interactions between metabolic resistance and Plasmodium immune response genes in An. funestus using functional genomics (RNAi).
This project will benefit from the expertise gained during my Wellcome Trust Training Fellowship including the successful rearing and establishment of experimental infections of field An. funestus using natural P. falciparum isolates.
|
| 23/06/2020 |
£103,661 |
|
ABRASCO |
The 2030 Agenda for Sustainable Development highlights the need to prevent and respond to violence against women and girls. It also affirms the need to invest in early childhood care for the promotion of sustainable development in low and middle-income (LMICs). Intimate partner violence (IPV) is one of the most common and extreme manifestations of gender inequality worldwide, and has a higher prevalence and more severe consequences for women and children living in LMICs. I aim to examine the association of IPV with parenting practices and early childhood development in LMICs. This will be done using data from nationally representative household surveys (DHS) carried out since 2010 in at least 10 LMICs, and a large population-based prospective cohort study in Brazil, following over 4,000 children born in 2015. A key objective of the project is to explore whether women´s mental health mediates the proposed associations, and the role of women’s empowerment levels in the associations under study. The empirical evidence generated from this project will contribute to increasing visibility of the intergenerational consequences of IPV on children and provide guidance for the direction of global resources to prevent gender-based violence.
|
| 23/06/2020 |
£241,245 |
|
AFRICA HEALTH RESEARCH INSTITUTE |
HIV induces B-cell defects that could impair the development of effective antibody responses, such as broadly neutralizing antibodies (bNAbs). However, some rare patients still develop anti-HIV bNAbs. Such responses can be mimicked with vaccines for protection against HIV. The B cells that develop breadth despite the ongoing HIV-induced immune defects could have unique profiles that enable their survival and functionality. The aim of this work is to characterize the transcriptional and phenotypic profiles of B cells that encode for anti-HIV bNAbs and their precursors/intermediates. I will use longitudinal clinical samples from well characterized HIV-infected individuals who have broadly neutralizing sera. I have already isolated a bNAb from this cohort by FACS-sorting of epitope specific memory B cells and cloning the immunoglobulin genes. I am currently isolating bNAbs from the other individuals. This will create a platform for subsequent characterization of the B cells that encode for the bNAbs. I will then characterize the phenotypic and transcriptional profiles of epitope specific memory B cells that encode for the bNAbs lineages using paired flow cytometry, cloning and single cell RNA-seq. This will reveal the profiles that, if induced with appropriate adjuvants, could promote elicitation of protective anti-HIV bNAbs after vaccination.
|
| 23/06/2020 |
£257,984 |
|
UNIVERSITY OF OXFORD |
Rickettsia typhi is an obligate intracellular Gram-negative bacterium causing murine typhus. The disease is globally distributed but neglected. It is an important cause of acute febrile illness in Laos. Although murine typhus is treatable, a clinical trial by Newton P et al. (2019) suggested that azithromycin is inferior to doxycycline. However conventional antibiotic susceptibility testing was not performed to corroborate this finding since no methods exist. Therefore, there is a need to develop a highly sensitive qPCR method comparable with the gold standard method of the plaque assay to assess antimicrobial susceptibility of R. typhi isolates as well as investigation of the genetics and/or metabolism of this bacteria, and to correlate the findings with clinical response to treatment. To estimate the rickettsia clearance, we will characterise the R. typhi DNA load using qPCR in patients from a pilot study of murine typhus patients receiving doxycycline or azithromycin. Moreover, optimised conditions for R. typhi growth including nutrient requirement for development of a host cell-free culture medium using R. montana as a model to simplify antibiotic susceptibility testing of this bacteria will be investigated. The proposed work will improve our understanding of appropriate murine typhus treatment in Laos.
|
| 23/06/2020 |
£292,294 |
|
COLLEGE OF MEDICINE, UNIVERSITY OF IBADAN |
Depression is a common and disabling condition among the rapidly growing population of older people in low- and middle-income countries (LMICs). The burden is particularly high among older Nigerians. Yet, there is a large unmet need for treatment, possibly in part because available care is inaccessible and not age-appropriate for the older person. In line with global priorities, as envisioned in the Sustainable Development Goals to leave no one behind in the provision of quality health care, there is a pressing need for an integrated model of community-based mental health care that encompasses health, social, and informal care for older people in LMICs. Building on prior considerable work by our group to scale-up mental health care with the aid of the W.H.O Mental Health Gap Action Programme Intervention Guide, we now wish to leverage on the e-version of the tool, by 1) adapting it for the care of older persons with late-life depression through a user driven iterative loop process in which contextual, socio-cultural and health factors in the lived experience of late-life depression are incorporated; and 2) testing, in a pilot hybrid (effectiveness-implementation) design, effectiveness, cost-effectiveness, and factors that may affect the delivery of the intervention in routine care.
|
| 22/06/2020 |
£17,900,000 |
|
UNIVERSITY OF OXFORD |
The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:
1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.
2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.
3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.
Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.
|
| 22/06/2020 |
£24,589,618 |
|
UNIVERSITY OF OXFORD |
The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:
1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.
2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.
3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.
Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.
|
| 22/06/2020 |
£1,052,228 |
|
UNIVERSITY OF OXFORD |
The Wellcome Thailand AAP has conducted high quality impactful research for 40 years on infectious diseases of major public health concern, leading to the widespread adoption of new approaches and treatments for many of them including malaria, melioidosis, and rickettsial infections. In our fifth decade we will focus on ensuring sustainable impact and influence on policymakers by strengthening our research network and developing the capabilities of our partner institutions. Our vision is to:
1. Through research continue to address public health problems with regional and global relevance, using cutting edge approaches to seek affordable and deployable solutions to disease prevention, diagnosis and patient management.
2. Maximise our public health research’s uptake and impact, incorporating health economics analysis and goal-driven engagement with policymakers, national academic institutions, hospitals, industry partners, communities and the general public.
3. Work with our local host institutions to increase their national and global impact by integrating activities including training programmes, joint research projects, and supporting partner-led programmes to translate research into policy and practice.
Our goal is to improve life quality and expectancy by reducing the adverse impact of infectious diseases, which account for much of the disparity in health metrics between low and high income countries.
|
| 18/06/2020 |
£39,193 |
|
KING'S COLLEGE LONDON |
This research project will develop a framework for systematically incorporating ethical values into WHO Evidence Informed Policy Network (EVIPNet) Europe policy dialogues. Although ethical values are central to the appraisal of evidence and deliberation that is involved in policy dialogues, there is currently no explicit guidance for facilitators or participants on how to identity, define, interpret and evaluate key ethical values, nor how to recognise and work towards resolving tensions between different values. Explicit consideration of ethical values in this context is essential to the accountability and legitimacy of policy dialogues in the health policy decision-making process. Without it, discussions and decisions risk being shaped by unacknowledged and potentially unfounded assumptions, and risk recommending policy solutions which do not adequately take into account their moral and social costs and benefits. My project will aim to identify and evaluate the major existing accounts of moral reasoning for complex, real world deliberative contexts, and to develop and defend a model which is appropriate for policy dialogues. Policy dialogues are highly pragmatic tools which do not seek to pre-determine the values, knowledge and reasoning that participants bring to the table, and an ethical framework for this context must be similarly inclusive and pragmatic.
|
| 18/06/2020 |
£23,143 |
|
UNIVERSITY OF EXETER |
There is a growing recognition within public and third sector organisations that outcomes-based commissioning and management ignores the complexity (at an individual, organisational and systems level) in which services operate. Some in the sector are experimenting with more developmental, collaborative, place-based approaches. However strategic development has recently been disrupted by Covid-19, which has forced services to change overnight whilst increasing support needs within communities.
This project will analyse the ways in which community organisations have evolved during the crisis, and identify implications for future practice, not only in terms of service delivery models but also change processes and evaluation methods.
CoLab is a cross-sector ‘wellbeing hub’ hosting 30 organisations from community, social enterprise and public sectors supporting people with complex needs (e.g. homelessness, mental ill-health). As an embedded researcher I will work with staff and users as co-researchers, drawing on research tools from different methodological approaches (e.g. participatory action research, ethnography, developmental evaluation) to explore their experiences of using, delivering and adapting services in a rapidly changing context.
Key goals include producing recommendations for service development, identifying appropriate research methods to sustain an ‘action research’ culture moving forward, and sharing learning more widely within the sector and related academic fields.
|
| 18/06/2020 |
£6,181 |
|
UNIVERSITY OF GLASGOW |
Initiatives such as ‘The NHS at 70’ show strong public interest in the histories of public health in the UK. Such discussions have particular resonances in Scotland with the country’s reputation for poor public health and devolved responsibilities for healthcare. During my secondment, I will research the representation of hospitals, institutions of care and healthcare professions in Scotland, as found in the National Library of Scotland’s Moving Image Archive. The collections include documentaries, promotional and public information films, amateur works and newsreels, from the 1890s to the present day. My project will involve researching, contextualising and connecting key recordings to create appropriate narratives about public health in Scotland. I will research the histories and legacies of key Scottish institutions represented in the archive (such as East Fortune Sanatorium for tuberculosis patients, the innovative ‘therapy communities’ at Dingleton Hospital and ‘modern’ institutions such as Glasgow’s Stobie Hospital), situating this within a larger context of changing attitudes and policy about health and healthcare professions. I will create a curated interactive package, including clips and additional written information, for display at the Kelvin Hall premises.
|
| 18/06/2020 |
£35,349 |
|
UNIVERSITY OF BRISTOL |
The overarching aim of this project is to provide theoretical and measurement expertise in the economics of health and wellbeing into the work of a UK-based charity, Centre for Thriving Places, and specifically, their Thriving Places Index (TPI). More specifically, this project will be developing a better understanding of the key indicators that influence the wellbeing of individuals at different stages of the life course. Currently the TPI is summarised at the local authority level in England and Wales and is arranged into three headline elements: Local Conditions for wellbeing, Equality and Sustainability. This project will seek to inform how reflective TPI is of different population groups wellbeing at different stages of the life course, looking at wellbeing in younger and older population groups in particular. Specifically, this research project will focus of wellbeing at different stages of the lifecourse based on the indicators that feed into the TPI. The Centre for Thriving Places would use the work from this secondment to better inform local authority decision-making targeted as specific populations in their community. For instance, different public health policy responses may be required depending on the age profile of diverse local authority populations.
|
| 18/06/2020 |
£14,673 |
|
UNIVERSITY OF YORK |
Alternative indices of poverty may classify different individuals as being ‘poor’; these mismatches are problematic for charities and policy makers who aim to identify and reduce poverty. I will compare mismatches in poverty indices by considering distributional changes over time amongst different groups in the population. The analysis follows from Meyer and Sullivan (2008), who identify changes over time in consumption and income poverty in the USA. I will extend their analysis to the development context; using the Uganda National Panel Survey dataset (n≈3,000) multiple poverty measures will be constructed at the household-level, across the period 2009-2016. By focusing on distributional changes over time, mismatches between these measures can be identified, providing insights for policy makers trying to identify poverty trends. By disaggregating these measures a more in-depth analysis on the attributes of well-being, rather than aggregate summary statistics, will be conducted. Utilising a panel structure to follow individual households over time will allow for insights into potential causes of declines in well-being and the consequences of volatility. The paper will provide a methodological contribution to poverty analysis in the developing world, and offer policy relevant analysis of poverty in Uganda.
Keywords: Poverty Mismatches, Development Economics, Distributional Effects
|
| 18/06/2020 |
£17,912 |
|
UNIVERSITY OF OXFORD |
Fast Track Cities (FTC) is a multi-partner initiative aimed at addressing the challenge that cities bear a large share of the global HIV burden. London signed up to FTC in 2018 with the aim of eliminating HIV from the capital by 2030. The Healthy London Partnership (HLP) is the delivering organisation for London, bringing together representatives from Public Health England, NHS England, the Mayor of London and the London Councils. The aim of this fellowship is to work closely with HLP and support translation of the global goals of the FTC programme into the local context of London-specific initiatives, which include: funding and facilitating a quality improvement collaborative to increase HIV testing, access to HIV care and support for people living with HIV; and developing strategies to end HIV-related stigma. This project builds on my HIV social science research and on the extensive work on complexity in healthcare by our Oxford team, including current Medical Research Council and Wellcome Trust funded projects on context and complexity in health interventions. I plan to increase synergy between methodological research (Oxford) and gain experience of the translation of city-wide HIV policies and interventions through to implementation activities (HLP), with benefits to both partners.
|
| 18/06/2020 |
£16,413 |
|
UNIVERSITY OF OXFORD |
To control the spread of the 2019 coronavirus disease (COVID-19) outbreak governments around the world have introduced public health measures including social distancing, isolation, and quarantine. This has created conflicts between competing ethical values, particularly protecting the publics’ health and safety v. respecting individuals’ liberty and preferences.
Concerns have been raised about the impact of currently-implemented measures on people’s mental health. Children and young people may be affected in unique ways, due to their younger age and specific role in society. Yet, their mental health needs may be easily overlooked when professional care is devoted to those who are in most immediate need, i.e. the immunocompromised and the elderly.
The aim of this project is to conduct a systematic review of the evidence on the impact of social distancing, isolation, and quarantine on young people’s mental health and wellbeing, and to interpret it in light of the ethics literature on public health emergencies. This work will be used to develop a UNICEF working paper focused on ethically-robust policy recommendations, so that public health measures that will be implemented in future infectious disease outbreaks are mindful of children’s mental health needs.
Children, young people, COVID-19, mental health, ethics, UNICEF, systematic review
|
| 18/06/2020 |
£15,224 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
There is evidence that the global value of health co-benefits that result from climate action, are greater than the financial costs of mitigation measures around climate change. However, policy decisions at national and sub-national levels seldom reflect a connection with these global assessments. The World Health Organisation (WHO) has recognised this as an area of priority, and over the course of 2020-21 are committed to work with Health Economists to provide economic evidence that can be integrated into national level considerations, and specific policy measures for climate change.
As a Health Economist, I will work with the Department of Environment, Climate Change and Health at WHO headquarters, to support the generation of reliable country-level estimates of potential health gains and savings from national climate mitigation commitments of member countries. I will use mixed methods in my research, including cost-benefit analysis for feasible interventions and policy analysis to appreciate successful policies in neighbouring countries. The outputs of my work, which will highlight the health implications of climate change for policy-makers within and outside the health sector, will include a policy report highlighting country level health benefits due to reduced emissions, as well as a paper for submission to an academic journal.
|
| 18/06/2020 |
£13,629 |
|
GOLDSMITHS, UNIVERSITY OF LONDON |
The proposed project will support the Science Museum with idea development for a future exhibition on health activism through research in three interrelated areas. Firstly, knowledge will be built around the recently acquired quilt block #3 of the Dutch AIDS Quilt by gathering information about the NAMES Project Netherlands Foundation (donor of the quilt) and the 8 individuals commemorated in quilt block #3. Suitable parties will also be identified for interviews regarding the history of the quilt. The relationship between Amsterdam and London with regards to health activism and quilting will also be investigated. Secondly, by exploring the symbolism and materials used in the quilt block, the project seeks to understand the myriad of different purposes the quilt serves. Given that the quilt and its functions are tied up with an array of different emotions, the project also aims to study how quilt, affect and health activism are entangled. Relatedly, if the planned exhibition is conceived also as a form of activism, what role then might emotions play in the organisation of the exhibition? Lastly, the project will also examine contemporary forms of health activism so as to identify potential artefacts for collection and display by the museum.
|
| 18/06/2020 |
£15,521 |
|
UNIVERSITY OF CAMBRIDGE |
This project investigates the function and value of material culture associated with contemporary women’s experiences of health, such as menstruation, fertility and contraception. Drawing on recent work in LGBTQ+ and health activism, I will systematically research related objects in the Science Museum’s collection, share my findings through the museum’s online public engagement networks, identify further areas for collecting, and create a collecting proposal for consumer products designed to control, restore or facilitate bodily functions. This project asks four questions: What is the material culture of contemporary women’s experiences with health, and how does it fit into museum collections? What types of objects should be collected to represent the contemporary material culture of this theme? How can these objects be used in public engagement work in the present and the future? How can they be used to support ongoing efforts to break cultural taboos about women’s health and bodies in the context of museums? An analysis of these objects and their collection will shed light on their historical significance and reveal new ways that they might be used to highlight experiences of women’s health and medicine in the past, present and future.
|
| 18/06/2020 |
£7,625 |
|
UNIVERSITY OF WARWICK |
In 2019, the NHS Long Term Plan and GP Contract committed doctors to making online their default patient access point by 2023. The widely used NHS app and web-based appointment and repeat prescription systems will be updated to facilitate, e.g. video consultation and remote monitoring. England's provider, NHS Digital, claims these changes will increase capacity and cut costs by reducing physical attendance. Many consumer champions and academic experts have questioned the lack of independent evaluations of the technology, and stress the likelihood that privileging digital access will exacerbate existing healthcare inequalities. The expedited roll-out of these technologies required by the current COVID-19 crisis may heighten such concerns by evidencing a 'digital divide'.
A rapid review will bring together current research from academia, the public sector, industry, and third sector. This will demonstrate the current state of digitisation and each group's specific concerns and interests in implementation. Interviews will then concentrate on areas of consensus surrounding best practice, establishing several case studies of leadership.
For policymakers, it will set out possible solutions for avoiding the exclusion of patients from specific age, income, or ethnic backgrounds; and draw attention to the possibilities for partnership by highlighting shared interests across stakeholding groups.
|
| 17/06/2020 |
£1,016,701 |
|
UNIVERSITY OF EDINBURGH |
Stroke patients are increasingly surviving long-term after the primary neurological insult. Post-stroke complications have thus rapidly become an area of unmet clinical need. Infection is a common and dangerous complication of stroke associated with increased death and disability. Stroke-induced immune suppression is associated with infection susceptibility, but the majority of studies have focused on short-term (hours to days) changes to immune function. My recent data show early reduced numbers of lymphocytes and dendritic cells in experimental and clinical settings. It is unknown whether this impacts adaptive immune function and immunological memory. Using experimental animal models and parallel analysis of population health data sets, key goals of this proposal are:
1. To understand the extent and persistence of changes to adaptive immune cells after stroke and how this relates to infection susceptibility.
2. To determine if previously generated adaptive immunological memory is lost after stroke.
3. To determine if generation of new adaptive immunological memory is impaired after stroke.
This will generate understanding of the extent of adaptive immune memory deficits after stroke and the window of susceptibility in which stroke patients are vulnerable to infection and could result in new therapeutic approaches to reduce infection and improve long-term patient outcome.
|
| 17/06/2020 |
£916,159 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Almost half of the 435,000 malaria deaths each year occur in countries of the Sahel region of Africa, and the majority of these deaths occur during the three-four month rainy season. Monthly seasonal malaria chemoprevention (SMC) is highly effective in these areas, reducing malaria cases by 75-80% in trials, and malaria-specific mortality by 40-50% under programmatic conditions. However, malaria remains a leading cause of disease and death in several countries deploying SMC.
The key goals are therefore to understand how to 1) maximise the impact of SMC as currently designed (e.g. by timing it more accurately in different areas), 2) modify the SMC strategy to make it more effective (e.g. by identifying the causes of severe malaria in the context of SMC), 3) use other control tools, including seasonally-targeted vaccination, alongside SMC and 4) understand how improving malaria prevention in childhood would affect naturally-acquired immunity.
Analysis of data from a comprehensive evaluation of SMC in 7 countries, an SMC trial in 20,000 children, and the first-ever trial of seasonally-targeted vaccination alongside SMC provides a unique opportunity to answer these questions. Mathematical models incorporating these results will enable malaria prevention packages to be optimised according to the local epidemiology.
|
| 17/06/2020 |
£1,163,672 |
|
UNIVERSITY OF EDINBURGH |
Macrophages are essential mediators of tissue repair but we lack fundamental knowledge about how they are regulated in the endometrium. Androgens regulate macrophage function in other tissue repair contexts but their role in endometrial repair has not been defined. This project will determine how macrophages are regulated in endometrial repair by assessing their turnover and phenotype and how this is affected by androgens by using a highly reproducible mouse model of endometrial repair that we have developed.
The key goals of this project are;
to determine whether monocytes contribute to the endometrial macrophage function in repair,
to define how androgens mediate intrinsic and extrinsic effects on endometrial macrophage function and
to investigate how androgen excess alter macrophage function in aberrant repair.
This will be achieved by using fate-mapping techniques, transcriptomics analysis, multiparameter flow cytometry and immunohistochemistry combined with pharmacological and genetic approaches to modulate androgen action.
These studies will establish that macrophages are critical mediators of endometrial repair and modulation of their phenotype by androgens determines the balance between healthy and disordered tissue repair. These important insights will provide a platform for assessing macrophage AR as a potential therapeutic target in reproductive health.
|
| 17/06/2020 |
£413,761 |
|
UNIVERSITY COLLEGE CORK |
The recently discovered crAssphages are the most abundant group of viruses in the human body, reaching up to 20% of gut microbial DNA. They infect bacteria of the order Bacteroidales and demonstrate incredibly stable, sometimes years-long colonisation of the human gut. Our preliminary results, based on the first isolation of a crAss-like phage in culture, indicate that they use an unusual mechanism of infection that allows them to continuously co-exist with the bacterial host population at high levels. I hypothesize that bacterial interactions with their phage ‘partners’ is an essential aspect of microbiome functionality. The long term persistence of crAssphages in the human gut microbiome is an epitome of such phage-host interaction. My key research question is to provide a mechanistic and structural explanation of this interaction and gain insights into its significance for host physiology and overall microbiome structure. My research program consists of three specific aims: 1) developing methods for genetic manipulation with crAss-like phages; 2) using structural biology to get insights into mechanisms of phage-host interaction; 3) investigate persistence mechanism and its effect on community structure. Taken together these efforts should significantly advance our understanding of this new and elusive group of viruses in the human microbiome.
|
| 17/06/2020 |
£1,196,484 |
|
UNIVERSITY OF LEEDS |
Membrane-less organelles (MLOs) are multicomponent structures that form by liquid-liquid phase separation (LLPS) of proteins/RNA. They play key roles in organising cells, signalling, stress and viral factory formation, whilst aberrant LLPS is associated with several neurodegenerative diseases (e.g. MND). MLOs are heterogeneous and dynamic, making it challenging to elucidate their composition, structure and biogenesis. New tools are urgently needed to study LLPS in vitro and in vivo to address fundamental questions of the molecular mechanism of LLPS, and to unravel how it contributes to homeostasis and disease. Here, I will develop a toolkit of MS-based methods to study LLPS, focussing on two systems: TDP-43, implicated in MND, and NSP2/NSP5, involved in Rotavirus viral factory formation. This will reveal new insights into the structure/dynamics of these proteins (which promote/suppress LLPS) and the protein-protein/RNA interactions which nucleate LLPS. I will study LLPS in vivo using, and developing, structural MS methods to reveal the proteins recruited into MLOs and the interactions mediating recruitment. This toolkit of MS methods, reinforced with biochemical/cellular/functional assays, will afford new mechanistic insights into two important systems, uncover new targets to combat neurodegeneration and viral infection, and open the door to revealing how LLPS controls many other cellular processes.
|
| 17/06/2020 |
£1,547,266 |
|
UNIVERSITY COLLEGE LONDON |
In humans, as with all mammals,, the loss of auditory sensory hair cells (HCs) is irreversible. However, different degrees of HC regeneration occur in vestibular sensory epithelia, at early developmental stages, or in non-mammalian species. HC regeneration results from division and/or trans-differentiation of neighbouring supporting cells (SCs). It is generally accepted that poor/absent HC regeneration relates to the differentiation state reached by SCs and HCs, but the mechanisms behind this are unknown.
What dictates HC regeneration potential? Taking on a multi-layered approach, combining single-cell multi-omics, in-situ sequencing and transcriptional manipulations, I will study the vestibular utricle to evaluate the connection between maturation and HC regeneration potential. First, I will identify the cell/tissue level factors that interact during maturation to distinguish the mouse (marginally-regenerating) and chick (fully-regenerating) utricle. Second, I will study the regeneration trajectories of postnatal and adult mouse utricle to zoom-in on the factors driving the age-related decrease in regeneration potential. Finally, I will perform simultaneous transcriptional manipulation of identified targets aiming to overturn the poor HC regeneration of the adult mammalian utricle.
My research will generate unprecedented cell/tissue-level insight on the maturation and regeneration of sensory epithelia, identifying potential novel therapeutic avenues for recovery from pathological HC loss.
|
| 17/06/2020 |
£1,065,085 |
|
UNIVERSITY OF CAMBRIDGE |
Enteric viruses are a major cause of mortality and morbidity in the young, the elderly, and the immunocompromised. Even after decades of research, it is still poorly understood why these viruses replicate particularly in the gastrointestinal tract and what triggers virus dissemination beyond the gut. Despite their worldwide prevalence, and recently emerged neuropathogenic strains, astroviruses represent one of the least studied groups of human RNA viruses, mainly due to difficulties with culturing and molecular manipulations.
My research will focus on understanding the molecular determinants of astrovirus infection – starting with basic replication mechanisms and moving towards physiologically relevant translational outputs. Key goals include:
Characterisation of the viral RNA structure and replication strategy to understand their role during virus infection.
Functional dissection of the astrovirus polyprotein processing strategy and its role in virus infection.
Identification and assessing the importance of gut-specific determinants in virus infection.
Identification of the molecular mechanisms responsible for neurovirulence.
Elucidation of the fundamental molecular biology of astroviruses underpins an understanding of their pathogenesis, both in the gut and in the central nervous system. It will also facilitate the development of vaccines and antiviral therapies, addressing an unmet need for young children in developing countries.
|
| 17/06/2020 |
£1,178,961 |
|
UNIVERSITY OF CAMBRIDGE |
Endocytosis is a highly dynamic process that determines the composition of the plasma membrane (PM). The dysfunction of endocytic pathways is a causal factor behind a number of human genetic diseases, and its dys-regulation can contribute to neurodegeneration.
Despite the critical role that endocytosis plays in health and disease, surprisingly little is known about how it is regulated. A major potential regulation point is the dynamic phosphorylation of endocytic components by kinases. However, it is poorly understood which kinases (and phosphatases) control endocytosis and the PM proteome, even though they represent potential targets for disease-modifying therapies.
My long-term vision is to understand the integration of protein kinases within membrane-trafficking machinery. My starting focus is on the Numb-associated kinase family (NAK). NAKs were identified as a susceptibility factor in Parkinson’s disease and neuropathic pain but the molecular mechanisms behind this are not clear.
I will elucidate the key cellular functions of NAKs: (1) which cellular processes and substrates are associated with NAKs (2) the consequences of their activity for cellular physiology and (3) the regulatory processes and interaction partners which govern NAK activity states.
|
| 17/06/2020 |
£1,113,271 |
|
UNIVERSITY COLLEGE LONDON |
Tuberculosis is the leading cause of death from infectious diseases and requires a long treatment. Various initiatives aim to develop shorter and more effective treatment. However, this is complicated by the (1) absence of a biomarker that can predict treatment response during early phases of treatment and; (2) interactions between drugs when given together which makes dose selection/optimisation difficult.
My aim is to address these shortcomings by, for the first time, studying relationships between pharmacology, microbiology and immunology markers, using data from patients with drug sensitive and multidrug resistant tuberculosis and statistical modelling. This will help developing a test that predicts cure during the first 2 months of treatment which can contribute to improved efficiency of clinical trials evaluating tuberculosis treatment. Secondly, I aim to characterise overall antimicrobial activity and emergence of persistence and resistance, whilst accounting for drug-drug interactions using an innovative combination of in-vitro kill-curve and hollow-fibre experiments, in-vivo pharmacokinetic data and statistical modelling. This will inform optimisation of tuberculosis treatment.
I will undertake this work at University College London in collaboration with the University of Cape Town, South Africa, giving me access to a large and diverse tuberculosis patient population and state of the art laboratory facilities.
|
| 17/06/2020 |
£1,551,810 |
|
CARDIFF UNIVERSITY |
Aerobic glycolysis (AG) plays a vital role in brain disease, development, and ageing. Elevated AG has been linked to axonal elongation and synaptogenesis in childhood, synaptic plasticity in adulthood, and is a hallmark of cancer. There is also evidence of a significant reduction in AG in older age and in neurodegeneration. The development of a non-invasive method for imaging AG has the potential for significant impact in basic neuroscience and clinical practice. For example, in cancer therapy, post-treatment mapping of AG is anticipated to be a sensitive measure for assessing recurrence and for the planning of salvage therapy.
I propose to develop ultra-high field (7T) MRI methods to safely and non-invasively map aerobic glycolysis and tissue oxygen availability in the human brain, providing a new window into brain metabolism and metabolic dysfunction. The methods development involves two main paths. 1) Glucose labeled deuterium imaging to directly map cerebral AG. 2) Development of vascular imaging methods, including deuterium perfusion and blood volume imaging. The combination of these two methods will enable calculation of cerebral glucose metabolism, oxygen metabolism, and tissue oxygen availability. These methods will be validated experimentally using a controlled pharmacological modulation of aerobic glycolysis with sub-anaesthetic ketamine administration.
|
| 17/06/2020 |
£789,591 |
|
UNIVERSITY OF CAMBRIDGE |
Blood formation ultimately relies on the function of rare haematopoietic stem cells, canonically defined as multipotent and serially transplantable (c-HSCs). Mounting evidence, primarily from mouse models, indicates that these cells are activated in situations of extreme stress (e.g. transplantation). Day-to-day haematopoiesis and responses to less severe stresses are postulated to be instead driven predominantly by cell types that do not fulfil the canonical definition of HSCs, herein termed non-canonical (nc-) HSCs. nc-HSC generation, regulation and functional relevance remain unclear because reliable models to study them are lacking, especially in human.
During my current fellowship, using state-of-the-art single cell approaches, I identified and provided purification strategies for two types of human nc-HSCs. During the extension, I will i) investigate how nc-HSC are generated from c-HSCs, characterising a newly-derived model of human nc-HSC formation at the cellular, transcriptional, proteomic and epigenetic level. Focusing on erythroid differentiation, I will then ii) validate novel molecular mechanisms that drive lineage commitment of nc-HSCs; iii) define to what extent nc-HSC contribute to responses to stress.
These experiments will 1) provide proof-of-principle of the functional relevance of nc-HSCs to human haematopoiesis; 2) establish a much-needed tractable experimental framework to further study their role in ageing and disease.
|
| 16/06/2020 |
£60,000 |
|
INTERNATIONAL LIVESTOCK RESEARCH INSTITUTE, KENYA |
Antimicrobial resistance (AMR) is a global health threat, associated with increased morbidity, mortality, and financial costs. Identifying the potential reservoirs of antibiotic resistance and resistance mechanisms is an important task to tackle AMR. Klebsiella pneumoniae and Escherichia coli which can cause severe and often fatal infections such as septicemia and pneumonia are among the identified priority antimicrobial-resistant pathogens by the World Health Organization in 2017. Cephalosporins and Carbapenems are considered critically important antibiotics in the treatment of Gram-negative infections however their resistance has been reported in clinical settings.
The contribution of livestock as potential reservoirs and source of resistance genes to humans, which can be acquired by direct contact or through the environment and food-chain in Kenya is not known.
This study will investigate antibiotic usage, knowledge and practices amongst farmers and levels of AMR in different cattle dairy production systems to give an insight to Antimicrobial Usage and AMR, in particular focusing on the carriage of Cephalosporins and Carbapenem-resistant Enterobacteriaceae (E. coli and K. pneumoniae). Moreover, we will investigate the genetic determinants conferring resistance and mobile genetic elements harboring resistant genes. Additional information on AMR would aid further research focused on combating AMR in developing countries.
|
| 16/06/2020 |
£60,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Malawi suffers a substantial burden of chronic respiratory diseases (CRDs) which causes significant morbidity and loss of economic productivity, and affects patients, families and health systems alike. CRDs are a major risk factor for Coronavirus Disease 2019 (COVID-19). Pharmacotherapy for CRDs is of limited benefit and costly. Its rational use could be complemented by non-pharmacologic treatments. For chronic obstructive pulmonary disease, pulmonary rehabilitation (PR) is well established as highly effective intervention which improves symptoms, quality of life and survival. PR is comprehensive package of interventions including exercise training. PR is now sufficiently understood to obviate further randomized trials in High Income Countries (HICs). However, given the design and delivery of programmes should be adapted to patient groups and context, high-quality data are needed outside HICs. My pilot study will determine feasibility and acceptability of PR in Malawi. Specifically, I will: (1) co-design, with service users and stakeholders, a locally appropriate PR program for patients with functionally limiting CRDs in Malawi, (2) examine lung function, exercise capacity and health status of participants before and after their participation in a PR program, and (3) examine participants’ levels of attendance, participation and adherence to the programme.
Keywords: chronic respiratory diseases, pulmonary rehabilitation, Malawi
|
| 16/06/2020 |
£120,000 |
|
UNIVERSITY OF OXFORD |
Burkholderia pseudomallei (Bp) is a Gram-negative environmental bacterial pathogen. It causes melioidosis, a deadly infectious disease endemic in tropical and subtropical countries. Despite an increase in prevention efforts, the mortality rate of human melioidosis is still high. Bp is intrinsically resistant to several classes of antibiotics, which limits treatment options. The bacterium also synthesises antibiotics primarily to compete against other organisms in its soil habitats. I am testing the hypothesis that antibiotic resistance in Bp is either evolved as a self-protection mechanism against the antibiotics produced by itself, or interspecific competition or both. Using a dataset of 2,500 whole-genome sequences of Bp, I propose to mine the genes involved in the antibiotic synthesis, antibiotic resistance and their associated mobile genetic elements, thereby creating the first comprehensive antibiotic resistance and synthesis database for Bp. Long read sequencing will be employed to aid further identification of mobile genetic elements which will help determine the route of acquisition of these genes. I will use several bioinformatics methods to test the co-inherited patterns of antibiotic synthesis and resistance genes, their evolutionary stability and their mobility. Together, this will provide new ecological insights into antibiotic synthesis and resistance mechanisms in Bp and other bacteria.
|
| 11/06/2020 |
£100,000 |
|
UNIVERSITY COLLEGE LONDON |
In low-resource settings, the locus of care for women during childbirth, and for sick and/or vulnerable newborns, has shifted dramatically from community-based contexts to formal facility-based settings. Furthermore, low-cost digital quality improvement solutions such as the NeoTree, are increasingly part of the healthcare landscape.
How mothers, caregivers, families and communities experience and perceive an increasingly biomedical, institutional model of newborn care, is not well understood. During our field visits to Zimbabwe and Malawi in developing the project, and in 2019 on commencement of the grant, our partners expressed concern that some mothers/caregivers fear the use of digital technologies, and formal health providers may lack sensitivity to patients’ social and cultural beliefs surrounding childbirth and the newborn. Furthermore, the benefits of digital health innovations, including electronic data capture, are not widely distributed within communities.
Our vision is to strengthen the partnerships between patients, families, communities and facility-based health professionals to ensure that quality improvements achieved by the NeoTree under our main award are sustainable and equitable. By the end of this enrichment activity, we will have achieved the following:
Empowered parent/caregivers to articulate and represent their experiences of using facility-based health care via participatory art methodologies;
Created opportunities for parents/caregivers and families to disseminate these experiences and spark critical reflection and dialogue with researchers, health professionals and policy makers;
Established and strengthened links between communities including participatory women’s groups and the NeoTree team/system.
Built public engagement capacity and disseminated lessons learned among our partners and research communities in our partner countries.
|
| 11/06/2020 |
£78,960 |
|
UNIVERSITY OF LINCOLN |
Converging environmental, health, welfare and political agendas make the future of food and farming one of today’s most contested issues. Media representations are often unhelpfully polarised. Criticisms rest frequently on simplistic understandings coloured by false memories of an earlier ‘golden age’, while defensive farmers can struggle to articulate the challenges they face. In creating opportunities for more inclusive, reflective, non-judgemental exchanges, our enrichment work - based around creative practices that engage with livestock health and farmer/livestock relationships - will encourage farmers and diverse consumers to work through their differences, and develop mutual respect, empathy and understanding. Achievement of these objectives will be assessed through formative and summative evaluation.
Three creative professionals - an artist (of any media), photographer and filmmaker, who are experienced with socially engaged art practices - will reside with the project's researchers and the farming communities they are studying. Their outputs will be taken back to these communities, and to various consumers, in conjunction with other engagement activities that are built around project research and its historical resources. Participants will be invited to respond, reflect, remember, converse, comment and learn about each other's perspectives on livestock health, welfare and production, and to engage with farmer/livestock relations in the past, present and anticipated future. To promote interactions between farming and non-farming audiences, the filmmaker will capture early participants’ reactions before adding their documentary to the exhibition. Researchers, farmers and practitioners will reflect on, and share their experiences of working together. Afterwards, the MERL will accession creative outputs.
|
| 11/06/2020 |
£94,290 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
COVID-19 has helped to illuminate the fundamental importance of young people and scientists effectively communicating the urgency of infectious disease. This project will develop the ways in which our science explains and communicates discoveries to a wider audience, using story and narrative devices familiarly used in animation and graphic novels as gateways to complex ideas. The body of work created will be a snapshot of where Mostowy lab research is in 2020, and a tool to develop the way in which the lab communicates its research.
The project will be made with members of the Mostowy lab, with input from students and young people in London and Manchester, collaboratively producing an animated film examining central research concerns of the Mostowy lab including; Shigella, superbugs, antimicrobial resistance in a post-antibiotic environment, and the global health challenge these present.
Inclusive sharing events will bring together the professional film we make with the creative work made by young people, giving an opportunity for us to discuss and appraise the learning from each experience. The work will be shared, at different stages of its development, at public events in London and Manchester, online, and at festivals internationally.
Developing from the award-winning Wellcome Trust funded animation Loop (2016), this new project will be a legacy tool to explain the lab’s most recent discoveries to a non-scientific audience, as well as to any researcher, healthcare professional or stakeholder. It will include ideas from young people as well as researchers, creating engaging visuals about compelling material.
|
| 11/06/2020 |
£245,213 |
|
BIRKBECK UNIVERSITY OF LONDON |
Shameless! is a bold and exciting cross-arts festival intersecting academic research, activism and art in confronting sexual violence. A three year project with each edition of the festival hosted in the UK and Brazil; London 2021, Rio de Janeiro 2022, and sharing learning across the UK in 2023. Shameless! brings together diverse communities of survivors and the expertise of researchers, medical, psychiatric and legal professionals, artists and activists in a transformative programme of talks, performances, workshops, ‘how to’ clinics, wellness spaces, and a schools’ programme.
A wide range of partners will be engaged in varying capacities. Our principal partner, The WOW Foundation (WOW), will co-produce the two festival editions in London and Rio de Janeiro. Given WOW’s robust experience and network, including in Brazil, Shameless! will implement WOW’s methodology in producing both festivals. Shameless! will also work with national, international and grassroots organisations and charities, and commission local artists and wellness practitioners to facilitate safe spaces for dialogue and healing. Offering a unique environment for children, families, young people, women, gender- and trans-diverse people, the festival will provide safeguarding measures to protect members from vulnerable and marginalised communities (race, class, abilities, sexualities and genders).
In 2023 Shameless! will share our public engagement and festival programmes with UK universities through a series of workshops, conferences and publishing reflective articles.
Shameless! aims to revolutionise conversations around sexual violence between survivors and professionals; burst open the constructed and inherited ideas of shame; and create an emboldening attitudinal shift from stigma to agency.
|
| 11/06/2020 |
£56,388 |
|
UNIVERSITY COLLEGE LONDON |
What the activity will look like:
We will bring together health-interested publics and population-health decision-makers for a series of workshops engaging with key aspects of the AI System and co-producing a toolkit of resources to facilitate appropriate trust in AI systems applied to population health.
What we will have achieved
1: Co-produced toolkit of resources
Exact nature of the resources will depend on outcomes of the workshops. We envisage resources that explain and prompt questioning about key features of the AI System and promote consideration of personal values/preferences regarding those aspects to decide upon trust in the System. The toolkit will also be applicable to discussions of trust in other AI systems applied to population health.
2: Multi-media documentation of discussions in workshops
Developed in partnership with participants
Made publicly available online
Documenting issues raised and providing case studies of public engagement
3: Interactive public talk on facilitating appropriate trust in AI in population health decision-making
With live web video link and video-recording
Opportunities for Q & A’s during and after
4: Additions to the HBCP AI System user interface
Toolkit resources will be linked to the System’s online interface and their use promoted to people querying the AI System.
Overarching these achievements will be efforts to achieve long-lasting and widespread reach
The dissemination and engagement strategy will be both broad and targeted, maximising exposure to and engagement with the outputs, including a social media campaign. Long-term availability of the outputs will be ensured through hosting them on the HBCP website.
|
| 04/06/2020 |
£89,973 |
|
EUROPEAN MOLECULAR BIOLOGY ORGANIZATION |
A scaleable, interoperable mechanism to establish transparent peer review in scientific journals and preprints as a standard optimized for the browsing, interpretation and assessment of research papers and preprints. The proposed tools and standards will allow inclusion of peer review formally in research assessment by funders and research institutions.
|
| 04/06/2020 |
£62,082 |
|
MICROBIOLOGY SOCIETY |
This project aims to convert one of our journals, Access Microbiology, into an Open Research Platform (ORP), offering greater peer review transparency and fast-tracking the communication of valuable research, maximising potential for impact and influence.
At submission, articles will be made available on microbiologyresearch.org with a DOI, with clear links to open data, methods, and code, and accompanied by the reports from the machine learning review tools (e.g. Statcheck). Peer review will be transparent, and a version history maintained from preprint to Version of Record.
Many societies are seeking new ways to serve their communities but are reluctant to adopt the pre-existing F1000 ORP software. This may be because they wish to maintain a single portal for access to all the work they publish; they are reluctant to enter into a publishing agreement with a commercial player; or they are concerned that the concept may not be embraced by their communities. Through this project, we hope to prove that an ORP can be provided using software in common use by publishers of all types, and that self-publishing societies can set up such a platform independently. We also hope to provide a financial model that proves ORPs can be financially self-sustaining.
|
| 04/06/2020 |
£82,906 |
|
AMERICAN SOCIETY FOR CELL BIOLOGY |
The proliferation of scholarly content and implementation of transparent peer review are creating challenges for readers and evaluators to assess research significance and review outcomes, and for journals to curate field-specific content. We propose controlled experiments in which we test the utility of badges and impact statements to signal the significance of articles published by the American Society for Cell Biology (ASCB) in its research journal, Molecular Biology of the Cell (MBoC). We will devise badges that alert readers to article attributes such as new concept, broadly relevant, technical advance, teaching resource, etc. We will also experiment with new peer review processes, including a streamlined process designed to concisely identify points of significance and key issues, and one in which authors, reviewers, and editors work together to craft concise impact statements for display on articles. The effects of these innovations will be assessed relative to traditional practices by comparing article-level metrics including article views, downloads, and Altmetrics attention scores and by surveys. We will then use these innovations and the expertise of ASCB members, including early career scientists, to curate preprints and articles in other venues with the goal of providing standard, portable tools for use by other publishers.
|
| 03/06/2020 |
£20,000 |
|
MANCHESTER METROPOLITAN UNIVERSITY |
Reimagining:
On completing the activities, I will have collaboratively re-imagined rhythms, pace, practices, planning and policies of an inclusive, interdisciplinary research cycle and research culture
I will have forged trusting, authentic, sustainable connections with staff, students and research partners, that values difference in generating and making knowledge culturally relevant, usable and accessible.
I will have developed a collaborative inquiry to inform equitable and inclusive research bids
Make valued, recognised contribution to improving D & I
Researchers are energised and motivated to submit bids that research partners feel improve working conditions for diverse researchers and lives of communities and make research culture inclusive
My university, communities, networks are proud of contributions, perceive research as a valuable and researchers as authentic leaders shaping the future of inclusive research internally, in wider academic networks and society.
My university will have a sense of the barriers that prevent inclusive research, an action plan/tools to work with in order to remove barriers, an example of a research cluster that has proved it possible and a culturally relevant race equality chartermark action plan
Potential PhD students, researchers and future partners will recognise our efforts and want to learn from our research cluster. We will have tools, practices and approaches to onboard them to our inclusive ways of working.
Sharing and extending our influence
Researchers, partners, senior leaders will identify, invest further (time/money) and be positioned to plan, share and embed with peers, centres and networks the ethical principles, road map and practice map through which success was achieved.
|
| 03/06/2020 |
£3,995 |
|
STREETINVEST |
The 30 street-connected children trained as researchers represent a diverse range of gender identities, ethnicity, religions and castes, however staff report that one major barrier to inclusion remains: literacy. During the process of recruitment, several children volunteered, but were unable to engage with the project materials and tasks required, including the development and delivery of surveys and documentation of responses.
This activity will in the first instance address this barrier for the remainder of the project by ensuring that children with low or no literary participate equally in the interpretation and dissemination of findings, including formulating messages and demands for health responses. Secondly, it will ensure that materials are accessible to all, regardless of literacy, so that research respondents can understand the findings. Thirdly, this activity will strengthen the research toolkit and training manuals by specifically addressing the issue of literacy.
This will ensure all children regardless of their literacy level, who have responded to the 500 surveys completed to date, are included in the sharing of research findings and 30 with low or no literacy play a central role in developing demands and messages for health service providers, so that all children have the opportunity to inform responses to their health needs. In the future, teams will be equipped with the methodology, tools and and training to make it possible for children of all literacy levels to participate as Street Champions.
|
| 28/05/2020 |
£50,000 |
|
UNIVERSITY COLLEGE LONDON |
The underlying software code for the NeoTree is open source and the NeoTree system provides an exemplar vehicle with which to facilitate and accelerate the sharing and re-use of nationwide newborn care data. Our proposed goals of this proposal are to maximise the efficient and meaningful sharing and re-use of data collected via the NeoTree, and the re-use of the NeoTree source code. This moves beyond the delivery of an open research database and is transformative in its approach to substantially enhance the impact of the overall project to improve newborn care in resource-poor settings. This work will showcase the potential impact and pathways of conducting open research in newborn care, maximise impact of the NeoTree platform for use in other disease and patient groups and enhance capacity for international partners to re-use the NeoTree data and thus improve population health and health systems delivery. We will deliver the following:
A guide for downloading and adapting the NeoTree code (to be hosted alongside the source code in GitHub under the MIT license);
A guide for implementing the NeoTree in a new setting, including downloading and setting up the open source code, configuring the technology to match the local healthcare setting and extending and adapting the code;
Data pipeline and guide for deployment;
Metadata for the full NeoTree data;
Training manuals for interrogation of NeoTree open data.
|
| 28/05/2020 |
£49,929 |
|
UNIVERSITY OF OXFORD |
The main aim of this proposal is to enable wider access to analysis tools that we are developing within our collaborative award, with particular emphasis on usability for non-technical, time-poor researchers and clinicians. This will primarily be achieved by focusing on the development of open, interactive visualisation tools that allow users to have an easier and more intuitive interaction with a wider set of our imaging and non-imaging outputs. Such interactive tools will lead to greater uptake of our analysis methods and a greater understanding and application of the research outcomes.
The secondary aim, supporting the primary aim, is to increase engagement and provide greater leadership to the open science neuroimaging community. This will be provided by going beyond the adoption of current methods of data structuring (BIDS) and containerisation of code (BIDS apps), by integrating them into the core level of the interactive visualisation tool. This tool will create simple, interactive ways of calculating and applying normative biomarkers, without requiring users to spend substantial amounts of time in training and installation of our current software tools. To do this we need to refine and extend the current neuroimaging open science data structures (BIDS), especially for atlases, spatial transformations and population-level measurements. Increasing the usability and access will encourage a wider variety of users and associated datasets, leading to greater feedback about our research tools and outcomes, which will form a crucial feedback loop and be a prime factor in measuring and improving the reproducibility of all of our research.
|
| 14/05/2020 |
£63,753 |
|
BLACK CULTURAL ARCHIVES |
The project has three central activities.
One: Access. Cataloguing the papers of Melba Wilson OBE (fl. 1965-2010). Wilson’s career included leading national and regional mental health programmes, policy units and services, specifically with a focus on minority ethnicity people.
Two: New descriptive practice. The cataloguing of Wilson’s papers will be used as a springboard into new approaches around cataloguing and dissemination of archival sources.
Three: Collections development. Scoping hidden histories of activism in the intersection of race and mental health, including the histories/ archives of organisations such as Ipamo (1995-1998) a Lambeth based Black mental health initiative, and the Afiya Trust (founded 1997) a national charity that works to reduce inequalities in health and social care provision.
Supporting these three strands is our collaborative studentship with the University of Roehampton, and a programme of public engagement to disseminate the outputs of the project and to ensure a wider impact of the project outcomes.
The key outcomes of the project are:
Enhancing the resources available in this field of research.
Creating new opportunities for discursive research.
Making a lasting change to the availability and range of minority mental health archive collections.
Innovating in the field of archival practice.
|
| 14/05/2020 |
£326,594 |
|
UNIVERSITY OF WARWICK |
This is a project to conserve, catalogue and exploit the archives of the National Union of Mineworkers (NUM). It presents the opportunity to develop a nationally significant archive for occupational and industrial health at the MRC and a Midlands network for coal related archive collections. The NUM records are currently held in poor conditions at the union’s headquarters in Barnsley. The project involves the removal of the archives to professional conservation facilities for drying and cleaning prior to storage at the MRC. It includes the sorting and cataloguing of the collection for research use as well as a public engagement programme. The project will:
Remove the collection to Harwells for conservation treatment
Re-box, sort and summarise the collection for immediate access and use in promotional activities
File/item list the collection for full online catalogue access
Select and digitise items for research, teaching and exhibitions.
Develop a project website
Co-host seminars with the Centre for the History of Medicine (Warwick) on coal, industry and health
Develop a Midlands network of coal related archive collections for future collaboration, education and outreach activities
Use the NUM archive as a focus for the development of a national industrial health and welfare archive
|
| 14/05/2020 |
£52,532 |
|
THE MULBERRY BUSH ORGANISATION |
Since 1989 the Planned Environment Therapy Archives have been unique in their remit to capture and preserve the records of therapeutic communities and care.
In 2002 the Archives acquired the papers of the psychoanalyst Harold Bridger. The collection spans the whole of Bridger’s career, from his pioneering work as the Commanding Officer at the Second Northfield Experiment, through his role as a founding member of the Tavistock Institute of Human Relations, and on to his groundbreaking work concerning team dynamics in the workplace.
Bridger’s papers have enormous research potential in the fields of psychiatry, psychology and sociology as well as the history of medicine, economics and social reform.
The project will look to address the under-use of Bridger’s Archive by cataloguing the collection to international standards, identifying and carrying out preservation work, and promoting the collection.
To achieve this, a Project Archivist will be appointed to appraise, arrange and describe the materials. During the project, the post holder will carry out basic preservation to support long term use of the collection, and will oversee the digitisation of obsolete media. The Project Archivist will promote the collection by creating a network of stakeholders and attending relevant conferences and events.
|
| 14/05/2020 |
£209,931 |
|
UNIVERSITY OF LEEDS |
Women’s Aid Federation England (WAFE) is the national coordinating body for all local and domestic violence services, including refuges in England. It provides information, training and resources to these services as well as to other agencies. It monitors the experiences of and the provision for women and children suffering abuse. It lobbies, advocates and campaigns throughout England.
The archive encapsulates the broad spectrum of its work. Growing out of the Women’s Liberation Movement in 1974 the organisation moved in twenty years from being one which met with aggression from the police to one which was highly regarded for its knowledge and research. The organisation marks its 50th year in 2024. WAFE is working in collaboration with the University of Leeds Special Collections and the Feminist Archive North (FAN) to safeguard the historical record and make it accessible for research. Collection, appraisal, documentation and preservation will ensure the collection is publicly available before this milestone year. New research collaborations will become active, learning resources will be created, and knowledge of WAFE's activity and significance will be shared and exchanged. The collection has interdisciplinary research significance and is a major resource for WAFEs own understanding of its contribution to health and society.
|
| 14/05/2020 |
£154,842 |
|
LONDON METROPOLITAN ARCHIVES |
The aim of this project is to make accessible for research three recently acquired archive collections held by London Metropolitan Archives which together illuminate two important threads of the AIDS crisis of the 1980s and its aftermath: pioneering medical treatment, care and support; and lived experience of not only those diagnosed with HIV/AIDS, but their carers, partners, relatives and friends. They comprise: Mildmay Hospital archive including 4000 patient case files; 103 interviews of people with AIDS, their families, partners and carers, filmed by the AIDS Since the 80s project; and the archive of peer-led support charity Positively UK (formerly Positively Women). The key outcomes will be: freely available online catalogues to item level of all three archives; a research database of key information extracted from the Mildmay Hospital case files, and full digital access to the 150 hours of filmed interviews supported by time-coded summaries, transcriptions and captioning. The archives, and the areas they inform such as the history of sexuality, science and medicine, as well as social and cultural change, and the methodologies used to make them discoverable, will be promoted through a conference, two professional skill-sharing events and two film-screenings, building on existing demonstrable interest in these archives.
|
| 14/05/2020 |
£236,339 |
|
UNIVERSITY OF BIRMINGHAM |
This 24-month project focuses on cataloguing and preserving the archives of two influential youth movements:
The Young Men’s Christian Association (YMCA)
The Youth Hostels Association (YHA)
Both archives are held at the Cadbury Research Library, University of Birmingham.
Health and welfare of young people are guiding principles of these charities. Since their creation, both organisations have focused their activities on improving the mental and physical health of young people, with emphasis on working with those from disadvantaged backgrounds.
The YMCA archive comprises 978 boxes and the YHA archive comprises 405 boxes; all of which require detailed cataloguing in order to realise their full research potential. Both collections include minutes, reports, publications, photographs and ephemera. Material documents the work of both charities in improving young people’s physical health, mental wellbeing, and general fitness.
The outcome of this project will be two fully searchable electronic catalogues which will enable access and reveal the full research potential of these internationally significant collections.
Engagement activities with academics, researchers, students and members of the public will ensure that the collections are visible across a broad range of audiences.
|
| 06/05/2020 |
£84,054 |
|
UNIVERSITY OF CAPE TOWN |
The research questions are - How has indigenous medicine responded to the substance abuse crisis in SA? What might future interventions look like?
An auto-ethnographic reflection on addiction and recovery, that seeks to deepen local understandings and narratives to include notions of historical trauma, dispossession and ‘insecure attachment’ to ancestors, nature and land.
Working with indigenous health practitioners (IHPs), the research will explore indigenous medicine’s response to the high levels of substance abuse in South Africa. Drawing inspiration from indigenous-led treatment programmes in Canada, Peru and the United States, that fuse indigenous and biomedical approaches, future interventions will be explored with indigenous and allopathic health practitioners, researchers and people in recovery as co-researchers.
The project will experiment with various research methods; introducing the notion of dreaming as a research method; story-telling; and indabas. We aim to collectively envision interventions that integrate ancient indigenous methods, biomedical/psychological approaches and technological tools. The research will be based in Cape Town but will include participants from all over South Africa.
Public engagement methods will be decided collectively during indabas to tailor the dissemination of findings to the various communities needs, this could be through podcasts/community radio, web-based audio-visual material, community indabas, ceremonies and performances.
|
| 06/05/2020 |
£85,336 |
|
UNIVERSITY OF EDINBURGH |
This research examines the relationship between the biotechnology industry and consumers, to determine what effect(s) this relationship may have on the outcome of clinical trials. Despite regularly being referred to as the ‘new genetics’, there has been little substantive change over the past two decades in the ways we have studied social aspects of genetic testing. Studies are largely embedded in the dichotomy of ‘consumption’/‘production’, treating 'patients'/'industry' as discrete categories in an unchangeable hierarchy. However, medical biotechnologies do not exist in a theoretical vacuum: they are continuously evolving products of social, political and economic endeavours, which have social, political and economic consequences. This research will follow the Phase 3 Study of RG6042 (previously IONIS-HTTRx), the first drug specifically targeting the mechanism responsible for HD, and a Phase 1 trial of a novel gene therapy. Methodology includes interviews, group interviews, and participant observation to determine how information moves and mutates, and how this effects medico-social pathways. Drawing on concepts of translational science, this research will examine how/when/why and to what effect 'scientific' knowledge is communicated among and between actors, and what effect this may have on the outcome of the trial for both participants and industry.
|
| 06/05/2020 |
£114,971 |
|
UNIVERSITY COLLEGE LONDON |
This proposal is for a year-long ethnography of an internet addiction rehabilitation centre in rural Washington State. It will develop an anthropological understanding of internet addiction, the study of which has so far been limited to neuroscience, psychology, and psychiatry. This will allow the cultural, social, and systemic background to the condition to be revealed.
The ethnography will be phenomenological, exploring the changes in the experience of space and time that rapid withdrawal from the digital causes – putting the living body at the centre of study. I will do this with the aim of establishing how use of the digital changes the experience of everyday life, explaining internet addiction through these changes. I will also ask whether the experience of extreme cases is shared by ordinary users.
I will investigate whether the condition can be used to denaturalise the broader category of addiction, unpacking and challenging suppositions established in the study of addiction and mental health.
As well as generating new knowledge and raising awareness, I will assist in the formation of patient groups, as well as supporting charities and healthcare facilities dealing with the condition. I will also aim to persuade healthcare services to fully recognise the condition.
|
| 06/05/2020 |
£98,900 |
|
UNIVERSITY COLLEGE LONDON |
My research focuses on XIII-XV Old Norse medical treaties featuring classics and continental models, to assess the extent to which Mediterranean medical practices were assimilated and re-elabotared within the Old Norse framework to understand the cultural dialogue between medieval Scandinavia and the continent. I will provide annotated translation of remedies, herbaria and antidotes contained in manuscripts preserved in Copenhagen and Reykjavík, comparing them with their continental counterparts at the British Library, Cambridge and Oxford. Consequently, the nature and the usage of these texts as sources of healing will be problematised and I will challenge the obsolete term "pseudoscientific" used in scholarship to refer to medieval medical practices and elaborate a new interpretive frame of understanding. I will demonstrate that Old Norse participated to the cultural syncretism in the Middle Ages by assimilating the occurrence of Classics and continental medical knowledge in manuscript context. This will lead to study a materiality of practices which allowed for a physical impact on the body. My research will address the cultural biases that have greatly affected certain topics within Old Norse scholarship which have not been considered in a comparative perspective and have led to the study of Old Norse culture in isolation.
|
| 06/05/2020 |
£108,868 |
|
UNIVERSITY OF OXFORD |
This mixed-methods project will treat Greater Manchester’s integrated budget in 2016 and the delayed roll-out of Integrated Care Systems across the country as a quasi-natural experiment.
I will use a nested-analysis method with qualitative research and three ‘diverse' cases studies will be chosen non-randomly to understand how each Local Care Organisation are specifying their policy delivery according to different population needs.
The hypotheses from the small-n analysis will then be tested by further large-n analyses. My research will use advanced methods in order to isolate causal effects of the intervention of integrated care in Greater Manchester. I will use synthetic control methods to create a synthetic counterfactual trend of Greater Manchester if it had much less developed health and social care integration. My synthetic control will be developed from weighted trends from other city-region combined authorities in England. This method is an alternative to traditional methods such as difference-in-differences.
This research is interested in the consequences of integrating healthcare at a city-region geography on population health outcomes, this project hopes to understand whether this policy trend is likely to induce new inequalities into the health system, tackle those already in place, or both.
|
| 06/05/2020 |
£72,174 |
|
UNIVERSITY OF OXFORD |
I am invested in researching the history of the female body in British colonial Punjab from 1885 - 1947, as it lived and experienced British colonial medicine. I want to study the character of the relationship between British colonial medicine and the princely states of Punjab, and between biomedicine and religious nationalism, and the impact of these relationships on women’s bodies, and their motility, mobility, and embodied subjectivity. I have located hitherto unutilised primary sources – women’s magazines, journals, and quasi-medical magazines run by women written in Punjabi, and medical and administrative records of local women’s hospitals in the six princely states of Punjab – in order to investigate the lives of Punjabi women who experienced the biomedical regime through practicing medicine or becoming patients.
Through the position and practices of women under investigation, I wish to question the conceptualisation of ‘medicalisation’ that has often been applied to understand the impact of biomedicine on societies such as India. I wish to understand women’s decisions and choices during this period not only as representative of the medical-religious dichotomy or alliance, but also as representative of the impact biomedicine had on their experiences of their own bodies.
|
| 06/05/2020 |
£97,554 |
|
UNIVERSITY COLLEGE LONDON |
The 1960s and 1970s marked a decisive change in the history of psychiatry critique, when in the UK, in Germany, and the US therapeutic communities and patients’ collectives formed outside of psychiatric institutions. Some of them were guided by psychiatry reformists, for instance R. D. Laing, others were self-managed by psychiatric patients as a counter-reaction to existing psychiatric institutions.
My research pursues two main goals: first, to offer an understanding of critical psychiatry as an international counter-cultural network which circulated knowledge and subversive practices across national borders; second, to analyse how psychiatry critique became a powerful tool for patients to confront social marginalisation, lack of rights and isolation.
Based on original oral history, archival sources, and literary sources, I will map out a transnational historiography of critical psychiatry that revises existing narratives within the limits of national borders. My project constitutes the first attempt to examine in depth the Philadelphia Association, the governing body of various housing projects for psychiatric patients in London, as well as it does justice to the under-researched critical psychiatry scenes in Germany and the US.
In sum, I will produce new perspectives on key historical developments that have lead up to critical psychiatry’s contemporary significance.
|
| 06/05/2020 |
£106,077 |
|
UNIVERSITY OF OXFORD |
Psilocybin-assisted psychotherapy is likely to become a licensed treatment in the US within two years. However, clinically-relevant doses have a number of surprising ‘side-effects’: they can cause long-term changes to political values and personality, increase prosociality and aesthetic appreciation, and induce mystical experiences of long-lasting spiritual significance connected to changes in religious belief. These changes remain under-researched but challenge several ethical concepts, including authenticity and autonomy, beneficence, and informed consent. The project will begin by systematically reviewing the non-clinical changes reported in the empirical literature to develop a conceptual analysis of these changes within a medical ethics framework. In addition, the perspectives of patients and practitioners of psilocybin-assisted psychotherapy concerning these changes remain unknown, and they are not addressed either in the informed consent process or in therapist training manuals. As such, the project’s second stage will use qualitative empirical methods to provide an account of their experiences and understanding of these changes. Together, the two elements of the project will demonstrate how psilocybin-assisted psychotherapy challenges orthodox conceptualisations of psychiatry, which marginalise spirituality and experiences of awe, as well as requiring policymakers such as NICE and their National Collaborating Centres to revise their approach to foreseen-but-unintended consequences of treatment.
|
| 06/05/2020 |
£93,106 |
|
UNIVERSITY OF WEST LONDON |
Particular reproductive technologies can make visible elements of the process of biological procreation, but this is not a neutral process. How these technologies see, and are themselves seen, influences the way reproduction itself is understood. Even within current feminist theorising, there is insufficient research into the role of visual cultures of reproductive technologies in the construction of cultural imaginaries surrounding biological reproduction.
Using social reproduction theory as a framework, this PhD will explore the gender politics of the visual representation of historical and emerging reproductive technologies, and investigate the cultural impact of this representation. It will use archival research (extending to advertising, product design, media coverage, and activist ephemera) to explore three case studies: 1. Conception – egg-freezing and IVF; 2. Gestation in process – from ultrasound to the artificial womb; 3. Political contexts – alternative feminist reproductive technologies.
The thesis will explore the gender (and racialised) politics of how historical and emerging reproductive technologies represent gestation, and how they themselves are visually represented. It will analyse the effect of this representation of reproductive technologies on the cultural imaginary, particularly in terms of its role in facilitating or prohibiting social recognition of gestation as a form of reproductive labour.
|
| 06/05/2020 |
£173,371 |
|
UNIVERSITY OF BRISTOL |
Existing research and training in palliative care ethics appear not to focus on, or be tailored to, practice in China. This research aims to fill these gaps by: first, identifying and exploring the ethical challenges Chinese healthcare professionals have confronted during their provision of palliative care; second, identifying the ethical training they have received and the extent to which they feel prepared to address relevant challenges; and, third, proposing changes, for example, to existing training in order to better equip these professionals. The significance of this research includes offering up-to-date knowledge of palliative care provision and relevant ethical training in China, assessing the utility of these training schemes and eventually making insightful suggestions.
This is an empirical bioethics project, which has three phases (mapping-framing-shaping). The mapping phase involves literature reviews. The framing phase involves qualitative research. The researcher plans to retrieve and thematically analyse empirical data via one-to-one semi-structured interviews. Considering the unique cultural and social background, the data collection will be undertaken in Mandarin in selected hospitals in China. The shaping phase then combines the previous theoretical and empirical findings, using an empirical bioethics methodology - reflexive balancing - with a view to making recommendations for future practice.
|
| 06/05/2020 |
£96,988 |
|
UNIVERSITY OF DURHAM |
A growing body of psychological research has identified a population of individuals who hear voices outside of the context of pathology. These "non-clinical" voice-hearers have been the subject of a variety of studies aimed at understanding their relationship with clinical voice-hearers. This research, which often relies on standardized psychological measures, fails to explore the broader context in which these experiences occur. Non-clinical participants are often recruited from spiritual communities who accept anomalous experiences and offer meaningful frameworks in which to understand them. The proposed research will address this gap in the literature. Drawing on theory and methodology from anthropology, psychology, and philosophy this research will explore the ways in which the voice-hearing experiences of these individuals are shaped by the larger contexts of their lives. In particular it will seek to understand the ways in which community attitudes towards anomalous experience such as voice-hearing may impact appraisals of these experiences.
|
| 06/05/2020 |
£174,156 |
|
UNIVERSITY OF CAMBRIDGE |
Early modern Paracelsian physicians, natural historians, chemists and lay practitioners were united in their belief that a plant’s morphological resemblance to a human body part indicated its curative effect. My doctoral research will result in the first monograph to examine how the doctrine of signatures was applied, developed and transformed through medicinal and chymical practice in Germany and England. Through the exploration of personal archives, prescriptions and recipes, I will trace the formation and transmission of this doctrine among chymical physicians, apothecaries and domestic practitioners. I hope to connect histories of mystical philosophy and intellectual developments with recent works on the practices of healing and knowledge transmission. I hold that the doctrine of signatures was not a unified mystical theory once proposed and discredited by "modern science", as argued by philosophers and historians since Michel Foucault, William Ashworth, James Bono or Peter Harrison. Instead, it was a fluid, malleable set of ideas developing in conversation with humanistic learning, experiential knowledge and everyday practice, which survived well into the late seventeenth century. In this way, I hope to challenge the still-dominating narrative on the rise of modernity and scientific revolution.
|
| 06/05/2020 |
£111,099 |
|
UNIVERSITY COLLEGE LONDON |
This interdisciplinary PhD explores how different stakeholders involved in water delivery affect access to water in the Makoko settlement in Lagos, and which implications this holds for socio-spatial health inequalities. In Lagos, vested interests behind public health agendas manifest through urban water insecurity while informal water networks emerged as a counter-narrative to public service absenteeism partly rooted in a colonial urban planning legacy. The main hypothesis is that the reproduction of power relations along socio-spatial gradients is facilitated by reinforced idioms of informality, aiming to justify the lack of water infrastructure and underservicing of specific low-income groups and thereby intrinsically re-producing the very informal networks that disrupt municipal water services and leading to a widening of the urban health gap. Methodologically, I will intersect statistical and geographical data with cognitive mapping, semi-narrative qualitative interviews and dwellers’ self-report on health conditions. Further linking historical explanations for the water crisis to empirical data, my research strives to challenge orthodox development and planning discourses based on notions of an "African exceptionalism" vis-à-vis the "European master narrative" while contributing to the theoretical and empirical development of the "right to health" as a prerequisite for the "right to the city" and the universal human rights.
|
| 06/05/2020 |
£84,857 |
|
UNIVERSITY OF GLASGOW |
This thesis will consider experimental form in female-authored representations of mental illness in British and American writing, 1965-present. The narrative and formal experimentation of modern women’s literature challenges both literary conventions and the valorisation of testimonial mimetic narratives about mental illness within the Medical Humanities. Previous study on the topic of women and madness focuses on the content of women’s writing about mental illness more than their formal strategies, thus assessing their writing for its testimonial value rather than its literary sophistication. This thesis will locate illness, not as a metaphor or a device, but as an embodied state, which produces rich aesthetic possibilities and textual forms. It will investigate the opportunities that intermediality - images and non-standard typography - offers for challenging narrative homogeneity and how women writers have critiqued the narrative expectation of empathy in the context of mental health. Considering women’s experimental literature as a genre, I will look at prose fiction, graphic novels, and zines. By comparing the relationships between activism and art, personal experience and experimental fiction, image and text in women's writing, this thesis will offer a fresh framework for approaching the representational politics of mental health across disciplines and within mental healthcare provision.
|
| 06/05/2020 |
£147,166 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Vaccine policy agendas, decision making process and influences to the decisions highly vary across countries. In recent years, mandatory vaccination policies have been introduced globally, to enforce specific vaccinations on target populations in a country. The policies pose various ethical and legal dilemmas that have been highly debated by academics, policy makers, and country citizens. Some studies have evaluated the policy impact on vaccine coverage and discussed ethics and perspectives of stakeholders. However, research has been geographically biased to Europe and United States; though the policies have been adopted globally, including among the member states of the Association of Southeast Asian Nations. Given the disparities in results and controversy of the policy, the policy decision-making on mandatory vaccinations have not been well understood. To fill this gap in research, this qualitative study will select two countries in ASEAN as cases, and apply policy theories to data collected through literature reviews and key-informant interviews. The study aims to understand the emergence of mandatory vaccinations in policy makers agenda and the actors involved, context of policy adoption and the process and influences of the policy decision. This study aims to develop a vaccine policy decision framework to guide future vaccine policies.
|
| 06/05/2020 |
£102,177 |
|
UNIVERSITY OF OXFORD |
The NHS is currently facing a ‘perfect storm’ of challenges: increasing demand, a rise in chronic disease, and increasing resource constraints. It is increasingly argued that the 'solution' to these challenges lies in making the NHS more informationally mature, able to capitalise on the opportunities presented by digital, data and – especially - artificial intelligence. Developing this strategic intent is, however, only one half of the ‘solution.’ The other half is provided by the operational implementation of new technologies which is a far more complex and under-researched problem.
The objective of this proposed research is, therefore, to contribute to current work addressing: (a) the slow adoption and spread of technology throughout the NHS; and (b) the development of governance frameworks for emerging technologies, by researching and developing a conceptual framework that can identify the process for the safe, effective and ethical implementation of AI into the NHS. As such, it will aim to answer:
How do social, structural and contextual factors influence the willingness and readiness of different levels of the NHS to adopt Artificially Intelligent technologies? And to what extent does variation in these factors influence the ‘success’ of implementation from the perspective of safety, efficacy and ethics?
|
| 22/04/2020 |
£300,000 |
|
THE FRANCIS CRICK INSTITUTE |
Groups of cells called 'organizers' release signals to induce cell fates during development. Remarkably, organizers can undergo ‘self-organization’ in 3D organoids. Understanding this phenomenon has profound implications for engineering and regenerating patterned tissues with bonafide cell-type complexity and 3D-architecture.
Mouse pluripotent stem cells (PSCs) can form neural-tube (NT) organoids. Timely retanoic acid (RA) addition induces scattered precursors that self-organize into a floorplate organizer, which drives ventral-dorsal patterning. I will create cognate human (h)NT organoids from single naïve hPSCs. Exploiting advanced bioengineering technologies, I will isolate organoids from confounding inter-organoid communication and promote robust self-organisation. This interdisciplinary approach will enable me to probe previously inaccessible questions regarding complex mechanisms.
Using this system, I will study how cellular competence to express morphogens is subject to strict temporal regulation. Why is there a restricted window-of-competence for RA response, and how does this trigger self-organization? I will molecularly profile the transient competent state, functionally define the gene-regulatory basis for competence restriction, and investigate how molecular changes at this time serve as the basis for long-range self-organizing behaviour.
This will provide a 3D model for critical stages of human nervous system formation, and reveal how self-organization processes are adapted for human-specific developmental size and timing.
|
| 22/04/2020 |
£300,000 |
|
THE FRANCIS CRICK INSTITUTE |
The aryl hydrocarbon receptor (AHR) has essential functions in the intestine, protecting mice from infection and cancer. However, the underlying mechanisms are still unclear as research has been hindered by the complex regulation and multiple feedback loops governing mammalian AHR. I will therefore use a simpler model system. Spineless, the homolog of AHR in Drosophila, binds the same DNA motif as AHR, but is regulated only on the gene expression level. My preliminary data suggest that Spineless may have similar functions to AHR, influencing epithelial regeneration and survival during infection. I will take advantage of this simpler pathway and the genetic tools and ease of manipulation in the fly in order to rapidly dissect how AHR/Spineless expression is regulated and to systematically analyse its target genes. I will first generate the necessary tools and then answer three main questions: what are the target genes of Spineless, how is Spineless gene expression regulated, and how does Spineless function in the context of intestinal infection. Results obtained from these experiments will be compared with existing data from the Stockinger group on AHR in mice to advance our understanding of intestinal physiology and the critical functions of AHR/Spineless that are conserved across species.
|
| 22/04/2020 |
£300,000 |
|
CARDIFF UNIVERSITY |
Emerging evidence suggests that sleep traits could be useful indicators of risk, relapse and potential treatment targets for mood disorders. However, the longitudinal and genetic relationships between sleep and mood disorders are complex and remain poorly understood. In this fellowship, I will address these gaps and build on my previous work by using cutting edge methods in genetic epidemiology, sleep neurophysiology and longitudinal data analysis.
Key goals:
(1) Determine the neurophysiological correlates of genetic liability to sleep traits and mood disorders using polysomnography – the gold-standard objective measure of sleep. Examining this in healthy populations will circumvent medication effects and bidirectionality, major confounds in existing polysomnography research.
(2) Examine genetic and longitudinal relationships between adolescent sleep and depression to determine whether genetic variants for sleep traits in adult populations also influence sleep in younger populations, and delineate prospective associations between sleep and depression onset.
(3) Investigate whether sleep disturbances can be used as an indicator of liability to relapse in bipolar disorder. Using in-depth longitudinal data from digital technologies will elucidate the role of sleep in predicting mood episodes in bipolar disorder.
This work will inform sleep interventions and further knowledge on the role of sleep in mood disorders.
|
| 22/04/2020 |
£300,000 |
|
UKRI-MRC |
The process of endosomal sorting, where internalised transmembrane proteins (cargoes) are sorted for lysosomal degradation or recycled back to the cell surface, maintains and regulates the cell surface proteome. Thus, endosomal sorting regulates numerous cellular processes including cell signalling.
A fine-tuned amount of endosomal branched actin is required for recycling of cargoes from endosomes to the cell surface. Yet the mechanistic roles of endosomal actin in this process are not understood. Moreover, cargo such as the beta-2 adrenergic receptor (beta2-AR), signal in actin-decorated endosomal recycling domains, suggesting that endosomal actin plays a role in both endosomal recycling and signalling. My project aims to determine the mechanistic and physiological roles of endosomal actin.
I will focus on the major endosomal actin polymerisation machinery – the Arp2/3 activating Wiskott–Aldrich syndrome protein and SCAR homolog (WASH) complex. I will investigate the intrinsic regulation of the WASH complex and how external factors it recruits, cumulatively regulate polymerisation of endosomal actin. Furthermore, I will develop new tools including blocking nanobodies and in vitro reconstitution. In combination, these multi-disciplinary approaches will establish a mechanistic and quantitative model of the role of endosomal actin in sorting and signalling. This will further our mechanistic understanding of endosomal recycling.
|
| 22/04/2020 |
£300,000 |
|
IMPERIAL COLLEGE LONDON |
Parkinson’s disease (PD) is diagnosed by a clinical examination which typically comes 20 years after the initial symptoms. By this time approximately 70% of vulnerable dopaminergic neurons in the substantia nigra (SN) have already been lost. The nigrosomes (small clusters of dopaminergic cells in the SN) have differential histopathological features which make them ideal targets for detecting and monitoring PD.
MRI is highly sensitive to the pathological iron accumulation in the nigrosomes, which is a hallmark of the earliest stages of PD, but quantitative imaging on this sub-millimetre scale is beyond the limits of traditional techniques. I have developed a non-traditional approach to MRI, based on super-resolution approaches from optical microscopy, which can surpass these limitations and rapidly generate quantitative images of the nigrosomes in vivo. I will develop this as an accurate measure of iron accumulation in PD.
The aims of this fellowship are:
Producing accurate microstructural maps at sub-millimetre resolution
Modelling and correcting for subject motion
Testing the hypothesis that microstructural MRI measures in the nigrosomes distinguish PD subjects from healthy controls
If successful, this would enable PD diagnosis in its earliest stages, and maximise the likelihood of finding an effective therapy.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Professional phagocytes engulf bacteria inside phagosomes that mediate cargo degradation via lysosome fusion. Some intracellular pathogens evade this fate by disrupting the phagosomal membrane, which triggers antibacterial autophagy. While autophagy may eliminate bacteria for host defence, more recent studies have demonstrated that autophagy can also promote intracellular bacterial survival or be irrelevant for bacterial restriction. Recently, Endosomal Sorting Complex Required for Transport (ESCRT) proteins have been shown to repair small membrane disruptions, potentially providing an alternative pathway for bacterial restriction. The interplay between autophagy and ESCRT machinery during phagosomal damage, the factors triggering each pathway and their contribution to intracellular bacterial killing are poorly understood.
Using the important human pathogen Staphylococcus aureus, I will:
(1) investigate the interplay between autophagy and ESCRT machinery;
(2) identify novel bacterial components that modulate autophagy and ESCRT recruitment; and
(3) uncover unknown host regulators of autophagy, ESCRT and cell-autonomous immunity.
To complete these objectives, I will use high-resolution microscopy to follow bacteria recruiting autophagy and / or ESCRT machinery at the single bacterial cell level. Additionally, I will use high-content genetic screens to discover novel bacterial (using transposon libraries) and host factors (using CRISPR/Cas9) shaping host-pathogen interactions.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Cancer stemness is linked to therapy resistance and metastasis. Emerging evidence suggests that PIK3CA-H1047R, a hotspot mutation in breast cancer and the PIK3CA-related overgrowth spectrum (PROS), elicits a stemness phenotype characterised by dedifferentiation and cell plasticity. Nevertheless, PIK3CA-H1047R does not cause malignancy in PROS, perhaps reflecting molecular differences between mammary (cancer) and endothelial (PROS) cell lineages.
By learning and applying novel systems biology tools, I aim to address the mechanism(s) behind PIK3CA-H1047R-driven stemness in a quantitative manner, taking into account cell type, genetic mosaicism and the strength of genetic PI3K pathway activation. I will generate mosaic cell models with doxycycline-inducible PIK3CA-H1047R expression, focussing on human breast epithelial cells and human endothelial cells due to their relevance for breast cancer and PROS, respectively. The cells will be exposed to short- and long-term PIK3CA-H1047R expression, followed by temporal assessment of: 1.Cell-state-transitions by single-cell RNA sequencing; 2.PI3K signalling dynamics by candidate-based quantitative single-cell imaging. Next, I will use data integration and mathematical modelling to infer the underlying regulatory principles. My ultimate goal is the identification of PIK3CA-mutant- and cell type-specific pharmacological therapies for reversal of aberrant stemness regulation, followed by validation in physiologically-relevant 3D models based on the established mosaic cell systems.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
The aim of this fellowship is to accelerate detection of and response to infectious disease outbreaks, particularly where surveillance, diagnosis, and control are under-resourced.
My first goal is to develop and validate machine learning methods to rapidly infer outbreak properties. I have demonstrated proof-of-concept for this approach, and I expect to be able to train machine learning models on synthetic outbreak data to infer outbreak properties almost instantaneously from data. By building on this approach, understanding its validity and weaknesses from application to historical data, and creating a database of simulations and trained models, I hope to allow outbreak data to be interpreted more quickly and simply than currently possible.
My second goal is to complete and test—first against historical data and then prospectively—algorithms for aetiological identification of outbreaks. These algorithms have the potential to allow outbreaks to be detected and controlled faster, as well as to improve guidelines for syndromic surveillance.
Finally, I plan to integrate these analytics for outbreak identification and analysis into lightweight software tools. After testing them in collaboration with field epidemiologists, I hope to enable public health officials to take advantage of epidemiological insights with minimal training, supporting capacity of public health systems.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
I will develop powerful statistical methods that leverage estimated genealogies to reveal the key processes driving human genetic diversity and how these have evolved over time. Genealogies have the potential to transform how we analyze genomes, by providing a single framework for addressing a broad range of population and statistical genetics questions, and by substantially increasing power compared to conventional approaches.
I have four key research aims that will impact distinct areas. Firstly, I will develop a novel method for uncovering how genetic structure changes through time and along the genome. This method can uncover unknown ancestral groups; for example, I will characterize previously-reported deeply diverged ancestry of unknown origin in the genomes of modern Africans. Secondly, I will develop a framework for incorporating ancient genomes of diverse ages and data quality into genealogies of modern individuals, enabling the direct study of how ancient and modern genomes interrelate. Thirdly, I will study the evolution of complex human traits through time under various modes of selection, to explain genetic architectures observed in genome-wide association studies. Fourthly, I will investigate the evolution of the molecular mechanisms of recombination, a key driver of human genetic diversity and hybrid incompatibility.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Gestational diabetes mellitus (GDM) is a serious and common pregnancy complication that can evolve in type-2 diabetes (T2DM) years after delivery. Placental hormones have wide-ranging effects on maternal physiology, including the regulation of glucose metabolism. However, we lack information on whether placental hormones could drive changes in maternal metabolism that leads to GDM and the subsequent progression to T2DM. This fellowship aims assess this by using a newly-developed genetic mouse model of placental endocrine malfunction. This is achieved by selectively disrupting the expression of the imprinted Igf2-H19 locus in the placental endocrine cells. Using this approach, I obtained data showing that mice with placental endocrine malfunction have metabolic disturbances, including high blood glucose concentrations during pregnancy. Also, these females show changes in their metabolism in the months after delivery. This project will further these findings in the model by using state-of-the-art in vivo metabolic tests and use transcriptomics, proteomics and methylome analyses to identify how placental hormones induce changes in maternal tissues that cause metabolic problems during and after pregnancy. My long-term aim is to identify biomarkers that could be explored as diagnostic tools or therapeutic targets to prevent the development of GDM and T2DM.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF OXFORD |
Efficient T cell responses rely on heterogeneity, characterized by the rise of effector and memory cells. Autophagy, responsible for homeostatic degradation and recycling of cell cargo, is crucial for T cell differentiation. Upon ageing, autophagy is impaired, which is detrimental for the generation of memory cells retaining stemness. Interestingly, I have observed that naïve CD8+ T cells from aged mice are unable to undergo asymmetric cell division (ACD) (unpublished). ACD is a conserved mechanism to generate diversity, by endowing daughter cells with different fate determinants. As both autophagy and ACD are involved in T cell differentiation and impaired upon ageing, unravelling how they synergistically influence T cell stemness is at the centre of this project. We propose to use state-of-the-art imaging, proteomics, and metabolomics to investigate whether autophagy impacts cell asymmetries upon T cell mitosis. Functional validation will be addressed by using the novel combination of autophagy-deficient and organelle-tagged cells (SnapTag mice), which will enable us to evaluate whether asymmetry inheritance of cell cargoes leads to asymmetric fates in vivo. We anticipate that this research will be relevant to better understand how stemness is coordinated, and potentially lead to the development of therapeutic strategies in the context of regenerative medicine.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Unconventional myosins of class I can directly associate with membranes, thereby providing a dynamic link between the actin cytoskeleton and the plasma membrane or intracellular organelles. Immune cell-specific myosin 1F and myosin 1G (MYO1F and MYO1G respectively) have roles in immune cell migration and regulation of membrane tension. Studies show both motors are upregulated in microglia during neuroinflammation. To uncover the temporal regulation of these motors, a number of biophysical assays will be employed, such as in vitro motility assays, optical trap experiments and stopped-flow spectroscopy. The molecular interactions of MYO1G that determine cellular function will be explored using a combination of proteomics and cell biological assays to identify the motors’ interacting partners and elucidate its spatial regulation in vivo. The effects of two distinct phosphorylation sites on motor domain activity of MYO1G will be explored with mutations to mimic the non- and phosphorylated states. Protein crystallography studies of MYO1F and MYO1G will enable the design of small molecule inhibitors using structure-based in silico screening, with the ultimate goal to treat neuroinflammation in humans. Taken together these approaches will elucidate the cellular and physiological role of these motors and uncover the potential use of MYO1F and MYO1G as therapeutic agents.
|
| 22/04/2020 |
£300,000 |
|
QUEEN MARY UNIVERSITY OF LONDON |
When hearing voices, we can perceive a wealth of information about the speakers, such as their identity, regional background, and age. This project will investigate how listeners achieve this, thus probing fundamental mechanisms of person perception from voices. To achieve this, I will take a broad perspective to integrate the usually distinct fields of identity perception and the perception of other speaker characteristics.
Through a programme of behavioural research using acoustic signal processing and methods from the statistical or distributional learning literature, I will first explore how listeners form representations of voice identities through a programme of training studies: What is the acoustic content of mental representations of voices? What kind of information is encoded in such representations?
I will then extend these findings from voice identity perception to the perception of other speaker characteristics: Are such population-level representations formed based on similar mechanisms to identity representations or are there differences?
Finally, I will conduct a magnetoencephalography (MEG) study to describe the timecourse of person perception from voices: Which speaker characteristics are decoded by listeners at which point during perception? Does familiarity with a person change the processing of that voice? Can the low-level acoustic properties (partially) explain the timecourse?
|
| 22/04/2020 |
£300,000 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
Understanding how cell fate decisions are regulated is a key question in molecular biology. Building on the CRISPR revolution, exciting technologies (e.g., CROP-seq or direct capture Perturb-seq) induce a genetic perturbation that is characterised, alongside the transcriptome of the cell, by single-cell RNA-sequencing. This enables a range of experimental designs that can, in principle, shed light on the transcriptional response to gene perturbations, its pathogenic and non-pathogenic variation, and the role of gene regulation during differentiation.
However, current computational methods do not exploit this potential: in particular, the ability to accurately measure the effect of a given perturbation is lacking, and the potential to efficiently explore the space of all possible perturbations and conditions remain untapped.
To address this, I will develop a comprehensive suite of computational tools (i) to infer transcriptomic effects of gene knockouts unconfounded by perturbation efficacy, (ii) for optimal experimental setup to increase insights gained from experiments and improve their scalability, (iii) to identify differences in gene regulation across individuals, and (iv) for the study of knockout effects during differentiation. This will lead to an improved understanding of gene regulation, its variation across individuals, and to improved differentiation protocols, with important consequences for cell therapy.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Motivation: Interventions mobilising communities in collective action for their own health are some of the most effective known global health interventions. However, they do not always succeed and we cannot presently predict or explain why this happens.
Aim: Taking as an example a community mobilisation programme to prevent violence against women in urban slums in Mumbai, India, I will test theory concerning the drivers of collective action from behavioural economics and social psychology.
Method: (1) To unpack how a community mobilisation programme may stimulate collective action in urban India, I will collect and analyse qualitative interview, media and observational data.
(2) To uncover the determinants of participation in collective action, I will conduct cross-sectional and difference-in-differences analysis of secondary data from a randomised controlled trial of the same community mobilisation programme.
(3) To produce causal evidence for the drivers of collective action, I will conduct a behavioural experiment to test the behavioural effects of changing key messages on programme participants. I will use the answers to (1) and (2) to guide message design.
Impact: The study results will be able to guide policy-makers and practitioners on when, how and why complex participatory interventions work to promote health and gender equality.
|
| 22/04/2020 |
£300,000 |
|
UNIVERSITY OF OXFORD |
I will explore how structural variation can be used to understand the evolution of antimicrobial resistance (AMR) on mobile genetic elements (MGEs).
Most previous research is biased towards nucleotide-level variations in the core genome (high-effect SNPs). Now, the availability of complete genomes means that resolving the larger structural variation of MGEs is both possible and increasingly relevant for the spread of AMR. I will develop a framework to model the non-mutational processes which generate this variation, then apply this to the linked evolution of MGEs and their ‘host’ genomes.
During this fellowship, I will sequentially:
Aim 1. Develop a tool to quantify structural variation and resolve common blocks around the flanking region of AMR genes, which I have previously shown can be used for phylogenetic reconstruction.
Aim 2. Apply this to longitudinal datasets and obtain rate estimates for non-mutational processes.
Aim 3. Investigate the compensatory evolution of MGEs as they move between genomic backgrounds.
Two major applications will be:
Application 1. Small transposons, leading on from my pioneering work on the mcr-1 transposon.
Application 2. Clinical class 1 integrons, which carry multiple AMR genes.
This proposal tackles questions of fundamental importance for the evolution of flexible genomes.
|
| 22/04/2020 |
£300,000 |
|
ROYAL VETERINARY COLLEGE |
Yellow fever virus (YFV) outbreaks are escalating worldwide despite the existence of a vaccine. Global travel raises the chance that YFV will become established in Asia, where populations are not vaccinated and an outbreak would be catastrophic. Our ability to predict and control YFV outbreaks is reduced by our lack of knowledge about (i) transmission of YFV in its sylvatic reservoir (non-human primates) and (ii) how YFV escapes from this reservoir to spread amongst people in urban areas. Severe under-reporting in both humans and non-human primates hampers our ability to directly study YFV transmission behaviour. Recent advances in portable genome sequencing and virus genomic epidemiology (including phylodynamics) offer new opportunities to use virus genomic data to reconstruct unobserved outbreak dynamics, even when sampling is sparse. I will combine these techniques to improve our understanding of YFV epidemiology, by: (i) integrating viral genomic data into newly-refined YFV mathematical models for improved outbreak prediction; (ii) implementing phylodynamic approaches to identify drivers of sylvatic transmission, and; (iii) exploiting new strategies to generate virus sequences from traditionally neglected times and locations. My Fellowship research findings will improve YFV outbreak prediction and contribute to the development of refined vaccination strategies.
|
| 31/03/2020 |
£1,391,495 |
|
UNIVERSITY OF EXETER |
More than 1 in 5 UK pregnant women are clinically obese, a condition associated with heterogeneous health outcomes for mother and baby. Only limited understanding of the associations (e.g. gestational diabetes and high birth weight, hypertension and preterm birth/low birth weight) has been possible in traditional observational studies due to complex interrelated exposures and outcomes. My research will use human genetics to dissect causal pathways and understand how a higher maternal BMI can lead to such diverse outcomes. I hypothesise that maternal effects on fetal growth and gestational duration are moderated by fetal genetics. My first aim is to understand how a fetus regulates its own growth and gestational duration in different maternal environments. We will apply results of new genome-wide association studies of placental weight and umbilical cord insulin to give mechanistic insights. My second aim is to understand how raised maternal BMI impacts gestational duration and growth, and my third aim is to examine whether fetal genetics can influence the maternal environment. By identifying causal mechanisms, this fellowship will be an advance towards better targeting of antenatal healthcare and advice to pregnant women, according to their level of risk to reduce the incidence of adverse pregnancy outcomes.
|
| 31/03/2020 |
£1,639,257 |
|
UNIVERSITY OF WARWICK |
Kinesin-microtubule systems transport intracellular cargo in eukaryotes and are essential for life. Recently, we discovered that dynamic microtubules can respond to kinesin by changing their conformation, lattice spacing, curvature and stability, and conversely that kinesin stepping can sense and respond to conformational shifts in the microtubule lattice. These insights fundamentally redraw our picture of the function of kinesin-microtubule transport systems. I now propose to dissect the mechanical mechanisms by which kinesins and microtubules instruct one another, using protein engineering combined with single molecule optical trapping at unprecedented resolution. Working with both wild-type and mutant kinesins and tubulins, principally from S. pombe, we will determine the structural requirements for different microtubule lattices to control kinesin substeps, backsteps and bidirectionality; and the converse requirements for kinesins to manipulate the conformation and fate of microtubules. Our experiments will reveal how tubulins communicate mechanically with one another and with kinesins. Illuminating the molecular mechanisms of active mechanical feedback in kinesin-microtubule systems will transform understanding of the transport machinery and open the way to improved chemical biological manipulation of its in vivo function.
|
| 31/03/2020 |
£2,035,881 |
|
KING'S COLLEGE LONDON |
I propose to use my SRF to investigate the intergenerational transmission of mental health problems. Previously, in my Sir Henry Dale Fellowship, I have developed statistical models for use with genetically informative intergenerational data (composed of many extended families) for use in distinguishing genetic transmission from the potential causal effects of parent on child. In my SRF I will build on this work:
1. I will establish to what extent the treatment of mental health problems in parents reduces the transmission of problems to children (and vice versa).
2. Combine pedigree-based approaches with genomic data to draw on the strengths of each. This will enable the identification of the direction and magnitude of intergenerational causal effects, and identify polygenic scores involverd in gene-environment interplay relevant to the intergenerational transmission of mental health problems.
3. Explore the biases inherent in our use of volunteer based cohorts to understand mental health aetiology.
4. Extend my own children-of-twins study, funded as part of my SHDF, CoTEDS (the Children-of-TEDS). CoTEDS is the second generation of an ongoing twin study, and the first twin study in the world to include information on parents and children from birth.
|
| 31/03/2020 |
£4,119,965 |
|
UNIVERSITY OF CAMBRIDGE |
Building on advances during our successful connectomics collaboration (2016-20), we now propose a very ambitious new goal: a complete, high-quality connectome for the male Drosophila central nervous system (CNS). With Wellcome support and leveraging Janelia’s unique electron microscopy imaging capability, we could turn image data into a fully analysed connectome. This would be the first CNS connectome of an animal with complex motor and cognitive behaviours. In contrast to existing fly datasets, it will be bilaterally complete, include brain and nerve cord and have intact sensory-motor connectivity.
This connectome should have an enormous impact on the understanding of CNS-spanning circuitry underlying complex behaviour. We will publicly release initial draft and high-quality versions as soon as they are complete. We will immediately use it to study multisensory integration, memory recall, decision making, modification of brain states, the flexible organisation of motor behaviour, and sexually dimorphic circuits. It will provide a critical resource for > 200 labs worldwide studying Drosophila neurobiology (with impacts on developmental biology and molecular cell atlases) and provide new opportunities for theoretical neuroscientists to study complete, biologically-defined neural networks in a richly investigated organism. We expect general principles, applicable to all nervous systems, including those of humans, to emerge.
|
| 31/03/2020 |
£1,909,584 |
|
UNIVERSITY OF DUNDEE |
The Type VI secretion system (T6SS) is used by many Gram-negative bacteria to deliver toxic ‘effector’ proteins into rival bacterial cells as a means of inter-bacterial competition. The T6SS likely plays a central role in shaping many polymicrobial communities, but important aspects of effector delivery and action in target cells, and the ‘real-life’ relevance of T6SSs in a clinical context remain elusive. We will investigate the journey of individual and co-operating groups of effectors, from their recruitment by the T6SS to their fate and action in targeted cells, and dissect the mechanism of individual anti-bacterial effectors. We will also consider the global availability and mobility of anti-bacterial effectors and how the T6SS and its effectors can influence bacterial success in a clinical context. Using multidisciplinary approaches, we aim to:
Determine the mechanism of toxicity of novel anti-bacterial effectors
Elucidate the fate of effectors inside target cells
Define mechanisms of versatile effector recruitment and delivery in attacker cells
Use genomics to reveal the diversity, evolution and real-life relevance of T6SS effectors
Our findings, combining mechanistic detail with insight into biological relevance, will provide fundamental advances in our understanding of T6SS-mediated anti-bacterial activity and may inform future strategies to counter bacterial pathogens.
|
| 31/03/2020 |
£689,181 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Our research programme will deliver mechanistic understanding of how cyclic nucleotide signalling controls the development of two key phases of the malaria parasite lifecycle: the asexual blood stage that causes pathology, and gametogenesis that is required for transmission to the mosquito vector. We have previously shown that there is a temporal switch from cyclic GMP (cGMP) signalling to cAMP signalling as the asexual parasite progresses from egress (escape from its host erythrocyte) to invasion. Cyclic GMP signalling also controls egress of sexual stage parasites to enable fertilisation in the mosquito. In both lifecycle phases, egress requires cGMP-dependent calcium flux. We have recently identified a unique, essential membrane-bound binding partner of the cGMP-dependent protein kinase (PKG). We have also identified a set of high confidence targets of cAMP signalling required for invasion and subsequent parasite development, and have obtained exciting new insights into how cGMP production is governed. We now want to: (1) determine the mechanisms underlying the interrelationship between cGMP and calcium signalling; (2) dissect the role of cAMP-dependent phosphorylation in erythrocyte invasion; and (3) identify the parasite proteins that interact with cyclase and phosphodiesterase enzymes (which balance cellular levels of cyclic nucleotide) to understand how the pathways are regulated.
|
| 31/03/2020 |
£669,703 |
|
THE FRANCIS CRICK INSTITUTE |
Our research programme will deliver mechanistic understanding of how cyclic nucleotide signalling controls the development of two key phases of the malaria parasite lifecycle: the asexual blood stage that causes pathology, and gametogenesis that is required for transmission to the mosquito vector. We have previously shown that there is a temporal switch from cyclic GMP (cGMP) signalling to cAMP signalling as the asexual parasite progresses from egress (escape from its host erythrocyte) to invasion. Cyclic GMP signalling also controls egress of sexual stage parasites to enable fertilisation in the mosquito. In both lifecycle phases, egress requires cGMP-dependent calcium flux. We have recently identified a unique, essential membrane-bound binding partner of the cGMP-dependent protein kinase (PKG). We have also identified a set of high confidence targets of cAMP signalling required for invasion and subsequent parasite development, and have obtained exciting new insights into how cGMP production is governed. We now want to: (1) determine the mechanisms underlying the interrelationship between cGMP and calcium signalling; (2) dissect the role of cAMP-dependent phosphorylation in erythrocyte invasion; and (3) identify the parasite proteins that interact with cyclase and phosphodiesterase enzymes (which balance cellular levels of cyclic nucleotide) to understand how the pathways are regulated.
|
| 31/03/2020 |
£2,141,982 |
|
INSTITUTE OF CANCER RESEARCH |
Splicing and polyadenylation are two essential steps of gene expression that account, to a great extent, for the complexity of eukaryotes. The two processes are catalysed by the spliceosome and the polyadenylation apparatus – two macromolecular machines of megadalton-size which contain more than 70 and 20 proteins, respectively.
The two machines associate physically to form composite assemblies, where cross-talk events support emerging layers of regulation of splicing and polyadenylation. These assemblies are primarily unexplored from a mechanistic perspective, due to their excessive size, complexity and dynamics.
By employing state of the art technologies and our long-standing expertise in the structural biology of splicing, the time is now ripe for a thoroughgoing investigation of these assemblies. Thus, we aim to stall and isolate composite assemblies relevant for: (i) the coupling between splicing and polyadenylation, (ii) the definition of exons during constitutive and alternative splicing and (iii) protection of genes from premature polyadenylation. Afterwards, we will characterise their 3D structures and functions by electron cryo-microscopy and complementary biochemical methods. The proposed research is expected to be eye-opening and bring a substantive contribution to our understanding of how fundamental processes of gene expression integrate mechanistically.
|
| 31/03/2020 |
£2,049,477 |
|
UNIVERSITY OF EDINBURGH |
As cells build the body, they use information from localised secreted signals to guide differentiation and morphogenesis. It is often assumed there is unidirectional flow of information from these biochemical signals to the resulting morphological changes, but this 'linear' model cannot explain how development is orchestrated with such remarkable reproducibility.
We have found that changes in epithelial structure provide a previously underappreciated source of information that feeds back into differentiation decisions by modulating biochemical signalling. Using mouse gastrulation as a paradigm we have identified candidate molecular mechanisms that mediate this feedback: 1) A cadherin-mediated community effect that dampens anti-neural signals to synchronise neural differentiation 2) a cell-clustering process that amplifies juxtacrine pro-mesoderm signalling to coordinate differentiation across collectives of cells.
We propose that these two interlinked mechanisms coordinate distinct sources of information across different time scales. We will test this in vitro and in vivo using a unique toolkit based on molecular and biophysical manipulation of epithelial structure, mosaic analysis, and custom-developed quantitative image analysis software.
Generalisable principles emerging from this work will help resolve the currently unpredictable relationship between signalling-input and differentiation-output to give us better control over in-vitro differentiation, organoid formation, tissue repair, and tumorogenesis.
|
| 31/03/2020 |
£2,580,251 |
|
UNIVERSITY COLLEGE LONDON |
This proposal examines the neural mechanisms supporting decision-making and prospective planning. We will examine how prefrontal cortex (PFC), hippocampus, and entorhinal cortex (EC) interact to support these processes. We will examine how non-human primates (NHPs) make choices in large decision spaces, particularly when novel choice-values have to be inferred ‘online’. We will test different models of value-coding, particularly whether PFC uses a ‘place-like’ and ‘grid-like’ code to construct cognitive maps of values spaces. We will examine how NHPs make ‘online’ choices when sequentially navigating between stimuli/states as rewards move or paths blocked. We will test whether ‘replay’ provides a neural mechanism supporting model-based planning. We will use Transcranial Ultrasound Stimulation to selectively disrupt regions of PFC/hippocampus/EC to examine its effect on neural selectivity and behaviour. These tasks are high-dimensional, yet amenable to mathematical description, and will be combined with high-density recordings to map these computations. Exp.3 will integrate our home-cage training system with wireless data-logging to record neural data continuously, across tasks and sleep, to examine how neural signatures change across days with learning, and acquisition of ‘learning set’. This provides the technology to continuously map the NHP brain during performance of diverse and naturalistic tasks, radically transforming primate neuroscience.
|
| 31/03/2020 |
£1,580,335 |
|
UNIVERSITY COLLEGE LONDON |
Many severely and profoundly deaf children struggle to learn to read because written text is a visual representation of spoken language, to which they have limited access. I have shown that speechreading (lipreading) relates to deaf children’s reading development. Fully understanding the mechanisms underlying the speechreading-reading relationship is fundamental to harnessing speechreading as a tool to improve deaf children’s reading. My goal is to investigate this mechanism in 1) a longitudinal study, to determine the relationships between speechreading, phonological skills, language skills and reading over time and 2) in neuroimaging studies with deaf children and adults to investigate neural representations of visual speech and written text and the relationships between them.
All deaf participants involved in the studies above will use speechreading. A subset will also have learned British Sign Language from an early age. Good quality early sign language exposure is beneficial to reading development in profoundly deaf children. However, the mechanism underlying this relationship is unclear. I will employ parallel methods to those used in the speechreading studies to examine 1) the longitudinal relationships between sign language, fingerspelling and reading and 2) the neural representation of these visual language inputs in deaf children and adults.
|
| 31/03/2020 |
£2,236,593 |
|
UNIVERSITY OF SUSSEX |
Retinal ganglion cells (RGCs) are the vertebrate eye’s only projection neurons to the brain. Through RGCs, species transmit ~50 visuo-ecologically relevant image features in parallel. However, what these features are, and how their information is used by central circuits to inform visual decisions remains unclear in any species. A key difficulty has been to link the activity of RGCs in the in vivo eye with behaviour. To address this major knowledge gap, I will capitalise on the visual system of the larval zebrafish where the activity of RGCs in the eye and their presynaptic terminals in the brain can be non-invasively monitored and manipulated in the live animal. I will ask:
What information does the fish’s eye send to the fish’s brain?
Does the brain "tune" its own input from the eye?
How does the brain use information from RGCs to guide behaviour?
Taking reference of our and others’ data on RGC processing from mice and primates, we ultimately aim to arrive at a more general theory of how an eye can communicate with its brain, that encompasses coding strategies employed by diverse species with distinct visual abilities and requirements.
Key-words: Vision, projection neuron, zebrafish, 2-photon imaging
|
| 31/03/2020 |
£2,078,748 |
|
UNIVERSITY COLLEGE LONDON |
Animals accomplish goal-directed behaviours by performing sequences of motor actions. A central goal of neuroscience is to understand how neural circuits regulate behaviour in accordance with external events and internal drives and precisely choreograph diverse actions for a successful outcome. To meet this challenge, I will exploit the unique accessibility of the larval zebrafish and focus on a conserved behaviour – hunting – in which a sequence of discrete, specialised actions mediates pursuit and capture of prey. I will use a powerful experimental strategy that combines cellular-resolution calcium imaging, behavioural analyses, optogenetic circuit manipulations, neuroanatomical tracing and computational modelling to discover how brain-wide circuits operate at the cellular level to flexibly control the expression and coordination of behaviour. This paradigm will enable me to discover (1) how sensory and internal state information are integrated to control the sensorimotor decision to hunt, (2) how specific hunting actions are generated and (3) how command signals operate alongside dynamic sensory inputs to assemble a goal-directed sequential behaviour. Overall, the project will produce a mechanistic, cellular-resolution circuit model that explains how the brain controls and patterns multi-component behaviour. I expect this will reveal fundamental principles about the operational logic of the nervous system.
|
| 31/03/2020 |
£2,381,203 |
|
UNIVERSITY OF CAMBRIDGE |
This project aims to identify new strategies to target the gut for the treatment of type 2 diabetes and obesity. Intestinal hormones regulate intestinal nutrient absorption, insulin secretion and appetite, and therapeutics based on the gut peptide GLP-1 are widely used for type 2 diabetes and obesity. Bariatric surgery causes weight loss and resolves diabetes at least in part via gut endocrine changes.
This project will characterise human enteroendocrine cells using intestinal organoid cultures, building on our previous work using transgenic mouse models. To identify cells of interest, organoids will be engineered by CRISPR/Cas9 to express fluorescent sensors driven by hormonal promoters, allowing cellular analysis by transcriptomics, electrophysiology and real-time fluorescence imaging of e.g. Ca2+ and cAMP. We will characterize nutrient sensing pathways and identify receptors and signaling pathways potentially modifiable therapeutically. Using mouse and human tissues, we will identify circuitry involved in bidirectional cross-talk between gut endocrine cells and enteric/autonomic nerves.
Building on our new methods to analyse peptides and the low molecular weight proteome by mass-spectrometry, we will investigate how plasma peptides respond to nutrient ingestion in health and metabolic diseases including diabetes, obesity, lipodystrophy and anorexia nervosa, and following bariatric surgery or dietary calorie restriction in obesity.
|
| 31/03/2020 |
£2,214,779 |
|
UNIVERSITY OF CAMBRIDGE |
Plasmodium falciparum parasites still cause nearly half a million deaths each year. The repeated emergence of antimalarial drug resistance and the lack of a highly effective vaccine mean that there is an urgent need to identify new intervention targets. Erythrocyte invasion is an excellent target as it is essential for both parasite survival and for malaria pathology. Invasion involves multiple parasite ligands, but little is known about their function at the cellular level and even less about how they fit into the broader network of invasion proteins. This proposal will revolutionise our understanding of the function of two families of P. falciparum invasion ligands, the EBLs and the RHs, that are together responsible for the key decision point in the invasion process. The key goals are to:
Systematically dissect functional equivalence between EBLs and RHs
Establish the roles that EBLs and RHs play in discriminating between erythrocyte variants within and between humans
Use innovative combinatorial approaches to move from a gene to a network understanding of EBL and RH function.
The proposal will provide a step change for the field, both biologically and technically, and will identify new candidates for testing in a rationally designed, multi-component invasion-blocking vaccine.
|
| 31/03/2020 |
£1,914,685 |
|
UNIVERSITY OF BRISTOL |
An intracellular nexus for regulating the membrane trafficking of many of the 5,000+ integral proteins encoded by the human genome is the endosomal network. Composed of vesicular and tubular early and late endosomes, the network’s principal role is to sort integral proteins (termed ‘cargoes’) arriving from the cell surface and the biosynthetic pathway between two fates: either sorting to the lysosome for degradation, or retrieval from this fate for export to the cell surface, the biosynthetic pathway or other specialised organelles. Whilst the molecular details of degradative cargo sorting have been well documented, those events that conduct cargo retrieval and export remain poorly understood. Our research has sought to fill this fundamental void in metazoan cell biology.
A master conductor of endosomal retrieval and export is the retromer pathway - in human cells this orchestrates the sorting of > 900 cargoes. Establishing how this pathway functions is central to understanding the evolution, organisation and activity of endosomal sorting. With Wellcome support we will address two integrated questions:
The fundamental question of how the retromer pathway is organised and integrated with other pathways to orchestrate global endosomal cargo sorting.
How understanding of retromer pathway function may provide vital insight into neurodegenerative diseases.
|
| 31/03/2020 |
£2,025,694 |
|
UNIVERSITY OF CAMBRIDGE |
To treat and prevent dementia in patients, it is essential to understand how microscopic changes in the human brain cause complex cognitive and behavioural disorders. My program addresses this critical gap in translational research, to facilitate clinical application of basic science discoveries. I have three goals, set in the context of frontotemproal dementia and progressive supranuclear palsy.
First, I will develop quantitative biophysical models of human brain function that capture key cellular and pharmacological pathologies in vivo, with regional, laminar and synaptic specificity. These models of degenerating neuronal circuits are informed by individual measures of synaptic density (PET imaging with a SV2a ligand), GABA and glutamate (ultrahigh-field MR spectroscopy). They are optimised in vivo by inversion to magnetoencephalography, and tested post-mortem against neuropathology. This synergy of multi-modal imaging, together with Bayesian model comparison of Dynamic Casual Models, means one can drill down to the best mechanistic model of the human cognitive disorder.
Second, I will show how harmful effects of dementia like apathy can be explained in terms of changes in synaptic density and loss of precision in hierarchical brain networks.
Third, I will I demonstrate the readiness of my approach for experimental medicine, through longitudinal designs and pharmacological interventions.
|
| 31/03/2020 |
£875,659 |
|
UNIVERSITY OF CAMBRIDGE |
The molecular mechanisms by which mitochondrial reactive species, metabolites and redox signals contribute to physiology and pathology are unclear. This is in large part because these processes are difficult to assess and modulate in vivo. Our goals are to establish general chemical biology approaches to determine the mechanisms of mitochondrial physiology and dysfunction in vivo and from this develop new therapeutic strategies. The aims are based on the success of our previous Joint Investigator Award, but the specific chemical biology approaches to be used, the insights to be attained and the models have been refined and developed, based on our work over the past four years. These goals will be achieved by addressing three research challenges in cells and in vivo:
A: Can we determine how mitochondria operate during normal physiology, and are disrupted during pathology, by targeting probes to measure reactive species and alterations to signaling pathways?
B: Can targeting bioactive molecules to mitochondria prevent pathological disruption of mitochondrial function and generate potential therapies?
C: Can the above methods to monitor and modulate mitochondrial function be assessed in animal models of human diseases and thus drive the development of rational, translatable therapies?
|
| 31/03/2020 |
£803,027 |
|
UNIVERSITY OF GLASGOW |
The molecular mechanisms by which mitochondrial reactive species, metabolites and redox signals contribute to physiology and pathology are unclear. This is in large part because these processes are difficult to assess and modulate in vivo. Our goals are to establish general chemical biology approaches to determine the mechanisms of mitochondrial physiology and dysfunction in vivo and from this develop new therapeutic strategies. The aims are based on the success of our previous Joint Investigator Award, but the specific chemical biology approaches to be used, the insights to be attained and the models have been refined and developed, based on our work over the past four years. These goals will be achieved by addressing three research challenges in cells and in vivo:
A: Can we determine how mitochondria operate during normal physiology, and are disrupted during pathology, by targeting probes to measure reactive species and alterations to signaling pathways?
B: Can targeting bioactive molecules to mitochondria prevent pathological disruption of mitochondrial function and generate potential therapies?
C: Can the above methods to monitor and modulate mitochondrial function be assessed in animal models of human diseases and thus drive the development of rational, translatable therapies?
|
| 31/03/2020 |
£2,654,295 |
|
IMPERIAL COLLEGE LONDON |
This application will test the hypothesis that pulmonary immune homeostasis is maintained by a network of tissue resident cells that continually monitor environmental change. Disruption of local neuro-immune-stromal interactions either by genetic or environmental factors, alters the threshold for immune responses to usually innocuous particles such as dust, pollen or dander leading to chronic airway inflammation and tissue remodelling. I will ascertain the cellular and molecular composition of the airway wall parenchyma in children and adults with severe asthma and use machine learning tools and mouse models to determine the impact on lung function. Viral infection and pollution are common triggers for asthma severity, and I will establish how the immune/stromal niche communicates with the external environment to react to these inhaled stimuli, focussing on interaction with neuronal systems. I will examine how these interactions differ in severe asthma and contribute to the ensuing inflammation, remodelling and lung dysfunction. I will investigate the cellular interactions between fibroblasts, extracellular matrix and type 2 immune cells that facilitate repair versus remodelling during severe asthma. Ultimately this programme will reveal insight into mechanisms underlying tissue remodelling versus repair during severe asthma.
|
| 31/03/2020 |
£1,639,854 |
|
UNIVERSITY OF GLASGOW |
Proteins entering the secretory pathway at the endoplasmic reticulum (ER) undergo a vast array of post-translational modifications some of which are essential for correct folding, assembly and secretion. Failure to fulfil these functions results in several diseases due to the lack of secretion of proteins such as insulin and antibodies, or due to cell death triggered by an unfolded protein stress response. The ER provides a unique environment for protein modifications such as disulfide formation and glycosylation. To ensure efficient protein folding and secretion the cell maintains the environment within the ER that ensures these processes occur efficiently and reacts to situations of cell stress. This proposal builds on exciting new observations from my group to dissect molecular mechanisms involved in secretory protein biogenesis. Our particular focus will be on how the cell maintains ER redox balance, how the repertoire of ER folding factors orchestrate correct protein folding and N-linked glycosylation and how the UPR sensor ATF6 is activated following proteotoxic stress. Our aims will be achieved using a combination of innovative new technological approaches and previously established robust assays to follow protein folding and assembly in both reconstituted and cellular systems.
|
| 31/03/2020 |
£2,088,673 |
|
THE FRANCIS CRICK INSTITUTE |
Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for faithful chromosome segregation during cell division. The ring-shaped cohesin complex is a multisubunit ATPase that topologically loads onto DNA in the G1 phase of the cell cycle. The first part of the proposal will elucidate the molecular mechanism of cohesin function. We will employ and develop biophysical, structural and DNA-protein crosslink mass spectrometry tools to map the trajectory by which DNA enters the cohesin ring, fuelled by ATP-dependent conformational changes. The second part of the proposal examines the establishment of sister chromatid cohesion during S phase. We will investigate how, as the replication fork moves along DNA, cohesin transitions from containing one DNA to embracing two newly replicated DNAs. This includes the functional characterisation of replisome components with roles in sister chromatid cohesion, known as ‘cohesion establishment factors’. Furthermore, we will take advantage of recent success with the biochemical reconstitution of complete DNA replication and work towards recapitulating sister chromatid cohesion establishment in vitro. This will open unique experimental opportunities to understand the process. Together, this programme will provide insight into the molecular mechanism of how cohesin safeguards faithful chromosome segregation.
|
| 31/03/2020 |
£1,756,223 |
|
UNIVERSITY OF MANCHESTER |
The evolution of antibiotic resistance is a threat to modern medicine. Patients with chronic bacterial infections are at particular risk from antibiotic resistant genotypes, which typically arise from within the infection. However, a lack of controlled studies means that we don't understand how antibiotic resistance evolves within the human host environment, and why the emergence of resistance varies among patients.
We identify randomised clinical trials (RCTs) of new antibiotic treatments as a powerful way to study resistance evolution in action during a controlled, replicated natural experiment. We will exploit a unique opportunity to perform an evolutionary analysis of two parallel Phase-III RCTs for inhaled ciprofloxacin treatment of chronic lung infections caused by Pseudomonas aeruginosa, which is a WHO Priority-1 pathogen in critical need of improved antibiotic therapies. Ciprofloxacin resistance emerged in ~40% of the treated patient infections but this patient-to-patient variation is unexplained.
We aim to explain why resistance evolved in some patients but not in others. To do this, we will (1) discover the evolutionary mechanisms of resistance emergence in patient infections, (2) identify the bacterial and host properties that drove resistance evolution, and then (3) test how well biomarkers of these drivers predict resistance emergence in other patients.
|
| 31/03/2020 |
£2,280,346 |
|
KING'S COLLEGE LONDON |
Undernutrition during the early years of life has a harmful and irreversible impact on child growth and cognitive development. Many of the interventions tested to improve outcomes across infancy have had disappointing or inconsistent impact, a common feature being the absence of any attempts to provide nutritional supplements to infants during the first six months. With increasing evidence of micronutrient deficiencies in this age group, alongside strong evidence that growth and developmental deficits begin before six months, a renewed focus on the micronutrient status of infants is required.
Here I propose a randomised efficacy trial of micronutrient supplementation to mothers (during pregnancy or pregnancy and lactation) and infants (birth to six months) in rural Gambia, where rates of micronutrient deficiencies are high. 600 pregnant women (
This novel research will identify the most efficacious way of improving micronutrient status in infancy, and assess impact on infant developmental outcomes, providing an evidence base for future effectiveness trials and policy recommendations.
|
| 31/03/2020 |
£2,464,967 |
|
MRC LABORATORY OF MOLECULAR BIOLOGY |
The co-ordinated development and differentiation of lymphocytes is critical to producing the bespoke immune responses required to combat specific pathogens, but also to maintaining tissue homeostasis and repair. However, dysregulated immune reactions underlie undesirable chronic inflammation and autoimmunity. Our discovery of type-2 innate lymphoid cells (ILC2) and the description of other ILC subsets has highlighted additional, previously unappreciated, complexity in the processes of lymphocyte specialisation. Our challenge is to unravel the microenvironmental cues, critical cell-surface receptors, and key transcription factor interactions that lead to lymphocyte specification, tissue-specific roles and cellular interactions. We will employ a unique repertoire of lymphocyte transcription factor reporter "polychromILC" mice in combination with CRISPR-mediated screens to identify new regulators of lymphocyte development, differentiation and function. To facilitate the investigation of these new pathways in specific lymphocyte subsets in vivo we will produce a new generation of mouse strains designed to limit off-target events by employing multiple positive and negative determinants, comparable to Boolean operators (AND, OR, NOT or AND NOT). Finally, using a combination of genetic screens and in toto adaptive light-sheet microscopy we aim to define molecules and cells that delineate the migration and development of ILC in the context of the stromal environment.
|
| 31/03/2020 |
£2,407,240 |
|
KING'S COLLEGE LONDON |
The majority of lung cancer deaths result from ineffective treatment of late-stage disease. Currently, there is no satisfactory way to identify patients that will not respond to standard-of-care treatments. Positron emission tomography (PET) imaging offers a potential solution to this clinical problem through the non-invasive assessment of molecular processes that underpin therapy-resistance. The identification of cancer patients that are refractory to treatment will allow the selection of second-line therapies that have the potential to improve patient response and survival.
For this SRF, I will develop novel PET radiotracers to predict therapy resistance in mouse models of non-small cell lung cancer. These radiotracers will non-invasively image the aberrant activity of key antioxidant pathways that are causal to therapy resistance. Specifically, I will use structure-activity relationships and in vivo imaging to design highly-specific radiotracers for the cancer stem cell marker, aldehyde dehydrogenase 1A1; nuclear factor erythroid 2-related factor 2, the master regulator of the antioxidant response; and de novo glutathione synthesis. Our library of redox radiotracers will subsequently be used to detect drug resistance in syngeneic, isogenic and patient-derived models of lung cancer. Finally, I will use the radiotracers developed in this programme to assess response to immunotherapy in drug-resistant lung cancer.
|
| 31/03/2020 |
£1,734,742 |
|
UNIVERSITY COLLEGE LONDON |
During development the embryo needs to generate functional organs composed of many different cell types, often originated in different embryonic location. Thus, it is clear that cell differentiation and migration need to be tightly coordinated, although they are often studied as independent processes. Here I will test the hypothesis that cell migration and differentiations are coordinated by tissue mechanics in vivo. Specifically, I will challenge the current view that cell migration is the result of differentiation, by testing instead whether the reverse occurs, i.e. migration controls differentiation. I will use neural crest cell, a multipotent embryonic cell population in which cell differentiation is always linked to cell migration.
One of the problems to study biomechanics in vivo is the limited number of tools to measure and modify mechanical properties in vivo. Here I will develop new tools to analyse and change tissue stiffness in vivo. We will analyse how these mechanical changes influence cell migration and differentiation, and we will identify the molecular response elicited in the neural crest cells. We expect that this multidisciplinary project will provide answers to a central yet unresolved question in developmental biology: how cell fate and migration are integrated during embryo development.
|
| 31/03/2020 |
£532,692 |
|
BABRAHAM INSTITUTE |
The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.
|
| 31/03/2020 |
£338,511 |
|
MEMORIAL SLOAN KETTERING CANCER CENTER |
The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.
|
| 31/03/2020 |
£389,120 |
|
THE FRANCIS CRICK INSTITUTE |
The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.
|
| 31/03/2020 |
£507,346 |
|
UNIVERSITY OF OXFORD |
The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.
|
| 31/03/2020 |
£2,379,992 |
|
UNIVERSITY OF CAMBRIDGE |
The cell fate decisions that accompany exit from pluripotency and entry into gastrulation and early organogenesis establish the vertebrate body plan. Recent advances in single-cell multiomics have allowed transcriptomes and epigenomes to be mapped at single cell resolution during mouse embryogenesis. These studies suggest that cell fate decisions can be made autonomously, where cell fate derives from an intrinsic regulatory programme, or signalling-based, in which fate is determined by the reception of local extrinsic cues. The potency of precursors is progressively restricted as fate is allocated, but separate developmental routes can lead to convergent cell fates. To understand the fundamental principles of these cell fate determination processes, we will combine in vivo mechanistic studies and quantitative mechanistic modelling. We will integrate cell lineage relationships with spatial information and single cell multi-omics, using (epi)genome editing to perturb cell fate decisions in vivo. By comparing early organogenesis across the three germ layers, we will seek to understand the shared and unique features of the mechanisms that establish the underlying fate map.
|
| 31/03/2020 |
£3,181,816 |
|
UNIVERSITY OF OXFORD |
Having founded the new Centre for Prevention of Stroke and Dementia (CPSD) to allow junior/intermediate colleagues to develop their programmes, my own research will continue to focus on better phenotyping of TIA and stroke and of known risk factors in order to substantially improve the targeting of preventive treatments. My work involves four core themes:
Understanding the distinct temporal trends in incidence of different stroke subtypes to monitor the effectiveness of prevention and to develop new strategies;
Obtaining reliable data on prognosis of different TIA/stroke subtypes to better target preventive treatments;
Having proved the impact of better prediction and prevention of early recurrent stroke, I aim to substantially improve prevention of later recurrent stroke, focussing particularly on the utility of more detailed phenotyping (e.g. identification of occult atrial fibrillation, intracranial stenosis, and PFO, and remote monitoring of home-BP);
By more detailed assessment of BP I will inform the treatment of hypertension in primary prevention of stroke (by studying long-term pre-morbid BP) and in secondary prevention (home telemetric BP-monitoring);
Taken together the results of this work will impact on the treatment of almost all patients with TIA or stroke (2 million prevalent cases in the UK alone).
|
| 31/03/2020 |
£1,933,956 |
|
CARDIFF UNIVERSITY |
Adoptive transfer of patient T-cells expressing cancer-targeting chimeric antigen receptors (CARs) has achieved remarkable success with some soluble tumours. Unfortunately, CAR-T therapy cannot treat solid tumours. Contrastingly, tumour-infiltrating lymphocyte and checkpoint inhibitor therapies demonstrate that natural T-cells can eradicate end-stage solid cancers in some patients raising interest in engineering T-cells with T-cell receptors (TCRs) for "TCR-T" therapy. Conventional anticancer TCRs recognise endogenous proteinaceous antigens as short peptides presented by human leukocyte antigen class I (HLA-I) allowing killer T-cells to scan the internal proteome and eliminate cells bearing anomalies associated with cancerous transformation. Unfortunately, even the best conventional TCR approaches are only applicable in a minority of patients due to substantial variation in HLA across the population. The ultimate TCR-T therapy would bypass HLA-restriction to enable targeting of shared cancer antigens in all individuals. Our recent discoveries that some T-cells can recognise multiple types of cancer without the need for HLA could represent a major advance for immunotherapies. I want to understand the molecular mechanisms by which such ‘HLA-agnostic’ T-cells recognise cancer and utilise these remarkable cells to identify the cell surface changes that distinguish normal from cancerous cells. These potential cancer-biomarkers and cognate TCRs could underpin novel, broad-spectrum immunotherapies.
|
| 31/03/2020 |
£1,773,692 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
There is increasing concern about the long-term vascular health of the large and growing population of cancer survivors. I recently showed that survivors of most types of cancer have increased risks of one or more cardiovascular diseases, beyond those explained by shared risk factors such as smoking.
The key priorities now are to understand (i) the drivers of these increased risks, and thus how and when we can most effectively intervene; and (ii) whether broader vascular-related outcomes, in particular dementia and kidney disease, are also affected.
In this fellowship I will address these two priorities by conducting analyses underpinned by cutting-edge statistical and epidemiological methods, and capitalising on rich UK and international e-Health datasets, including game-changing new cancer treatment data.
I will investigate in detail the role of anti-cancer treatments (e.g. chemotherapies/radiotherapy) and changes in traditional vascular risk factors (e.g. blood pressure, BMI) in driving late cardiovascular risk. I will then investigate whether, and through what mechanisms, cancer history affects risk of vascular dementia, chronic kidney disease, and pre-clinical cognitive and renal outcomes (uniquely identifiable in the 500,000-strong UK Biobank cohort).
Throughout, this research will contribute actionable evidence informing clinical/public health policies to improve the long-term outlook of cancer survivors.
|
| 31/03/2020 |
£2,299,755 |
|
UNIVERSITY OF OXFORD |
Antibody affinity maturation occurs in germinal centers (GCs) through iterative rounds of somatic hypermutation (SHM) in dark zones (DZs) and selection in light zones (LZs). Current models state that, following SHM, DZ cells exit cell cycle and move to LZs to test their newly mutated B cell receptors by competing T cell help. High affinity B cells preferentially "win" in receiving help, and this causes them to undergo cyclic reentry (defined by S phase initiation and DZ re-entry). We recently demonstrated the possible existence of a second checkpoint, because BCR expression is required for LZ entry. We propose testing the nature of BCR-dependent signals required for this (e.g. cognate vs tonic signaling). Next, we will re-examine the fundamental principle that affinity enhancements are favored by LZ cells competing for cyclic re-entry promoting cues. In unpublished studies, we unexpectedly find that T cell help in not required for initiating cyclic re-entry. We will therefore test whether LZ cells compete for other non-T cell-derived cues, or whether instead cyclic re-entry is controlled independently of selection events. Finally, we will investigate whether GCs utilize innate cell types and signaling pathways for sensing the continued presence of foreign material and for determining GC longevity.
|
| 11/03/2020 |
£20,000 |
|
UNIVERSITY COLLEGE LONDON |
The Imbizo is a 3-week long summer school designed to connect young African computational neuroscientists with the international community. Computational Neuroscience (CN) is underdeveloped as a research field in Africa. The Imbizo is changing this, providing educational and career development opportunities in a place where they are very scarce. We are applying for continued funding to run the Imbizo for the years of 2021-2023, in Cape Town, South Africa.
The Imbizo brings together world leaders in CN and machine learning with approximately 18 African and 12 non-African students. Students come from diverse quantitative backgrounds including computer science, mathematics, physics and engineering. These disciplines are strong in several African countries. The intensive course comprises of lectures, tutorials, coding and brainstorming sessions. Extra-curricular team building and networking opportunities also take place. We organise workshops and surgeries on grantsmanship, manuscript writing, and CV clinics to prepare candidates for future job applications.
After 18 days of intense course work, we will have exposed some of Africa’s most talented analytic students to a new field and helped them build networks with experts. We will create opportunities for students from relatively disadvantaged institutions to move into CN and potentially grow collaborations and develop their skills and scientific ideas. Every year we see more students take up internships and graduate school positions that would have not been available to them without the Imbizo. This is a direct injection of diversity into the international CN community, and an investment in Africa’s CN future.
|
| 04/03/2020 |
£1,199,999 |
|
UNIVERSITY OF OXFORD |
The spliceosome produces mRNAs in two sequential transesterifications – branching and exon ligation. The post-branching C complex is remodeled by the ATPase Prp16 into the C* complex. Prp16 allows binding of the exon ligation factors Cactin and FAM32A, which stabilise docking of the 3’-splice site (3’SS) at the active site. While in yeast Prp18 is constitutively bound to C* spliceosomes, in humans Prp18 and other exon ligation factors of unknown function appear to engage the C* spliceosome in a transcript-specific manner. Here, I will reconstitute the C to C* transition in vitro in mammals and use biochemistry and cryo-electron microscopy to isolate and visualize novel intermediates and dissect the structural mechanisms by which Cactin, FAM32A, Prp18, and additional exon ligation factors cooperate to promote Prp16-mediated remodeling and to ensure correct 3’SS choice. In parallel, iCLIP studies will reveal where these exon ligation factors bind across all human pre-mRNAs and how RNA sequences around the splice sites determine the association of subsets of factors on specific pre-mRNAs. This work will elucidate how Prp16 drives remodeling of the human catalytic spliceosome and will investigate whether exon ligation factors regulate alternative splicing in a sequence-specific manner while proofreading 3'SS recognition during exon ligation.
|
| 04/03/2020 |
£1,017,466 |
|
UNIVERSITY OF OXFORD |
Blood flow is critical for maintaining the steady supply of oxygen and nutrients to the brain, and blood flow changes are present in a range of diseases including stroke and dementia. Conventional methods for in vivo blood flow mapping have limitations and often cannot be used for longitudinal monitoring or research.
In this proposal I aim to develop highly sensitive imaging methods for measuring brain blood flow based on a non-invasive magnetic resonance imaging technique, arterial spin labelling, applied at ultra-high field. The main goals of this research are:
To establish a robust platform for ultra-high field arterial spin labelling by developing novel approaches to overcome a range of technical challenges associated with this technique;
To develop advanced imaging approaches which allow richer cerebrovascular information to be obtained, including high resolution angiography and vessel-selective imaging;
To demonstrate the high sensitivity achievable with these novel methods by measuring changes in white matter perfusion in patients with vascular cognitive impairment, and probing the brain’s response to tonic pain at unprecedented spatial resolution.
These new methods will be actively shared with local, national and international collaborators, enabling previously unfeasible clinical and basic science research studies to be performed.
|
| 04/03/2020 |
£1,392,083 |
|
UNIVERSITY OF BRISTOL |
Many adult epithelial tissues lose cells from constant environmental stress. Thus, an epithelium’s ability to sense stress, defend itself and stimulate repair (e.g. by stem cells) is vital to prevent tissue dysfunction, degeneration, inflammation and cancer.
Despite its importance, this process is poorly understood. Using the adult Drosophila intestine and its unparalleled genetics, combined with proteomics, transcriptomics and fixed and live imaging, I will determine how stress signalling promotes epithelial resilience, maintenance and regeneration focussing on three main aims.
1) Reactive oxygen species (ROS) produced by damaged fly intestinal epithelial cells (IECs) promote intestinal stem cell (ISC)-mediated regeneration, partly via p38 signalling in IECs. I will determine how ROS promote intestinal regeneration by identifying ROS-controlled regulators of regeneration and determining molecular responses to ROS/stress signalling.
2) I have recently found that some stress pathways display rhythmic, circadian activation. I will investigate their role in intestinal maintenance.
3) I have shown that when new IEC production by ISCs is inhibited, IECs increase their lifespan to prolong epithelial maintenance. I will identify adaptive mechanisms that extend IEC lifespan when new cell production is blocked.
Understanding these processes could provide novel therapeutic strategies for tissue regeneration, inflammatory diseases, cancer and age-related pathologies.
|
| 04/03/2020 |
£1,241,815 |
|
BABRAHAM INSTITUTE |
In mature B-cells, the generation of antibodies of different isotypes relies on class switch recombination (CSR) mechanisms. Although crucial for adaptive immunity, CSR imposes challenges to genome integrity as it involves programmed induction of DNA double-strand breaks (DSBs) in rapidly proliferating B-cells. A key player in the cellular response to CSR DSBs is the protein kinase ataxia telangiectasia mutated (ATM). Evidence suggests RNA-dependent mechanisms control the DNA damage response by ATM, although there is very limited understanding of how these function in B-cells and which RNA-binding proteins (RBPs) are required for CSR. This proposal aims to define the critical roles of RNA helicases as integrators of ATM signals to control class switch recombination mechanisms in B-cells. I propose an integrative approach combining genomic and proteomic methodologies together with ex vivo B-cell differentiation systems and conditional gene-targeting in mice. I will determine RNA helicase-dependent mechanisms controlling the cell-cycle and CSR DSB-repair and investigate their roles in B-cell immune responses. This work will provide new insight into RNA helicase-mediated pathological mechanisms resulting in CSR deregulation and the development of immune disease or B-cell lymphomagenesis.
|
| 04/03/2020 |
£1,255,243 |
|
UNIVERSITY OF SHEFFIELD |
Neuronal axons can be a metre long and are maintained for a lifetime, making them acutely vulnerable to defects in microtubule mediated long distance transport. There are two broad categories of axonal transport in neurons, fast and slow. Slow axonal transport carries at least three times the material of fast transport, but ten to a hundred times more slowly. Protein moved by slow transport can be months old in the distal axon, and this process slows further with aging. Despite dysfunctional axonal transport being common in neurodegeneration, where aging is the major risk factor for disease, the mechanisms that regulate slow transport are very poorly characterised. Critically, whether transport time directly affects the accumulated damage and function of its protein cargo is unknown. The aim of this project is to understand how slow transport is regulated, whether transit time can influence the half-life and function of proteins, and further - whether it’s possible to reverse age-related decline in transport. To do this I will employ a multidisciplinary approach through the application of single-molecule light microscopy techniques. This project will define the relationship between the machinery of transport and the life cycle of axonal proteins.
|
| 04/03/2020 |
£1,131,741 |
|
UNIVERSITY OF SHEFFIELD |
Compromised wounds are increasingly prevalent, affecting quality of life for millions of sufferers and incurring a substantial burden on the NHS. I will define how macrophages control angiogenesis to drive wound healing and how this process breaks down to result in compromised wounds, particularly in the context of diabetes, using zebrafish and human co-culture models. Using RNAseq, I will profile zebrafish macrophages and endothelial cells in response to wounding, identifying the critical signals driving angiogenesis and how these fail in diabetic mutants. I will visually verify the roles of these key signalling genes by generating zebrafish transgenic reporters to live-image their wound response. In combination with novel CRISPR gene editing tools, I will establish specific manipulations to clinically relevant candidates, defining their functions and developing models of compromised wounds. The macrophage-HUVEC co-culture model will complement these zebrafish studies, corroborating the functions of macrophages from healthy versus diabetic patients. Expanding on this assay, I will use siRNA knock-down in monocyte-derived macrophages to dissect the role of clinically relevant candidates in perturbing macrophage control of angiogenesis. Together, these fish and human tissue culture models will provide a platform to identify novel therapeutics and propel the translation of these treatments towards the clinic.
|
| 04/03/2020 |
£1,057,974 |
|
UNIVERSITY OF GLASGOW |
The malaria parasite (Plasmodium falciparum) has a complex life cycle in which it must transit through multiple environments in a vertebrate host and mosquito vector. Transmission begins with ingestion of an infectious blood meal by one of 40 potential Anopheles mosquito species capable of transmitting the disease. This initiates the most extreme population bottleneck in the life cycle in which the parasite must rapidly undergo fertilisation, develop into an invasive form and transit through the midgut epithelium. The overarching goal of this proposal is to understand how this transmission through the mosquito vector drives selection on the parasite. I hypothesise that parasites have adapted to their local vector community composition, and this shapes their ability to infect sympatric and allopatric vector species. Using large-scale transmissibility assays and single-cell RNA-sequencing, I will identify genomic and transcriptomic vector-dependent signatures of transmission. I will then generate allelic-replacement parasites to unambiguously attribute phenotypic variation in species-specific transmission to specific loci in the parasite. Comprehensively understanding how vector communities shape parasite populations will guide future interventions and vector control programs by providing information that will allow for strategies to be locally tailored based on parasite genomic-surveillance and entomological surveys.
|
| 04/03/2020 |
£1,393,480 |
|
UNIVERSITY OF CAMBRIDGE |
Protein coding and non-coding RNA can spread between cells and tissues of an organism. RNA mobility between organisms has been documented within and among different kingdoms of life including fungi, plants and animals. However, the underlying mechanisms and roles of such transmissible RNA are poorly understood. Our recent studies demonstrated that honeybees share biologically active RNA among members of the hive through secretion and ingestion of worker and royal jellies. The jellies harbor naturally occurring exogenous (e.g. viral) and endogenous RNA. These findings suggest that RNA transfer plays a role in social immunity and signaling between honeybees. Therefore, the key goals of this proposal are: to establish a metabolic RNA labeling system in honeybees; and to apply this system to study natural RNA transfer-mediated antiviral immunity and impacts on the physiology of recipient bees. To achieve these goals, I will combine RNA biology techniques and imaging with high-throughput sequencing to establish a functional transmissible RNA pathway in honeybees. This project will provide knowledge and tools that will enable studying the biology of RNA flow in other organisms, including humans, in diverse biological aspects; hence, will ultimately contribute to the development of RNA-based applications to promote health and disease control.
|
| 04/03/2020 |
£1,153,494 |
|
UNIVERSITY OF OXFORD |
Host and pathogen genetic variations are major causes of clinical outcomes of infectious diseases. Traditionally, genetic studies of infectious diseases have sought to explain between-individual variation in disease by assessing genetic factors separately in humans or pathogens, under the assumption that these factors are independent. However, there is strong theoretical evidence that genetic interactions between host and viruses play a major role in viral disease aetiology. The major limiting factor to date has been the lack of cohorts with paired host-virus data. Recent technological developments and reductions in the cost of high-throughput viral sequencing from clinical samples have provided new opportunities to analyse host-virus genomic data generated from the same patients. In this project I propose to analyse paired host-virus genomic data from patient cohorts infected with HBV, HCV and HIV (clinically the most important chronic viruses worldwide) to answer the following questions:
1) What are the host genetic pressures driving virus evolution across different host populations and virus lineages?
2) What host and virus genetic interactions drive disease phenotypes?
3) What are the host genetic variants and pathways linked to disease phenotype across the three chronic viral infections of HBV, HCV and HIV?
|
| 04/03/2020 |
£1,256,713 |
|
UNIVERSITY OF SUSSEX |
The project aims to uncover why and how behavioural states like arousal affect neural processing in the early visual system by recording from the retina and superior colliculus in awake mice using techniques I have previously developed. Behavioural states affect task performance but their effect on early sensation is unclear; understanding their impact on early visual processing will reveal fundamental computational principles of adaptation.
Our objectives are:
determine the effects of behavioural states on different cell types in the early visual system by recording activity of retinal and collicular neurons classified by function, genetics and projection targets in awake mice.
determine the purpose of behavioural state modulation in terms of information processing in the early visual system by recording activity of retinal and collicular cell types in awake mice viewing visual stimuli that elicit nonlinear responses or are behaviourally relevant.
determine the mechanisms by which behavioural states influence early visual processing by measuring and manipulating the activity of neuromodulators, serotonin and noradrenaline, controlling behavioural states while recording from retinal and collicular neurons.
The results of this project impact on basic neurosciences and other fields including the development of artificial intelligent systems and the treatment and diagnosis of psychiatric disorders.
|
| 04/03/2020 |
£844,817 |
|
UNIVERSITY OF MANCHESTER |
How do vision and motor actions interact? A textbook will answer that vision guides movements but this view has been challenged over the last decade. The most striking realisation was the extent to which locomotion modulates neural activity in primary visual cortex, thalamus dLGN, superior colliculus and even the retina (collectively Early Visual System or EVS). Therefore movements can guide visual processing but the nature of this effect is unknown.
The most pressing question regards the specificity of these interactions. In EVS different visual features (size, luminance, colour, direction ...) are processed along parallel channels, at least 30 in the mouse retina. Since different motor actions (e.g. picking a fine thread, kicking a ball) require different visual features, I expect the interactions between vision and movements to be quite specific to the nature of the actions performed.
Due to technological limitations the only available data are obtained in head-fixed animals where only one type of action – locomotion – can be observed. To overcome these limitations I developed a system to quantify movements in unconstrained animals. I will use this system to understand how different movements affect distinct visual channels in EVS, modify the neural code(s) and ultimately influence behaviour.
|
| 04/03/2020 |
£828,055 |
|
UNIVERSITY OF OXFORD |
Rare diseases (prevalence 250 million people globally. Current approaches for identifying the genetic cause of a disease focus on regions of the genome that code directly for protein, finding a disease-causing variant in only ~50% of cases.
My aim is to identify novel genetic variants outside of these protein-coding regions that lead to disease, and the mechanisms through which they do so.
I will do this by applying computational and statistical methods to pioneering large-scale genomic datasets, totalling ~700,000 individuals.
My approach will focus on ‘near-coding’ regions, defined as those directly adjacent to protein-coding sequence that have important functions regulating protein expression. I will use complementary approaches that (a) look for near-coding variants in rare disease patients without a causative coding variant and (b) assess the strength of negative selection acting on categories of near-coding variants to predict which are deleterious and cause disease.
The findings from my work will be translated into clinical care to enable more patients to receive a valuable genetic diagnosis. In addition, increasing our understanding of the near-coding variant types that are deleterious will inform on genetic mechanisms underlying disease and suggest novel therapeutic strategies.
|
| 04/03/2020 |
£617,868 |
|
UNIVERSITY OF SHEFFIELD |
TB is a global crisis and treatment requires lengthy regimens of failing antimicrobials to clear infection. I propose that strategies that target the host, alongside antibiotics, would be more efficacious and combat the increasing prevalence of bacterial resistance. I have shown that HIF (hypoxia inducible factor) manipulation can activate pro-inflammatory responses against mycobacterial infection, specifically via Hif-1alpha stabilisation and resulting neutrophil activation. In addition, I can now demonstrate that arginase, a transcriptional target of Hif-2alpha, acts as a negative neutrophil immunoregulator, that on removal can activate neutrophils via an alternative mechanism to control mycobacteria. These findings indicate that neutrophils can be differentially activated via HIF manipulation, and that their protective properties could be therapeutically tuned during disease to clear infection. Therefore, I propose to address the following aims:
Determine the proinflammatory properties of Hif-1alpha-activated neutrophils
Characterise Hif-2alpha/arginase immunoregulation and their control of neutrophil phenotypes
Develop therapies to fine-tune neutrophil behaviours in infection
This work will extend our understanding of therapeutic targeting of HIF as a host-derived therapeutic strategy against multi-drug resistant infections. This extension will allow expansion and implementation of exciting neutrophil zebrafish models and the first steps translating these findings to human systems.
|
| 04/03/2020 |
£679,929 |
|
ZOOLOGICAL SOCIETY OF LONDON |
We know little about how future climate change, habitat destruction, human population increases and greater globalisation processes will impact human zoonotic diseases. Here, I investigate the use of dynamic, seasonal host population models to better predict the impact of real-time environmental change on disease-carrying host species, within a general systems-dynamics, disease framework. Specifically, I will combine a mathematical compartmental disease model with a host population ecology model, within a spatial and temporal Bayesian framework. Using this approach, I will first model Lassa Fever using climate and land-use observations, collaborating with the Nigerian government. I will then augment my model to account for animal movement patterns and vector species abundances, to examine arboviral disease spread in North America. Then, I will integrate these threads into a general, dynamic modelling framework for zoonotic diseases, which will contain both the newly developed components and my previously developed model of human movement and behaviour. Working with the World Health Organisation, I will create short- and long-term disease forecasts for a set of high priority zoonoses. Once validated against human case data, these mechanistic models can be used to test interventions and create future disease management plans that are robust to upcoming global change.
|
| 02/03/2020 |
£4,707 |
|
THE AGA KHAN UNIVERSITY, PAKISTAN |
I conducted research for my Masters thesis to explore, identify and examine ethical guidelines available for genetic studies and to then analyse and describe the extent to which researchers in Pakistan, comply with existing ethical standards specified for genetic research. I report in my thesis that there are no guidelines for genetic research, gene therapy or gene editing in Pakistan. I also found some other patterns in the studies reviewed that I would like to present in the form of a publication in a peer reviewed journal as I feel they will provide a foundation of behavioural practises of researchers in Pakistan.
I would also like to use the findings as a starting point to develop and propose guidelines for researchers for genetic research, gene therapy and gene editing in Pakistan. I want to propose guidelines that can be incorporated effectively into practise for which I will need to identify effective training, implementation and monitoring of the guidelines.
Key goals:
1. Develop a better understanding of the ethical review process of international collaborations in the UK
2. Produce a draft of a paper for submission to a peer reviewed journal
3. Propose an outline of guidelines for researchers in Pakistan
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| 02/03/2020 |
£7,340 |
|
UNIVERSITY OF IBADAN |
The purpose of this proposal is to develop an African, Regional interdisciplinary forum on the ethics, governance, engagement and social acceptability of Genome Editing in Africa. In spite of the discussions on Genomics, most African countries are yet to adequately engage in the critical debate on the regulation and ethics of genome editing. It is pertinent to have collaborative partnerships to focus on prudent research-based advocacy, to ensure truly informed policy decision making on gene editing in Africa. The key goals of this proposal is to disseminate the key outcomes of the 2019 GFBR meeting on" Genome Editing for Human Benefit: Ethics, Engagement and Governance", and to develop a proposal to take the outcome of this meeting further so as to begin an African oriented discussion on genome editing from the perspective of Africans. There will also be a research paper to be published in a peer-reviewed journal. Also, the focus of this proposal is to have a two-day workshop in Nigeria with key stakeholders from Africa discussing the ethical, governance and engagement issues relevant to Africa in Genome Editing that arose from the Singapore meeting.The meeting will promote collaborations between African Countries on the best practices in Genome Editing
|
| 02/03/2020 |
£7,459 |
|
NO ORGANISATION |
The novel biotechnology of the CRISPR-Cas9 method has certainly precipitated unprecedented interest as well as concern with regard to the scientific reality of human genome editing. This excitement and anxiety become even more acute in resource-limited settings where there is limited awareness and engagement between the experts in human genomics and gene editing and the public. Hence, there is an urgent need for effective public engagement. The purpose of my fellowship is to get vital mentorship in public engagement with human genome editing. My aim is to benchmark with best practice at NHGRI and work towards developing an appropriate African framework for public engagement with human genome editing. My visit will also be a unique opportunity for me to network and cultivate opportunities for north-south collaborative partnerships. Besides, the acquired knowledge and skills will greatly contribute towards Africa’s capacity-building. I plan to effectively disseminate my work, including at least one publication in a reputable peer-reviewed journal. Thus my trip is in line with GFBR’s goal of bringing together key stakeholders from developing and developed countries in addressing frontier bioethical concerns in research. It is also relevant to GFBR’s goals of capacity-building and of fostering effective collaborative partnerships.
|
| 02/03/2020 |
£5,841 |
|
UNIVERSITY OF CAPE TOWN |
There is established bio-ethical literature related to genomic research and technology, with this literature increasingly also focussing on gene drive technologies. While such questions are important, these questions often do not critically engage with how gene drive technologies interact with social, political and economic spheres. Furthermore, there is very limited critical discussion about these technologies from scholars situated in the global South, where some first field trials are set take place.
During this fellowship, I will work on a journal article for publication critically interrogating the social, political and economic dimensions of gene drive technology. This paper will focus on questions such as, why are the first field trials of this controversial technologies organised in one of the poorest countries in the world, who actually benefits from such research, especially given the convergence of funding from Western governments, philanthropic funders, and the commercial agricultural sector, and what is the impact of these arrangements of local communities and governance structures where gene drive technologies have been proposed to be used. The publication will begin to articulate these kinds critical questions that must be engaged with, if we are to ensure gene drive technologies does not reproduce historic patterns of inequality.
|
| 02/03/2020 |
£7,783 |
|
NO ORGANISATION |
The main intention of this fellowship is to document the distinct ethical issues related to the use of genome research in eradicating Malaria. This will then result in identifying an ethical acceptable framework for genome editing that necessitates the progress of scientific research. The following key goals are expected to be met in the 6 week period.
Review and document the National commission for science and technology NSCT regulations and guidelines in regards to genome editing.
Review the regulations, guidelines and policies used by ethics committees and regulators at McMaster and some sub-Saharan countries that incorporates genome editing for malaria eradication.
Establish and document evidence that aid advocacy to implicating policies that are favorable for researchers to conduct genome research and at the same time beneficial for human health IN Malawi
Recommend ethical acceptable approaches and frameworks that can address the ethical issues surrounding genome research
|
| 02/03/2020 |
£7,790 |
|
NO ORGANISATION |
The project aims to develop a better understanding of the general public and various stakeholders views on human gene editing in Argentina. Focus group sessions will be conducted for an in-depth exploration and description of the general public, patients and members of REC attitudes and perceptions towards human gene editing.
Key goals are:
The findings of the project will contribute to strengthening the evidence on an unexplored topic in Latin America.
The results will also serve as a basis for future research in Argentina and other Latin American countries.
The information obtained will provide information to Ministry of Health policymakers for future policy.
An academic paper for publication in a peer-review journal will be produced.
Key actors in Latin American countries will be identified to facilitate the dissemination of the findings.
A human gene editing workshop with experts for research participants to disseminate the findings of the project and to promote dialogue among stakeholders will be conducted.
|
| 02/03/2020 |
£5,429 |
|
NO ORGANISATION |
To organize two meetings for the general public to raise awareness about gene editing in Argentina so they can be enriched with reliable information. The idea is to repeat the event held in Buenos Aires in 2018 that I presented in the Forum in Singapore 2019, in two different cities in Argentina: Santa Fe and Entre Ríos, in order to reach more people about the importance of this technology. A registration form will be available for the general public to sign up for the meetings.
On the other hand, Ana Palmero will apply to another Meeting Fellowship to organize a workshop to ask patients of gene therapies, which in the future could require treatment with gene editing, their opinion about the technique. This way, she will gather data.
Even my project can be carried out independently, the idea is to work together to empower the workshop of Ana Palmero. The patients of the interest for the workshop will be invited to participate in the meetings in where they will receive information that will be able to use later in the workshop. An informed person, can elaborate better answers.
This way, two ministries of Argentina will work together: Science and Health
|
| 02/03/2020 |
£7,469 |
|
UNIVERSITY OF BOTSWANA |
The continuous growth and recent technical advances that have improved the precision, cost and simplicity of new gene editing technologies such as Somatic and germline therapy have since given birth to new hope in the fight against the burden of disease such as HIV in developing countries (sources). Despite facing dis-proportionally higher prevalence HIV rates, communities in Botswana to our knowledge the technologies have not been tried hence Batswana remain understudied in gene editing research. Therefore, I am proposing a study to engage with local communities to educate them about gene-editing technology research and collect their perspectives on how their cultural values norms and beliefs can have positive or negative implications on their benefiting from this technology.
1. The overall goal of the project is to explore the perceptions of communities in Botswana regarding perceived and real social ethical issues (cultural values, norms and beliefs) surrounding gene-editing technologies regarding its use for health benefits?
2. The project also aims to empower communities with knowledge through education and engagement about gene-editing technology for better informed decisions in preparation for participation in gene-editing technologies as well as learning about its potential benefits, risks and use of genomics, gene-editing technologies.
|
| 28/01/2020 |
£629,208 |
|
UNIVERSITY OF BIRMINGHAM |
Whilst perceived as a centralised, statist service, the NHS allows scope for voluntary financial support of its institutions, and for private provision of services outside the NHS. This has taken several forms: teaching hospital endowments; pooled endowment funds for non-teaching hospitals; and voluntary fundraising for individual institutions. Voluntary sector provision of health care has also continued: several voluntary hospitals disclaimed by the state in 1948 continued in existence, and a number of NHS hospitals have transferred back into charitable ownership.
These contributions to a public health service are little-known and our research is concerned with the distinctive contribution they make and the challenges they pose for policy. We therefore chart the scale, distribution and growth of these initiatives, as well as the niches which they occupy. We analyse how policy has been framed with reference to them – in other words how the balance between voluntary initiative and central planning has evolved over time – and we explore their role in innovation in the delivery of health and care, and their importance in engaging the public in supporting their local services. Overall this research programme provides novel insights into the debatable borderlands between statutory and voluntary initiative.
|
| 28/01/2020 |
£259,753 |
|
UNIVERSITY OF EDINBURGH |
Whilst perceived as a centralised, statist service, the NHS allows scope for voluntary financial support of its institutions, and for private provision of services outside the NHS. This has taken several forms: teaching hospital endowments; pooled endowment funds for non-teaching hospitals; and voluntary fundraising for individual institutions. Voluntary sector provision of health care has also continued: several voluntary hospitals disclaimed by the state in 1948 continued in existence, and a number of NHS hospitals have transferred back into charitable ownership.
These contributions to a public health service are little-known and our research is concerned with the distinctive contribution they make and the challenges they pose for policy. We therefore chart the scale, distribution and growth of these initiatives, as well as the niches which they occupy. We analyse how policy has been framed with reference to them – in other words how the balance between voluntary initiative and central planning has evolved over time – and we explore their role in innovation in the delivery of health and care, and their importance in engaging the public in supporting their local services. Overall this research programme provides novel insights into the debatable borderlands between statutory and voluntary initiative.
|
| 28/01/2020 |
£244,631 |
|
UNIVERSITY OF STRATHCLYDE |
Whilst perceived as a centralised, statist service, the NHS allows scope for voluntary financial support of its institutions, and for private provision of services outside the NHS. This has taken several forms: teaching hospital endowments; pooled endowment funds for non-teaching hospitals; and voluntary fundraising for individual institutions. Voluntary sector provision of health care has also continued: several voluntary hospitals disclaimed by the state in 1948 continued in existence, and a number of NHS hospitals have transferred back into charitable ownership.
These contributions to a public health service are little-known and our research is concerned with the distinctive contribution they make and the challenges they pose for policy. We therefore chart the scale, distribution and growth of these initiatives, as well as the niches which they occupy. We analyse how policy has been framed with reference to them – in other words how the balance between voluntary initiative and central planning has evolved over time – and we explore their role in innovation in the delivery of health and care, and their importance in engaging the public in supporting their local services. Overall this research programme provides novel insights into the debatable borderlands between statutory and voluntary initiative.
|
| 28/01/2020 |
£281,133 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Whilst perceived as a centralised, statist service, the NHS allows scope for voluntary financial support of its institutions, and for private provision of services outside the NHS. This has taken several forms: teaching hospital endowments; pooled endowment funds for non-teaching hospitals; and voluntary fundraising for individual institutions. Voluntary sector provision of health care has also continued: several voluntary hospitals disclaimed by the state in 1948 continued in existence, and a number of NHS hospitals have transferred back into charitable ownership.
These contributions to a public health service are little-known and our research is concerned with the distinctive contribution they make and the challenges they pose for policy. We therefore chart the scale, distribution and growth of these initiatives, as well as the niches which they occupy. We analyse how policy has been framed with reference to them – in other words how the balance between voluntary initiative and central planning has evolved over time – and we explore their role in innovation in the delivery of health and care, and their importance in engaging the public in supporting their local services. Overall this research programme provides novel insights into the debatable borderlands between statutory and voluntary initiative.
|
| 28/01/2020 |
£740,926 |
|
UNIVERSITY OF EXETER |
Humans have a deep-seared proclivity to feed animals, a behaviour implicated in the origins of animal domestication (the Commensal Pathway to domestication). While animal domestication is widely considered a phenomenon of the deep human past, our hypothesis is that the process is not only continuing but accelerating. Today, humans are feeding wildlife, pets and captive animals at unprecedented levels. This exceptional human intervention has ramifications for global health.
However, the situation is complex and beyond the comprehension of any single discipline. This is because while animal-feeding decisions are cultural, with deep histories that reflect political-economy, identities and attitudes to the natural world, their impacts are biological and evolutionary, affecting behavioural ecologies, biodiversity and well-being.
The interconnected nature of animal-feeding and how decisions can have catastrophic effects on the health of all concerned is exemplified by the BSE outbreak, which manifested across livestock, pets, zoo animals and humans alike.
This One Health project will use a transdisciplinary ‘engaged research’ methodology to explore the drivers and consequences of animal feeding in Britain (500BC to the present). Through the shared conceptual lens of commensalism we will examine how bird-feeding, cat-feeding and zoo-animal feeding are shaping our collective futures.
|
| 28/01/2020 |
£193,448 |
|
NATIONAL MUSEUMS SCOTLAND |
Humans have a deep-seared proclivity to feed animals, a behaviour implicated in the origins of animal domestication (the Commensal Pathway to domestication). While animal domestication is widely considered a phenomenon of the deep human past, our hypothesis is that the process is not only continuing but accelerating. Today, humans are feeding wildlife, pets and captive animals at unprecedented levels. This exceptional human intervention has ramifications for global health.
However, the situation is complex and beyond the comprehension of any single discipline. This is because while animal-feeding decisions are cultural, with deep histories that reflect political-economy, identities and attitudes to the natural world, their impacts are biological and evolutionary, affecting behavioural ecologies, biodiversity and well-being.
The interconnected nature of animal-feeding and how decisions can have catastrophic effects on the health of all concerned is exemplified by the BSE outbreak, which manifested across livestock, pets, zoo animals and humans alike.
This One Health project will use a transdisciplinary ‘engaged research’ methodology to explore the drivers and consequences of animal feeding in Britain (500BC to the present). Through the shared conceptual lens of commensalism we will examine how bird-feeding, cat-feeding and zoo-animal feeding are shaping our collective futures.
|
| 28/01/2020 |
£276,268 |
|
ROEHAMPTON UNIVERSITY |
Humans have a deep-seared proclivity to feed animals, a behaviour implicated in the origins of animal domestication (the Commensal Pathway to domestication). While animal domestication is widely considered a phenomenon of the deep human past, our hypothesis is that the process is not only continuing but accelerating. Today, humans are feeding wildlife, pets and captive animals at unprecedented levels. This exceptional human intervention has ramifications for global health.
However, the situation is complex and beyond the comprehension of any single discipline. This is because while animal-feeding decisions are cultural, with deep histories that reflect political-economy, identities and attitudes to the natural world, their impacts are biological and evolutionary, affecting behavioural ecologies, biodiversity and well-being.
The interconnected nature of animal-feeding and how decisions can have catastrophic effects on the health of all concerned is exemplified by the BSE outbreak, which manifested across livestock, pets, zoo animals and humans alike.
This One Health project will use a transdisciplinary ‘engaged research’ methodology to explore the drivers and consequences of animal feeding in Britain (500BC to the present). Through the shared conceptual lens of commensalism we will examine how bird-feeding, cat-feeding and zoo-animal feeding are shaping our collective futures.
|
| 28/01/2020 |
£309,806 |
|
UNIVERSITY OF READING |
Humans have a deep-seared proclivity to feed animals, a behaviour implicated in the origins of animal domestication (the Commensal Pathway to domestication). While animal domestication is widely considered a phenomenon of the deep human past, our hypothesis is that the process is not only continuing but accelerating. Today, humans are feeding wildlife, pets and captive animals at unprecedented levels. This exceptional human intervention has ramifications for global health.
However, the situation is complex and beyond the comprehension of any single discipline. This is because while animal-feeding decisions are cultural, with deep histories that reflect political-economy, identities and attitudes to the natural world, their impacts are biological and evolutionary, affecting behavioural ecologies, biodiversity and well-being.
The interconnected nature of animal-feeding and how decisions can have catastrophic effects on the health of all concerned is exemplified by the BSE outbreak, which manifested across livestock, pets, zoo animals and humans alike.
This One Health project will use a transdisciplinary ‘engaged research’ methodology to explore the drivers and consequences of animal feeding in Britain (500BC to the present). Through the shared conceptual lens of commensalism we will examine how bird-feeding, cat-feeding and zoo-animal feeding are shaping our collective futures.
|
| 28/01/2020 |
£932,125 |
|
UNIVERSITY OF BIRMINGHAM |
Background: This project will provide a comprehensive understanding of the processes by which schools and workplaces invest in mental health promotion. This is urgently needed, as these organisations, though not traditionally designed for this function, are increasingly seen as a key influence on individuals’ mental health across the life-course.
Goals: The project will: (i) Establish the diversity of attitudes to mental health promotion (MHP) in schools and workplaces; (ii) Develop a typology of resource use for MHP and way of tracking resource needs; (iii) Identify the way in which evidence is used and needed in schools and workplaces to support investment decisions; and (iv) Explain how investment and provision decisions relating to MHP in schools and workplaces are made in practice.
Methodologies: A diverse set of case study schools and workplaces will be recruited. Interviews and focus groups will be conducted with individuals with responsibilities for MHP investment (managerial staff, senior teachers, wellbeing specialists). Targeted techniques will used to study participants' attitudes, reactions to evidence, and investment decisions.
Outputs: The research programme will guide policy-makers and researchers as to how to inform, support, resource, incentivise and regulate mental health promotion in schools and workplaces.
|
| 28/01/2020 |
£984,271 |
|
UNIVERSITY OF SHEFFIELD |
Orphan drugs are a class of medicines that treat rare diseases. Their development has been incentivised to address the needs of neglected patient groups. They are growing rapidly, highly profitable and stimulating new business models based on high cost products for niche markets. However, the very high price of some orphan drugs has led countries, including the UK, to refuse to pay for them. This has provoked growing political concern that patients are being denied access to life saving therapies. A major international debate on how to improve access is ongoing, raising important questions about the value of these medicines and the ethics of resource allocation. Patient organisations have responded by sponsoring more sustainable, lower cost orphan drug development. This project will look systemically at the coproduction of industrial and technological change, the politics and governance of orphan drugs, and new forms of collaborative knowledge production. It is innovative in developing a new concept, "orphanisation", to understand contemporary change in the biopharmaceutical sector. Specifically, it will ask to what extent is orphanisation occurring in the UK and USA, how is it being shaped by different technologies, institutions and actors, and what are the implications for industry, health policy and patients?
|
| 28/01/2020 |
£1,009,755 |
|
UNIVERSITY COLLEGE LONDON |
This four year project examines birth cohorts as sites of knowledge, practice and participation in the UK, Europe and Latin America. It aims to understand how they provide an infrastructure for and are a technology of biosocial science. It is the first study to take birth cohorts as an object of ethnographic inquiry in comparative national contexts.
In an era of post-genomics, studies that follow research participants over their lifetimes have become vital to understanding how material and social environments ‘get under the skin’ and are dynamically shaped across the lifecourse. This is increasingly described as ‘biosocial science’, reflecting the importance to this field of the interaction between social and biological factors. Whilst a notion of the biosocial is not new, singular nor uncontested it is now being re-shaped in global research terrains with longitudinal cohort studies as important tools and technologies.
By examining the ‘biosocial lives’ of birth cohorts in the global north and south, I will provide insight on the socio-cultural specificity of these developments. Comparison will inform theorisation of what the biosocial is, whilst an ethnographic perspective will facilitate methodological innovation in examining and intervening on birth cohort research and how biosocial science is coming into being.
|
| 28/01/2020 |
£305,001 |
|
UNIVERSITY OF CENTRAL LANCASHIRE |
Zines (self-published magazines, graphic memoirs and comics) are rich, yet currently untapped, sources of knowledge about mental distress and psychosocial disabilities - how they are lived with, challenged and understood. This research will identify, analyse and co-produce Madzines: self-published magazines, comics and graphic memoirs, created by people with lived experience, which communicate critical ideas about mental health. Specifically, this research will explore how zines, due to their unique format, craft contention about mental health knowledge and practice. It will investigate how zines:
Challenge prevailing psychological, psychiatric and medical understandings, diagnoses and treatments;
Articulate specific forms of contention about controversial and hidden diagnoses; pathologised identities and experiences;
Communicate new understandings of mental health diagnoses, identities and experiences;
Function as a unique form of psychiatric survivorship offering new repertories of contention for the psychiatric survivor movement;
Utilise diverse styles of contention such as humour, parody and subversion.
This investigation will define a new genre of Madzines and help transform the way zines are researched, understood and theorised. It will be used to explore how zines can contribute to formal and informal learning about mental health, challenge stigma and discrimination and inform policy and practice.
|
| 28/01/2020 |
£917,922 |
|
UNIVERSITY OF EDINBURGH |
Suicide Cultures: Reimagining Suicide Research (SC) will undertake a transformational, qualitative mixed-methods study of the social contexts and cultural meanings of suicide in diverse communities across Scotland. The project aims to shift understandings of what suicide research can be and do, contributing to innovation in how societies might best respond to suicide as a social and cultural phenomenon. SC consists of five inter-related workpackages. WP1: a qualitative sociological autopsy study of up to 390 cases of suicide across 3 areas of Scotland. Data will include formal reviews of suicide deaths (300), and interviews with family/friends bereaved by suicide (90 cases). WP2: qualitative, in-depth interviews with 60 people, recruited from the same 3 areas, who have self-harmed– those who may have died, but who did not. WP3: will explore understandings of suicide among different community groups, using collaborative arts-based methods. WP4: entails close, ethnographic study of up to 6 localities, identified iteratively during fieldwork, and studied in-depth to develop social and cultural explanations for particular features (e.g. clustering, demographic peculiarities) of suicide in particular places. WP5: an embedded PhD studentship will analyse how race/ethnicity shape understanding and meanings of suicides, ensuring this sorely neglected area is addressed.
|
| 28/01/2020 |
£816,955 |
|
UNIVERSITY OF MANCHESTER |
What does it mean to sleep well? This is not just a modern concern but something that has exercised individuals and communities throughout history. This project will be the first to address this question by assessing how people's efforts to sleep well c.1500-1750 were influenced by a distinctive set of environmental relations and linked 'environing practies' in which people engaged with their physical surroundings to optimise their sleep timings, bedding materials, and to prepare soporific tonics. A PI-led team will reconstruct the principal agents, materials, and 'environing' practices that were used to manage sleep in ecologically distinct parts of Britain, Ireland and England's emergent American colonies of Virginia and Newfoundland, alongside the bodies of medical, botanical, climatic and material knowledge associated with them. The research is important because it brings a fresh environmental history perspective to bear upon cross-disciplinary debates about the significance that physical environments play in shaping healthy and unhealthy sleep habits. It will also be the first to assess the immediate and longer-term impacts of early modern processes of environmental change in shaping people's sleep care practices, which will encourage a reassessment of the assumed primacy of 'watershed' moments such as industrialisation in shaping human sleep fortunes.
|
| 21/01/2020 |
£286,353 |
|
UNIVERSITY OF YORK |
Vets and doctors are both involved in managing death, but the changing ways in which the professions are involved in end of life care have not been studied together. Nor has there been systematic examination of how the two professions might learn together in this field. Using cutting-edge post-human theories and inter-species empirical and ethical approaches, this project will drive forward such research. First, it builds on the small but growing literature which shows how companion animals are increasingly conceptualized as family members and can provide metaphors and models by which to discuss the care of human family members. Second, it responds to observable changes in practice by which the the end-of-life treatment of humans and non-humans animals are becoming much less distinct, for example, through the emergence of animal hospices and increasing discussion of medically assisted dying.
The project examines how contemporary trends might contradict and complicate the legal and ethical basis of both overlapping and divergent clinical practices. At a time when approaches to end of life care are being redrawn, it will create opportunities for the veterinary and medical professions to learn together, through accessing shared ideals and valued differences within the negotiation of a ‘good death’.
|
| 21/01/2020 |
£201,207 |
|
UNIVERSITY OF MANCHESTER |
Digital sensing promises new solutions to animal healthcare in farming through real-time capture and analysis of animals’ physiological and behavioural data. Sensor technologies influence routines, devices and everyday strategies for animal disease and stress prevention adopted by farmers and veterinarians. This reorganisation of healthcare practices has implications for human-animal relations and animal health assessment, including the wellbeing of animals and their carers and the control of diseases that pose a risk to human health. This project sits at the intersection of medical humanities, animal studies and science and technology studies (STS) to be the first to offer an investigation of the relationship between digital sensing, knowledge production and social relations within animal healthcare practices in farming. Drawing on historical and ethnographic research of the case of cattle farming in the UK and France, the research contributes unique methodological and theoretical insights on sensing practices by asking: Why and how sensor technologies have become part of animal health and welfare management in cattle farming? How does digital sensing influence knowledge production and understandings of cattle health, illness, and wellbeing? And, how does digital sensing transform social relations, including human-animal relations, in the context of cattle healthcare in farming?
|
| 21/01/2020 |
£250,779 |
|
LIVERPOOL JOHN MOORES UNIVERSITY |
The phenomenon of human enhancement through drugs (HEDs) has sparked intense public debates and a growing body of interventions and research from the social and health sciences. Sociological and philosophical inquiries have explored the ethics of such drug use and how such practices shape identities and ideas of what it means to be human. As new substances, modes of use and attitudes are popularised amongst people of diverse backgrounds, new risks for physical, mental and social health and wellbeing are being identified and assessed. This research aims at investigating the emerging trend of microdosing psychedelics as a new facet of human enhancement through drugs. Attracting significant media and scientific attention in recent years, microdosing is the regular use of sub-perceptive threshold doses of substances such as LSD or magic mushrooms. Self-reported benefits include enhancements in cognitive performance, mood, creativity, physical energy and inter-personal relations, as well as decrease in depressive and anxious symptomatology. Employing a combination of qualitative methods, the research will investigate this fascinating phenomenon and situate it in the larger context of the current psychedelics renaissance that is marked by new scientific investigations, policy change, a use and advocacy movement, and commercial interests in these substances.
|
| 21/01/2020 |
£189,726 |
|
NORTHUMBRIA UNIVERSITY |
Sleep is in crisis in the twenty-first-century Global North. People fail to sleep the eight hours recommended by the WHO and sleep disorders are on the rise. In the first study to investigate cultural engagements with this public health issue, I consider a wide range of twenty-first-century Anglophone writings: fiction, non-fiction (memoirs and self-help manuals), and digital culture (mHealth apps and sleep hygiene blogs).
This focus on cultural production serves to interrogate the crisis’s affective dimension. Informed by critical theory, my literary/cultural analyses explore the affects and concerns about contemporary life mobilised by the discourse of a sleep crisis and what these reveal about the relationship between individual health and neoliberal ideologies. My aim is to articulate a new theory of the affects (such as insomnia, exhaustion, burnout, and anxiety) flourishing under the neoliberal temporal regimes and forms of subjectivity that arguably underlie the sleep crisis.
The project proposes an innovative medical humanities intervention, since sleep has only recently become an object of inquiry for the humanities and an exclusive consideration of sleep in twenty-first-century writings is lacking. With its timely exploration of mental health issues rife under neoliberalism, my project will have impact on mental health practice and activism.
|
| 21/01/2020 |
£544,026 |
|
UNIVERSITY OF SHEFFIELD |
This research will provide essential new knowledge for the design of successful policies to improve the health of Europe’s Roma populations. Roma, the largest ethnic minority in Europe, have faced generations of structurally sanctioned racism. Their health is the worst of any group in the region. Despite increasing policy attention, Roma disadvantage is increasing. Before we can know what needs to change in order to improve the situation, we need to understand the nature of the ‘problem’. Understandings must reflect Roma knowledge in order to challenge their on-going oppression. This study will employ critical participatory methods to begin a dialogue with specific self-defined Roma populations in England and Hungary. Creative approaches will bring to life contextually-embedded subaltern perspectives on the ‘who’, ‘what’ and ‘how’ of ‘Roma health’. Post-structuralist interviewing techniques will encourage policy specialists to reflect on contingent nature of policy understandings and the work that is required to sustain dominant discourses. The research programme will culminate in series of innovative workshops, performances, exhibitions and presentations that bring together policy specialists and Roma to share alternative accounts of ‘Roma health’ so that currently privileged policy problematisations can be rethought.
|
| 21/01/2020 |
£353,392 |
|
UNIVERSITY OF EXETER |
This project tackles the question of how people in the Middle East have experienced ‘addiction’ and how governments and social agents have reacted to changing drug phenomena in states of disruption (war, revolution, human displacement).
It explores the consumption of mind-altering drugs in Iran and Lebanon, and their respective displaced communities (Afghans, Syrians), unearthing an alternative framing of pleasure/illness/care and ways of living ‘addiction’ that differ from the West-centric scripts on health/illness.
Focusing on the life trajectories of past and present drug consumers during and after dramatic political change, armed conflict and human displacement, it questions how states of disruption affect the lived experience of ‘addiction’, how people make use of mind-altering drugs in dealing with unsettling conditions, and how health institutions and social agents transform their public agenda because of them.
The project considers the case of drug consumers, ‘addiction’ scientists, and religious/spiritual healers. This leads to the reframing of the cultural, scientific and political environments that have made ‘addiction’ into a biomedical and ethical category in the contemporary Middle East. It adopts a transdisciplinary approach to ‘addiction’ using regional archives, bottom-up oral history, ethnographic immersion and visual data collection, engaging them in debates across history, politics and anthropology.
|
| 21/01/2020 |
£188,162 |
|
UNIVERSITY OF WARWICK |
In recent decades, the 'safety' of patients and staff has become a pressing concern in the British National Health Service (NHS). However, little is understood about how and why these ideas and practices evolved historically, and were spread throughout the NHS.
My project, Hazardous Hospitals, addresses this lacuna by exploring ideas and practices around 'safety' in NHS general hospitals from 1960-2012. It analyses the development, promotion and institutionalisation of 'safety cultures': ideas, values and behaviours around safety, as well as the systems and processes which support and sustain them. My outputs will be a major monograph exploring the history and meaning of 'safety' in the NHS, an article in History & Policy, as well as 2-3 journal articles exploring sub-topics, such as occupational health. I ask:
1. What defines the ‘safety culture’ of NHS hospitals? How can these ‘safety cultures’ vary?
2. How was safety in hospitals assessed, and in what ways did it come to the attention of NHS managers and policymakers after 1960?
3. How did NHS managers promote safety among their staff?
4. What role did groups such as patient organisations, safety campaigners and the press play in depicting, challenging and promoting reform of hospital ‘safety cultures’?
|
| 21/01/2020 |
£255,244 |
|
UNIVERSITY OF LEEDS |
People with a learning disability have low rates of participation in health research. The acceptability of health interventions and medication are rarely tested on them in population based studies. This project examines 2 time points at which their participation in health research is subject to under-researched interactions and interpretations. It scrutinizes the operation of ideas of capacity, consent and autonomy at those time points.
This study will use ethnographic and interview methods to examine the role of NHS research ethics committees in their discussions of studies, looking for the ways intellectual disability is conceptualised and how this influences research design and approval. It will utilize autoethnographic and interview methods to tease out how researchers negotiate the everyday ethics of implementing mental capacity guidance during research. Thirdly, it will work with people with a learning disability to gain their perspective on health research participation, consent and capacity.
This project will generate innovative empirical data, ambitious theoretical engagement with concepts of capacity, consent and autonomy. I will also create practical guidance for ethical review committees, researchers, people with learning disabilities and the general public to challenge the lack of diversity in research samples and the inequality in research participation.
|
| 21/01/2020 |
£193,757 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
This project explores how HIV-affected people built and maintained families in Edinburgh, influencing national and international policy and practice through daily acts of love, care, and activism between 1981-2016. Adopting the broad understanding of ‘family’ deployed by queer scholars, it scrutinises how HIV-affected families of choice, origin, and necessity worked with – and included – communities of friends, activists, and health and social care practitioners, to meet the emotional, educational, and medical needs of the HIV-affected. In doing so, the project will trouble and historicise the varied definitions of ‘love’, ‘care’, ‘activism’, and ‘family’ deployed by actors to interpret acts, objects, and spaces involved in building and maintaining HIV-affected families. The key aims are to uncover how HIV-affected families’ needs were defined and met; to what extent meanings of ‘family’ and ‘activism’ were changed by the necessities of HIV-related care work; and what influence, if any, the experiences of HIV-affected families had on conceptions of reproductive politics and childcare. The project draws new links between histories of family, reproduction, risk, pleasure, social care and activism, identifying new actors, networks, and objects, advancing voices which, while present in the archive, are muted in the current historiography.
|
| 21/01/2020 |
£274,182 |
|
UNIVERSITY OF GOTHENBURG |
Patient behaviour plays a key role in determining whether health systems are able to maintain and promote health. One area where it is crucial to study patient behaviour is maternal and neonatal health, particularly in low and middle-income countries (LMICs). Every day, over 800 women in LMICs die from preventable pregnancy and childbirth related complications. Key international policy goals, such as the third Sustainable Development Goal, reflect the view that patient behaviour – specifically related to care-seeking, facility delivery and use of antenatal care (ANC) services – is key for preventing maternal deaths. Understanding patients’ healthcare-seeking behaviour and addressing barriers to uptake, is therefore crucial for improving maternal and neonatal health in LMICs.
This fellowship will generate new evidence on the determinants of patients’ healthcare-seeking behaviour, and its effects on maternal and neonatal health and survival in Kenya. It has four objectives:
Analyse the link between trust in the health system and care-seeking behaviour
Explore the relationship between perceived quality of care and care-seeking behaviour
Determine the effect of care-seeking behaviour on health outcomes in Kenya, including heterogeneity based on the quality of care and socio-economic status
Disseminate findings to policymakers and researchers
|
| 21/01/2020 |
£231,000 |
|
UNIVERSITY OF SHEFFIELD |
What are the implications for health professionals and patients when cancer develops during pregnancy? To what extent might existing care practices become reconfigured within this context? This Fellowship will address these questions through novel research exploring a rare condition: Gestational Trophoblastic Disease (GTD). GTD only arises following conception, and can result in the development of (pre-)cancerous tissue in place of a viable foetus. Nevertheless, in many cases women experience symptoms of pregnancy and anticipations for future parenthood. GTD disrupts conceptual boundaries between cancer and pregnancy as corporeal phenomena, posing vital questions around the status of foetal and malignant entities, and definitions of pregnancy and loss.
An exploration of this unique condition through the lens of medical sociology will enrich social scientific explorations of foetal personhood and pregnant embodiment. Further, whilst cancer is often studied sociologically, this research will prompt dialogue around cancer and pregnancy. This clash of life potential with life-threatening illness provides unique opportunities to explore how experiences of anticipated parenthood, loss, and cancer ‘survivorship’ co-exist. Key goals will be the interrogation of societal definitions of pregnancy/cancer as reproduced and reimagined through the phenomenon of GTD, exploration of women’s experiences, and the generation of relevant insight for clinical practice.
|
| 05/12/2019 |
£1,268,713 |
|
UNIVERSITY OF CAMBRIDGE |
Mitochondria are cellular organelles primarily involved in energy production. They are considered to be key to the function of eukaryotic cells. Nevertheless, mitochondrial diseases often only present in adulthood with tissue-specific symptoms. This means that cells and tissues must have coping strategies which temporarily maintain normal function when confronted with mitochondrial dysfunction.
This proposal aims to test the hypothesis that cell-type composition and metabolic interactions between different cell types renders specific tissues more or less vulnerable to mitochondrial dysfunction.
The neural stem cell (NSC) niche in the developing Drosophila brain is a powerful in vivo model for the microenvironment of neurons and NSCs in our human brain. I plan to study the in vivo metabolic requirements of Drosophila NSCs (Aim 1), and the metabolic and transcriptional response of surrounding niche cells upon mitochondrial dysfunction (Aim 2). In the last part of my proposal, I will investigate how metabolic regulation of the nuclear genome provide both a nuclear sensing mechanism and a buffer to tissue-wide mitochondrial dysfunction (Aim 3).
Elucidating generic mechanisms of the tissue-wide response to mitochondrial dysfunction will lead to better insight into metabolic origins of neurodegenerative diseases and cancer and has the potential to uncover novel therapeutic approaches.
|
| 05/12/2019 |
£755,905 |
|
UNIVERSITY COLLEGE LONDON |
Seizures are a common manifestation of brain injury in newborn infants. Controversies still exist over whether seizures may themselves cause further damage to the developing brain, when to treat them, what drugs to use and how to improve detection. There is an urgent need for a better understanding of the pathophysiological changes to improve our management strategies.
My key goal is to assess the impact of seizures on the newborn brain. I propose to use a new optical platform (combined broadband near-infrared spectroscopy and diffusion correlation spectroscopy) for a comprehensive real-time assessment of cerebral metabolism (using oxCCO and CMRO2), haemodynamics (using CBF and CBV) and oxygenation (using TOI) together with video-electroencephalography(EEG) at the cot-side to investigate seizure-induced changes inside brain. I aim to deliver a translational and clinical strategy to investigate these changes in healthy brains of an animal model and in a cohort of babies in neonatal intensive care who developed seizures after brain injury. I will further investigate the impact of phenobarbitone on brain metabolism and haemodynamics. Short and long-term impacts will be assessed with neuroimaging and neurodevelopmental outcome data.
These findings will improve our understanding and will support an evidence-based approach for the management of neonatal seizures.
|
| 05/12/2019 |
£697,263 |
|
UNIVERSITY OF EDINBURGH |
My research aims to further define the pathological biochemistry of RPGR-mediated X-linked Retinitis Pigmentosa (RPGR/XLRP), an inherited retinal dystrophy that causes blindness and has no treatment. I hope better understanding of disease mechanism will help identify potential therapeutic options.
Photoreceptor outer segments have evolved from primary cilia to compartmentalise the visual pigment rhodopsin into an elaborate structure of folded membranes, known as discs, enabling normal vision. Failure of disc morphogenesis results in photoreceptor degeneration; the hallmark of Retinitis Pigmentosa (RP).
Recent work suggests that photoreceptor disc formation is an actin-mediated process, but the exact mechanism by which they form is unknown. RPGR mutations account for 20% of RP and my previous work suggests RPGR regulates actin turnover in the photoreceptor connecting cilium.
I hypothesise that RPGR acts as an assembly platform that recruits actin binding proteins to promote morphogenic membrane curvature at the distal connecting cilium, resulting in disc formation.
My work in this application will examine my hypothesis. I will use animal models of RPGR/XLRP and endogenously tagged proteins to determine the biochemcial processes that underpin the disease using a combination of molecular biology, novel interactomic experiments and super-resolution imaging.
|
| 05/12/2019 |
£999,519 |
|
UNIVERSITY OF EXETER |
We are now in the genomics era where clinical and pre-emptive genetic testing is common. This has raised new problems in monogenic disorders such as Maturity-Onset Diabetes of the Young (MODY), a rare genetic form of diabetes: 1) identification of wide variation in the clinical features of people with MODY mutations, including non-diabetic individuals. 2) identification of people who are ‘MODY-like’ (slim, young and not on insulin) but without a MODY mutation and therefore without a known cause for their diabetes.
During my fellowship, I will address these new problems using our unique cohort of MODY/MODY-like diabetes and clinical and genetic data on 500,000 people from UK Biobank. I hypothesise that polygenic risk of diabetes-related traits will explain variation in the MODY phenotype and characterise new subtype(s) of diabetes which presents as classic MODY, but is due to extreme polygenic risk of diabetes-related traits (polygenic-phenocopies).
The outcomes of this research will be to provide accurate prediction of which people with MODY mutations will get diabetes and when, and define and characterise a new type of diabetes. This work will have important implications for individuals with MODY, for the wider diabetes community and will provide framework for other genetic disorders.
|
| 05/12/2019 |
£1,393,685 |
|
IMPERIAL COLLEGE LONDON |
Regulation of gene expression by DNA methylation (5mC) in response to genetic and environmental risk factors is considered important to human obesity and type-2 diabetes (T2D) pathogenesis. Yet, difficulty finding causal 5mC changes in humans is limiting downstream clinical applications. I have discovered 5mC changes robustly associated with obesity and their predicted effector genes in human adipocytes. I have then refined these loci and genes using human genomics, cross-species transcriptomics and biological evidence to 3 top candidates for discovery of novel mechanisms of disease – the MEDAG, FGFRL1 and TXNRD1 loci.
I will use sophisticated gene targeting to investigate the causal effects of the MEDAG, FGFRL1 and TXNRD1 genes on obesity and T2D in a mouse model of human disease, and detailed phenotyping to examine the pathophysiological mechanisms. In parallel, I will use functional and experimental genomics to explore the regulatory significance of obesity-associated 5mC sites on MEDAG, FGFRL1 and TXNRD1 gene expression, and the underlying epigenetic mechanisms, in human adipocytes. These complementary lines of evidence will establish whether locus-specific 5mC variations and subsequent gene expression changes impact on human obesity phenotypes, and may define epigenomic and molecular targets for new obesity and T2D therapies.
|
| 05/12/2019 |
£1,198,669 |
|
INSTITUTE OF CANCER RESEARCH |
Prostate cancer (PC) is a leading cause of cancer-related death in men globally. Advanced PC responds to androgen receptor blockade but inevitably remains lethal. Novel therapeutic strategies are urgently required, incorporating disease molecular stratification.
I have acquired data demonstrating that a gene cassette on chromosome (ch) 1q, incorporating the anti-apoptotic gene MCL-1, is amplified in 16% of lethal PC. Furthermore, patient-derived tumour models with ch1q (MCL-1) amplification are resistant to established treatments but respond to MCL-1 inhibition. I hypothesize that, interrogation of MCL-1 biology will elucidate superior strategies to target MCL-1. Consistent with this, RNA splicing factor SF3B1 knockdown drives expression of its pro-apoptotic isoform MCL-1S, and deubiquitinating enzyme UCHL3 knockdown degrades MCL-1 protein, inhibiting PC growth. Furthermore, UCHL3 is deleted in 7-13% of lethal PC which may reduce MCL-1 expression and sensitise to BCL-XL/BCL-2 inhibition.
I will therefore: (1) evaluate the impact of ch1q (MCL-1) amplification on PC cellular processes and response to standard therapies; (2) develop novel strategies to target MCL-1 (and other BCL-2 family members) in PC; and (3) identify novel targets to deliver innovative therapeutic strategies for ch1q (MCL-1) amplified PC. I envision that this work will improve outcome from this commonest of male cancers.
|
| 03/12/2019 |
£706,995 |
|
UNIVERSITY COLLEGE DUBLIN |
The idea that the brain forms decisions by accumulating evidence up to a criterion or "bound" has been the major driver of decades of fruitful theoretical, behavioral, neuroscientific and clinical research into decision making. However, the most prominent competing model variants disagree on whether and how the extent of accumulation is limited through either of two means: 1) growing "urgency" to respond, which effects a collapsing decision bound, and/or 2) "leakage" of past evidence. These model variants are indistinguishable based on the quality of behavioural data fits for most tasks, yet can yield fundamentally discrepant interpretations of the same data. Our recent discovery that sensory evidence encoding, evidence accumulation and motor preparation can be simultaneously traced in neurophysiological recordings from the human brain has opened a new path to gaining definitive, convergent insights into the operation of these mechanisms in any task. Pioneering a unique approach which exploits these dynamic neural signatures to construct, constrain and validate multi-tiered decision models, we will establish when and why urgency and leakage are invoked and adapted across diverse decision scenarios encompassing expanded judgements, discrete discriminations and continuous monitoring. These fundamental insights will have wide-ranging impact on basic and clinical research into cognition.
|
| 03/12/2019 |
£2,167,448 |
|
NEWCASTLE UNIVERSITY |
Acquired somatic mutation continually modifies the genomes of multicellular organisms, inevitably causing human disease. The over-arching aim of this proposal, is to define how somatic mutation impacts upon macrophages, immune cells that are critical for defence, regulation, and repair. Macrophages were thought to arise through continual recruitment of monocytes, but recent data indicate that they originate and renew in diverse ways. The first aim is to use silent mutation to study the origin of human macrophages. This will discern the difference between microglia, thought to arise exclusively from a primitive origin, self-renewing macrophages derived from definitive haematopoiesis, and macrophages that require a continual input of monocytes. The second ai, will study macrophages in clonal haematopoiesis. Somatic mutation in the bone marrow has the potential to alter macrophage function and accelerate prevalent diseases such as atherosclerosis. The final aim is to explore somatic mutation in clonal macrophage populations as a novel aetiology of idiopathic inflammatory disorders IgG4-related disease, granulomatosis with polyangiitis and sarcoidosis. These are noted for their overlap with histiocytosis, the archetype of a new class of inflammatory myeloid neoplasm. Together these studies will define novel functions of macrophages in pathology that reflect their independence or connection with haematopoiesis.
|
| 03/12/2019 |
£2,249,535 |
|
UNIVERSITY COLLEGE LONDON |
The brain utilises cortical and subcortical pathways to transform sensory information into action, giving rise to learned and instinctive sensory-guided behaviours. How these pathways interact to generate flexible behaviour, allowing animals to react differently to the same environmental stimuli depending on circumstance, remains poorly understood. We propose that inhibitory circuits in the thalamus are essential for flexible control of sensory-guided actions. Our pilot data show that the ventral lateral geniculate nucleus (vLGN) - a prethalamic structure composed of different classes of inhibitory projection neurons - provides inhibitory control of an instinctive visually-evoked behaviour. We will identify the neural circuit mechanisms of this control and determine when it is engaged. Moreover, since the vLGN is extensively connected with visual circuits in the neocortex and the midbrain, we will test if and how this nucleus can coordinate these visual pathways to guide both instinctive and learned visually-guided behaviours. We will achieve these aims by combining genetic tools with calcium imaging, electrophysiological recordings, cell-type specific optogenetic manipulations and quantitative behaviour in animals performing visually-guided tasks. This work will generate detailed understanding of mechanisms by which the brain can orchestrate behavioural responses to environmental stimuli.
|
| 03/12/2019 |
£1,884,223 |
|
UNIVERSITY OF EDINBURGH |
Protein synthesis is essential for the strengthening and weakening of synaptic connections between neurons, and it is pathologically altered in multiple genetic models of Autism Spectrum Disorders and Intellectual Disability (ASD/ID). The identities of the mRNAs translated to sustain changes in synaptic strength are not known, nor is the mechanism linking aberrant translation to functional changes in ASD/ID.
This proposal will address two key questions: (1) How does dysregulated translation lead to altered synaptic function in Fragile X Syndrome (FX), the most common monogenic cause of ASD/ID? And (2) How are specific mRNAs translated to support opposite changes in synaptic strength?
I will test the predictions that reduction of ribosome production can correct neurological phenotypes in the Fmr1-/y mouse model of FX, and that mRNAs translated to support synaptic strengthening (LTP) and weakening (LTD) are differentially regulated by ribogenesis. To do this I will use Translating Ribosome Affinity Purification (TRAP) and RNA-seq along with electrophysiological and behavioral assays. These studies will identify the link between excessive protein synthesis and synaptic disruption in FX and explain how translation is specified to support opposing changes in synaptic strength.
|
| 03/12/2019 |
£2,200,879 |
|
IMPERIAL COLLEGE LONDON |
While emerging antimicrobial resistance is widely recognised in bacteria, the emergence of fungi that are resistant to antifungal drugs is underappreciated yet is compromising our ability to treat these serious diseases worldwide. The most widely used class of chemicals, the azoles, are driving the evolution of fungal multidrug resistance through their dual-use in both agricultural and clinical settings. However, we lack critical insights into how these antifungal chemicals are leading to changing patterns of disease in humans. We focus on Aspergillus fumigatus, an environmental fungus to which all humans are exposed causing disease in millions, and which is rapidly evolving resistance to azole antifungal drugs worldwide. Our project aims to understand the risk that azole-resistant aspergillosis presents to public health by identifying the extent to which patients are acquiring resistant infections from environmental sources. We will explore whether the emerging spectrum of mutations that confer drug resistance come with a fitness cost, how these mutations impact upon the global population of A. fumigatus with respect to undesirable phenotypes such as virulence and infectivity. The science that our study produces will be focused on tackling this pandemic in order to retain the efficacy of essential current, and incoming, clinical antifungal drugs.
|
| 03/12/2019 |
£1,905,114 |
|
UNIVERSITY OF EDINBURGH |
Liver fibrosis is a major global healthcare burden. Iterative liver damage, secondary to any cause, results in progressive fibrosis, disrupted hepatic architecture and aberrant regeneration, defining characteristics of liver cirrhosis. Currently, treatment options for patients with chronic liver disease are limited to removal of the underlying cause, if possible, or liver transplantation. However, demand for transplantation greatly outweighs donor organ supply. Therefore, effective antifibrotic therapies are urgently required. To enable true precision medicine-based therapies, we need to significantly increase our understanding of the cellular and molecular composition of the fibrotic niche across the different forms of human liver fibrosis, and therefore this application is deliberately human disease-focused. In this proposal, we will define and interrogate the interactome of the human liver fibrotic niche using cutting-edge single-cell transcriptomic approaches including single-cell and single-nucleus RNA sequencing, spatial transcriptomics and machine learning, and single-cell epigenomics. These studies should greatly advance our understanding of how the fibrotic niche operates across different forms of human liver fibrosis, generating aetiology-specific, relevant and potentially druggable therapeutic targets to treat patients with liver fibrosis. By the end of this Fellowship, if awarded, we aim to have multiple therapeutic targets entering Phase I clinical trials.
|
| 03/12/2019 |
£1,700,629 |
|
UNIVERSITY OF LEEDS |
Remodelling of the heart is linked to a poor prognosis for patients with cardiac disease. While the mechanisms underpinning this process are only poorly understood, changes in the microstructural architecture of the myocardium are considered to play a key-role. Cardiac diffusion tensor imaging (cDTI) has enabled insights into the microstructure non-invasively through the assessment of the diffusion of water molecules in the myocardium. cDTI provides quantitative diffusion metrics such as Fractional Anisotropy, Mean Diffusivity and Helix Angle, which can serve as biomarkers of disease. Nevertheless, cDTI is technically challenging due to its sensitivity to motion, strain and perfusion. Moreover, the diffusion tensor is an oversimplified representation of the underlying tissue structure. More realistic tissue models as developed for the brain are presently prohibited by MR scanners hardware limitations, particularly magnetic field gradient strength. The aim of this project is to establish cardiac diffusion MRI on the Connectome scanner, which features gradients 4x stronger than those available on clinical scanners, in order to develop next generation MRI techniques for the non-invasive, microstructural characterisation of the beating heart in humans, with the ultimate aim to detect subtle remodelling of cardiac tissue earlier, and with higher accuracy than ever before.
|
| 03/12/2019 |
£1,600,709 |
|
UNIVERSITY OF ABERDEEN |
In low-income countries, rodents have very significant impacts on health and well-being. Annually cereals lost to rodents could feed hundreds of millions of people, whilst rodent-borne infections (RBI) kill thousands. A major research challenge is developing holistic rodent management strategies that deliver both improved food security and reduced disease burdens, and are sustainable for communities. I will work with health and agricultural stakeholders and communities to fill key knowledge gaps and adapt and test innovative management techniques developed in the agricultural sector, primarily in Asia, to other ecological and socio-cultural contexts. Working in Madagascar, I will combine empirical and modelling studies to explore how localised control impacts on the risk from a range of RBI with contrasting transmission routes, determining in what circumstances control increases or decreases risk. I will test the cost-efficiency of different strategies, using an approach that incorporates agricultural losses, disease burdens and management costs. With communities I will explore the impacts of socio-cultural practices, identifying opportunities and constraints for community-led control. To optimise management strategies, adaptive research experiments will be co-developed and evaluated with communities and stakeholders. Active engagement with national and international stakeholders throughout the project will facilitate scaling up and policy impact.
|
| 03/12/2019 |
£3,027,479 |
|
UNIVERSITY OF OXFORD |
The movement of proteins within eukaryotic cells is an essential process that maintains internal organelle integrity and underpins normal cell function. Despite the identification, several decades ago, of the receptors controlling protein trafficking, the molecular mechanisms of selective retention and export of ER and Golgi resident proteins still remain poorly understood. However, this recently changed when our study on the KDEL receptor revealed the structural basis by which a trafficking receptor can signal across a membrane to cytoplasmic coat protein complexes to initiate retrograde trafficking. We now aim to determine the mechanisms that underpin protein trafficking by other receptors within the early secretory pathway. We have developed an integrated approach involving cell biology and structure-based methods, including lipid-based crystallisation and single particle cryo-electron microscopy coupled with advanced protein engineering, super resolution light microscopy, and multiscale molecular dynamics analysis of trafficking complexes. Specifically, we will determine the mechanism for several cargo-receptor systems that control anterograde and retrograde protein sorting and address how sorting receptors recognise cargo proteins, and the mechanism(s) by which these receptors signal across membranes. Ultimately, we expect to understand the molecular basis for cellular trafficking, providing fundamental insights into crucial pathways involved in human protein folding diseases.
|
| 03/12/2019 |
£2,061,387 |
|
UNIVERSITY OF GLASGOW |
The proposed research aims to (i) build fundamental understanding of mechanisms of immune evasion by helminth parasites, (ii) explore helminth modulation of the intestinal tissue niche; and (iii) to develop a new strategy towards vaccination to prevent infection. Helminths exploit a key immunological pathway within the immune system to induce suppressive regulatory T cells, and dampen innate effector cells. We have discovered a key player to be a novel parasite mimic of TGF-beta (TGM), which we will analyze structurally and funtionally on (i) immune cells and (ii) intestinal epithelium. The intestinal environment will be modelled through organoids (enteroids) in which parasites can modify stem cell differentation and therefore epithelial composition; we will investigate whether this is caused by TGM or an unrelated mediator. To promote immunity to infection, we focus on extracellular vesicles (EVs) released by parasites, which we have shown inhibit innate cell activation but can be neutralised by specific antibodies. In this model, antibodies to EVs direct them to uptake by phagocytes and lysosomal degradation, abolishing the inhibitory effect on immune cells. Taken together, the research will define how helminths may modify host signals and pathways, and how we may best interrupt this process to achieve protective immunity.
|
| 03/12/2019 |
£1,917,147 |
|
THE FRANCIS CRICK INSTITUTE |
The DNA replication checkpoint senses perturbation of DNA replication forks by a wide variety of agents. We know the protein components and the overall architecture of the checkpoint pathways, but we do not understand how very different fork stalling events can signal via a common pathway. The first aim of this proposal is to use the fully reconstituted DNA replication system we have developed together with purified checkpoint proteins and defined DNA templates to elucidate in molecular detail the mechanisms by which the checkpoint pathway is activated.
One of the main functions of this checkpoint is to prevent irreversible replication fork arrest (IRFA). From a whole genome siRNA screen, we have recently found that loss of the HLTF DNA translocase suppresses IRFA. Furthermore, we have found evidence that HLTF generates a toxic recombination intermediate and that this is conserved in yeast. Our second aim is to use genetics in human cells along with biochemistry with yeast proteins to understand how IRFA is generated and how the DNA damage checkpoint protects forks from IRFA.
|
| 03/12/2019 |
£2,844,723 |
|
UNIVERSITY OF OXFORD |
I aim to understand how the brain represents the relationships between objects and events in the world, and how these representations can be generalised to allow flexible behaviour in new situations. By combining modelling with experiments in human and macaque, I will investigate these computations at both the cellular and systems level. We have developed models that abstract relational knowledge and predict detailed neuronal representations in rodent hippocampal-frontal circuitry. I will ask whether these building blocks can be extended to explain the sophisticated abstractions and inferences commonplace in primate behaviour. In primates, such abstractions compound hierarchically, and can be combined together, allowing deep inferences. To study these computations, I will develop novel tasks that are high-dimensional, yet amenable to mathematical description. I will use state-of-the-art techniques in humans, validated by high density cellular recordings in macaques, to study representations underlying abstraction, generalisation and inference in medial temporal and frontal cortices. In doing so, I will build new bridges between human and animal neuroscience, between biological and artificial intelligence, and new analytical and experimental tools for integrating across scales of neural activity. Developing such tools is important to bridge the precision of modern neuroscience to humans and thence clinical populations.
|
| 03/12/2019 |
£2,097,551 |
|
UNIVERSITY OF OXFORD |
IBD affects over 1.5 million and 2 million people in North America and Europe respectively. A significant proportion fail to respond to current treatments. In IBD genetic, environmental and intestinal barrier defects combine to precipitate dysregulated immune responses in the mucosa that manifest in disease. Recently we have utilized single cell technologies to chart the behaviour of diverse cell types making up the mucosal barrier in health and early diagnosis IBD. This has demonstrated the nature of cellular remodeling occurring in the human colon in inflammation revealing trajectories of differentiation, the connectedness of different cell states together with describing novel epithelial, mesenchymal, T, B and myeloid cell states that hallmark disease. In this work we will build on these findings to explore functional pathways and barrier cell relationships revealed by this analysis that maintain commensal symbiosis in health but lead to breakdown in tolerance driving inflammation in IBD. Specifically, we will focus on defining how the colonic epithelia remodels to lose cell intrinsic barrier protective function, how the supporting mesenchyme fuels inflammation and how heterogenous colonic myeloid cells handle commensal bacteria in health and IBD to drive aberrant adaptive responses.
|
| 03/12/2019 |
£4,041,766 |
|
UNIVERSITY OF CAMBRIDGE |
Primary Immunodeficiency (PID) has a devastating impact on the lives of patients and their families, and management is aided by genetic diagnosis. 80% of PID patients have no overt family history, and thus have been intractable to gene discovery. Our recent pilot study explored whole genome sequencing (WGS) to enhance diagnosis in PID, and found only 8% of such patients carried disease causing mutations in known PID genes. By applying new Bayesian analytical techniques, we identified multiple new PID-associated genes; causative deletions in regulatory regions; and interplay between novel high-penetrance monogenic and common variants, beginning to explain the variable penetrance of PID. We will expand this WGS PID cohort, already the world’s largest, and develop additional specialised statistical tools to incorporate deep clinical, immunophenotyping and antigen receptor repertoire data to enhance WGS analysis techniques. We will use genetic association data from immune-mediated diseases to increase power, and use genetic information to characterise the clinical features predictive of PID and enhance diagnosis. This collaborative effort will enhance understanding of PID biology, define phenotypic variability, discover new disease associated genes, increase diagnostic yield - but importantly develop mechanisms for WGS-based gene discovery in cohorts of sporadic patients, applicable beyond PID.
|
| 03/12/2019 |
£1,740,984 |
|
UNIVERSITY OF MANCHESTER |
Tissue morphogenesis is associated with dramatic changes in cell morphology. Whilst these cell shape changes may define final tissue form, how they impact and/or direct other key morphogenetic processes remains unclear. I aim to redefine our understanding of the role of cell shape in tissue formation by revealing that, far from simply a structural feature, cell shape encodes critical instructive information that directs diverse morphogenetic events. Using the vasculature and neural crest as morphogenetic models and combining zebrafish live-cell imaging, in-vitro micropatterning and computational modelling, this proposal will investigate (1) if acquisition of specific cell geometries in interphase determines whether cells will divide symmetrically or asymmetrically to direct post-mitotic cell fate, (2) whether signal-induced cell shape changes create positive-feedback that amplifies signal to expedite fate decisions, and (3) how local cell shape remodelling, driven by polarised mRNA targeting and translation, functions to orient motile cell polarity and tissue movements. As such, this work will determine if cell shape unexpectedly encodes diverse morphogenetic cues that direct fundamental decision-making processes underpinning tissue building. Considering that cell shape change is an inherent feature of almost all forming tissues, mechanisms uncovered here may be broadly conserved and of therapeutic relevance in numerous tissue contexts.
|
| 03/12/2019 |
£1,758,388 |
|
UNIVERSITY OF CAMBRIDGE |
I first identified mutations in the anion transporter SLC26A7 as a novel genetic cause of human and murine congenital hypothyroidism (CH), but its molecular role in thyroid hormonogenesis remains unclear. I will investigate SLC26A7 function in cultured primary thyrocytes, initially evaluating its role in pH regulation, seeking new insights into thyroid hormone biosynthesis.
The incidence of CH with a normally-located gland-in-situ (GIS CH) is increasing, but its determinants are poorly defined. In a case-control study, I will investigate the roles of genetic variants, micronutrients (iodine, selenium, iron) and endocrine disruptors (perchlorate, thiocyanate and nitrate), in the pathogenesis of permanent and transient GIS CH. Confirmed involvement of environmental factors will have public health ramefications and mandate future trials of micronutrient supplementation for treatment or prevention of CH. The study will also provide insights into the aetiology of transient CH, a clinically important entity for which the cause is largely unknown.
DUOX2/DUOXA2 mutations impair thyroidal H2O2 production, often causing transient CH. I will investigate whether maternal heterozygosity for DUOX2/DUOXA2 mutations in association with increased gestational demand for thyroid hormone biosynthesis, causes hypothyroidism during pregnancy. Gestational thyroid dysfunction would mandate future studies of childhood neurodevelopmental outcome and levothyroxine treatment in such patients.
|
| 03/12/2019 |
£2,158,990 |
|
UNIVERSITY OF CAMBRIDGE |
Filopodia are finger-like actin rich projections from cells that are ubiquitously present during cell movement, are involved in cell connectivity, and are hijacked for internalization by pathogens. We established a cell-free system of filopodia-like structure formation using supported lipid bilayers and frog egg extracts, which has generated hypotheses about where and when filopodia form. My first aim is to discover how endocytosis and phosphoinositide lipid metabolism contribute to the time and place of filopodia formation and suppression in retinal ganglion cell neurons. We will examine the timing and contributions of neurotrophic factor signalling through PI(4,5)P2, PI(3,4,5)P3, PI(3,4)P2 and PI(3)P to membrane deformation and filopodial protrusion. We will explore filopodia in axon guidance, terminal arborization and synaptogenesis, and recovery from neuronal injury. My second aim is to identify the proteins needed for formation of filopodia-like structures to increase our understanding of the molecular mechanisms that determine filopodia function in cells. Where filopodia form determines the direction of cell movement, their length determines the extent of signal sensitivity and their lifetime determines the strength of signaling or duration of migration and adhesion. Our molecular and cellular studies may also give us information needed to manipulate actin regulation therapeutically.
|
| 03/12/2019 |
£1,947,412 |
|
UNIVERSITY OF CAMBRIDGE |
Peptide presentation on MHC-I molecules is central to mounting effective antiviral and antitumoral immune responses. However, we currently lack full insight regarding how peptides are selected onto these extremely polymorphic molecules. Following our discovery that TAPBPR is an MHC-I peptide editor which shapes the final antigen repertoire displayed for immune recognition, we have recently identified that polymorphism in MHC-I significantly impact on their ability to be edited by TAPBPR. Our findings question the concept that all MHC-I molecules undergo peptide selection via a largely identical manner. Our overarching aim is to gain insight into how polymorphisms in MHC-I influence the mechanism by which they gain peptide.
We will focusing on three aspects:
What impact do polymorphisms in MHC-I and TAPBPR have on the molecular mechanism of peptide selection?
What is the specific biological function of TAPBPR?
Can further molecular dissection of the presentation pathway reveal new insight into MHC-I biology and novel therapeutic targets?
This work will enable deeper insight into how peptides are selected onto MHC-I. It will help uncover why specific MHC-I alleles are associated with particular disease. Furthermore, it will help in the development our novel TAPBPR-based therapeutics and maximise their full potential in cancer immunotherapy.
|
| 03/12/2019 |
£2,251,660 |
|
UNIVERSITY OF CAMBRIDGE |
The mechanisms that regulate cell fate promise fundamental insights into the pathways that promote tumour growth. Through advances in genetic lineage tracing and single-cell profiling, the functional identity, lineage relationships and fate behaviour of stem and progenitor cells have begun to resolve. Applied to epithelial tissues, these studies have challenged prevailing models, emphasizing the role of stochastic renewal programmes, fate priming and the flexibility of cell states during regeneration. Using a novel lineage tracing strategy based on variants of the multicolour Confetti reporter system, we will use quantitative modelling-based approaches to target the cellular and molecular mechanisms of epithelial cell fate, and how these programmes become subverted following the activation of oncogenic mutations. With a focus on columnar and squamous epithelia, where a foundational understanding of associated signalling pathways and transcriptional programmes is in place, we will define at clonal resolution the changes that take place in cell fate following the acquisition of oncogenic mutations, targeting tumour cells and the reaction of surrounding normal tissue – the tumour microenvironment. As prominent sites of disease, we will contrast tumour cell dynamics in the closed glandular arrangement of the intestinal epithelium and the open organization of the interfollicular skin epidermis and oesophagus.
|
| 03/12/2019 |
£2,286,425 |
|
UNIVERSITY OF OXFORD |
Bacteria need to control import/export of charged molecules across their relatively impermeable membrane(s) which also house many nano-machines critical for motility and hence infection. These processes are often driven by harvesting the energy stored in ion gradients across the inner-membrane by ion flow through inner-membrane resident channels.
Unpublished work from my group has demonstrated that bacterial inner-membrane ion channels which couple ion flow to protein secretion, nutrient import and bacterial motility unexpectedly share a common architecture within their membrane domains. The architecture revealed unexpectedly suggests rotation between components may be mechanistically important and this application seeks to test this hypothesis. The question will be assessed by a series of structural and mechanistic studies that will seek to determine what commonalities in mechanism underlie this shared architecture and how this is adapted to perform the very different biologies achieved. Specifically, what adaptations allow coupling of uni-directional ion flow to achieve work on both sides of the inner-membrane. Using structural and functional tools developed in my group we will study the ion channels in more native contexts both in terms of the membrane bilayer and in terms of the protein interactions that couple ion flow to work to tease out molecular mechanisms.
|
| 03/12/2019 |
£1,439,158 |
|
UNIVERSITY OF OXFORD |
Understanding the factors determining the occurrence of de novo mutations (DNMs) in the human genome is central to genetic disease and genome biology. DNMs arise predominantly in the male germline and increase in frequency with paternal-age. Despite the fact that germline mutation rates are intimately linked to spermatogenesis, very little is known about testicular homeostasis in humans. This proposal aims to address this gap in knowledge by focusing on a new disease-mechanism whereby pathogenic DNMs are preferentially transmitted because they hijack the mechanisms controlling spermatogenesis. This selfish selection process relies on principles similar to oncogenesis to explain why some paternally-derived mutations occur spontaneously up to 1000-fold more frequently than background.
Exploiting our current knowledge of selfish selection, this proposal will deploy novel methodologies to describe mutations/genes/pathways subject to this phenomenon, including (1) cataloguing DNMs at single-seminiferous tubule resolution, in geographically-mapped testicular biopsies and in sperm; (2) modelling clonal DNM distribution in tubules to describe spermatogonial dynamics; (3) mining large DNM databases from family trios to detect mutational enrichment. We will also investigate 'selfish mitotic drive', a novel mechanism of mutation enrichment.
Together these approaches will allow us to assess the significance of selfish selection for human disease and genome evolution.
|
| 03/12/2019 |
£2,475,352 |
|
UNIVERSITY OF CAMBRIDGE |
Heritability has traditionally been thought to be a unique feature of the genetic material of an organism, notably its DNA sequence. However, from studies of a variety of organisms, it is now clear that non-DNA sequence-based inheritance exists from microbes to mammals. The molecular mechanism(s) operating in humans remain opaque. However, understanding the impact of non-DNA sequence-based mechanisms is likely key to a full appreciation of heritability in health and disease. Here we will take ground-breaking steps towards understanding non-DNA sequence-based inheritance mechanisms and consequences. For this work we will focus on the imbred C. elegans model where we have the advantage of extensive genetic tools, a three day generation time and large numbers. In addition, we have identified the African Rift Lake cichlid radiation as a unique opportunity to dissect the contribution of epigenetics to plasticity, adaptation and heritability of phenotype in a vertebrate. While C. elegans gives us the ability to discover new mechanisms de novo we now also have developed paradigms to investigate the role of epigenetic inheritance on the plasticity and adaptivity in C. elegans and in cichlids. The latter is an important step towards a better understanding of inclusive inheritance in vertebrates more generally.
|
| 03/12/2019 |
£715,470 |
|
UNIVERSITY OF BRISTOL |
Platelets are essential for haemostasis and play critical roles in innate immunity, angiogenesis and tissue repair. They are derived from megakaryocytes, each of which generates several thousand platelets. A major goal is to generate platelets in vitro, to address shortage of platelet supply for transfusion, and to enable fundamental discovery of gene function. To date, however, only very small numbers (approximately 10 per megakaryocyte) of platelets can be made in vitro.
We propose a step change using novel in vitrosystems, to increase generation efficiency by 1-2 orders of magnitude. We will use two in vitrosystems (mouse lung vasculature and microcirculation microfluidics) using forward-programmed iPSC-derived megakaryocytes. Our new data show that passage of megakaryocytes through lung vasculature ‘educates’ them to undergo a sequence of changes: reversible deformation, enucleation and abscission to release platelets. We aim to understand the detailed biology of these processes using CRISPR-edited megakaryocytes. We also show we can make human platelets in our novel microfluidic system and will optimize this to bioengineer large quantities of cells, by learning from the biology of the ex vivolung preparation. This is potentially transformative for fundamental understanding of human platelets and megakaryocytes, and for their bioengineering for clinical uses.
|
| 03/12/2019 |
£593,451 |
|
UNIVERSITY OF CAMBRIDGE |
Platelets are essential for haemostasis and play critical roles in innate immunity, angiogenesis and tissue repair. They are derived from megakaryocytes, each of which generates several thousand platelets. A major goal is to generate platelets in vitro, to address shortage of platelet supply for transfusion, and to enable fundamental discovery of gene function. To date, however, only very small numbers (approximately 10 per megakaryocyte) of platelets can be made in vitro.
We propose a step change using novel in vitrosystems, to increase generation efficiency by 1-2 orders of magnitude. We will use two in vitrosystems (mouse lung vasculature and microcirculation microfluidics) using forward-programmed iPSC-derived megakaryocytes. Our new data show that passage of megakaryocytes through lung vasculature ‘educates’ them to undergo a sequence of changes: reversible deformation, enucleation and abscission to release platelets. We aim to understand the detailed biology of these processes using CRISPR-edited megakaryocytes. We also show we can make human platelets in our novel microfluidic system and will optimize this to bioengineer large quantities of cells, by learning from the biology of the ex vivolung preparation. This is potentially transformative for fundamental understanding of human platelets and megakaryocytes, and for their bioengineering for clinical uses.
|
| 03/12/2019 |
£3,803,801 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Conflict-affected populations across the world are vulnerable to alcohol misuse and psychosocial distress. This is a direct consequence of exposure to war, violence, and ongoing stressors in their new areas of settlement such as impoverishment, unemployment, and discrimination. Alcohol may be used as strategy to cope with adversities which refugees and internally displaced people might face, and may cause or result from psychosocial distress. Despite the major health, social and economic consequences of alcohol misuse, there is a notable absence of interventions addressing alcohol use disorders (AUD) among conflict-affected populations. This proposal seeks to complement a WHO evidence-based psychological intervention for people living in adversities ("Problem Management Plus" (PM+)) with strategies to reduce alcohol misuse, thereby developing an intervention which prioritises alcohol misuse but also addresses other underlying mental health problems of conflict-affected populations. We will develop our intervention called PM+/AUD through a comprehensive formative research process, and evaluate the final intervention through two independent randomised controlled trials among South Sudanese refugees living in Uganda, and internally displaced persons in Ukraine. Our project will include social science research on implementation and scaling-up, and will produce guidelines for the treatment of AUD among conflict-affected populations.
|
| 03/12/2019 |
£2,832,201 |
|
UNIVERSITY COLLEGE LONDON |
Hearing is critical to human communication and intelligence. The cascade of neuronal processes that enable hearing remain poorly understood, particularly in computational terms. These gaps in knowledge limit our ability to design treatments for hearing impairment. The proposed research has three goals. First, to develop new computational models that can account for human perceptual abilities and neuronal responses. Second, to reveal representational transformations within auditory cortex that contribute to auditory recognition. Third, to use these models to develop auditory prostheses that augment human hearing. The overarching hypothesis is that the functional organization and tuning properties of the auditory system are constrained by ecologically important tasks (speech recognition, sound localization etc.), such that task-optimized models may converge to the structure of the auditory system. We will leverage deep learning to develop new neural network models of auditory computation. These models will be evaluated for their matches to behavior and brain data using sound synthesis methods introduced by the PI. Candidate hearing aids will then be derived by backpropagating recognition errors through the model to optimize a front-end audio transformation. Such audio transformation should restore model performance given an impaired model cochlea. We will then test their benefits for hearing-impaired listeners.
|
| 03/12/2019 |
£1,166,334 |
|
IMPERIAL COLLEGE LONDON |
Multicellular organisms use systemic signals to transmit biological information across tissues in order to co-ordinate responses to stress or infection. Discovering such signals, how they spread and what responses they trigger is therefore of paramount importance for organismal development. We have previously introduced the first tractable animal system to investigate a diverse group of eukaryotic pathogens, the oomycetes, which cause deadly infections in humans, as well as the model organism Caenorhabditis elegans. We have now discovered that C. elegans is able to sense these pathogens in neurons and mount a protective transcriptional response, the hallmark of which is the induction of conserved chitinase-like proteins in its epidermis. We propose to use comprehensive molecular genetics, cell biology, biochemistry, metabolomics and developmental imaging to determine the host response underlying pathogen recognition and elucidate the molecular gene network underlying the mounting of this response via neuron-to-epidermis signal exchange. Studying intercellular signalling requires a system-wide approach and, to this end, C. elegans offers a great opportunity to investigate this fundamental problem at the whole organism level. The proposed work will expand our knowledge on core cell and developmental biology mechanisms of intercellular signal exchange and immune response in the context of oomycete recognition.
|
| 03/12/2019 |
£1,902,595 |
|
UNIVERSITY OF CAMBRIDGE |
Glycosphingolipids (GSLs) are specialised lipids enriched in the outer leaflet of the plasma membrane (PM) and defects in GSL metabolism underlie a range of devastating diseases. I have shown for the first time a direct link between GSL metabolic defects and changes in the abundance of disease-associated PM proteins. Changes to the cell surface abundance of these proteins are driven by trafficking defects and gene expression changes: pathways that may be mechanistically linked. My preliminary work highlights that the role of GSLs in membrane trafficking has been under-appreciated. I now seek to define the molecular mechanisms that link GSL abundance to disease pathways: how do specific GSL-protein interactions direct membrane trafficking; and what are the consequences of this mistrafficking? We will target specific enzymes in GSL metabolic pathways, monitor lipid and protein changes using quantitative mass spectrometry and visualise co-ordinated protein trafficking from the endoplasmic reticulum using an innovative fluorescence-based secretory assay. Using high-resolution structural techniques we will determine how the specificity of GSL-protein interactions is defined and exploit these insights to feedback into our cell-based assays. My research proposal implements a multidisciplinary strategy that will reveal crucial new insights into how this important class of lipids influence cell fate.
|
| 03/12/2019 |
£2,400,000 |
|
UNIVERSITY OF OXFORD |
We will define the extent of RNA polymerase II (Pol II) transcription units (TUs) across mammalian genomes, both protein coding (pc) and long noncoding (lnc). For each TU class, termination sites and mechanisms will be scrutinised, especially by definition of XRN2 "torpedo" entry sites at positions of co-transcriptional endonuclease cleavage. Multiple endonucleases will be investigated including CPSF-73, Drosha and Integrator-S11. For lncRNA their mechanism of transcriptional initiation will also be investigated, especially R-loop dependant promoters. Pilot experiments show that R-loops promote antisense lncRNA particularly at pc-gene promoters and enhancers, so defining a new class of Pol II promoter that we intend to fully characterise at a molecular level. Histone genes represent an unusual, ubiquitous Pol II pc-gene class. We will also characterise the termination mechanism for these genes and in particular the role of the novel endonuclease MBLAC1. Finally, we will study the particular case of the H2AX gene that employs both a histone like, poly(A)- termination mechanism as well as a poly(A)+ mechanism. Overall, we will characterise mechanisms that define gene TUs across mammalian genomes to better inform gene function in the rapidly expanding repertoire of genomic sequences being generated for normal and pathogenic human cells.
|
| 03/12/2019 |
£1,979,621 |
|
UNIVERSITY OF GLASGOW |
Allodynia and hyperalgesia occur in neuropathic and inflammatory pain states, and depend on circuits involving dorsal horn excitatory interneurons. Recent studies have identified several neurochemical/transcriptomic populations among these cells. We will use a multi-disciplinary approach, involving molecular-genetic targeting of these populations, to investigate their involvement in pain mechanisms at circuit and behavioural levels. We have found that neurons expressing gastrin releasing peptide receptor (GRPR) correspond to vertical cells, which transmit information to lamina I projection neurons, and are implicated in both neuropathic and inflammatory pain. We will use anatomical, electrophysiological and behavioural approaches to determine whether the GRPR cells fulfil this role. If not, we will investigate another population defined by expression of neuropeptide FF. Cells with PKCgamma are critical for neuropathic allodynia, but these can be assigned to two populations that express neurotensin or cholecystokinin. We will determine whether these are functionally different, and whether both contribute to allodynia. Finally, we will establish whether any other excitatory interneurons are interposed between PKCgamma cells and vertical cells in the pathway for tactile allodynia. The study will provide important information about synaptic circuits for pain, and the roles of different interneuron populations.
Keywords: pain, spinal cord, neuronal silencing, chemogenetics, optogenetics
|
| 03/12/2019 |
£1,495,073 |
|
NEWCASTLE UNIVERSITY |
The main goal of this research is to develop and apply advanced statistical methods to help elucidate the biological mechanisms and causal pathways underpinning the correlations seen between genotype and phenotype in complex genetic disorders, with specific emphasis on liver and kidney disease. This will allow us to better understand the biological processes leading to disease development, thus enabling the development of potential therapies and cures. Identifying genes and their protein products which alter disease risk will point to potential new drug targets and allow opportunities for re-purposing of existing drugs.
We will use measurements of genetic factors and potential intermediate processes like gene expression, DNA methylation and protein levels, available through long-standing collaborations with clinical colleagues. A key goal of our research is to develop methods that integrate these different data types with one another and with similar data from external sources.
We will expand the data available through UK-PBC (SNP-genotypes and gene-expression profiling in 100 pre-treatment cases plus 50 controls), by adding CpG-methylation and serum proteomics, enhancing our ability to identify causal pathways in disease development/progression.This will inform disease biology, subsequent treatment response, and the extent to which it can be predicted from baseline measures.
|
| 03/12/2019 |
£1,533,479 |
|
UNIVERSITY OF DUNDEE |
To maintain genetic integrity, eukaryotic cells must properly segregate sister chromatids to opposite spindle poles during mitosis. This process has important medical relevance because chromosome mis-segregation plays causative roles in human diseases such as cancers and congenital disorders, which are often characterized by chromosome instability and aneuploidy. For proper chromosome segregation, it is vital to establish correct kinetochore–microtubule interaction in early mitosis, prior to segregation. We will investigate how kinetochores initially interact with microtubules on the mitotic spindle and how errors in kinetochore–microtubule interactions are resolved to establish correct interactions. In particular, we will address the following questions:
A) What are the molecular mechanisms regulating the kinetochore–microtubule interface during early mitosis?
B) What are the mechanisms resolving errors in kinetochore–microtubule interactions and stabilising correct interactions in a tension-dependent manner?
To address evolutionarily conserved mechanisms, we use budding yeast as a model organism because, in this organism, a single microtubule attaches to a single kinetochore in metaphase – this considerably simplifies our analyses. We use methods in cell biology, molecular genetics, biochemistry and computer simulation, and address not only molecular mechanisms but also the biological significance of step-by-step development in the kinetochore–microtubule interaction.
|
| 03/12/2019 |
£1,944,579 |
|
UNIVERSITY OF CAMBRIDGE |
Obesity is strongly associated with common metabolic diseases (T2DM, fatty liver and cardiovascular disease) which collectively account for a huge global health burden. Insulin resistance underpins this association and our goal is to understand, and reverse, its molecular pathogenesis.
Having worked on rare monogenic lipodystrophies, almost all of which are associated with the metabolic diseases typically seen in obesity, for ~20 years, we have recently convincingly shown that subtle forms of lipodystrophy are a major factor in common insulin resistance/metabolic disease. Specifically we showed that SNPs associated primarily with reduced hip (femorogluteal) fat, are as strongly associated with T2DM and cardiovascular disease risk as variants associated with central adiposity.
We will build on this step-change in understanding by:
Deepening understanding of the molecular mechanisms by which adipocytes form and then store surplus energy in unilocular lipid droplets
Performing an experimental medicine intervention study designed to demonstrate the clinical and molecular impact of alleviating energetic overload using a very low energy diet in patients with partial lipodystrophy.
Investigating the source and action of two hormones (GDF15 and FGF21) which we hypothesize to be stress signals released in response to sustained overnutrition. Both of these molecules represent exciting therapeutic opportunities.
|
| 03/12/2019 |
£1,361,584 |
|
UNIVERSITY OF DUNDEE |
Human life utilises hundreds of cell types with massive diversity in function defined largely by which proteins they express. We will determine how regulation of the mRNA cap modification coordinates the gene expression required in different cell types. The cap protects mRNA from degradation and recruits processing and translation factors. The enzymes which catalyse cap formation were perceived as acting on all genes, in every cell. Our research reveals that the capping enzyme complexes are differentially expressed in different tissues and have gene-specific impacts. During cell differentiation, we demonstrate that changes in capping enzyme complexes result in coregulation of gene families, which we hypothesise co-ordinates the gene regulation required for new cell identities to emerge.
Key goals are to determine:
mechanisms governing capping enzyme gene-specificity
how co-factors influence capping enzyme functionality
the impact of mRNA cap regulation in differentiation
In pluripotent cells, the components of mRNA capping enzyme complexes will be characterised and their impact on enzyme kinetics, cap formation and sequence-specific RNA selection determined. During differentiation, how mRNA capping enzyme regulation impacts on enzyme function and gene expression will be investigated. This project will determine the dynamic impact of mRNA capping enzyme regulation.
Keywords: gene regulation; mRNA; cell function
|
| 03/12/2019 |
£2,042,009 |
|
UNIVERSITY OF EDINBURGH |
Meiotic cell division is defined by a unique and highly dynamic programme of events that results in homologous chromosome segregation following crossover formation. In mammals, the telomeric ends of chromosomes become tethered to the nuclear envelope by the meiotic telomere complex (MTC), where they undergo rapid movements, driven by microtubule forces transmitted by the LINC complex, that facilitate the identification and alignment of homologous chromosome pairs through recombination. Once established, homologue chromosome pairs become synapsed along their length by the zipper-like assembly of the synaptonemal complex (SC), which provides the unique three-dimensional architecture necessary for recombination intermediate resolution and crossover formation. We will uncover the structure, assembly mechanism and recombination function of the SC, the mechanistic basis of nuclear envelope tethering by the MTC and the mechanism of force transduction by the LINC complex. This will be achieved through a structural biology approach of biophysics, crystallography and cryo-EM, coupled with collaborative structure-directed mutation in mouse meiosis. Our work will result in unprecedented molecular understanding of how the mammalian SC, MTC and LINC complex operate together as an integrated molecular machine to achieve their essential functions of mammalian meiosis, and crucially how their dysfunction leads to human infertility, miscarriage and aneuploidy.
|
| 03/12/2019 |
£1,843,933 |
|
UNIVERSITY COLLEGE LONDON |
The cerebral vasculature and glial cells play crucial but poorly understood roles in initiating Alzheimer’s disease (AD) and related dementias, contributing to cognitive decline via a loss of synapses and neurons. We have shown that:
(i) a major reduction of cerebral blood flow occurs early in human AD because oligomeric amyloid beta (Aß) evokes constriction of brain capillaries by contractile pericytes;
(ii) the blood flow reduction in AD may reflect microglia controlling pericytes;
(iii) microglia-mediated phagocytosis, which removes both Aß and synapses, is regulated by ion channels and receptors;
(iv) decreased blood flow and AD alter node of Ranvier length in myelinated axons, which will change axonal conduction speed and thus neural circuit function.
Now, focusing on Aß and decreased blood flow, we will investigate how vascular and glial function contribute to dementia, by:
(A) defining the mechanisms underlying Aß-evoked capillary constriction, and developing therapeutic approaches to restoring blood flow;
(B) characterising how microglia and astrocytes remove Aß and synapses, and investigating how to control this;
(C) studying how Aß and decreased blood flow damage myelin and nodes of Ranvier, and how to prevent this.
Together, this work will identify novel non-neuronal therapeutic targets for treating dementia.
|
| 30/11/2019 |
£764,996 |
|
UNIVERSITY COLLEGE LONDON |
Across much of sub-Saharan Africa, pneumococcal disease (otitis media and pneumonia) and malaria are leading causes febrile illness, and therefore drivers of both appropriate and inappropriate antibiotic use. Prevention through vaccination has the potential to influence antimicrobial resistance (AMR) both directly and indirectly. We are in a unique position to leverage two large funded cluster-randomised vaccine evaluations in Malawi: 13-valent pneumococcal conjugate vaccine (PCV13) schedule change (3+0 to 2+1; extending immunity and potentially herd protection); and RTS,S malaria vaccine introduction. We will ask what are the direct and indirect selective effects of pneumococcal and malaria vaccines on antibiotic resistance, febrile illness and antibiotic usage in young children in Malawi? We will determine whether in children S. pneumoniae carriage isolates; the upper respiratory tract resistome; and stool carriage of extended spectrum beta-lactamase (ESBL) E. coli or Klebsiella. We will assess whether the pneumococcal or malaria vaccines alter the frequency of febrile illness and antibiotic use in children
|
| 30/11/2019 |
£177,986 |
|
WASHINGTON STATE UNIVERSITY |
We are initiating a CDC-funded study of antimicrobial-resistant bacteria in the western highlands of Guatemala. This study is in collaboration with investigators at Washington State University (WSU, USA), University de Valle de Guatemala (UVG), the Guatemalan Ministry of Health and Social Assistance (MSPAS), and the Central America Regional Office of the Centers for Disease Control and Prevention. The goal of this two-stage randomized, cross-sectional study (n=577 households) is (1) to estimate the prevalence of three groups of antimicrobial-resistant bacteria and Group A Streptococcus at the community-level, and (2) to identify risk factors for carriage of the target organisms including antibiotic use and hygiene variables. If funded, the current proposal will add 326 households (with participants Enterobacteriaceae. All vaccinations will be considered, but with the proposed design we hypothesize that we will detect a statistically significant vaccine effect relative to rotavirus and-or pneumococcal vaccinations. Findings from this study will inform the MSPAS vaccination efforts and will be shared with the local, national and international communities (e.g., PAHO and WHO).
|
| 30/11/2019 |
£267,005 |
|
EMORY UNIVERSITY |
Rotavirus is the most common cause of severe gastroenteritis in infants and young children. The primary benefit of rotavirus vaccination is prevention of severe diarrheal disease and hospitalizations have been reduced dramatically since vaccine introduction. Rotavirus vaccination may impact antibiotic prescribing and resistance by two mechanisms. First, bacterial agents of gastroenteritis are often treated with antibiotics. Since aetiology is usually not known at the time of the medical encounter, antibiotics are frequently prescribed for viral gastroenteritis even though they are not recommended. Second, antibiotics, whether prescribed for gastroenteritis or infection at other sites, may disrupt the enteric microbiome. This may in turn lead to other secondary bacterial infections, mainly Clostridium difficile infection (CDI). C difficile is inherently resistant to most groups of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and fluoroquinolones, hence treatment options are limited. In this study, we aim to 1) estimate the effect of rotavirus vaccination on antibiotic prescribing 2) estimate the effect of rotavirus vaccination on CDI. We will conduct a large retrospective cohort study constructed from MarketScan databases. Analysis will be performed using longitudinal, individual-level data. These findings can provide evidence for national and international bodies for vaccine decision-making and antimicrobial resistance control strategies.
|
| 30/11/2019 |
£232,239 |
|
HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH |
Prioritizing vaccine development to focus on pathogens that drive the most antibiotic prescribing will have multiple advantages: reducing the burden of disease, reducing the extent of antibiotic use, and thus reducing the selective pressures driving antimicrobial resistance. In this proposal, we will (1) test the hypothesis that recent declines in outpatient antibiotic prescribing in the US are associated with reductions in pneumococcal disease attributable to PCV13 uptake and (2) estimate the antibiotic prescribing attributable to the most common pathogens and variation by age, demographic, and geography. To do so, we will use large representative nationwide datasets from the US, including insurance claims, public health surveillance, and a national immunization survey. The deliverables from this project will include estimates of the impact of PCV13 on outpatient prescribing and quantification of the expected reductions in antibiotic prescribing given vaccines for common pathogens. We expect that the results from these studies will establish (1) robust estimates of the reductions in outpatient antibiotic prescribing achieved by PCV13, as an exemplar of what vaccines can accomplish; and (2) priorities for vaccines to target in terms of impact on antibiotic prescribing and thus on antimicrobial resistance.
|
| 30/11/2019 |
£237,892 |
|
UNIVERSITY OF LIVERPOOL |
Vaccination should reduce antibioticl prescribing (AP), the driver of antimicrobial resistance. Looking for reductions in Randomised Controlled Trials of vaccine is problematic as they are usually powered for large effect sizes of specific end-points. An alternative approach is to undertake observational studies using large routine data sources. The problem with this approach is ensuring major confounding is identified and accounted for when linking vaccine status and outcome and, demonstrating a causal relationship.
We will conduct an observational study using the Clinical Practice Research Datalink (2007-2019) and The Health Improvement Network (THIN) (2007-2019) from the United Kingdom. Our primary aim is to measure AM prescribing in adults over 65 and children under 5 by frequency of influenza vaccination.
We will use three complimentary approaches and different methods to adjust for confounding:
1 A Self-controlled case series – comparing annual AM prescribing within individuals by annual receipt of influenza vaccine and vaccine/pathogen match.
2 A Cohort study - balancing comparator populations using propensity scoring to control for major determinants of health care utilisation and underlying health status.
3 An Interrupted time series analyses – investigating paediatric influenza vaccine uptake (September 2013) and AM prescribing
|
| 30/11/2019 |
£201,273 |
|
UNIVERSITY OF MANCHESTER |
Antimicrobial resistance (AMR) threatens public health and individual patient care. Gonococcal (GC) infection incidence has been increasing year on year for the last decade in the UK. AMR in GC infection is relatively low in the UK, but it has been increasing too.
We propose to develop, simulate and parameterise a model for Neisseria gonorrhoeae and Neisseria meningitidis circulation. Control of gonorrhoea is likely to become increasingly difficult due to widespread antibiotic resistance. While vaccines are routinely used for N. meningitidis, no vaccine is available for N. gonorrhoeae. Recent studies where meningococcal B (MenB) vaccine is given to adolescents reported a reduction in incidence rates of GC in those vaccinated, as the vaccine potentially offers some cross protection. Counterfactual scenarios can be investigated with a model (with potential uncertainty in outputs) to consider appropriate health economic evaluation.
Goals:
Develop a transmission model of GC and MenB infection for the UK
Investigate the cost-effectiveness of MenB vaccine in infants, adolescents and targeted at-risk populations in reducing MenB and GC infection incidence and AMR.
Investigate the potential impact in areas of low, medium and high incidence of GC infection and low and high level AMR in GC.
|
| 30/11/2019 |
£678,619 |
|
AMSTERDAM INSTITUTE FOR GLOBAL HEALTH AND DEVELOPMENT |
Rotavirus is the most common aetiology of serious gastroenteritis in young children. Despite antibiotics not being indicated in its treatment, gastroenteritis remains a very common cause for antibiotic prescribing in low-income settings. We hypothesize that effective rotavirus vaccination can reduce diarrheal episodes and thereby unnecessary antibiotic usage in young children in low-income settings.
This study aims to evaluate the impact of rotavirus vaccination on antibiotic usage. Specifically, the study will quantify how differences in rotavirus vaccine efficacy impact days of prescription and non-prescription antibiotic usage in the first 2 years of life among two large cohorts of children in Zambia and Ghana.
The key goal is to understand the effect of rotavirus vaccine efficacy on antibiotic usage and household antibiotic costs. This will generate evidence needed to inform policy-makers seeking to introduce new rotavirus vaccines into national vaccination programmes, ofpotential, and often under-appreciated, secondary effects of rotavirus vaccine implementation on antibiotic usage.
This proposal will be conducted within a planned phase III randomised controlled trial comparing the efficacy of a new parenteral trivalent P2-VP8 subunit rotavirus vaccine to the oral live attenuated vaccine, Rotarix®, against severe rotavirus gastroenteritis in the first 2 years of life in Zambia and Ghana.
|
| 30/11/2019 |
£179,852 |
|
UNIVERSITY OF NEW SOUTH WALES |
In high income countries the greatest use of antibiotics is in community (primary care) settings in the context of acute respiratory tract infections. Within these settings, both the very young, the very old and those with respiratory conditions such as asthma and chronic obstructive pulmonary disease are known to be the greatest antibiotic users. While there are a number of vaccines routinely provided that protect against acute respiratory tract infections, there is limited empirical data quantifying the potential benefit of vaccines to reduce antibiotic use for respiratory tract infections, particularly in adult populations.
In this project we will use a large-scale database of electronic general practice records to quantify, in older adults, the effectiveness of influenza, pertussis and pneumococcal vaccines in reducing primary care presentations for acute respiratory tract infections and subsequent antibiotic prescribing. We will focus on high risk groups defined by age and/or co-morbidity (asthma and chronic obstructive pulmonary disease). We will use these estimates of vaccine effectiveness to model the absolute reductions in antibiotic use that could be obtained by increasing vaccine coverage in different adult sub-groups. This evidence will enable policymakers to better prioritise strategies to increase uptake of these vaccines.
|
| 30/11/2019 |
£404,673 |
|
MURDOCH CHILDREN'S RESEARCH INSTITUTE |
PCVs prevent pneumonia and invasive pneumococcal disease (IPD). The serotypes contained within PCV are those which carry most antimicrobial resistance (AMR). PCVs reduce the carriage of PCV serotypes, and also limit the use of antibiotics by preventing pneumococcal infections. In the US, the 13-valent PCV (PCV13) reduced childhood IPD AMR by > 75%. Despite a high pneumonia burden in Asia, very few countries have adopted PCV into their national immunisation programs. PCV may have a substantial role in reducing AMR and it is vital that the role of PCV in reducing AMR in this region is determined.
PCV introduction has also led to serotype replacement with serotypes that are not included in the vaccine (NVTs). It is therefore important to define pneumococcal population changes and identify emergent clones in the post-PCV era. In 2013, we commenced pneumococcal carriage surveillance in Laos in children aged 2- 59 months with acute respiratory infection (ARI). Our proposed study in Laos will:
a) determine the PCV13 effectiveness against AMR in pneumococcal carriage isolates;
b) determine the AMR and virulence of emerging NVTs; and
c) investigate using a life-like system the recombination frequency for the acquisition of resistance genes, and secondary chromosomal insertions, in pneumococcal NVTs.
|
| 30/11/2019 |
£429,266 |
|
HARVARD T.H. CHAN SCHOOL OF PUBLIC HEALTH |
Vaccines against viruses can reduce antibiotic prescribing by reducing the incidence of viral infections that are inappropriately treated with antibiotics, as well as by reducing the incidence of secondary bacterial infections caused by viral infections. We will estimate the magnitude of this effect for influenza vaccination and the potential magnitude for Respiratory Syncitial Virus (RSV) vaccination and enhanced influenza vaccination. First, we willestimate the antimicrobial prescribing attributable to RSV and influenza in the Kaiser Permanente population in Northern California, USA, in total and by drug class and age group. Next, we will estimate the antimicrobial prescribing currently averted by influenza vaccination by comparing antimicrobial prescribing in (1) persons who have not received influenza vaccine vs. (2) persons who have, controlling for age and location within northern California, in aggregate and stratified by age and antimicrobial class. Using these results, we will estimate the number and proportion of antimicrobial prescriptions that may potentially be averted by improved influenza vaccines and (separately) by RSV vaccines that are now investigational, assuming various possible levels of coverage and effectiveness. Notable features of our analysis will be extensive measures to avoid confounding and an examination of waning of influenza prescribing effects with time since vaccination.
|
| 30/11/2019 |
£239,190 |
|
UNIVERSITY OF VIRGINIA |
Diarrhoeal disease, caused by leading aetiologies of Shigella and rotavirus, is a major contributor to antimicrobial resistance (AMR) due to increasing incidence of drug-resistant episodes and frequent treatment with antibiotics. We propose to quantify the comprehensive impact of enteric vaccines in combating AMR by preventing drug-resistant diarrhoea episodes and reducing antibiotic use using data from the MAL-ED study, a longitudinal birth cohort conducted in 8 low-resource sites. Specifically, we will: 1) quantify the incidence of antibiotic use and of antibiotic exposure to subclinical enteric infections that is attributable to the treatment of aetiology-specific diarrhoea episodes, 2) estimate reductions in the incidence of aetiology-specific diarrhoea and antibiotic exposure achievable by vaccines against Shigella, rotavirus, and other enteric pathogens, and 3) estimate the worldwide impact of enteric vaccine introduction on aetiology-specific diarrhoea, antibiotic use, and antibiotic exposure to subclinical infections using data from Demographic Health Surveys and Multiple Indicator Cluster Surveys. These results will generate precise estimates of enteric vaccine impact, most importantly for Shigella vaccines, which have been prioritized for development, and for rotavirus vaccines, which continue to be adopted globally. These quantitative estimates will inform advocacy efforts for continued support and provide relevant data for comprehensive analyses of cost-effectiveness.
|
| 30/11/2019 |
£193,863 |
|
UNIVERSITY OF SHEFFIELD |
Typhoid fever is a common cause of non-specific febrile illness in low-resource settings. Empirical treatment for typhoid may be a major driver of AMR in typhoid-endemic communities, where estimates suggest that up to 25 additional cases receive antimicrobial treatment for each one confirmed. Harare in Zimbabwe has experienced a major increase in typhoid since 2016, with recent emergence of ciprofloxacin-resistance. In February 2019 a mass typhoid vaccine campaign was performed, targeting infants and children living in 9 affected suburbs with the new typhoid conjugate vaccine (TCV). In work being performed at primary health clinics in these densely-populated suburbs as part of the FIEBRE study, which aims to assess the causes of febrile illness in low-resource settings, we have already identified a significant reduction in typhoid in vaccinated children. In this project our key goals are to investigate the impact of the 2019 mass TCV campaign on antimicrobial resistance in S. Typhi and on antimicrobial prescribing and related practices in community clinics. Defining these effects will have major policy implications for TCV use, both locally, in determining the benefits of further routine/repeat vaccination, and internationally to inform estimates of the direct and indirect impacts on AMR infection and antimicrobial use.
|
| 30/11/2019 |
£193,504 |
|
BIOMEDICAL RESEARCH & TRAINING INSTITUTE, HARARE |
Typhoid fever is a common cause of non-specific febrile illness in low-resource settings. Empirical treatment for typhoid may be a major driver of AMR in typhoid-endemic communities, where estimates suggest that up to 25 additional cases receive antimicrobial treatment for each one confirmed. Harare in Zimbabwe has experienced a major increase in typhoid since 2016, with recent emergence of ciprofloxacin-resistance. In February 2019 a mass typhoid vaccine campaign was performed, targeting infants and children living in 9 affected suburbs with the new typhoid conjugate vaccine (TCV). In work being performed at primary health clinics in these densely-populated suburbs as part of the FIEBRE study, which aims to assess the causes of febrile illness in low-resource settings, we have already identified a significant reduction in typhoid in vaccinated children. In this project our key goals are to investigate the impact of the 2019 mass TCV campaign on antimicrobial resistance in S. Typhi and on antimicrobial prescribing and related practices in community clinics. Defining these effects will have major policy implications for TCV use, both locally, in determining the benefits of further routine/repeat vaccination, and internationally to inform estimates of the direct and indirect impacts on AMR infection and antimicrobial use.
|
| 30/11/2019 |
£453,415 |
|
UNIVERSITY OF EDINBURGH |
Vaccines can, in principle, alleviate antibiotic resistance by preventing infections and reducing the need for antibiotic use. However, the impact of pneumococcal conjugate vaccines (PCVs) on antibiotic resistant disease is unclear because resistance in non-targeted serotypes is increasing and we do not understand the mechanisms driving this phenomenon. To overcome this issue , we have assembled a multidisciplinary team to leverage an ongoing three-year Phase IV cluster-randomised PCV trial in Vietnam which will provide unparalleled predictive power to calculate the long-term consequences of PCV on resistant infection. First, we will develop a suite of novel bioinformatics tools to determine antibiotic susceptibility using deep sequence data that will allow us to evaluate both the dynamic changes in antibiotic resistance in the three years following PCV introduction and, for the first time, the frequency of resistant–sensitive strain co-colonisation. Second, we will analyse surveys to evaluate the longitudinal impact of PCV on antibiotic use. Third, we will integrate these results into a mathematical modelling approach to disentangle the mechanisms driving pneumococcal resistance. We will use this calibrated model to predict the long-term effect of PCV on pneumococcal resistance. Our results will, for the first time, accurately predict the wider health impact of PCVs.
|
| 30/11/2019 |
£31,008 |
|
WELLCOME TRUST SANGER INSTITUTE |
Vaccines can, in principle, alleviate antibiotic resistance by preventing infections and reducing the need for antibiotic use. However, the impact of pneumococcal conjugate vaccines (PCVs) on antibiotic resistant disease is unclear because resistance in non-targeted serotypes is increasing and we do not understand the mechanisms driving this phenomenon. To overcome this issue , we have assembled a multidisciplinary team to leverage an ongoing three-year Phase IV cluster-randomised PCV trial in Vietnam which will provide unparalleled predictive power to calculate the long-term consequences of PCV on resistant infection. First, we will develop a suite of novel bioinformatics tools to determine antibiotic susceptibility using deep sequence data that will allow us to evaluate both the dynamic changes in antibiotic resistance in the three years following PCV introduction and, for the first time, the frequency of resistant–sensitive strain co-colonisation. Second, we will analyse surveys to evaluate the longitudinal impact of PCV on antibiotic use. Third, we will integrate these results into a mathematical modelling approach to disentangle the mechanisms driving pneumococcal resistance. We will use this calibrated model to predict the long-term effect of PCV on pneumococcal resistance. Our results will, for the first time, accurately predict the wider health impact of PCVs.
|
| 26/11/2019 |
£209,673 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
The aim of the public engagement programme is to improve youth engagement with health services and to have them as active partners in design and delivery of health interventions. We aim to utilize a crowdsourcing approach where a large group of individuals attempt to solve a problem, and share solutions with the public, to identify solutions to overcome barriers to engagement with health services. We will organize a national contest for 16-24 year olds in Zimbabwe, soliciting entries in three artistic categories: 1) music 2) drama and 3) visual images, specifically themed on how to improve engagement of youth with health services. We will hold a national festival where entries will be showcased. Winning entries will then be implemented within my Wellcome Trust funded trial (CHIEDZA) that is evaluating community-based provision of HIV and sexual and reproductive health services for youth. We also run a Youth Researcher Academy to train youth researchers who will then conduct mentored research projects to evaluate the CHIEDZA intervention. Findings will help improve the configuration and delivery of the intervention.
The project will be delivered in partnership with local community-based organisations and other key stakeholders. Our team combines expertise in research with youth, leaders in the arts in Zimbabwe and experts in crowdsourcing and process evaluation. The project will be evaluated and lessons learnt will be shared with stakeholders through a variety of channels. The project will provide a framework for youth engagement that can be used in other areas of health and research.
|
| 26/11/2019 |
£189,632 |
|
IMPERIAL COLLEGE LONDON |
An estimated 1.07 million people in Vietnam are infected with hepatitis C virus (HCV). In the ‘VIETNARMS’ trial, we are investigating the efficacy of HCV treatment strategies that could be used to treat underserved populations (e.g. ultrashort or intermittent therapy). Should these strategies have efficacy as hoped, it will be crucial to develop innovative ways to engage with underserved populations. We propose a ‘bottom up’ approach using community based participatory research (CBPR) to explore barriers to HCV care and to determine what actions must be taken to improve engagement with these populations at risk for HCV.
In this project, we will first conduct stakeholder mapping of organizations working with populations at risk for HCV and create two advisory groups, one at the NGO level and the second at the community level. Next, we will conduct CBPR with 3-5 communities in Ho Chi Minh City over the course of one year. Using CBPR methods, we will work with communities to identify barriers, facilitators, and health priorities related to HCV, as well as design and implement strategies to overcome the problems identified in each group. We will hold dissemination meetings in the communities where CBPR took place, with the local advisory groups, and with regional stakeholders to determine how to integrate dialogues from underserved communities at risk for HCV into larger policy conversations centering on HCV care and treatment. The questions raised and strategies implemented in the communities could also inform future operational research questions within our context.
|
| 26/11/2019 |
£11,900 |
|
INTERNATIONAL CENTRE OF INSECT PHYSIOLOGY AND ECOLOGY |
The Research Enrichment activity will involve a participatory health education to increase awareness and encourage good practices related to the prevention and control of malaria and other vector-borne diseases in Samia sub-county, Busia County in western Kenya. Activities will be coordinated by the International Centre of Insect Physiology and Ecology (icipe) in collaboration with local health and education authorities. Activities will start with engaging school teachers, community health volunteers and parents in open space meetings to discuss and explore community perceptions and issues related to vector-borne diseases, and suggestions for improved control. Participants in open space meetings will be purposively selected from communities where the on-going study is implemented. Issues raised in open space discussions will inform development of action plans for the health education targeting children aged 12-15 selected from at least 12 schools from the study area. Practical demonstrations will include the use of traps for vector surveillance, dippers in aquatic habitats and screening for malaria parasites. Initially, children will be taught about biology of common vector-borne diseases, their prevention and control, using fun and interactive approaches. The participatory health education will culminate into World Mosquito Day on Thursday, 20 August 2020, where the children will participate in the dissemination of information related to prevention and control of vector-borne diseases using entertaining techniques. In groups, the children will develop their own relevant disease-themed projects, such as drama, for presentation. This exercise is aimed at encouraging participants to be messengers of good practices to improve control of vector-borne diseases.
|
| 26/11/2019 |
£18,596 |
|
CARDIFF UNIVERSITY |
Gwyddoniaeth wrth y tân (Fireside Science) aims to promote open dialogue and mutual understanding between non-clinical NHS staff and academic scientists in Wales. Welsh NHS staff are a vital link between the kind of projects funded by Wellcome and translational outcomes in the clinic. However, the 37,000 non-clinical Welsh NHS staff are not directly involved in research and may question any investment therein when the NHS is under-resourced.
This project draws on the traditional Welsh culture of storytelling, using it as a means to facilitate conversations between non-clinical NHS staff and scientists about their working lives. A 2-day workshop for 20 scientists and NHS staff will teach transferable communication and storytelling skills. The workshop will culminate with 20 short 10-minute conversational recordings between, a scientist and a member of NHS staff.
Audio content will be disseminated via three routes: for time-poor NHS staff, podcasts will be available to the general public on standard podcast platforms, promoted via NHS newsletters and targeted social media. Audio recordings will also be released to the Welsh Community Radio Network. Finally, audio recordings will be used in a travelling installation hosted in hospital atria and National Museum sites across Wales. The installation will be themed around a traditional Welsh miner’s front room, with two armchairs using speakers in the headrests to deliver audio, alongside a fireplace and a lamp. The concept will engage NHS staff with human stories about science and healthcare in Wales in a comfortable and welcoming environment.
|
| 26/11/2019 |
£66,550 |
|
BOOTS UK LTD |
Boots Archives would develop a well-researched, high quality travelling exhibition to promote awareness of this now publicly accessible collection. Located in Boots stores this display would engage with new audiences and challenge people's perceptions of the relevance of corporate archives. The exhibition would appear in 25 flagship Boots stores across the country during a seven month tour. The installation would use material from the archive to illustrate changes in community pharmacy. By using the Boots collection as a discussion tool, I aim to show that the value of corporate archives goes beyond their originating organization, providing a long-view on social issues. The exhibition, in illustrating the developments in pharmacy services, would seek to understand people's attitudes towards the role which community pharmacy plays in providing healthcare services in the UK today. Content would be drawn from recent research and I would work with an academic and museum professionals to create a visually engaging and stimulating display. The exhibition would aim to draw comparisons between the role of Victorian pharmacists and the current NHS positioning of retail pharmacists as the first point of contact for minor ailments. By demonstrating the extent to which pharmacist diagnosis was common practice prior to the inauguration of the NHS in 1948, it is hoped that this installation will raise questions and gauge opinions on the current and future role of community pharmacy.
Additional events would be held in Nottingham which would include a community screening of pharmacy related archive footage and public talks.
|
| 19/11/2019 |
£120,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Malaria control programmes are increasingly encouraged to define the variation in malaria risk within their countries and districts to help them take evidence informed decisions how to make the best use the available malaria control tools and resources. While variations in vector ecology, environment, and malaria control efforts may all contribute to variations in malaria risk and disease burden in place and time, control programs need tools that can be part of their existing routine malaria surveillance system. As an extension of previous work which focused on the use of malaria infection prevalence data to model and map malaria risk and develop adaptive sampling methods for household prevalence survey, we propose to use under five uncomplicated malaria hospital cases to identify hotspots, risk factors, and map heterogeneity in malaria burden, to inform targeting of malaria control interventions in an area with declining clinical malaria burden due to intense malaria control interventions in Malawi. Utilizing the DHIS2 linked tracker tool, we will explore geostatistical method to model sub-district level malaria incidence e, accessible, and cost-effective option available to national control programmes to model and map malaria heterogeneity and understand risk factors in areas with declining malaria burden to guide malaria control.
|
| 19/11/2019 |
£120,000 |
|
UNIVERSIDAD DEL VALLE DE GUATEMALA |
Cutaneous leishmaniasis (CL) is a vector borne-parasitic neglected tropical disease (NTD) that affects the low and middle-income countries, such as Guatemala. The transmission cycle of CL involves the bite of an infected sandfly and a possible vertebrate reservoir. In Guatemala, CL lesions are mainly found in poor populations. Alta Verapaz, a northern department of Guatemala, reports, along with Petén, 90% of CL cases of the country; of this department the community Fray Bartolomé de las Casas reports the highest levels of CL endemicity of the department. The Alta Verapaz population is mainly Mayan, without health services access and located in the forest edge. However, despite being one of the focus of CL in Guatemala, eco-epidemiological information of the transmission cycle of CL in Alta Verapaz is not known. Because of this, intervention by the Guatemalan Ministry of Health targets case treatment, but prevention and vector control activities are not implemented. Therefore, in order to improve disease control and develop a CL prevention strategy, this research project proposes to identify the transmission cycle of Leishmania spp in Fray Bartolomé de las Casas by genotyping the Leishmania species circulating in humans and sandflies, and the host-feeding preferences among sandflies.
|
| 19/11/2019 |
£120,000 |
|
INTERNATIONAL CENTRE OF INSECT PHYSIOLOGY AND ECOLOGY |
There has been recent research interest in the prospect of modifying mosquito vectors to make them resistant to Plasmodium infections. One method of modifying mosquitoes involves symbiotic microbes which protect their hosts from infection and are known to persist across multiple generations (transmitted from mother to offspring). Our team has recently isolated a novel fungal symbiont (microsporidia) which occurs naturally in the Anopheles mosquitoes. The symbiont confers mosquitoes a protective phenotype against malaria, both in the wild and under controlled laboratory settings. This finding offers a potential avenue to develop a novel malaria control strategy. To ensure the symbiont is useful as part of a control strategy, we will need to find a way to increase the infection rate in wild mosquitoes (5-10% of Anopheles mosquitoes harbor this fungal symbiont). The proposed research will investigate two possible methods to increase infections rates; a) dissemination of fungal symbiont spores b) Using a pathogenic fungus to kill uninfected mosquitoes (hence increasing the proportion of infected ones). The outcome of this research will be a better insight into methods to practically modify a mosquito population to harbor an enduring transmission blocking microbe.
|
| 19/11/2019 |
£120,000 |
|
INTERNATIONAL CENTRE OF INSECT PHYSIOLOGY AND ECOLOGY |
Despite the vast diversity of arboviruses endemic in East Africa, most research efforts have focused on just a few key viral pathogens. Additionally, estimates of arbovirus diversity in the tropics are likely to be underestimated, especially in Anopheles spp. Many arboviruses are vertically transmitted in mosquitoes, as are recently identified clades of insect-specific flaviviruses (ISFVs). Some ISFVs can either inhibit or enhance replication of other arboviruses in mosquitoes and thus impact both horizontal and vertical transmission of arboviruses. However, whether Anopheles-specific flaviviruses affect arbovirus or malaria (Plasmodium) transmission remains unknown. This study will 1) culture these viruses in Anopheles cell lines and examine their effect on secondary arbovirus inoculations; 2) secondarily infect Anopheles gambiae with arboviruses (Wesselsbron , Semliki Forest, and o’nyong-nyong viruses) after infection with ANFV; 3) characterise vector and viral gene expression responses to primary AnFV infections and with arbovirus infections using transcriptome sequencing; and 4) investigate the effects of AnFVs on Plasmodium transmission. The results from this study will inform on the potential utility of vertically transmitted AnFVs for blocking the transmission of arboviruses and or malaria parasites in Anopheles mosquitoes.
|
| 19/11/2019 |
£120,000 |
|
UNIVERSITY OF OXFORD |
The burden of antibiotic-resistant bacterial infection (ARBI) in low and middle-income countries (LMICs) is largely unknown. Microbiology data is rarely analyzed and reported. Few publications available did not take account of bias caused by low number of blood culture utilization, categorize ARBI based on infection origin (community-onset or hospital-onset) and evaluate mortality attributable to ARBI.
I propose to evaluate the situation of ARBI in a tertiary-care hospital in 2015-2018 in Sulawesi, Indonesia. I will analyze three routinely available data sets; including microbiology, hospital admission and antibiotic prescription data sets. I will use standard methods to estimate prevalence, incidence rates and mortality attributable to ARBI among bacteremia patients. I will categorize infection origin as recommended by WHO GLASS. I will evaluate and describe timing of blood culture collection and antibiotic prescription among patients who had parenteral antibiotic prescribed. I will evaluate whether reported parameters for ARBI were associated with timing of blood culture collection and antibiotic prescription.
The results from this study will improve our standings on ARBI, diagnostic stewardship and antibiotic stewardship in Indonesia, and could be used to inform healthcare workers and policy makers in the country and other LMICs on resource allocation and intervention for actions against ARBI.
|
| 19/11/2019 |
£720,067 |
|
FAPEX |
Leptospirosis is a globally distributed zoonotic disease that has emerged as a major health problem in urban slums in developing countries. Open sewers are key transmission sources of leptospirosis in urban slums. We observed that urban communities from Salvador with condominial interventions, a simplified and cheaper sewerage approach with social participation, had a 6-fold decrease in leptospirosis incidence during a 20 year period. However, the impact of sewerage construction on leptospirosis has not been previously evaluated because sanitary interventions take years to implement and can hardly ever be randomized, and therefore are subjected to confounding. To deal with those methodological challenges, we will use complementary study designs to progressively understand the effectiveness and mechanism for which condominial sewer coverage protects from pathogen exposure, Leptospira asymptomatic infection and disease. We will: 1) evaluate prospectively the effectiveness of condominial and conventional closing sewer interventions in reducing risk of Leptospira infection in a cohort of slum residents; 2) elucidate the mechanism by which closing sewer interventions reduce direct human contact with sewage and environmental pathogen load in urban slums; and 3) determine the contribution of condominial and conventional closing sewer interventions to a decline in severe disease incidence in a large urban centre.
|
| 19/11/2019 |
£766,354 |
|
IFAKARA HEALTH INSTITUTE |
Long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS) have significantly reduced malaria burden across sub-Saharan Africa [1], but are increasingly threatened by challenges such as mosquito resistance against common public health insecticides [2]. This necessitates innovative complementary tools to sustain the gains [3].
Mosquito-driven autodissemination of pyriproxyfen (PPF) has previously been demonstrated to effectively reduce populations of the dengue vector, Aedes aegypti in field trials [4, 5]. In recent years, we have demonstrated similar potential against dominant malaria vectors, Anopheles gambiae and An. arabiensis under semi-field settings in Tanzania [6, 7]. This approach could potentially complement disease control by targeting mosquitoes in aquatic habitats [8]. However, it still needs field-validation and optimization for low-income endemic communities.
Here, I propose to optimize the PPF-autodissemination technology and demonstrate its entomological impact as a complementary intervention in Tanzanian villages where malaria persists despite widespread LLINs use. I will also simulate potential epidemiological impact and develop practical community-engagement approaches for scaling-up the technology. Unlike most insecticides for malaria control, Pyriproxyfen has lower resistance risk [9], and can control both susceptible and resistant mosquitoes through adult emergence inhibition and sterilization [10]. This project will cost-effectively accelerate overall malaria elimination goals.
|
| 19/11/2019 |
£195,361 |
|
INSTITUT DE RECHERCHE EN SCIENCES DE LA SANTé DIRECTION RéGIONALE DE L'OUEST |
Despite efforts developing entomopathogenic fungi as biocontrol agents against disease vectors, expectations have not been met due to their relatively poor efficacy compared to cheaper chemical insecticides. The vast majority of mosquito control studies have focused on a single fungal isolate. However, the recent discovery that native strains of entomopathogenic fungi in Burkina Faso confer exceptionally high virulence against Anopheles gambiae provide new evidence that could transform the effectiveness of these biocontrol tools. These strains showed LT80 as low as 7 days, which is an unprecedented improvement over previous studies where LT80 values are ~10 days.
The proposed research will investigate new ways to exploit local fungi strains for sustainable vectors control solutions. Specifically, using a combination of laboratory assays, semi-field experiments, and hut trials, I will investigate the practical utility of the native strain of Metarhizium from Burkina Faso for malaria vector control. This project will tackle the current challenges in the implementation of biocontrol strategies and will overcome the ecological barriers that have prevented the use of fungi for mosquito control and develop an effective entomopathogenic approach, which will be 1) applicable to other settings, 2) low-cost and biological, and 3) complementary to current vector control interventions.
|
| 19/11/2019 |
£321,051 |
|
BOTSWANA HARVARD AIDS INSTITUTE PARTNERSHIP |
Annually hepatitis B virus (HBV) kills at least 886 000 people as a result of the serious clinical consequences of the infection. Chronic HBV infection is usually diagnosed by the presence of the viral envelope proteins (HBsAg) in the serum using serological tests. However, in occult HBV infection (OBI), replication is HBsAg-negative. OBI, which is transmissible and can cause cancer, requires nucleic acid testing for its detection and is therefore not diagnosed in middle- to low-income settings where capacity and infrastructure are lacking.
Here we aim to determine the prevalence, kinetics and mechanisms of OBI in HIV-infected individuals in Botswana. Plasma samples from two HIV natural progression studies will be screened for markers of HBV infection at 6-month intervals. Genotyping will be performed by next-generation . The impact of mutations on the biological function of HBV proteins will be determined using in silico evaluation followed by functional analyses in tissue culture. Replication, transcription and translation competency will be assessed using Southern, Northern and Western blot. Representative OBI-associated mutations will be tested in vitro for infectivity, and the ability to be neutralised by HBV vaccine-induced antibodies using previously utilized methods. Understanding the mechanisms behind OBI guides future diagnostic and preventative strategies.
|
| 19/11/2019 |
£307,624 |
|
UNIVERSIDAD PERUANA CAYETANO HEREDIA |
Undernutrition is a major consequence of climate change. Biodiversity could enhance climate change resilience of local food systems by improving human nutritional outcomes and providing healthy local food resources during/after climate-related risks. What is unclear, however, is how food biodiversity (FBD) is linked to human nutritional status. This study aims to answer that question by investigating impacts of FBD on the prevalence of malnutrition-related anemia in Shawi Indigenous adults aged 15 to 60 years old and assess the role of FBD on the resilience of Shawi to extreme floods in past five years. This will be achieved through two complementary studies. In the first study, Shawi people who have experienced recent floods will have FBD measured using questionnaires and 24-hour recall. Anemia will be assessed using a novel, non-invasive, image-based application alongside measuring blood hemoglobin. Given that seasonal changes could affect FBD, a cross sectional study with repeated measurements will be conducted to explore if the association between FBD and anemia is stable at different times of year. In the second study, community-based participatory approaches will be used with Shawi participants to investigate the role of FBD on responding to extreme floods
Key words: nutrition, biodiversity, Amazonia, resilience, Indigenous people
|
| 19/11/2019 |
£223,772 |
|
UNIVERSITY OF OXFORD |
The gut microbiome and its dysbiosis play a central role in understanding infectious and non-infectious conditions. Evidence suggests Fusobacterium nucleatum, an oral anaerobic bacterial pathobiont, potentiates colonic tumourigenesis. My recent work in Vietnam indicates that Fusobacterium, including F. nucleatum, is also enriched in the gut microbiome of children during infectious diarrhoea. My aim is to define the role of Fusobacterium in the resolution of infectious diarrhoea and the development of colorectal cancer, through integrating 16S rRNA-based metagenomics in two distinct clinical studies in Vietnam. I will examine the impact of Fusobacterium gastrointestinal overgrowth and microbiome dysbiosis on diarrhoeal duration in children. Additionally, I will measure the prevalence and distribution of F. nucleatum in the microbiomes of gut mucosa taken from colorectal cancer patients. I will perform whole genome sequencing on the F. nucleatum isolated from collected saliva, diarrhoea stools, and colonic tumour mucosa. Using genomics and phylogenetic analyses, I aim to identify genetic factors associated with F. nucleatum colonization in different human body compartments (oral, colonic) and pathological states (tumour, non-tumour). These findings will enable future in-depth studies, contributing to the development of non-invasive diagnostic marker for colorectal cancer and targeted Fusobacterium therapies in these two diseases.
|
| 19/11/2019 |
£120,000 |
|
FUNDAÇÃO DE APOIO AO DESENVOLVIMENTO DA UNIVERSIDADE FEDERAL DE PERNAMBUCO (FADE) |
Candidiasis is the 7th most common bloodstream infection in Brazilian hospitalized patients and represents 74% of serious fungal infections in Brazil. Superficial forms of candidiasis can lead to disfiguration, disability, and can potentially become systemic and lethal. There is a limited number of antifungal drugs available and the unpaired increase of antifungal resistance highlights the urge to develop alternative technologies to treat fungal infections. Photodynamic inactivation(PDI) has been suggested as a promising antimicrobial technology, and no microbial resistance has been described against it. PDI uses light to produce reactive oxygen species and destroy pathogenic cells. Our group has been investigating the effect of PDI on Leishmania spp. and yeast-forms of Candida albicans using zinc porphyrins (ZnP). The organization of Candida in biofilms grants it a higher resistance to antifungals, including PDI. The association of PDI with metallic nanoparticles (ZnP-NP) has been suggested to improve the photodynamic efficiency in biofilms. We propose to develop a protocol to apply ZnP and ZnP-NP PDI for planktonic cells and biofilms of C. albicans and C. glabrata. The establishment of this technology to treat candidiasis will decrease the exposure of patients to antifungal drugs, preventing the emergence of new resistant Candida strains.
|
| 19/11/2019 |
£168,027 |
|
COLLEGE OF MEDICINE AND ALLIED HEALTH SCIENCES, UNIVERSITY OF SIERRA LEONE |
Lassa fever is a life-threatening viral haemorrhagic fever and a major public health burden in West Africa, causing tens of thousands of cases annually with high patient mortality. The signs and symptoms of LF mimic common febrile illnesses in the early phase of the disease which makes diagnosis of the disease difficult. Severe disease is characterized by bleeding, the pathogenesis of which remains unexplained. Clinical patterns of bleeding and data from the 1980s have suggested that platelet dysfunction may be a major cause. This research project will study Lassa fever in adults and children in Sierra Leone. This project will develop and evaluate novel LASV assays in portable RT-qPCR systems to facilitate early diagnosis at the point of need, and will investigate the haemostatic changes in Lassa fever using modern assays, focusing especially on platelet dysfunction. We will assess whether thromboelastometry and coagulopathy biomarkers correlate with bleeding and disease severity. Flow cytometry will further improve understanding of the underlying mechanism(s) responsible for the coagulopathy. This research has the potential to achieve rapid impact, strengthen laboratory capability and provide new international academic collaboration in a neglected disease designated a priority for research by the World Health Organization.
|
| 14/11/2019 |
£330,630 |
|
TRINITY COLLEGE DUBLIN |
On 25th May 2018, Irish citizens voted to remove the controversial "8th Amendment" to the Irish Constitution, opening the way for the introduction of legislation governing the termination of pregnancy in the State.
This project intends to provide long term preservation and access to the many at-risk archives generated by grassroots women’s reproductive health movements during the campaign.
There is no consensus on the best practice for archiving social media posts, which are supported on third party platforms. It has also been argued that archival curation has been skewed towards the dominant culture. As a result, many of the rich archives of reproductive health generated through the referendum campaign are at-risk.
This project aims to
· Ingest material from the six collaborating organisations for long term preservation in the DRI
· develop best practice for archiving social media
· create a registry of at-risk reproductive health archives and support further ingest to the DRI
· carry out social science research into best practice, ethics and legalities of archiving this material
· Provide training and expertise to reproductive health archives in archival best practice
· Collect and preserve additional material on the topic from the public
|
| 14/11/2019 |
£353,277 |
|
BRITISH MUSEUM |
This project makes available for the first time the world’s most standardised, structured and systematised corpus of medical literature prior to Galen: the "Nineveh Medical Encyclopaedia" from the library of Ashurbanipal, King of Assyria (669-c.630 BC). Its broken condition and its use of cuneiform script mean that, almost 200 years after their first discovery, still only glimpses of its content are accessible to medical historians. As such the importance of Assyria’s contribution to the history of medicine remains unrecognised.
While fragments of Ashurbanipal’s medical library have long been known, the existence of the Encyclopaedia has only recently been recognised thanks to the reconstruction and translation of an ancient medical catalogue. This discovery allows us now to reconstruct the whole Encyclopaedia from its broken fragments and translate it in full. We will then generate a complete index of drug names and technical vocabulary as found in the compendium, and correlate them against the symptoms they were designed to treat. All this material will be made freely available in enriched digital form. The project will therefore enable researchers to gain a clear understanding of ancient Assyrian medicine and its place in the broader history of medicine.
|
| 14/11/2019 |
£50,783 |
|
UNIVERSITY OF DUNDEE |
The project will catalogue the archive of the Brittle Bone Society which is primarily held by the University of Dundee Archive Services. Any material remaining at the Society headquarters will be transferred and catalogued and the catalogue will be available online. The material will be re-housed into appropriate archival quality storage containers and a proportion of the material will be digitised. An additional element of the project will be to conduct oral history interviews with Brittle Bone Society members and staff which will become part of the Society's archive. A project board will oversea the progress of the project and will assist in organising a dissemination event.
The archive will be fully catalogued allowing researchers to understand its content and identify relevant material
The material will be properly preserved ensuring its long term survival
The archive will be supplemented by recordings of people associated with the Society which add to the richness of the research resource
Awareness of the archive and its research potential will be increased, as will the likelihood of further accruals of material in future
Two interdisciplinary dissemination events will allow the discussion of archives relating to disability and the Brittle Bone archive in particular
|
| 14/11/2019 |
£169,117 |
|
BATH AND NORTH EAST SOMERSET COUNCIL |
The project will open up valuable new opportunities for research into the relationship between housing and health, answering a clear need for easily accessible archival resources for studies of housing at a local level. It will enable access to significant records relating to slum clearance, provision of council housing, and renovation of unfit properties in Bath between 1890 and 1995. These records are currently uncatalogued and in a poor state of preservation, inaccessible to the research community.
We will catalogue approximately 90 linear metres of records to ISAD(G), and publish the resulting catalogue online; the records will be repackaged in accordance with BS4971:2017; remedial conservation will be carried out on those records requiring it. The activities of the project will be strengthened through the input of an Academic Advisory Board which will advise on interaction with the research community and dissemination of the project.
As a result of the project, access to a significant collection of records will be assured for researchers now and in the future. It will make a valuable contribution to the evidence base for research into the relationship between local housing policy and health, encouraging a long-term perspective on current housing issues, and informing future policies.
|
| 14/11/2019 |
£104,661 |
|
LONDON BOROUGH OF BARKING & DAGENHAM |
This 18-month project aims to improve the accessibility of collections related to the construction, development, and management of the Becontree Estate through a programme of cataloguing, conservation, digitisation, and outreach utilising the following collections:
Building and estate plans
London County Council Property Management Files
Tuberculosis and Infectious Disease Registers
The Dagenham Digest
Community publications - tenants’ handbooks, tenants’ gazettes, gardening guides
Medical Officer of Health reports
Rent books
Key outcomes:
Creation of fully searchable catalogues to file- and item-level adhering to relevant international standards hosted on the Valence House Collections website and the Archives Hub
Conservation, including repair of damaged plans and registers of infectious diseases and the repackaging of other materials using suitable archival-quality packaging
Digitisation of key records - building and estate plans, tuberculosis and infectious disease registers, and Dagenham Digests - and long-term preservation of digital surrogates
Creation of a project website for dissemination of digitised materials, publication of blogs, and facilitating of comments/memory-sharing from Becontree residents past and present
Ingest of public comments from the website into archive catalogues
Outreach activities engaging local residents and aiming to build a stronger lasting relationship with an academic audience
Writing of research guides to all Becontree-related collections
|
| 14/11/2019 |
£54,548 |
|
UNIVERSITY OF EDINBURGH |
Speaking Out aims to catalogue, rehouse and selectively digitise archives created by the Lothian Gay and Lesbian Switchboard (LGLS), an activist-run mental and physical health service for LGBT people in the Lothians and beyond. The project will disseminate its findings to academics and the wider public, and address key ethical, visibility and sensitivity issues through collaborative engagement with scholarly and stakeholder communities.
Opening on 2 March 1974, LGLS was the UK’s first gay helpline and Scotland's first gay charity. Despite this pioneering history, LGLS archives remain largely invisible to researchers in their current, uncatalogued state. This project aims to open up this collection to researchers through:
cataloguing and indexing compliant with archival standards, at levels ensuring maximum general research access;
identifying sensitivities/ethical issues and applying appropriate closure periods;
using anonymised transcription to provide a way in to selected otherwise-confidential records (encouraging academic researchers to apply for access through established procedures);
rehousing records in archival-quality storage;
digitising selected material (such as locally-specific newsletters unavailable elsewhere in physical or digital form) to aid no-cost, remote research;
promoting the collection to research audiences through targeted activities;
recording a small number of oral histories (3 – 5), adding context for researchers.
|
| 13/11/2019 |
£45,360 |
|
UNIVERSITY OF OXFORD |
Measurement and characterisation of light — whether it is in everyday contexts or in experimental and research settings — is notoriously non-trivial. Part of this is due to the complexity of the underlying concepts (e.g. measurement geometry, propagation of light in space). The goal of this Research Enrichment activity is to make the characterisation of light and its derived quantities (luminance, chromaticity, alpha-opic quantities relevant for melanopsin-mediated signaling) more accessible using a free and open-access web-based platform for uploading, visualising, analysing and comparing data about light using a modern user-friendly graphical interface running directly in the browser. The lightbox education and research platform is targeted to three main audiences: (1) Researchers in the fields of visual neuroscience, vision science, experimental psychology, and visual chronobiology who use light as interventions, but wish to fully understand the effects of light on human behaviour and physiology; (2) Practitioners wishing to predict the effect of light on the human eye and circadian system; (3) Students and educators in the fields who wish to learn the basics of light, colorimetry, and photometry using an intuitive interface.
The lightbox platform will supplement my ongoing research programme on the effects of light on human circadian rhythms and sleep by increasing the impact of the analysis and visualisation tools I have developed as part of my research, and also of my research itself. Sustainable and continued use of the research beyond the scope of my own project is guaranteed after the funding period ends.
|
| 13/11/2019 |
£37,805 |
|
UNIVERSITY OF GLASGOW |
What the research enrichment activity will look like
We have created an in-house software tool – TableTidier – that converts idiosyncratic tabular data into a a standard layout, with string terms mapped across to established ontologies. This converts the data into a more open format.
The research enrichment activity is to develop the TableTidier so that unknown users (including those with diverse disabilities) can (1) modify and re-use the code in other projects and (2) use TableTidier to convert tabular data into open formats both for their own use and - in a crowdsourcing model - for the wider research community.
This development work will include new coding as well as documentation and testing of TableTidier. This work will be strongly informed by a series of workshops with the target audience – researchers working across diverse academic disciplines. We will also promote the tool to users throughout the UK and internationally via letters to journals and social media engagement as well as via established networks within the evidence synthesis field.
What we will have been achieved
As a result of the enrichment award we will have achieved the following:-
TableTidier will have been successfully used by researchers beyond our own university and across disciplines
A body of converted standard "open" format versions of tabular data will have been added to a searchable database, some of which will have been accessed by distinct users
Authors publishing findings will have created standard versions of their published tables in open formats
|
| 12/11/2019 |
£20,000 |
|
HEART N SOUL |
We aim to produce an accessible output that captures the essence of Heart n Soul at The Hub. While the project will generate research papers with accessible summaries and events, Robyn Steward and Pino Frumiento want to create something that shares the project’s story and what they have discovered with the public, forges connections between people with learning disabilities and others, and ‘proves that you can include learning disabled people all the way through the research process’ Robyn.
Robyn and Pino will lead a process, involving co-researchers and co-designers, to produce the output. Their current vision is of a book/zine and/or a song, although this may change. Robyn is a published author and gifted illustrator. Pino is a singer-songwriter. Both have the experience and skill to communicate with audiences in a compelling, heartfelt way: telling the human story.
The team will be supported by project artists, facilitators and lead academic researchers. This group will provide complementary skills and experience, ensuring the process is entirely accessible.
The output will complete our experimental journey through an accessible research process led by learning disabled people, enabling them to communicate their findings in their own way.
A book/zine may be published and promoted widely, including via Wellcome and networks such as the National Autistic Society. If a song, this will be performed at events, online and via radio.
The accessible output will spark connections between researchers, research findings and general audiences; connect at a human level; and shift attitudes among the public and academics.
|
| 12/11/2019 |
£18,500 |
|
UNIVERSITY OF CAMBRIDGE |
Diversity amongst staff and students in higher education is still demonstrably unequal, both in gender balance and ethnic balance (https://www.ecu.ac.uk/about-us/he-equality-challenges). Similarly, open source software developers self-report to be over 90% male and 15% or less self-report as BME (https://osf.io/preprints/socarxiv/qps53).
InterMine, as an open-source biological data warehouse, occupies both the academic and open source worlds. We propose to improve gender and ethnicity balance by mentoring interns from underrepresented backgrounds, helping to improve their software engineering skills. This will allow interns who have an interest in software engineering, academia, and/or data science/ bioinformatics to gain hands-on experience writing code for a project with real-world scientific applications, while working with a team of experienced software developers.
Past interns have benefitted in a number of ways: one has gained a first-author paper; some have returned to gain experience of mentoring in subsequent years; we have written them references to support successful applications for graduate education and jobs, and one has gained a full-time post within the InterMine team.
We propose that interns will be recruited via Outreachy (https://www.outreachy.org), an organisation dedicated to diversifying the open source community. Outreachy expressly encourages applicants from underrepresented backgrounds. Interns work remotely from May to August, videoconferencing with their mentors once a week and with the entire group of interns and mentors once a month for group workshops covering good coding practices and presentation skills.
|
| 12/11/2019 |
£20,000 |
|
KING'S COLLEGE LONDON |
Successful implementation of an inclusive environment means moving beyond representational diversity, to engaging and harnessing potential of the entire workforce.
We will develop a cultural change coaching and training programme for our Faculty Executive Board and School leadership teams, equipping them to champion cultural change across the institution. We begin with a facilitated discussion with our Executive Board, to explore our organisational culture and challenge perceptions, examine scenarios of interpersonal conflict specific to the Faculty, and provide a safe space for leadership to share experiences and challenges they experience in modelling inclusivity. Additionally, we will conduct direct 1-2-1 interviews with four members from the Executive, and hold four focus groups. Findings will be consolidated and inform a tailored coaching and training programme for leadership, and inclusive behaviours framework to support and monitor leaders’ actions to embed inclusivity and cultural change. We will evaluate the programme’s impact and produce a video podcast as information and guidance, to be disseminated across the institution.
This initiative will educate our leaders and provide them with the vocabulary, tools and confidence they need to model positive behaviours for cultural change and inclusivity, and to ensure these behaviours are represented across their communities. It builds on research we have undertaken into cultural barriers to inclusivity and bullying and harassment within the Faculty, alongside an existing aspirational agenda promoting diversity and inclusion. We will share our research and insights with leadership in King’s other health faculties and with leadership in other universities through a one-day targeted conference.
|
| 12/11/2019 |
£19,800 |
|
UNIVERSITY OF KENT |
By the end of the project a range of voices of those who are seldom heard by policy makers and academics, from a diverse range of backgrounds and groups, will be given a platform to communicate with those who make decisions affecting children’s and families’ lives. This includes Parliamentarians, policy makers, government, the civil service and the academic community. The Enrichment Award offers the means to:
Recruit a more diverse group of Experts-by-Experience from among disabled children, care leavers and parents whose children have received assessments
Support additional activities to involve these diverse Experts-by-Experience in planning, design, data analysis, communications and policy influencing
By the end of the project we will have:
Recruited from a more diverse and hard-to-engage range of Experts-by-Experience through intensive targeted recruitment with partner organisations who have links to diverse stakeholders. The Enrichment Award will allow us to locate a range of ethnicities and nationalities in the Expert-by-Experience groups, which is especially important given evidence of ethnic inequalities in child protection practice. We will also be able to seek within a range of social-economic and geographical locations within England, again of critical importance given evidence of vast inequalities.
Provided more extensive support for Experts-by-Experience to be involved and actively contribute. For Experts-by-Experience who experience disabilities, communication challenges, SEN or lack confidence, specialised support will be used to ensure active participation, such as small group work, one-to-one support or creative activities to encourage inclusion, going beyond what would be possible in the original Award.
|
| 06/11/2019 |
£300,000 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Some individuals who are naturally exposed to malaria infection acquire immune responses that stop Plasmodium development in the mosquito gut, whilst others are highly infectious despite relatively low gametocyte densities. I intend to investigate naturally acquired malaria transmission modulating immunity to improve our understanding of malaria transmission and provide insight for malaria vaccinologists. Key goals, methods, and outputs:
1. Identify effectors of Plasmodium transmission modulation
Methods: Immune profiling by Protein micro-array and luminex (cross-sectional samples with transmission endpoints)
Outputs: A comprehensive list of antibody correlates of transmission-blocking immunity (TBI); a serological platform for assessing sexual-stage antibody titres; a statistical model determining the impact of antibody, parasite and cytokine metrics on the association between gametocyte density and mosquito infection.
2. Characterise the dynamics of sexual-stage immune responses
Methods: Luminex (longitudinal cohort samples)
Outputs: Estimates of the association between gametocyte density and antibody titre; improved understanding of the dynamics of immune response to gametocytes after natural and controlled malaria exposure.
3. Examine the maintenance and effectiveness of transmission modulating immunity
Methods: Lab-based mosquito feeding assays, B-cell assays
Outputs: Novel assays for the quantification of sexual-stage immune memory; detailed analyses of the relationship between antibody titre and transmission modulation (transmission enhancement and reduction).
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Several long non-coding RNAs (lncRNAs) are capable of scaffolding ribonucleoproteins (RNPs) that condense and phase-separate nuclear membraneless compartments. Both, lncRNAs and RNPs play many key regulatory roles in development and their function in cell fate choice is further enhanced by their cross-regulation. To demonstrate the importance of such cross-regulation for fine-tuning developmental decisions I will build a framework of experimental and computational methods to study how lncRNAs scaffold nuclear RNP compartments and hence understand how interactions between lncRNAs and RNPs within these compartments create networks that coordinate molecular processes in early development. To interrogate the developmental role of these network motifs between lncRNAs and bound RNPs, I will also establish new tools that allow rapid manipulation of lncRNA condensation in advanced in-vitro embryogenesis system. Collectively, this proposal will reveal the cross-regulatory mechanism of nuclear rewiring by lncRNA condensation that plays a role not only in development, but when perturbed, could also be implicated in diseases such as ALS and cancer.
|
| 06/11/2019 |
£300,000 |
|
KEELE UNIVERSITY |
Current front-line venous thromboembolism (VTE) treatments involve the systemic administration of anticoagulants to control thrombus growth and/or the application of thrombolytic enzymes to try to lyse the clot, although both exert a systemic effect in the patient body, potentially leading to major bleeding. Iron oxide nanoparticles (IONPs) have been used to generate targeted hyperthermic responses to destroy pathological structures (magnetic hyperthermia - MH). Here size-controlled IONPs will be synthesised and multi-functionalised (mf-IONPs) with anti-fibrin IgG antibody and tissue plasminogen activator (tPa) through covalent bonding onto the IONPs surface using click-chemistry techniques. These mf-IONPs will target venous thrombi and in-situ magnetic stimulation will produce a localised hyperthermic stimuli to trigger the apoptosis/necrosis of thrombi-lodged erythrocytes and platelets, whilst also improving the action of the temperature sensitive tPa, therefore reducing the secondary effects associated with traditional therapies. Our study intends to demonstrate the clinical potential of this nanotechnological-based VTE therapy by using a tissue-engineered vein model that mimics the fluid shear conditions of human blood vessels. This model, together with limited in-vivo studies, will confirm the biocompatibility of this technique. The outcomes of this study will allow to endeavour further steps to pave the way for translation into the clinic.
|
| 06/11/2019 |
£300,000 |
|
THE FRANCIS CRICK INSTITUTE |
During embryogenesis, signals control gene expression to ensure cells types are formed in the right time, place and proportion. Biological signals are integrated by Regulatory Elements (REs), making these vital elements in the information processing mechanism of the genome that controls gene expression. REs often lie long distances from a gene suggesting some long-range communication is necessary for their function. Recent technological advances have revealed long range interactions between REs and promoters, yet the mechanisms that control these interactions and how they influence gene expression are only superficially understood. To this end, we will take advantage of a model we have developed in which two long ranges REs associated with the motor neuron specifier Olig2 act in different combinations in hindbrain and spinal cord tissue. We will use chromatin contact assays to identify interactions between Olig2 and REs. To determine function, we will use gene editing and targeted perturbations to study how the REs effect gene expression. Finally, we will use cutting-edge techniques to force contacts between Olig2 and REs to identify how they act in tissue specification. This study will offer unique insight into the formation, control and effect of chromatin contacts in a developing mammalian tissue.
|
| 06/11/2019 |
£300,000 |
|
IMPERIAL COLLEGE LONDON |
Group A Streptococcus (GAS) causes a wide range of diseases, from pharyngitis and scarlet fever to potentially fatal invasive disease. GAS bacteria can be subdivided into serotypes (emm-types), grouped in emm-clusters. The existence of serotype-specific immunity following infection is established, however the extent of cross-strain protection, has not been measured. Using a combination of longitudinal cohort, surveillance and genomic data, I will use transmission-dynamic modelling and learn genomic analysis to infer the protective efficacy of naturally acquired immunity to GAS, including the extent of type-specific and heterotypic immunity.
I will identify whether there is a biological basis for emm-cluster-level immunity – including whether emm-types predicted to produce immune cross-reactivity map to genetic similarity, or exhibit similarities in horizontally-acquired non-emm antigens. I will analyse the evolutionary epidemiological dynamics of GAS, to determine whether patterns of emm-type and emm-cluster prevalence over time can be explained by demographic replacement of susceptible individuals, or immune escape via pathogen evolution. The results of these analyses will allow me to inform key public health questions, including predicting the population-level impact of introducing a test-and-treat strategy for pharyngitis in UK children, and predicting the impact of polyvalent incomplete vaccines on antibiotic consumption in a US setting.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Cystic Fibrosis (CF) affects over 10000 people in the UK. It is a recessive monogenic disease caused by a double mutation in the gene encoding for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) and it affects multiple tissues, especially the lung. There is still no cure for this disease and patients require life-long treatment and eventually lung transplantation.
This projects aims to study a newly discovered cell type in the human airway epithelium. These cells have been called pulmonary ionocytes because of their ion-exchange function and their similarity to ionocytes in Xenopus and zebrafish. Because they express high levels of CFTR, they have been proposed to have a key role in CF.
I will derive airway epithelial cells, including ionocytes, from iPSCs from healthy and CF patients. I will do an extensive characterisation of the cells and I will study their role in the healthy and diseased epithelium using approaches such as single cell RNA-seq and assessment of cilia dynamics and mucus clearance.
Overall, this project will shed light into the role of pulmonary ionocytes in the epithelium and into the pathophysiology of CF. This will lead to the identification of potential therapeutic targets and future treatments for the disease.
|
| 06/11/2019 |
£300,000 |
|
THE FRANCIS CRICK INSTITUTE |
Growth of the developing brain is protected over that of the body when fetal nutrients and/or oxygen are compromised during intrauterine growth restriction (IUGR). This brain sparing phenomenon is well documented but the underlying mechanisms are poorly understood. Furthermore, even though ‘brain sparing’ protects overall brain size, it is imperfect - leading to long-lasting deficits in some adult brain functions. In this project, I set out to identify fetal brain sparing mechanisms and how they are linked to changes in adult brain anatomy. Neural stem and progenitor cells (NSPCs) are essential for the growth of the central nervous system in flies and mammals. Using a Drosophila model, the Gould lab showed that constitutive and starvation-resistant PI3K signalling in NSPCs is an essential part of the brain sparing mechanism. I now want to exploit a mouse IUGR model, established recently in the Gould lab, to pinpoint how NSPCs and their progeny change at the cellular and molecular level during mammalian brain sparing. To achieve this, I will examine PI3K and other candidate signalling pathways as well as using transcriptomics and metabolomics approaches. I will also follow up putative mechanisms for human brain sparing using in vitro models such as cerebral organoids.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF OXFORD |
The primary focus is to uncover computational mechanisms underlying material perception, with particular emphasis on "perceptual constancy" – the stability of judgements about objects in the world, despite changes in the proximal stimulus. My approach to this problem is to capitalise on recently developed deep-learning paradigms by evaluating and interpreting activation maps of convolutional neural networks (CNNs) that have been trained to replicate human performance in classifying material properties, such as colour, gloss and translucency, and to use these to identify candidate models of human perception.
The key stages are to (i) generate computer-rendered training images with diagnostic conditions of lighting, viewpoint and material parameters; (ii) obtain human perceptual labels for 15,000 images using online methods, validated with lab-based measurement; (iii) train CNNs with either ground-truth or human labels; (iv) interpret the CNNs using visualisation tools; and (v) run psychophysical tests of CNN-inspired models of human vision. The goal is to learn about mechanisms of human material perception by decoding the internal structures of these networks and comparing their behavioural responses to new images. Cue-perturbation methods will be used to test the importance of the recovered features for human perception. Perceptually labelled images will be additionally analysed with traditional methods.
|
| 06/11/2019 |
£300,000 |
|
MEDICAL RESEARCH COUNCIL |
Intracellular trafficking pathways depend on the opposing microtubule-based motors kinesin and dynein. Both types of motor can simultaneously bind the same cargo for bidirectional transport on microtubules. Kinesin and dynein bind to many of the same cargo adaptors (e.g. BICD-family). However, it is unclear how opposite-polarity motors are linked to the same vesicle and how adaptors regulate directional switches in the cell. My research goal is to use post-Golgi Rab6-vesicles to investigate how bidirectional transport is coordinated. Mechanistic insight into this process is necessary to understand how cells correctly distribute cargo to maintain their function. I will first structurally characterise how purified Rab6 recruits motors and adaptors. I will subsequently reconstitute bidirectional motility of Rab6-liposomes in vitro with purified proteins. With this tool, I will explore how combining different motors and BICD adaptors alters motile behaviour using single-molecule total internal reflection microscopy. To address how motors are organised during bidirectional transport, I will determine the architecture of a multi-motor Rab6-liposome complex on microtubules using cryo-electron microscopy and tomography. Structural observations will be validated using site-directed mutagenesis and imaging of Rab6-vesicles in cells using lattice light-sheet microscopy. Together, this will provide extensive structural and functional information about dynamic bidirectional transport mechanisms.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
The endoplasmic reticulum (ER), as a single continuous membrane network, coordinates a variety of biological processes across the entire cell, providing a platform for the spatiotemporal segregation of cytoplasmic biochemistry – a crucial feature for cell survival. Despite this, our understanding of how the ER corrals most cytoplasmic clients to specific sites on its membrane remains slim.
ER structure is partially governed by a series of hairpin proteins known to stabilise specific membrane curvatures. The Reticulons (RTNs) and Receptor Expression-Enhancing Proteins (REEPs) are two such families of protein. We have shown that RTN/REEPs cluster into ER microdomains and contain cytosolic-facing intrinsically disordered regions which enable the formation of biomolecular condensates, potentially tethering specific cytosolic proteins to the ER membrane. Thus, we propose the novel and testable hypothesis that membrane curvature-stabilising RTN/REEPs drive regional functional specificities at ER microdomains.
To test this, we will generate a comprehensive spatial map of RTN/REEP-microdomains using single-molecule localisation microscopy, with a custom optical-tweezer configuration used to quantify precise membrane curvature preferences for each hairpin. Using two orthogonal screens we aim to identify a complement of cytosolic proteins capable of co-condensing with each RTN/REEP, performing appropriate bioassays to assess the functional consequences of destabilising hairpin:cytoplasmic-partner interactions.
|
| 06/11/2019 |
£300,000 |
|
IMPERIAL COLLEGE LONDON |
G protein-coupled receptors (GPCRs) are the largest family of signalling receptors, regulating a variety of cellular functions including neurogenesis and synaptogenesis. Therefore, GPCRs are the main pharmaceutical targets, however, the lack of knowledge regarding the association between neuroplasticity and GPCR function makes them an underexploited target for neurodegeneration. GPCR signalling activity is regulated via their trafficking to intracellular compartments, namely endosomes. Membrane trafficking of neuronal receptors is an established mechanism in the regulation of synaptic plasticity, especially in those areas of the brain involved in learning and memory (e.g. hippocampus), although the molecular mechanisms and its link with signalling remain
poorly understood. Using beta-adrenergic receptors (BARs) as prototype GPCRs, we aim to target this knowledge gap by 1) identifying BAR trafficking pathways in hippocampal neurons; 2) generating a map of BAR signalling along their endosomal trafficking; 3) determining the role of BAR spatially encoded signalling on synaptic plasticity. Through the development of novel approaches to study the local organization of synapses, this project will help to understand how GPCR activity can be modulated via targeting receptors to defined cellular locations in the hippocampal neuron and specifically within individual synapses, offering the potential for novel GPCR-based therapeutic targets for neurodegeneration.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF BIRMINGHAM |
Megakaryocytes (MKs) are platelet-producing bone marrow cells with critical roles in the regulation of the bone marrow microenvironment. In myelofibrosis, a progressive and debilitating condition with inadequate treatment, MKs drive extensive fibrosis of the bone marrow. The mechanisms behind myelofibrosis remain unknown, largely due to limitations in existing assays which fail to replicate the complex and multicellular bone marrow milieu. There is a pressing need for better human models with which we can study MK biology and drive the development of therapies for severe conditions like myelofibrosis.
In this fellowship, I will generate the first artificial bone marrow organoid which replicates the architecture of this tightly regulated and carefully organised microenvironment in 3D. I will use this to study MK migration, maturation and platelet production in healthy and myelofibrotic conditions, and test my hypothesis that the fibrosis observed in myelofibrosis is the result of impaired MK migration leading to the intramedullary release of platelets and/or profibrotic cytokines.
By differentiating pluripotent stem cells in a 3D printed scaffold mimicking human bone marrow within a bioreactor, I will engineer an organoid which will be a paradigm-shifting tool not only for the study of haematopoeisis, but with broader applications in drug development.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF EDINBURGH |
African trypanosomes, parasites spread across sub-Saharan Africa by the tsetse fly vector, cause both human and animal disease, threatening millions of people and their livestock. In the blood of such mammalian hosts, a quorum sensing (QS) process causes the asynchronous differentiation of proliferative ‘slender’ form trypanosomes into arrested ‘stumpy’ forms, which are competent for transmission to the tsetse fly. However, the hierarchy of events from QS signalling, through cell cycle exit, to molecular and morphological differentiation are not defined. I propose to decipher this process using single-cell transcriptomics.
I will use single-cell RNA-sequencing to profile transcriptomes of individual Trypanosoma brucei parasites undergoing asynchronous differentiation into stumpy forms, where bulk RNA-seq is not informative. I will then generate a trajectory of differentiation by ordering cells across "pseudo-time" according to the gradual changes in their transcriptomes. By studying cohorts of genes which vary in expression across pseudo-time, I will identify the hierarchy of key events and identify putative regulatory genes. I will then validate these findings by generating null mutants of these regulatory genes, which will be assessed for their ability to differentiate.
Thus, I aim to understand differentiation control mechanisms that in the future can be targeted to interrupt disease spread.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Understanding the social cognitive mechanisms that enable people to learn from and interact with others has been of considerable interest to psychologists and neuroscientists for decades. Yet, the mechanisms underlying our ability to gather information from other people and to learn from them by integrating this information into our beliefs remain to be elucidated. Here, I proposed to use a neuro-computational approach, combining behavioural experiments, neuroimaging, brain stimulation, and computational modelling to provide an integrated framework of how information acquisition and integration are influenced by social contexts. Three key questions form the core of this proposal: How are choices of information sources influenced by social confirmation bias? How do people learn from misinformation in social contexts? How do these social influences interact with anxiety? Across four studies in three international sites, this research will (i) further our understanding of the behavioural and neural mechanistic computations underlying these processes, (ii) determine the causality of the neural mechanisms, and (iii) elucidate how these computations vary with psychiatric symptoms. Addressing these questions will not only contribute to advancing multiple disciplines, from social neuroscience to behavioural economics, but also has potential implications for wider societal questions, from mental health to policy−making.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY COLLEGE LONDON |
Acute pharmacological challenge and observational studies in humans have shown that cannabis can induce psychosis-like experiences. However, not all individuals exhibit adverse experiences, implicating individual differences in cannabis-sensitivity.
While a number of studies implicate a genetic contribution to cannabis-sensitivity, such evidence relies on genetic variables of limited interpretability, such as pre-selected candidate genes for schizophrenia or family history of schizophrenia. So far, there is no genome-wide evidence exploiting advanced methods from genetic epidemiology to elucidate the role of (genetic) vulnerabilities in cannabis-sensitivity. Furthermore, there is no evidence as to whether prediction models can effectively identify those at high risk for cannabis-sensitivity. The lack of evidence highlights the need for more research on this subject.
To advance the study on cannabis-sensitivity, my project has four main objectives:
to systematically summarise the available evidence on factors associated with cannabis-sensitivity,
to employ advanced genomic association and functional analyses to study biological pathways underlying cannabis-sensitivity,
to apply cutting-edge genetically informed inference methods (e.g. Mendelian randomization) to study the role of individual vulnerabilities (schizophrenia liability) and traits (e.g. neuroticism liability) in cannabis-sensitivity and
to use machine learning approaches to develop and evaluate prediction models for cannabis-sensitivity.
Keywords
Cannabis
Psychosis
Genetic Epidemiology
Prediction
Causal Inference
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF BRISTOL |
Urban (versus rural) upbringing is associated with a two-fold adulthood risk for psychotic disorder. My PhD research replicated this association for subclinical psychotic experiences among children and adolescents (e.g., hallucinations and delusions), which are a developmental risk factor for adult psychotic disorders and other severe psychiatric problems. Given that 70% of the world’s population will live in urban settings by 2050, understanding the link between cities and psychotic experiences is an increasingly urgent public health priority. I will investigate this using three UK-population datasets (ALSPAC, E-Risk and UK Biobank), by exploring:
The role of environmental features (air and noise pollution)
The interplay between environmental and social features (social cohesion and crime)
Biopsychological mechanisms (inflammation and cognition)
Genetic confounding (drift/selection)
This will be among the first research to take advantage of recent developments in high-resolution pollution models. By triangulating three datasets, taking a multilevel, longitudinal and life-course approach, and using advanced statistical methods for mediation and causal inference including causal mediation modelling and the co-twin control design, this research will provide novel insights into the nature of the urbanicity-psychosis association. Identifying modifiable risk factors in the urban environment will ultimately help to improve mental health outcomes in an increasingly urban world.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
Sugar-sweetened beverage (SSB) taxes are intended to reduce SSB consumption, and thereby reduce obesity and type 2 diabetes rates. However, SSB taxes vary greatly in terms of design and have been introduced in a variety of different contexts. It is unlikely that each of these taxes work in the same way. My goals are to 1) improve our understanding of how SSB taxes operate, and 2) produce evidence to inform best-practice development.
I will apply established social science methods to explore how we can synthesize evaluation evidence without oversimplifying differences in intervention and context. I will focus on SSB taxation, although this approach could be applied to a wide range of population health interventions. I will use a combination of process tracing, with in-depth case studies, and qualitative comparative analysis (QCA). Process tracing is an appropriate method for assessing how and why an intervention makes a difference, and QCA is an appropriate for identifying combinations of factors ("causal recipes") which lead to intervention success.
I will develop key theory around how SSB taxes work and produce evidence which can be used to inform the design of future SSB taxes to maximize potential health impacts.
|
| 06/11/2019 |
£300,000 |
|
UNIVERSITY OF EDINBURGH |
My research proposal aims to better understand LC3-associated phagocytosis (LAP) by exploring it for the first time in real-time in a living organism: Drosophila.
During the first four months in the Wood lab, I have demonstrated that LAP occurs in fly macrophages, and that these are a suitable experimental system to monitor LAP in real-time while in vivo.
I am now committed to achieving four goals.
To clarify LAP's cargo specificity in vivo: is LC3 recruited to all phagosomes, regardless of the nature of engulfed particles? To do so, I will assess LC3 recruitment to phagosomes engulfing apoptotic or necrotic debris, both generated at wounds.
To understand whether LAP has a role in macrophage priming: is it required to instruct naive macrophages on how to recognise immunogenic cues? To do so, I will perturb LAP and assess the effects on macrophage ability to recognise immunogenic stimuli.
To discover whether adipocytes rely on LAP to fulfil their biological roles. To understand this, I will monitor LC3 dynamics in adipocytes engulfing cell debris at wounds.
To explore the LAP/autophagy cross-talk: do the two processes compete for LC3? To clarify this, I will investigate how perturbing autophagy impacts LAP and vice versa.
|
| 06/11/2019 |
£300,000 |
|
NEWCASTLE UNIVERSITY |
Bacteria protect themselves against bacteriophage (phage) infection using defensive systems, with phages co-evolving counter-resistant strategies. Several anti-phage systems have been identified and their modes of action determined. Additionally, nine novel systems were recently reported, and thus remain to be characterised.
My proposed research builds upon this recent discovery and aims to dissect the molecular and structural details of the novel anti-phage system named Zorya. Two types of Zorya systems with distinct host range have been described, sharing two conserved components, ZorA and ZorB. These two proteins have been proposed to act through a conserved mechanism, based on formation of a putative ion-channel, to neutralise phage infection. I am to test this hypothesis with the following aims:
To probe the organisation and function of Zorya II in vivo
To define the mechanism by which Zorya II protects from phage infection
To identify the trigger of Zorya II anti-phage activity
Elucidating the molecular basis of interactions between bacteria and their viral predators and characterising the molecular mechanism of anti-phage systems is vital to understand the nature of bacteria-phage co-evolution and its capacity to shape the composition and dynamics of polymicrobial environments, with implication for therapeutic and biotechnological applications.
|
| 06/11/2019 |
£300,000 |
|
MEDICAL RESEARCH COUNCIL |
SMC complexes are key regulators of chromosome structure in all living organisms. In eukaryotes, the genome is compacted into chromatids in mitosis by condensin and sister chromatid cohesion is generated by the cohesin complex during DNA replication. While these proteins were considered to function as static topological devices it has recently become apparent that they are mechanochemical motor proteins that compact chromosomes by progressively enlarging DNA loops. Mechanistically, how they achieve this extraordinary behaviour is not known but it is thought that it is driven by large structural changes powered by their ATPase.
Several models for translocation exist that can be distinguished based on their conformational changes. Using in vitro single molecule imaging techniques and optical trapping with recombinant SMC complexes, I aim to measure these movements as the protein hydrolyses ATP, loads onto DNA and translocates.
This project will shed light on how SMC complexes influence the 3D organisation of chromosomes and will therefore have implications for our understanding of the developmental disorders and cancers that result from mutations in these proteins.
|
| 23/10/2019 |
£77,632 |
|
UK ASSOCIATION FOR SCIENCE AND DISCOVERY CENTRES (ASDC) |
The Vision: To support the UK Science and Discovery Centres in response to Coronavirus, by creating and delivering a National Resilience Programme accessible by all UK charitable Science Centres, and to further support the sector through a Leadership and knowledge exchange programme, and a Digital Resilience Programme working with Communities across the UK.
The Mission: To develop and deliver a National Resilience Programme to enhance Resilience of UK Science Centres during this time of restrictions due to Coronavirus and to ensure this is adaptable to what is needed by Science Centres and remains relevant across 2020 and 2021. To select 15 UK Science Centres and grant-fund these as part of a National Digital Resilience Programme to engage, inspire and involve under-represented children, families and communities with STEM and to raise the profile of the UK Science Centres over the coming year. |
| 16/10/2019 |
£43,415 |
|
UNIVERSITY OF VIRGINIA |
Primary deliverables (Linked Open Data for production)
integrate clinical trials cataloging data from sites like ClinicalTrials.gov into Wikidata
translate a limited vocabulary from ClinicalTrials.gov to underserved languages, namely Hindi, Bengali, and Swahili
Secondary deliverables (cultural products to promote diversity and good ethics)
document Wikidata as a research interface for clinical trials (English, Hindi, Bengali, and Swahili)
publish a general-interest essay on ethical considerations of making medical research data newly accessible
Wikidata is currently the central hub of the open Semantic Web and a portal to downstream reuse. While various sources such as libraries, repositories, and ClinicalTrials.gov provide open data, the easiest way to make information broadly accessible to the general public as well as professionals and researchers is integration into a Semantic Web portal like Wikidata which encourages further reuse.
This project will integrate ClinicalTrials.gov into Wikidata, making it accessible to the Open Semantic Web and beginning the process of mapping its metadata with PubMed, disambiguated names of researchers, geolocation of study sites, portfolio of sponsors, and drug databases .Furthermore, we will translate the search interface to those named underserved languages as a precedent in global collaboration.
If we are successful to the limits of our expectations, then clinical trials data published to date will be free and open and in the Semantic Web. Furthermore, we will set the precedent in this project that linguistic diversity must be central to open data projects of global interest.
|
| 16/10/2019 |
£49,267 |
|
UNIVERSITY OF ABERDEEN |
In the UK many types of routinely-collected data from the NHS and other government agencies are available for research. To protect privacy, data governance law requires that only project-specific portions of the data be extracted, filtered and anonymised before release for research.
Currently little information is provided to researchers on the methods used to produce their data. This lack of transparency results in an increased risk of undetected error propagation and leaves the resulting research difficult or impossible to evaluate and reproduce.
We will co-design, pilot, and evaluate methods for recording and reporting provenance for research using high-security data. The result will be a method to report data provenance that maintains privacy and makes the research more findable, accessible, interoperable, and reproducible.
Our approach recognises that meeting the needs of both data guardians and researchers requires active cooperation. It is a collaboration between data guardians, computing scientists specialising in provenance and trust, an expert in service evaluation methods, and a specialist in open science practice.
The project will provide a provenance ontology model for the high-security NHS Data Safe Haven environment and open-source resources for tracking and safely reporting provenance data for research therein. The method is designed to be scalable across the UK’s high-security environments that host a range of government data.
No tools for capture and reporting of data provenance from these environments exist. This project lays the groundwork for a process that is required for fair use of the public’s data for health care research and innovation.
|
| 16/10/2019 |
£38,832 |
|
IMPERIAL COLLEGE LONDON |
Large amounts of public and charity money have been spent on genomic studies. In non-model organisms, which make up over half of all available sequence data, sharing falls far short of the standards of democratisation and dissemination that funders and researchers envisage. Common issues include paywalled publications, needing to repeat expensive basic data processing steps, and difficulty even finding data. Overcoming these issues requires significant amounts of time, expertise and computational resources. A combination of inflexible database services, lack of advanced methods, and high hurdles to sharing published analyses have collectively led to this situation. Innovative solutions are desperately needed.
We will link datasets with inherently variable structures, searchable with new indexing tools and a novel ranking algorithm to make these invaluable scientific resources truly open. We will adapt technology used in the highly successful strategy employed by search engines, which index, rank and deliver results from billions of webpages which have no unified structure. Our new tool will allow users to search for sequences or other biological features, and group results by samples, species or projects. Results will be ordered by relevance, linked to downloads of published data and visualisations, and further enhanced with analysis performed by the tool itself. Both web and programmatic interfaces will be available.
Our solution’s flexibility, relaxing almost all format requirements imposed by databases on researchers, will lead to broad uptake. Many research communities will benefit (microbiology, immunology, bioinformatics, LMICs and public health), and we anticipate starting to shift open research practices within genomics.
|
| 16/10/2019 |
£49,997 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
The afrimapr project will create software building blocks in R and learning resources to facilitate the use of spatial data in health (and other) applications in Africa. The project will promote these resources in Africa and beyond to initiate a community of users and developers to maintain and improve them. The R building blocks will make it easier to perform spatial data management tasks that should be straightforward but seldom are, including 1. Summarising data by administrative regions of different levels, 2. Joining and displaying data referenced by administrative region names, 3. Access to environmental, socio-economic and health data (e.g. WorldPop, Malaria Atlas Project, OpenStreetMap), 4. Displaying data in static maps and interactive web applications. Components will be designed for ease-of-use to target new users of R. Focusing on Africa is a choice taken to promote usability. We will run workshops in at least Liverpool, Ethiopia, Malawi and South Africa trialling and promoting resources. By the end of the project there will be an R package accepted to CRAN (the Comprehensive R Archive Network) and the rOpenSci ecosystem. There will be an open-source book describing how components can be used for entry level taks with step-by-step reproducible instructions. There will be an evolving codebase on Github with a small but active community of users and developers. We will have have collected examples of how users in Africa and elsewhere are starting to use the components. We will have a business plan for how to sustain the project and resources.
|
| 16/10/2019 |
£50,000 |
|
MONASH UNIVERSITY |
Our goal is to facilitate the sharing and re-use of pathogen genomic surveillance data by public health reference laboratories for global public health benefit, using typhoid fever as the exemplar. This is motivated by the observation that the pathogen genome data now being generated routinely from infection cases in travellers returning to high-income countries from disease-endemic areas could be highly informative for disease control, but that this potential is currently not being realised due to practical and resourcing issues around the release of valuable travel information alongside the sequence data.
Our primary strategy is therefore to lower some of the practical barriers to sharing of genome data and travel data for public labs, through development of software to make the process easier and require fewer person-hours and resources. We also aim to put this data to use by developing a platform for collating and interacting with typhoid genomic surveillance data (TyphiNET), which demonstrates the utility of such data for public health and thus encourages more public health labs to participate.
Our longer term vision is that, through both lowering the bar to participate in open data sharing AND demonstrating the wider benefits of such activities using the examplar of typhoid fever (which is currently the target of new vaccines being rolled out in many disease-endemic countries), this project will have a wider impact on increasing the number of public health labs that share their pathogen genome data and epidemiologically relevant metadata.
|
| 16/10/2019 |
£50,000 |
|
UNIVERSITY OF NEW SOUTH WALES |
Reinforcement learning (RL) algorithms hold tremendous promise for personalising healthcare but their development has been hampered by lack of openly available data with sufficient clinical detail. We will create The Health Gym, a set of publicly accessible healthcare-related "benchmark problems" (tasks with patient record examples) for developing, testing and comparing RL algorithms. The first two RL problems distributed as part of The Health Gym will concern the management of sepsis patients in the intensive care unit (ICU) and the optimisation of antiretroviral therapy in HIV patients. In order to freely distribute the detailed clinical data required to solve the proposed problems, we will create synthetic, but realistic, patient records using privacy-preserving generative adversarial networks (GANs) [1] and publicly available datasets (MIMIC-III [2] and EuResist [3]). If the resultant GAN-generated datasets are sufficiently non-disclosive, we will generate further ICU and HIV synthetic datasets using our own clinical data. The benchmark problems will be distributed as a free and open source package for the Python programming language, a website with suggested "proof-of-concept" solutions and a wiki where researchers can share their solutions. We will also make the trained GANs and related software publicly accessible through an online software repository, for re-use to create further synthetic patient records and for educational purposes. At the end of the project, we will hold a two-day DataThon for teams of clinicians and data scientists, to help popularise The Health Gym platform and accelerate the development of robust and reproducible RL algorithms for application in healthcare.
|
| 16/10/2019 |
£937,568 |
|
ROSALIND FRANKLIN INSTITUTE |
Heparan sulfates (HS) are complex polysaccharides that mediate diverse structural and signalling interactions between cells and their extracellular matrix neighbours. They are essential for myriad physiological processes, ranging from glomerular filtration to developmental morphogenesis.
HS biosynthesis is currently very poorly understood. At least 26 different enzymes are involved, but many of these remain poorly characterized, and almost nothing is known about how they functionally co-operate. My project aims to establish a molecular understanding of HS biosynthesis. I will investigate the mechanisms of individual HS biosynthesis enzymes in vitro, using both biochemical and structural (crystallography, cryo-EM) approaches. These in vitro studies will complement tomographic imaging of HS biosynthesis events inside cells, allowing insights for individual enzymes to be synthesised into a unified understanding of how HS biosynthesis occurs within its native environments.
HS is intimately connected to human health. Aberrations in its regulation cause developmental disorders and can promote cancer growth. A molecular understanding of HS biosynthesis may provide insights into how such aberrations can be corrected to treat HS related disorders. HS and its derivatives also have considerable potential as therapeutically useful molecules. Characterizing the HS biosynthesis machinery will facilitate improved methods to produce defined HS molecules for such applications.
|
| 16/10/2019 |
£1,036,156 |
|
UNIVERSITY OF MANCHESTER |
Recruitment and positioning of immune cells is critical to biology, enabling tissue development and combating of infection. However, unregulated leukocyte recruitment can lead to inflammatory diseases including stroke, atherosclerosis and rheumatoid arthritis that contribute to 70% of global deaths.
The key control point in leukocyte recruitment to tissues is their movement from the circulation through the blood vessel wall. A crucial, but largely ignored, component of the blood vessel wall is the glycocalyx, an extracellular matrix barrier primarily composed of glycosaminoglycan (GAG) sugars.
I will determine whether:
The endothelial glycocalyx lines blood vessels to control leukocyte migration by masking leukocyte access to endothelial adhesion molecules.
This glycocalyx is physically remodelled by inflammatory proteins (chemokines) to allow leukocyte access to endothelial adhesion molecules and subsequent migration.
The composition of the glycocalyx is tuned to facilitate presentation of certain chemokines and recruitment of specific leukocytes at different sites.
This is one example where the extracellular matrix in the immune system has been overlooked. I will establish a unique approach encompassing biochemistry, biophysics and in vivo biology to produce unprecedented insight into the mechanistic role of the glycocalyx and chemokines during inflammation; informing future therapeutics to treat a wide range of diseases.
|
| 16/10/2019 |
£1,322,791 |
|
UNIVERSITY OF OXFORD |
Endothelial cells (ECs) are essential for organ development, homeostasis and regeneration, yet we still know relatively little about the early steps of their formation. I have shown that ECs from different embryonic lineages preferentially contribute to distinct parts of the vasculature; paraxial mesoderm (PXM) is the major source of lymphatic ECs, but its contribution to blood vessel endothelium is restricted to certain organs. This finding establishes a new model of how the vasculature is formed, however the underlying molecular mechanisms are unknown. Here I propose experiments to test the hypothesis that EC heterogeneity is underpinned by an intrinsic molecular memory established during differentiation from distinct embryonic sources. Building on my recent findings, we will the use the formation of lymphatic (PXM-derived), liver (partial PXM contribution) and coronary ECs (no PXM contribution) as paradigms to dissect the impact of lineage history on EC heterogeneity. Specifically, we will decipher the transcriptional and epigenetic mechanisms that control EC differentiation from distinct embryonic sources, and determine the impact of lineage history on the regenerative/fibrotic response of ECs. These analyses will provide insight into what makes ECs from distinct lineages different, and determine whether these differences impact organ development, function or regeneration.
|
| 16/10/2019 |
£800,070 |
|
UNIVERSITY OF MANCHESTER |
Circadian clocks are a ubiquitous feature of biology, driving daily rhythms in almost all biological processes. The brain is among the body-systems in which circadian rhythms are most prominent. Outside the master circadian pacemaker in the hypothalamus, those rhythms have largely been considered as mechanisms to adjust downstream behaviour/physiology. An open question is whether circadian clocks also regulate the brain’s core function of processing/transmitting information. Neural circuits are designed to efficiently extract, process and transmit relevant information, but as the optimal solution to this process can be time-of-day dependent, one might predict circadian control. Excitingly, my unpublished data in the mouse visual-system has revealed that neurophysiological responses to stylised stimuli do indeed vary across circadian time. This leads me to hypothesise that circadian clocks adjust information processing in the brain to meet predictable variations in demand. I will apply a multidisciplinary, system-level approach to address this hypothesis. I will determine how the clock optimises information processing across the mouse visual-system; what advantage this provides over well-described adaptive processes; and how this defines visual capabilities across the day. This work has the potential to establish new general principles of network-plasticity, and promises to advance our understanding of circadian and visual neuroscience.
|
| 16/10/2019 |
£927,042 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Medical and social scientists evaluating the effects of medicines or social policies (treatments) are interested in finding optimal treatment regimes, as well as identifying the best time for treatment initiation, changes or discontinuation. To achieve such tailored interventions, we need a step-change in our understanding of treatment-effect heterogeneity, which potentially depends on many factors.
Reliable inference is this area is notoriously challenging, because these are poorly-understood relationships involving a large number of confounders, effect modifiers and missing data.
This has triggered an interest in machine-learning to help obtain models which adapt to accurately capture the relationships of interest. However, quantifying uncertainty is very difficult since machine learning is primarily focused on prediction. Moreover, machine-learning estimates suffer from regularisation bias. Nevertheless, under certain assumptions, doubly-robust estimators can be combined with machine-learning, to obtain consistent estimates with valid confidence intervals (with the bias vanishing faster than for simple estimators).
This fellowship aims to exploit this potential, by extending existing doubly-robust estimators to use machine-learning estimation in obtaining valid inferences, by (1) choosing correctly-specified confounder models, optimised for estimating the true causal effects, (2) appropriately accounting for the observation process, (3) identifying the important effect-modifiers, and (4) finding optimal treatment regimes.
|
| 16/10/2019 |
£1,058,934 |
|
UNIVERSITY OF EXETER |
Aspergillus fumigatus (Af) fungal spores, abundant in the environment, are a major cause of asthma. Asthma is a broad disease, not just a type-2 eosinophil dominated disorder, with a crucial involvement of type-17 related neutrophil recruitment. However, the key innate immune cells (dendritic cells (DCs) and macrophages) that dictate this balance to anti-Af are unknown. The lung airways are another crucial yet underappreciated aspect, which I have found governs innate cell responses via modification of their metabolism. Compared to other mucosal sites the lung airways have distinct profiles of nutrients and mucus, but it is unknown whether these regulate innate cell induction of anti-fungal allergy. Here, I will define the DC and macrophage subsets that mediate type-2 vs type-17 anti-Af responses. I will identify if anti-Af allergy alters airway nutrients and/or extracellular factors, exploring if this controls innate cell anti-Af responses via altering cellular metabolism. Additionally, I will identify the critical fungal spore motifs that, along with environmental factors, induce innate cells to mediate anti-Af allergy. Together, this proposal will determine how lung nutrients and extracellular host/fungal factors cause DCs and macrophages to induce anti-Af allergic responses, enabling future design of novel strategies to treat asthma and fungal lung disease.
|
| 16/10/2019 |
£956,148 |
|
UNIVERSITY OF BRISTOL |
Cellular senescence is an established mediator of cellular and organismal ageing and clearance of senescent cells can extend healthspan and lifespan in mouse models.
Senescence is defined as an irreversible exit from the cell cycle; these cells however maintain robust activation of the master growth regulator, mTORC1. My previous work identified that mTORC1 becomes unresponsive to the removal of nutrients in senescence, supporting increased cell size and production of inflammatory cytokines. My project aims to identify new insights into nutrient-dependent mTORC1 signalling and how it is altered in senescence. I will specifically test the hypothesis that mTORC1 is supported by amino acids liberated via an increase in lysosome activity. Inhibition of mTORC1 and lysosomal degradation can cause senescent cell death suggesting the rewiring of cellular metabolism is essential for cell survival. A better understanding of the biology of senescence could therefore help identify new interventions to eliminate these cells and promote healthy ageing.
|
| 16/10/2019 |
£1,276,928 |
|
KING'S COLLEGE LONDON |
Viruses employ various approaches to avoid host cell defence-mechanisms. In Herpes Simplex Virus 1 (HSV1) and Influenza A Virus (IAV) these include strategies to inhibit transcription termination. This leads to non-terminated readthrough transcripts, likely nuclear retained and untranslated. Exactly how viruses inhibit transcription termination, and how this promotes their survival and efficacy is currently unclear.
Using my experience and expertise in transcription termination, I propose to systematically analyse the mechanism by which IAV alters 3’ end processing transcription termination and determine how this affects host gene expression. I will use biochemistry, molecular biology and structural biology, to identify the termination components affected by IAV, and reverse genetics to identify the IAV-component effecting termination inhibition. I will also employ sequencing of fractionated, cellular and ribosome-associated RNA to examine how virally-induced termination defects perturb mRNA-export and translation, as well as cell biology and genetics to identify the mechanisms and signalling cascades through which this change is realised. Finally, I will perform orthogonal studies in budding yeast to identify molecular mechanisms that can modulate the activity of transcription termination and RNA processing factors. Overall, my programme will scrutinize an under-explored yet fascinating mechanism to alter gene expression through modulation of transcription termination.
|
| 16/10/2019 |
£1,360,539 |
|
IMPERIAL COLLEGE LONDON |
Neural induction is the process responsible for the generation of the entire nervous system. A major question in the field is how this process results in the production of diverse cell types throughout the nervous system, and how it can be applied to regenerative medicine. I recently showed that CDX transcription factors are critical to establish spinal cord fate, but that their capacity to induce spinal cord is lost following neural lineage commitment. Moreover, my preliminary data suggests that CDX factors broadly impact posterior identity in cells, prior to germ layer segregation, that is critical for the generation of different neural subtypes in the nervous system in vivo. In this proposal, the key goals are to: investigate the regulatory mechanisms limiting Cdx2 expression in cells; evaluate how CDX2 represses alternative brainstem fates for the generation of spinal cord; and test the role of CDX in the divergence of neural cells, including neural crest cells, that form distinct fates within the nervous system, in vivo. Taken together, this work will provide molecular insight into how cellular diversity is established in the mammalian nervous system and more generally throughout the body plan.
|
| 16/10/2019 |
£1,098,771 |
|
UNIVERSITY COLLEGE LONDON |
The way we perceive the world is strongly influenced by our expectations about what we are likely to see at any given moment. However, the neural mechanisms by which the brain integrates sensory inputs and expectations, and thereby generates the contents of perception, have yet to be established. I propose that, upon presentation of a predictive cue (e.g., a siren), memory systems pre-activate templates of expected stimuli (an ambulance) in the deep layers of visual cortex, leading to biased processing of sensory inputs from the very moment they arrive. Such biased processing then leads naturally to biases in perception, in extreme cases even hallucinations.
I will test this proposal by addressing three complimentary questions: 1) How do the neural computations underlying perception unfold over time? 2) What is the fundamental computational architecture of visual cortex? 3) What is the neural source of expectations? I will combine psychophysical tasks probing participants’ perception with neuroimaging tools with exquisite temporal (MEG) and spatial (high-field fMRI) resolution to address these questions.
The overarching aim of my research is to provide a mechanistic account of subjective perception. Ultimately, these insights may improve our understanding of clinical disorders characterised by aberrations in perception, such as psychosis.
|
| 16/10/2019 |
£550,148 |
|
UNIVERSITY COLLEGE LONDON |
This project will investigate a mechanism for regulating cAMP-dependent protein kinase (PKA) that is not founded on cAMP fluctuations. Neuronal PKA activity is largely dictated by rates of binding and release of PKA catalytic subunits from inhibitory type II regulatory (RII) subunits. The balance of these rates determines the fraction of free catalytic subunits. According to the canonical model, reductions in PKA activity follow from decreases in cAMP concentration since cAMP-free RII subunits bind catalytic subunits with higher affinity. Dephosphorylation of a serine in the RII autoinhibitory sequence also generates a form of RII with higher affinity for catalytic subunits, but no plausible mechanism has been uncovered that involves regulation of this site. We will investigate whether anchoring of phosphatases in complex with RII subunits enables suppression of PKA activity by shifting the Michaelis constant for RII dephosphorylation into the physiological range. We will build and test models of neuronal PKA signalling to understand the kinetic basis of this mode of PKA regulation. We will examine whether RII dephosphorylation within a synaptic signalling complex is necessary for the induction of long-term depression of synaptic strength. Finally, we will investigate interplay between Ca2+ signalling and this novel form of PKA regulation.
|
| 16/10/2019 |
£624,991 |
|
UNIVERSITY OF SHEFFIELD |
The stringent response is a complex regulatory mechanism utilised by bacteria to survive stress. The response is controlled by the nucleotides (p)ppGpp, which function to shut down growth until conditions become more favourable. Our work has identified four ribosomal-associated GTPases (RA-GTPases) as (p)ppGpp-binding targets in Staphylococcus aureus. We showed that the activity of these RA-GTPases is inhibited upon binding to (p)ppGpp, leading to defects in ribosome assembly, slowed bacterial growth and tolerance to antimicrobials. However, our mechanistic understanding of how this occurs, the function of each RA-GTPase in ribosome maturation, as well as a general role for (p)ppGpp in stress-related processes, is limited. This project will use multidisciplinary approaches to characterise (p)ppGpp-controlled signalling pathways. Specifically, I will address three related but independent aims. I will:
1) use structure-function studies to understand how (p)ppGpp binding and inhibition of ribosome-associated GTPases impacts ribosome assembly;
2) identify additional (p)ppGpp-regulated pathways using capture-compound mass spectrometry and transposon mutagenesis;
3) determine the importance of this signalling system for virulence in immune cells.
These objectives will provide important mechanistic data on the crucial role for this signalling system in bacterial survival, and will identify essential cellular targets that may be exploited for therapeutic gain.
|
| 16/10/2019 |
£884,522 |
|
UNIVERSITY OF MANCHESTER |
The persistence phenotype is an epigenetic trait exhibited by a subpopulation of bacteria, characterised by metabolic dormancy. It is a model of bacterial survival in the host to enable it to spread pathogenically in niche environments. Persistent bacteria are the major cause of chronic and recurrent infections difficult to treat with antibiotics, thus has affected the world economy by billions of dollars. Yet, the molecular mechanisms of persistence are still unclear. My research has shown that sulfoglycolysis - a novel regulated primary catabolic pathway for an abundant type of sulfo-containing monosaccharide, sulfoquinovose, increases the persistence level of pathogenic E. coli and Salmonella. In this Fellowship Programme, I seek to demonstrate crosstalk between the sulfoglycolytic pathway and other persistence-conferring pathways using a multidisciplinary approach. I will investigate whether the structural and electrostatic similarities of sulfoquinovose and its catabolic intermediates to other anionic sugars lead to pathway activation, extracellular polysaccharide incorporation, and inhibition of glycolytic enzymes. To identify new drug targets against persistence, key enzymes in the pathway will also be investigated. My findings will establish the regulatory and structural roles of the sulfoglycolytic pathway in bacterial persistence and will lead to a novel approach to tackling antibiotic ineffectiveness.
|
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF DUNDEE |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF GLASGOW |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£197,340 |
|
KING'S COLLEGE LONDON |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£197,340 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£197,340 |
|
HEALTH DATA RESEARCH UK |
This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research.
Over 5 years of the Programme we encourage organisations to aim for:
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation.
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF BRISTOL |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF LEICESTER |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF NOTTINGHAM |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF CAMBRIDGE |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF OXFORD |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF MANCHESTER |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF EDINBURGH |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£197,340 |
|
UNIVERSITY COLLEGE LONDON |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF SHEFFIELD |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: <br>
<br>
-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. <br>
<br>
-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£166,500 |
|
UNIVERSITY OF EAST ANGLIA |
<p>This award is for 6 students per year for 5 years. It includes ?a salary at the national living wage plus holiday pay and national insurance or equivalent,?as well as?funds to cover or significantly subsidise accommodation and travel (£1500 outside of London and up to £2000 in London).??? It includes £500 to each studentship towards research expenses.??? Unspent funds can be repurposed on further students or recruitment costs. Wellcome wishes to ensure a greater diversity of students (in relation to socio-economic background and ethnicity) progress to postgraduate research. <br>
Over 5 years of the Programme we encourage organisations to aim for: </p>
<p>-At least 50% of students recruited to the programme to be from underrepresented or disadvantaged groups, depending on priorities set by each organisation. </p>
<p>-At least 50% of students recruited to the programme to be from non-Russell Group Universities. For the remaining 50%, organisations should consider how to recruit students from other universities as well as their own. Wellcome has included this recommended target as research indicates that most of the high-achieving STEMM graduates from minority ethnic backgrounds are located outside of Russell Group universities. </p> |
| 30/09/2019 |
£369,504 |
|
RINDA UBUZIMA |
<p>The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) and the recent identification of Ebola cases in the cities of Goma and Bukavu (which border Rwanda) are of particular concern and have prompted the Rwandan Government to take control measures for preventing cross-border spread of EVD. As demonstrated by the current outbreak, purely reactive measures may be insufficient to fight Ebola. Prophylactic approaches are needed that can prevent emergence of EVD in previously unaffected areas.We propose to conduct a large scale vaccination campaign targeting 196,000 individuals living and working in border-proximate areas; a clinical trial to evaluate the immunogenicity of the AD26.ZEBOV, MVA-BN-Filo vaccine in 2,000 people; and a clinical trial to evaluate the safety of the vaccine among 2,000 pregnant women in the context of this new framework of Ebola prevention. These 3 programs will together generate a large cohort that can be revisited for a long term follow up study to assess long term immunogenicity at different times following vaccination; an evaluation of a potential effect of booster doses and the optimal strategy for booster administration; and an evaluation of long term assessment of effectiveness using a test-negative case control study design.</p>
|
| 30/09/2019 |
£3,325,533 |
|
CENTER FOR FAMILY HEALTH RESEARCH |
<p>The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) and the recent identification of Ebola cases in the cities of Goma and Bukavu (which border Rwanda) are of particular concern and have prompted the Rwandan Government to take control measures for preventing cross-border spread of EVD. As demonstrated by the current outbreak, purely <em>reactive measures</em> may be insufficient to fight Ebola. <em>Prophylactic</em> approaches are needed that can prevent emergence of EVD in previously unaffected areas. We propose to conduct a large-scale vaccination campaign targeting 196,000 individuals living and working in border-proximate areas; a clinical trial to evaluate the immunogenicity of the AD26.ZEBOV, MVA-BN-Filo vaccine in 2,000 people; and a clinical trial to evaluate the safety of the vaccine among 2,000 pregnant women in the context of this new framework of Ebola prevention. These 3 programs will together generate a large cohort that can be revisited for a long term follow up study to assess long term immunogenicity at different times following vaccination; an evaluation of a potential effect of booster doses and the optimal strategy for booster administration; and an evaluation of long term assessment of effectiveness using a test-negative case control study design.</p>
<p> </p>
<p> </p>
|
| 30/09/2019 |
£405,745 |
|
CENTER FOR FAMILY HEALTH RESEARCH |
<p style="margin-left: 0in; margin-right: 0in">The ongoing outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of Congo (DRC) is of particular concern for the Government of Rwanda, when one considers the high population density of Rwanda and the number of people crossing the border between Rwanda and DRC on a daily basis. Janssen Vaccines and Prevention B. V. (Janssen) and the Rwanda Ministry of Health have recently entered into an agreement for a donation of 200,000 doses of the Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine. Rwanda FDA has granted conditional approval of the vaccine under exceptional emergency circumstances in accordance with SAGE recommendations to "put in place approvals for investigational medicines and vaccines as an immediate priority for preparedness".</p>
<p style="margin-left: 0in; margin-right: 0in">This Ebola vaccine initiative consists of: 1) a mass vaccination campaign that will target up to 193,000 individuals crossing or living in sectors/districts sharing the border with DRC; this program is known as UMURINZI (<strong>U</strong>nprecedented <strong>M</strong>ovement to drive a <strong>U</strong>nified <strong>R</strong>wandan <strong>I</strong>nitiative for <strong>N</strong>ational <strong>Z</strong>EBOVAC <strong>I</strong>mmunization); 2) a clinical trial to evaluate the immunogenicity of the vaccine regimen in 2,000 people; 3) and a clinical trial to evaluate the safety of the vaccine among 5,000 pregnant women.</p>
<p style="margin-left: 0in; margin-right: 0in">This proposal concerns start up of UMURINZI only.</p>
|
| 30/09/2019 |
£33,050 |
|
NEPAL PUBLIC HEALTH FOUNDATION |
<p style="margin-left: 0cm; margin-right: 0cm">Postpartum hemorrhage (PPH) is one of the most common causes of maternal deaths in Nepal. Tranexamic acid (TXA) is an anti-fibrinolytic medication that works to improve blood clotting and helps prevent excessive blood loss during postpartum bleeding, heavy menstrual bleeding,or other surgeries.Though available and frequently used, there is no policy to guide TXA use in the management of PPH as per recent recommendation of the World Health Organization.To date in Nepal, TXA, although widely available and relatively inexpensive, is used erratically, generally following WHO’s outdated guidelines of 2012. The Policy Dialogue project intends to i) raise awareness within the scientific community and with policy makers in Nepal on the global evidence regarding the effect of TXA in reducing maternal deaths and to ii) encourage the inclusion of this medicine in national policy guidelines for the management of PPH.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Key Goal: </strong>To reduce PPH-related deaths in Nepal through facilitating dialogue between experts and policy makers with the aim of updating the Nepalese guidelines and protocols on the treatment of PPH</p>
|
| 30/09/2019 |
£5,000 |
|
COLLEGE OF TEACHING LTD |
<p>This grant is to carry out the scoping phase of a proposal for teachers of science to be supported to engage with education research through online journal clubs. The intention is to run 8 journal clubs for primary school teachers and 8 for secondary school teachers but this could change during the scoping phase.</p> |
| 30/09/2019 |
£5,000 |
|
BEHAVIOURAL INSIGHTS TEAM |
<p>This grant is to carry out the <u>scoping phase</u> of a proposal for secondary school science teachers to be supported to engage with research by using lesson plans to support their teaching of a specific unit of physics to Y8 pupils. Lesson plans will have clickable links to digests of research evidence linked to the pedagogy.</p> |
| 30/09/2019 |
£5,000 |
|
STEM LEARNING LIMITED |
<p>This grant is to carry out the <u>scoping phase</u> of a proposal for teachers will be supported to under research methods (education research) to enable them to answer questions they formulate. They will conduct randomised control trials and then be supported to analyse the data they collect. Multiple replications of their protocols will also be carried out.<br>
</p> |
| 30/09/2019 |
£5,000 |
|
UNIVERSITY OF LINCOLN |
<p>This grant is to carry out the <u>scoping phase</u> of a proposal for primary and secondary school teacher trainees and their school-based mentors to be supported to use evidence based lesson plans.<br>
</p> |
| 30/09/2019 |
£9,925 |
|
NO ORGANISATION |
<p>As described in our preliminary application, we propose using the Wellcome Hub as a launchpad for a series of creative and participatory processes to explore potential relationships and partnerships, foster networks and experiment with new modalities for knowledge production and sharing around young people’s mental health in the global South and the global North. Our interdisciplinary team of artists, activists, researchers and mental health practitioners aim to work with young people as equal partners in an experimental and collaborative process to understand their mental health journeys and to develop innovative approaches to addressing them. To prepare for this submission, we will use this discretionary funding to run participatory processes in London and Cape Town, as well as between and across these two sites, to refine and develop our ideas for the Hub, and to actively involve services providers and young people in the project conceptualization. As such, these funds will primarily be used to explore potential partnerships/relationships so as to best ensure that the initial steps to informing the design of the project are mutually beneficial, inclusive and relevant to all.</p>
|
| 30/09/2019 |
£10,000 |
|
HEALING JUSTICE LDN |
<p><strong>Hub Award -Research and Development phase</strong></p>
<p>In this critical time of changing demographics in Britain, we observe new and emerging health care needs, with health provisions often unresponsive to marginalised people and health inequalities persisting. We recognise that knowledge transference between the margins and mainstream is necessary to develop multi-layered approaches for the sustainable, dignified and just healthcare systems we all deserve. In partnership with Wellcome Trust, we seek to connect strategies and solutions centring equitable participation and democratising research. We ask: how can a framework centring loss and grief investigate and innovate methods of equitable participation, through trauma-informed, somatic practices, research and cultural co-production? Our programme operates across research, cultural co-production, and public engagement, to produce outputs and outcomes. Using a two-staged approach we will firstly explore and address the impact of loss and grief on the body and mind - by building an evidenced clinical model integrating embodiment, somatic practices and trauma-informed practice. Alongside this, our cultural strategy would address participation barriers, and engage in creating the capacity to cope and develop a shared language and fluency, to redress the historical deficit of institutional barriers. We aim to broaden public perception on grief and loss individually and nationally.</p>
|
| 30/09/2019 |
£9,993 |
|
HEADWAY EAST LONDON |
<p>Project Title: What is the meaning of Brain Injury?</p>
<p>We will use these funds to cover the costs of developing the second stage application for the Wellcome Hub Award for this project. This application has been invited on the basis of an expression of interest submitted in June this year.</p>
|
| 30/09/2019 |
£10,000 |
|
UNIVERSITY COLLEGE LONDON |
<p>In Talking Funny, Sounding Different we will create a performance lab within the HUB, to experiment with, innovate and empower humans and their ‘funny’ voices, from the written word to live theatre, from beat boxing to comedy. We will study the performance of the human voice as a potential source of anxiety and difficulty, and as a route to confidence and social contact. We will work with people with clinical voice issues, scientists, clinicians and artists to explore new art, new therapies and apply cutting edge neuroscience to our understanding of the voice and its effect on the audience. For this discretionary award, we are asking for funding for:</p>
<p>meetings between the main collaborators, patient groups, and relevant artists and performers</p>
<p>live events and rehearsal time to plan and develop the live events: these events will explore the possibilities of vocal performances across different groups of people, with an emphasis on people who 'sound funny' with an emphasis on voices that are rarely heard.</p>
|
| 30/09/2019 |
£30,000 |
|
CLEAN AIR FUND |
<p style="margin-left: 0px; margin-right: 0px">In light of the Secretary Generals’ Climate Action Summit and its focus on the intersection between health and climate change, we will announce the Clean Air Fund as the first dedicated fund for air pollution. We are planning to launch the Clean Air Fund during the UNGA in September and are requesting a contribution of £30k from Wellcome. The event will highlight the links between air quality/health/children and climate change and bringing together funders, researchers, policy makers and campaigners to find and scale solutions that will provide clean air for all. </p>
|
| 30/09/2019 |
£498,240 |
|
UNIVERSITY OF OXFORD |
Spot Sepsis is a multi-site prospective observational cohort study, conceived by
the Mahidol-Oxford Tropical Medicine Research Unit (MORU) and Médecins
Sans Frontières Spain (MSF SPAIN). Over 15 months, we will enroll a minimum
of 4,900 children between the age of one month and five years with acute febrile
illness presenting to six regional hospitals across Asia (Indonesia, Philippines,
Cambodia, Laos, Vietnam and Bangladesh). We will collect key historical
variables, record presenting clinical features, measure host biomarker profiles,
and determine fever aetiology for key target pathogens. We will follow children
up and ascertain clinical outcome at 48-hours and 28-days. Using this data, we
will derive and perform external validation of a risk stratification algorithm, to
predict progression to severe disease in children presenting with acute febrile
illness in resource limited settings.
The project, a partnership between MORU and MSF SPAIN, is motivated by a
shared translational research vision: a desire to improve identification of children
with acute infections at-risk for progressing to severe illness or sepsis. This will
in turn allow more efficient and effective referral choices in more remote contexts,
particularly those affected by conflict, where the decision to refer a child to higher
care carries substantial risk or burden. We will benefit from the collaboration with
our project partners, who have considerable experience in biomarker
discovery/validation and clinical prediction rule (CPR) derivation and validation.
The project is being co-funded by MSF Spain and the Wellcome Trust through
the ‘Innovations for Impact in low and middle-income countries’ Flagship. |
| 30/09/2019 |
£1,980,040 |
|
MEDICAL RESEARCH COUNCIL |
Not available |
| 30/09/2019 |
£10,000 |
|
INVISIBLE FLOCK LTD |
<p>This proposal is to move forward with the development of our Hub Award project titled; Solastalgia – The impacts of Environmental Change on mental health. <br>
<br>
The project proposes a two year interrogation into the relationship between environmental change and mental health, exploring the psychological impacts of rapid urbanisation, agriculture, resource extraction, natural disasters, extreme weather, displacement and human animal conflict across the globe. <br>
<br>
Using human centred design, storytelling and new technologies to explore peoples connection with the natural world, placing first person perspectives at the forefront of understanding identity in rapidly changing landscapes. <br>
<br>
Through our core team’s practices and a pool of eclectic collaborators we will open up this urgent and timely discussion to mass and diverse audiences through multiple platforms and artforms.<br>
</p>
<p> </p>
|
| 30/09/2019 |
£75,161 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">The response to the Ebola epidemic in North Kivu and Ituri provinces, Democratic Republic of Congo has been described as one of the most complex that national and international communities have had to face.Given the complexity of this protracted epidemic, social science research has become a critically important part of the response in order to help contextualise strategies, investigate social determinants of infection, and inform understanding and reception of interventions employed for outbreak control. To routinely generate this intelligence, an innovative solution has emerged in the form of the Cellule d’Analyse en Sciences Sociales. UNICEF-funded, this group is made up predominantly of local and national social scientists. Other ad hoc social science research is also being conducted in the field. Through this proposal we aim to consolidate learning and articulate what is needed to replicate similar initiatives in future outbreaks. We will provide remote technical support, conduct structured critical appraisal of the field experience, capture lessons learned, and develop guidance and tools for the current and for future outbreaks. Our vision is to contribute to better outbreak prevention and response through excellence in social and behavioural science research, integrated into current and future responses to infectious disease threats. </p>
|
| 30/09/2019 |
£56,063 |
|
UNICEF UK |
<p style="margin-left: 0cm; margin-right: 0cm">The response to the Ebola epidemic in North Kivu and Ituri provinces, Democratic Republic of Congo has been described as one of the most complex that national and international communities have had to face.Given the complexity of this protracted epidemic, social science research has become a critically important part of the response in order to help contextualise strategies, investigate social determinants of infection, and inform understanding and reception of interventions employed for outbreak control. To routinely generate this intelligence, an innovative solution has emerged in the form of the Cellule d’Analyse en Sciences Sociales. UNICEF-funded, this group is made up predominantly of local and national social scientists. Other ad hoc social science research is also being conducted in the field. Through this proposal we aim to consolidate learning and articulate what is needed to replicate similar initiatives in future outbreaks. We will provide remote technical support, conduct structured critical appraisal of the field experience, capture lessons learned, and develop guidance and tools for the current and for future outbreaks. Our vision is to contribute to better outbreak prevention and response through excellence in social and behavioural science research, integrated into current and future responses to infectious disease threats. </p>
|
| 30/09/2019 |
£600,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
The Malawi Liverpool Wellcome Programme (MLW) is the largest science institution in Malawi. MLW has 2 aims: 1. research to benefit health, 2. training the next generation of researchers. Our science is focused on the prevention of death from infection and the reduction of transmission in the community.
MLW has world-changing translational research success in the management of malaria, HIV self-testing and rotavirus vaccination. MLW Research Groups each have a translational science plan and a pipeline of trainees.
The institutional translational partnership at MLW has 3 aims.1. Raising the priority of, and belief in translational science in scientists and the community at large; 2. Developing an exemplar portfolio of translational research in a majority of MLW Research Groups; 3. Improving the landscape/ecosystem to facilitate translational research in Malawi. |
| 30/09/2019 |
£50,000 |
|
GLOBAL HEALTHCARE INNOVATION ALLIANCE ACCELERATOR |
<p>GHIAA has created a global health Master Alliance Provisions Guide which includes agreement provisions for responding to major issues, including equitable access and ownership of intellectual property. </p>
<p>The framework chart summarizes the alternative approaches for addressing key issues in global health alliance agreements. </p>
<p>The goals of developing the online MAP Guide include to:</p>
<p>1. Share the breadth of ways that key provisions in global health alliance agreements can be drafted depending on the nature of the collaboration and parties involved;</p>
<p>2. Illustrate the way that policy language and terms such as “access” look as they are implemented in agreements between the parties so that discussions around them can be more productive;</p>
<p>3. Create a platform for sharing the evolving ways that these partnerships are implemented; </p>
<p>4. Providing a repository and source for agreements and provisions as the many global health stakeholders develop future policies and agreements; and perhaps finally,</p>
<p>5. Accelerate the negotiations of future agreements by providing a point of reference for a more experienced partner to share with new partners.</p>
<p>Overall the goal is to increase the visibility/ transparency of the ways in which these alliances come together and the policy issues which must be resolved between partners.</p>
<p> </p>
<p> </p>
<p> </p>
|
| 30/09/2019 |
£168,365 |
|
JOHNS HOPKINS UNIVERSITY |
<p>This project will continue to amplify the message of the PREVENT Guidance, assist stakeholders who wish to act on its recommendations or otherwise advance the interests of pregnant women and their offspring, and scope next steps for moving from PREVENT to PREVENT- in- Action, with a particular focus on Africa. </p>
|
| 30/09/2019 |
£10,000 |
|
CHARITé - UNIVERSITäTSMEDIZIN BERLIN |
<p>REWARD | EQUATOR Conference - Sharing Strategies for Research Improvement</p>
<p>We are pleased to present a diverse range of invited speakers, including Dr Kris Thayer, Director of the Integrated Risk Information Systems Division at the US Environmental Protection Agency; Dr Allison Harbin, freelance writer and editor whose blog describing her PhD experience has resonated with graduate students across disciplines; Sir Jim Smith, Director of Science at the Wellcome Trust, and Dr Jonathan Kimmelman, a bioethicist concerned with the social and policy dimensions of translational research. The meeting will include an inaugural EQUATOR Doug Altman lecture by Prof Isabelle Boutron, Université Paris Descartes, France. Further to submitted research (<strong>oral presentations/posters</strong>), we have created space for less traditional conference formats including so-called <strong>focus tracks</strong> (structured discussions between conference participants) and formats encouraging authors to present content that is relevant to the conference themes, however doesn’t fit into the research abstract format <strong>(„Concepts, Initiatives and Ideas”). </strong></p>
<p>https://www.reward-equator-conference-2020.com/</p>
<p>Our ambition has been to create a faculty of insiders and outsiders, of those immersed every day in the challenges of biomedical research and of others from outside this narrow world, that their perspective may bring new understanding to the problems we face.</p>
<p> </p>
|
| 30/09/2019 |
£60,000 |
|
UNIVERSITY OF READING |
<p>This proposal seeks to better understand the ways in which the digital revolution, which<br>
is being rapidly advanced through industry, can also be influenced at the intersection of<br>
scientific and artistic cultures to shape public perceptions of reality, inclusion and place. Over a<br>
period of one year, this transformative proposal will theorise around the values, conditions and<br>
public leadership required to steward the distribution, communal ownership and sharing of<br>
digital literacies emerging from publicly funded interactions with emerging technologies (the<br>
digital commons) . In considering the digital commons, this proposal seeks to reimagine how we<br>
can live together as part of the digital society, in a time of planetary uncertainty, at the<br>
intersection of social, environmental and digital movements.</p> |
| 30/09/2019 |
£20,000,000 |
|
UK BIOBANK LTD |
<p style="margin-left: 0cm; margin-right: 0cm">UK Biobank is an international resource with 500,000 richly phenotyped participants offering non-preferential access to bona fide researchers seeking to understand the determinants of disease.</p>
<p style="margin-left: 0cm; margin-right: 0cm">With investments being made by industry, government and charity, the resource is increasingly detailed and is already the most genetically characterised resource in the world. With anticipated inclusion of whole exome and whole genome sequence data, this will remain the case for many years to come. Together with imaging, cardiac monitoring, activity and metabolomics measures, the resource will comprise over 15 Petabytes of health-related data by 2025.</p>
<p style="margin-left: 0cm; margin-right: 0cm">These increasingly large and complex datasets mean it is no longer tenable for researchers to download data and requires new platform access methods to allow researchers to generate the scientific discoveries of the next decade.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Funding is sought to implement an informatics platform to allow access and analysis of UK Biobank data in-situ in conformance with access policies and security controls. The platform will further democratise access, ensuring researchers around the world can participate on the same, non-preferential basis with appropriate support.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Funding will cover implementation and management for a period of 5 years after which the platform will become financially self-sustaining through access charges.</p>
|
| 30/09/2019 |
£38,325 |
|
UNIVERSITY OF CAPE TOWN |
<p style="margin-left: 0cm; margin-right: 0cm">The Human Cell Atlas (HCA) seeks to create comprehensive reference maps of the cell states of all the cell types in healthy human bodies. Key values identified as guiding the development of the HCA are inclusivity, representivity and empowerment. The HCA leadership is currently developing an equity strategy, but a challenge facing this work is that it emphasizes practical solutions in the absence of a clear shared conceptual understanding of what equity means and why that is important for the HCA. Developing a robust equity strategy matters if the HCA wants to be a cutting-edge initiative that makes a real impact on health equity. In that case a solid account of what equity means is necessary to help to guide, sharpen and stratify equity goals in the short, medium and long term. The objective of this project is to develop a roadmap for equity that will help the HCA develop a coherent equity strategy. This will include: an account of how equity can be conceptualised for the HCA; why equity should matter to the HCA; and what equity means for the different levels of activity of the HCA. To achieve this objective, we will combine conceptual analysis with empirical research.</p>
|
| 30/09/2019 |
£440,000 |
|
ARTICULATED HEALTH CIC |
Patient Media CIC aims to break down barriers between health science and people with long term conditions by empowering them to play more active role in their own health and promote active collaboration between public and health scientists in driving healthcare innovation. This three year project will deliver the following impact:
Over 1 million people are engaged with health science and research and empowered and enabled to better manage their condition.
9,000 health scientists better understand patients’ lived experience, unmet needs, and learn new ways of patient engagement using eHealth tools.
A new impact framework for public engagement in eHealth interventions developed and shared across communities of interest
20 people recruited and trained to be closely involved in health sciences as a social or cultural activity.
We are requesting a grant which will be used to:
Set up social enterprise to deliver our social impact and business model
Expand the MS Reporters core product into epilepsy and one other new condition
Develop at least two new public engagement products in MS and epilepsy
Achieve financial sustainability to be able to grow the social enterprise without further Wellcome funding
|
| 30/09/2019 |
£25,323 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p>There is a desperate lack of quality assured antivenoms for use in Africa. Many antivenoms in current use have undergone only limited pre-clinical testing and have never had formal clinical evaluation. To address this problem, a substantial clinical evaluation programme of antivenoms will be needed. Clinical trials of antivenom are challenging. A number of factors including multiple species, multiple different antivenoms, heterogeneity of clinical manifestations, need for studies in different geographical locations and lack of clear endpoints have all contributed to a dearth of trials. This proposal is to undertake the preliminary work necessary for the establishment of a major antivenom clinical trial network. Following a review of existing studies and methodologies to inform the discussion, a workshop will bring methodology and snakebite experts together.<br>
<br>
Expected workshop outputs will be as follows:<br>
<br>
a) Preliminary identification of suitable sites<br>
b) Priorities for antivenom testing<br>
c) Agreed endpoints for clinical trials of a variety of species<br>
d) Agreed methodologies, including potential adaptive designs for rapid assessment of new antivenoms. </p>
|
| 30/09/2019 |
£600,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p>staff are expected to contribute to our translational agenda and that focus is reflected in all<br>
the strategic investments LSTM has made over the past 20 years. LSTM reviews its<br>
research portfolio regularly identifying new areas for strategic investment. Current priorities<br>
centre around antimicrobial resistance (AMR) and therapeutics (with a particular interest in<br>
biologics) and translational skills-training opportunities. A recurring theme LSTM has<br>
encountered is a lack of translational focus and understanding in Early Career Researchers<br>
(ECR) joining the School from other organisations. We propose to use the WT Translational<br>
Partnership fund to address gaps is these areas. Funding will be available to individuals<br>
who need to develop their translational skills either within LSTM or through secondment to<br>
industry. In addition funds will be used to develop a training programme (in partnership with<br>
other iPTAs in Liverpool and Malawi) in translational science relevant to LSTMs mission.</p> |
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF LIVERPOOL |
<p>The University of Liverpool will work with the Wei/come Trust to build a translational<br>
infrastructure to support local University and NHS staff that facilitates expansion and<br>
exploitation of existing and new programmes of research to help address the major health<br>
issues of the City region. This will involve development of" (i) an extended pump<br>
priming/seed funding scheme to develop translational projects, (ii) appointment of local<br>
specialist support to promote and enhance bids to key translational funders, (iii) improved<br>
availability of expertise for University and NHS staff through appointment of a Commercial<br>
Champion in Residence and establishing a full-time Professor of Translational Science, and<br>
(iv) education of the next generation of clinical and nonclinical researchers to develop critical<br>
mass and future translational leaders.</p> |
| 30/09/2019 |
£120,000 |
|
NESTA |
<p>In September 2018, the Centre for Collective Intelligence Design (CCID) launched a new grants programme aimed at advancing knowledge on collective intelligence design and application in fields with public benefit. The call for ideas was for practical experiments that could generate new insight into how to use collective intelligence to solve social problems. The proposals had to demonstrate that they would increase the evidence base on what works in designing and applying collective intelligence, create actionable insights for practitioners and have wider applicability to other contexts or issues. </p>
<p>We received over 200 high-quality expressions of interest from around the world, of which we invited 25 to submit a full application. Additional commentary on those applications was provided by a panel of expert external advisors as well as relevant Nesta colleagues. </p>
<p>Following the high interest in our grants programme and the number of high-quality proposals the call for ideas received last year, the CCID is planning to launch a second call for ideas for practical collective intelligence experiments in early September 2019 to generate new insights into how to design and apply collective intelligence to address social challenges.</p>
<p>Experiments will be funded with up to £20k each.</p>
|
| 30/09/2019 |
£174,699 |
|
FALLING WALLS FOUNDATION GGMBH |
<p>Science engagement holds the key to solving many of the grand challenges faced all over the globe. It is up to scientists and science-driven insitutions to find meaningful ways for engaging with non-scientists, in order to improve mutual understanding and bridge the perceived gap between the academia and its broader ecosystem. With the project Engage Globally we aim to become the most impactful platform for science engagement in the world. Over the next years, we will identify a wide range of best-in-class science engagement projects and connect with individuals running the most promising and innovative hidden champion projects worldwide. We will build and foster a global community that is connected in the digital space as well as through frequent real-life network meetings, on international and regional levels.<br>
We are convinced that collective progress in the field of science engagement can be achieved through the interdisciplinary and international collaboration of talented, motivated and creative individuals, connected across borders and cultural boundaries. However, since effective practices strongly depend on regional conditions, we also want to encourage community members to organise themselves in local hubs that can address region-specific challenges.<br>
</p>
|
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF WARWICK |
<p><br>
The University of Warwick will use the partnership to invest in fellowships and projects that<br>
focus on impact in the science of early life, human tissue models of disease, and disease<br>
control and prevention. The partnership will also enable the provision of supporting expertise<br>
in impact delivery, and strengthen links with partner institutions in both industry and our local<br>
hospital network.</p> |
| 30/09/2019 |
£1,999,998 |
|
KING'S COLLEGE LONDON |
<p>This proposed programme at King’s College London (King’s) and King’s Health Partners (KHP), and in close collaboration with University College London (UCL), will translate arts in health research into sustainable, standardised and scalable health interventions that make both clinical and economic sense. Our primary aim is to upscale three <u>known effective</u> arts interventions (Melodies for Mums for Postnatal Depression, Dance for Parkinson’s, and Stroke Odysseys) and embed them in a clinical pathway across KHP, thereby strengthening the case for NHS Clinical Commissioning Groups (CCGs) to recommend and fund such interventions in the long-term. We will seek to establish defined, clinical referral pathways, from either primary or secondary care settings. In addition, by examining larger cohorts than has hitherto been possible, we will gather further evidence of (i) the clinical effectiveness of our chosen interventions, and of the mechanisms underpinning it, (ii) the implementation effectiveness (i.e., acceptability, feasibility and appropriateness), and (iii) their economic effectiveness. The programme will further involve the largest implementation research centre outside North America, the King’s Centre for Implementation Science, as well as clinicians and researchers across King’s/KHP/UCL, and the three award-winning arts organisations, Breathe Arts Health Research, the English National Ballet and Rosetta Life.</p>
|
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF LEEDS |
<p>In order to build on our portfolio of biomedical research funding and to complement<br>
successful later stage translational programmes in the University, we are proposing to<br>
pilot an approach that will enable effective early stage translation and amplify the<br>
potential for longer term impact from Wei/come funded research at the University of<br>
Leeds.<br>
Objectives:<br>
• To establish early stage feasibility in promising areas of discovery science and<br>
technology development, and support the development of these projects so that<br>
they can access the range of later stage translational opportunities that are<br>
available;<br>
• To extend and embed more fully a culture of translation across the University,<br>
sharing best practice and targeting researchers at key career stages and in areas<br>
typically focused on earlier stage development.</p> |
| 30/09/2019 |
£952,000 |
|
INTERNATIONAL SOCIETY FOR INFECTIOUS DISEASES |
<p>The International Society for Infectious Diseases’ (ISID) Program for Monitoring Emerging Diseases (ProMED) requests funding to support ongoing activities and new initiatives that will meet the developing information needs of the global infectious disease community and expand the utility of ProMED data. This application for continued support reflects our shared vision for improved human and animal health through research and technology innovation. This proposal also incorporates a request for operational support for ISID/ProMED’s longstanding partner, HealthMap, based at Children’s Hospital Boston and Harvard Medical School. </p>
<p><br>
<em>ProMED Programmatic Enhancements and Research Support</em></p>
<ul>
<li>ProMED-AMR (Antimicrobial Resistance);</li>
<li>ProMED-China; and</li>
<li>Technology enhancements to expand the use of ProMED disease data for the development of predictive modeling algorithms.</li>
</ul>
<p>The support requested from the Wellcome Trust for these extended initiatives will ensure that ProMED continues to keep pace with technology, reflects changes in global populations, and addresses the emerging challenges facing the international infectious disease community.<em> </em></p>
<p><br>
<em>Ongoing Operational Support for ProMED and HealthMap</em><br>
We will use funding from the Wellcome Trust to support ongoing operations. The support requested from the Wellcome Trust will make a critical and significant contribution to ensuring that current ProMED and HealthMap services are maintained.</p>
<p><br>
</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p> </p>
|
| 30/09/2019 |
£7,500,000 |
|
JANSSEN BIOTECH, INC. |
<p style="margin-left: 0in; margin-right: 0in">Large-scale WGS of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease</p>
|
| 30/09/2019 |
£240,000 |
|
MQ TRANSFORMING MENTAL HEALTH |
<p>Problem: Diversity is lacking in participants of mental health research. A lack of diversity in mental health research means interventions based on this research is developed from a unrepresentative sample and may mean interventions don’t work for the larger population. <br>
<br>
Researchers want to have diverse participants but don’t have the resources to source a diverse range of participants or find ethics boards are adverse to new methods they are unfamiliar with and thus it is easier to use older methods of recruitment which have shown limited diversity. <br>
<br>
This project will be enhancing the current MQ research recruitment tool to include input from institutions, ethic boards, researchers and diverse groups of people so that researchers can use the tool ‘market’ their studies to a larger and more diverse audience and more participants will have a means to be included in mental health research that suits their needs.</p>
|
| 30/09/2019 |
£194,757 |
|
NEWCASTLE UNIVERSITY |
<p>The Wellcome Centre for Mitochondrial Research is committed to effectively engaging with our patients and the wider audiences, putting our patients at the heart of everything we do. Engagement enrichment funding will allow us to carry out strategically aligned and important activities that are additional to those specified within our current strategy. These activities will benefit our research, enhance and enrich our current programme of activities as well as engage and empower a wider cross section of our patient population. More specifically additional funding will help us to further:<br>
• <strong> ENGAGE</strong> patients across the entirety of mitochondrial research that we conduct at the Centre<br>
• <strong>ENHANCE</strong> capacity to enable a culture of effective, focussed and impactful public engagement amongst our researchers and patients <br>
• <strong>ENRICH</strong> and improve diversity and inclusion within our patient community<br>
• <strong>EMPOWER</strong> ourselves and key stakeholders to work smarter by extending and strengthening key partnerships and collaborations to achieve shared strategic aims <br>
The result of these enrichment activities will be to enhance trust and empowerment within the mitochondrial disease patient community to engage with the work of the Centre. This in turn will benefit our audiences, our research and provide a lasting impact.<br>
</p>
|
| 30/09/2019 |
£36,751 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p>Improved housing conditions can save lives, prevent disease, increase quality of life, reduce poverty, and help mitigate climate change. The WHO Housing and health guidelines bring together the most recent evidence to provide practical recommendations to reduce the health burden due to unsafe and substandard housing. The guidelines aim at informing housing policies and regulations at the national, regional and local level and are further relevant in the daily activities of implementing actors. To support Member States in adapting the guidelines to national contexts, WHO is convening an expert consultation to finalize the guideline’s implementation strategy and identify priority areas for implementation. Given the multisectoral nature of the guidelines, meeting attendees will include key stakeholders from the academic, public, private and civil society sectors with multifaceted expertise in the areas of housing and health. Meeting outcomes will inform the implementation of the WHO Housing and health guidelines as well as a broader urban health agenda closely linked to planetary health concerns. That is, through co-benefits of interventions, healthy and sustainable housing is expected to contribute to healthy urban environments, climate change mitigation efforts as well as enhanced health and social equality.</p>
|
| 30/09/2019 |
£732,933 |
|
EH!WOZA |
<p>Eh!woza was established in 2013 and exists today as a trans-disciplinary initiative involving researchers at the Institute of Infectious Disease and Molecular Medicine (IDM, University of Cape Town), South African (SA) conceptual artist, Ed Young, and youth from the peri-urban township, Khayelitsha. Its inaugural activity, a film documenting youth attitudes towards tuberculosis (TB) in a disease-endemic township, was planned as a once-off endeavour intended to provide a free online teaching resource. Since then, Eh!woza has developed multiple public engagement (PE) initiatives and partnerships over the subsequent six years. Here, we propose to consolidate and expand successful Eh!woza activities through strategic collaboration with local Wellcome-funded groups, ensuring quantifiable outcomes and accelerated capacity development. To do this, we will focus on four distinct, but synergistic focus areas: Learning and Consolidation (I); Capacity Development and Sustainability (II); Networking and Collaboration (III) and Tracking Change and Impact Assessment (IV). This will allow Eh!woza to evolve, from a predominately project-based programme, to Eh!woza+, a sustainable platform that has the potential to have a transformative impact both at the local scale and on the PE landscape within South Africa. </p>
|
| 30/09/2019 |
£800,000 |
|
UNIVERSITY OF GLASGOW |
<p>The University of Glasgow has a tradition of delivering excellent research and aims<br>
to develop 'worldclass, world changing' impact across social, economic and cultural<br>
areas. Our College of Medical, Veterinary & Life Sciences (MVLS) spans a diversity<br>
of disciplines with research into processes at every biological level from genes, to<br>
cells, organs, individuals, populations, and ecosystems. MVLS is grounded in the<br>
principle that all research can achieve impact, making a constructive difference in<br>
some way, and at some time, to ultimately benefit society. Our strategic aim to drive<br>
a partnership approach to translation aligns perfectly with Wei/come Trust's<br>
ambition for the Translational Partnerships (TP). Together we will further our<br>
ambitions to develop real world benefits from our research through the development<br>
of a positive and supportive culture in which our researchers and their translational<br>
ambitions will thrive. Our TP will enable us to:<br>
1. Grow and develop our translational pipeline - through a programme of research<br>
audits and the provision of support tailored to individual project needs<br>
2. Accelerate the journey of our translational projects - by providing researchers<br>
with the tools to access relevant resources and to work in partnership with industry,<br>
NHS and other stakeholders."</p> |
| 30/09/2019 |
£7,500,000 |
|
AMGEN INC |
<p style="margin-left: 0in; margin-right: 0in">Large-scale WGS of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease.</p>
|
| 30/09/2019 |
£1,000,000 |
|
KING'S COLLEGE LONDON |
<p>This partnership will enhance translational research at King's, accelerating the rate at which<br>
discovery science is converted into benefits to patients and building on our entrepreneurial<br>
culture. The partnership will focus on excellence in advanced therapies, neuroscience &<br>
mental health, healthcare engineering and physiological medicine (cardiovascular,<br>
immunology and cancer).<br>
To accelerate translation of research into patient benefit, the partnership will undertake three<br>
main activities:<br>
• Creation of the King's Translational Academy, which will provide group-level training<br>
and signposting for academics across King's who wish to develop their skills in<br>
translational research.<br>
• Creation of a new team of Translational Research Managers, providing dedicated<br>
support to academics embarking on translational research programmes.<br>
• Creation of a new Commercial Development Fund, supporting the development of<br>
research towards commercial transactions (partnerships, licensing and spinouts).<br>
These activities will act in synergy to enhance translational culture, support and activity<br>
across King's.</p> |
| 30/09/2019 |
£7,500,000 |
|
GLAXOSMITHKLINE |
<p>Large-scale WGS of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease<br>
</p>
|
| 30/09/2019 |
£150,000 |
|
BRITISH SCIENCE ASSOCIATION |
<p style="margin-left: 0cm; margin-right: 0cm">Although most festivals are committed to improving audience diversity, many audiences do not reflect the community in which they are based, rather those already ‘engaged’.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We think this is because festival organisers lack the evidence, knowledge, tools and resources to change established practices and they have little opportunity to reflect or develop their practice due to the cyclical nature of planning festivals. Pressures from funders also influence the more socially-driven ambitions that festival organisers may have to be less driven by activity and more focused on outcomes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This is a challenge facing the entire sector and the UKSFN are well placed to take a strategic approach to understanding where we are now and what we want festivals to become. Since BSA took over the running of the UKSFN in 2015, we have focused on understanding the landscape, particularly in terms of audience reach across the sector, and the strengths and opportunities across the sector - and with that in place, now is the time to ask the question - what do we want the sector to look like in 10-20 years’ time? What’s the vision and how can this vision be a joint one defined and owned by the community</p>
|
| 30/09/2019 |
£243,993 |
|
UNIVERSITY OF OXFORD |
<p>Mesh Community Engagement Network (<u>www.mesh-ce.org</u>) is a collaborative open-access webspace and networking project for people involved in community engagement with global health research (CE). Building on a successful pilot, we propose a new three-year strategic approach with a focus on measuring impact, using a <em>Theory of Change</em> to provide clarity on how we expect to make a difference to global health by supporting better research.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We have three aims: To ensure the value of CE is recognised by a diversity of global health stakeholders and is considered an integral part of research; to generate and strengthen leadership and capacity; and to increase outcomes-focussed, innovative CE. Mesh’s vision for the future is that all global health research incorporates high-quality CE built on evidence, good practice and strong networks.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Capitalising on the project’s impressive reach, geographical spread and high-level partnerships, we will secure a small team and move management from Wellcome to embed the project at The Global Health Network. A robust monitoring and evaluation plan will allow for greater agility and adjustments to the strategy and project delivery, increasing efficiency and leading to the development of Mesh as a low-cost and high-impact project in the future.<br>
<br>
Intro film (1min 43sec): <u>https://youtu.be/1jCHxbPLPlA</u></p>
|
| 30/09/2019 |
£66,902 |
|
OSWALDO CRUZ FOUNDATION |
<p>This proposal intends to support the initiative to develop a new Centre at Oswaldo Cruz Foundation (Fiocruz) dedicated to Humanities and Social Sciences on Global Health and inequities.</p>
<p>The Humanities and Social Sciences Centre for Global Health and Inequities will investigate scientific production, social, cultural and political challenges of developing cutting-edge research in a middle-income country. It will also investigate the translation of scientific knowledge into practices; the input of distinct methodologies, epistemologies and ontologies of communication, technical and informational tools, and frameworks on diffusion of social sciences innovations; the adaptation of such innovations to respond social needs such as inequities in health; and the role of economic and political imbalances and fragmentation in shaping scientific and technological production in Fiocruz and in the Global South.</p>
<p>This grant will enable to better define our cross-cutting themes and approaches by a series of workshops with world-leader researchers; visits to world reference centres to inspire and support a full proposal to be presented to Wellcome Trust; identify the best suited methodologies and researchers to integrate the Centre and to respond to new WT research funding strategies in social sciences and humanities in health, including institutions and challenges from the Global South.</p>
|
| 30/09/2019 |
£3,661,773 |
|
MEDICAL RESEARCH COUNCIL |
The UKPRP is an inter-disciplinary national initiative supported by an alliance of UK charities, Research Councils and the UK Health Departments, and established in recognition of the need for research into population-level strategies that will prevent non-communicable diseases (NCDs) and reduce inequalities in health. |
| 30/09/2019 |
£7,500,000 |
|
ASTRAZENECA PHARMACEUTICALS (UK) |
<p>Large-scale WGS of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease<br>
</p>
|
| 30/09/2019 |
£249,890 |
|
AMOS SUPERBUG LTD |
<p>Our aim is to create a global public mandate for action on antibiotic resistance (ABR) by:</p>
<p>1) driving home the deadly and growing threat ABR poses to every one of us. Here we can build on the Wellcome’s Comms Team’s framing work on the language and associations around ABR in different regions, delivering Sept 2019.</p>
<p>2) increasing the public’s interest in the science of bacteria and why they become drug-resistant. Our experts will help us present trusted research around ABR and make it accessible globally, allowing people to acquire knowledge about ABR from credible sources.</p>
<p>3) empowering the public with a sense that they too have a role to play: By adapting their own behaviour around antibiotics and infections, and most importantly speaking out to friends, family, medical professionals and political leaders, they can make a difference.</p>
<p>Now that the SUPERBUG movie is fully-financed, fund-raising to amplify and direct its impact can take place. This grant application will be used to develop the impact plan further; build impact infrastructure, beginning with a globally-accessible digital hub; build initial momentum on social media during production; and create highly-shareable video content for use around UNGA 2020.</p>
<p> </p>
|
| 30/09/2019 |
£57,169 |
|
CITY UNIVERSITY OF NEW YORK |
<p>This fellowship appointment will assist with the research and development phase of a new project looking at aspects of mental health with a specific focus on New York. Alongside pursuing self-directed research, the fellow will work closely in NYC with Center for the Humanities Director Keith Wilson and members of the Wellcome Culture and Society Directorate team under direction of International Cultural Producer Danielle Olsen to: </p>
<p>• Develop external partnerships across the city with partner organisations on the theme of mental health in NYC investigating potential archives, collections and institutions that could provide a focus for transdisciplinary research </p>
<p>• Serve as connector across participant spaces and places, developing creative new links with international city partners as the project develops</p>
<p>• Assist in developing interdisciplinary methods and processes between and across the Arts and Sciences on a mental health theme</p>
<p>• Convene a workshop in 2020 at the Graduate Center, CUNY for Wellcome staff and stakeholders on a global mental health theme with a specific NYC focus</p>
<p>• Explore crossover and hybrid experimental curatorial possibilities utilizing original creative work, events, and public programming.</p>
<p>The curatorial fellow will bring a museum lens to the research and development stage of this new initiative.</p>
|
| 30/09/2019 |
£831,660 |
|
THE GRADUATE INSTITUTE OF INTERNATIONAL AND DEVELOPMENT STUDIES |
<p style="margin-left: 0cm; margin-right: 0cm">The Lancet <em>Global Burden of Disease Study 2017: a fragile world </em>indicates that progress toward achieving the SDGs is highly uneven, within and between countries. There is great concern that health targets will not be achieved by 2030 unless there is an extraordinary global and domestic effort. While research has shown accelerated declines in child mortality, some countries, especially in sub-Saharan Africa continue to fall behind. Decades of neglect and chronic under-investment have had detrimental effects on the health and well-being of adolescents aged 10–24 years.<br>
While technology races ahead the response by international agencies and governments is slow to address issues of governance and regulation. Rapid digital transformation must urgently be used to improve the health of children and youth through reaching out to individuals, strengthening public health and improving service coverage, particularly at community level thus accelerating progress towards UHC. Ethical guidelines, institutional responsibilities, norms and standards need to be put in place as individual data - especially in health - become one of the most valuable resources on the planet. There are great expectations that digital health and AI could bring transformative benefits to health, but their use- especially in resource-poor settings - remains nascent and uncoordinated. </p>
|
| 30/09/2019 |
£188,452 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p>NITAGs (National Immunization Technical Adviory Groups), by providing evidence-based recommendations on vaccines and immunization programmes to national decision makers, play an important role in the development and sustainability of immunization programmes around the world. Providing adequate training for the NITAG secretariat and NITAG members is a crucial element to allow the committee to carry out its work effectively.</p>
<p>NITAG training material has been developed in the past years by different groups, such as the SIVAC initiative, CDC, WHO and the Task Force for Global Health to support NITAGs in their initial steps but also at later stages of their maturity. Different sets of material are currently used when training is provided. This adhoc approach has resulted in poor consistency of materials, outdated documents, lack of a systematic feedback process on the format and the training utility and finally in gaps in essential trainings.</p>
<p>The overall objective is to develop and make largely available a peer validated set of training materials of consistent format and content able to cover all the relevant training needs to allow NITAG to function effectively. </p> |
| 30/09/2019 |
£40,000,000 |
|
WELLCOME TRUST/DBT INDIA ALLIANCE |
<p>In January 2017, Wellcome in partnership with the DBT, conducted a review of the India Alliance. The Review Committee recommended that Wellcome approves £40m of funding for a further 5-year phase of the programme subject to the implementation of?their?recommendations (see BOG Paper). At the 10-11 April 2017 meeting, the Wellcome Board of Governors approved, in principle, up to £40m for a further five years of the initiative from April 2019 (Agenda item 8). </p>
<p>In March 2019 the Union Cabinet, chaired by the Prime Minister Shri Narendra Modi, approved the continuation of the Biomedical Research Career Programme (BRCP), and Wellcome Trust (WT) / DBT India Alliance beyond its initial 10-year term (2008-09 to 2018-29) to a new five-year phase (2019-20 to 2023-24) with Department of Biotechnology (DBT) increasing its commitment to two times that of Wellcome. The total financial implication will be Rs. 1092 crore with DBT and WT contributing Rs.728 crore and Rs.364 crore respectively. </p>
<p>The ratio of Wellcome: DBT funding will change from 1:1 to 1:2 for Phase 3. </p> |
| 30/09/2019 |
£120,350 |
|
WEFARM |
<p><strong>Wefarm is a digital peer-to-peer information sharing network, for the world’s 1 billion+ offline small-scale farmers, accessible by SMS. </strong><strong>With Wefarm, using just a basic mobile phone, farmers can share and access vital information on anything from how to increase their income by improving crop yields to battling a disease which is decimating their livestock. This is all without leaving their farm, spending any money... or having to go online. We have already connected over 1.6m users in Kenya, Uganda and Tanzania, and in the next 5 years will connect millions across Africa and Asia.</strong></p>
<p><strong>In line with Wellcome’s mission to reduce antibiotic consumption by humans and animals, and reduce the levels of antibiotics in the environment, we propose to achieve the following objectives:</strong></p>
<ol>
<li>
<p><strong>Provide a greater understanding of farmer’s perspectives on antibiotic usage for the benefit of policy makers, funders, agricultural and health research organizations. </strong></p>
</li>
<li>
<p><strong>Encourage the reduction of antibiotic consumption in farm animals. </strong></p>
</li>
</ol>
<p><strong>To do this, Wefarm will work in partnership with the Wellcome Trust and the KEMRI Wellcome Trust research programme, to engage small-scale farmers in a pilot project in Kenya with AMR. If successful the project could roll out in India in the next 18 months.</strong></p>
|
| 30/09/2019 |
£806,136 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
Globally, antimicrobial resistance (AMR) has been identified as a major threat to human health, but effective surveillance in lower and middle-income countries (LMICs) has been difficult to establish. Public facilities lack reliable basic infrastructure for microbiological services and antibiotic use is largely empirical. There are renewed global efforts to establish AMR surveillance and similarly Kenya has developed an action plan for tracking AMR. It is unrealistic to implement microbiology processes based purely on high-income country practice models, and a model appropriate to LMIC settings is required. We propose to demonstrate a hub-and-spoke embedded surveillance programme using the Clinical Information Network (CIN), an already established collaboration between KEMRI-Wellcome Trust Research Programme (KWTRP), the Kenya Paediatric Association (KPA), Kenya’s Ministry of Health and selected County Referral Hospitals in Kenya. Implementation will produce AMR surveillance data from CIN hospitals, but also demonstrate the feasibility of our hub-and-spoke approach for other settings, build capacity for uptake of microbiology data in Kenyan hospitals and describe the impact of these data in clinical practice. CINAMR will also feed into other initiatives such as ACORN network in Southeast Asia, WHO’s Global Antimicrobial Resistance Surveillance System (GLASS), and the Global Research on Antimicrobial Resistance (GRAM) Study
|
| 30/09/2019 |
£179,345 |
|
UNIVERSITY OF CAPE TOWN |
<p>Optimal healthcare decision making must be premised on high quality and timely evidence. Decision making on immunisation is increasingly becoming complex and challenging as the scope and costs of new vaccines increase, as well as changing epidemiology of vaccine preventable diseases. Therefore, at a country level, the Ministry of Health (MoH) should have access to evidence-based recommendations from experts in public health, medicine, and vaccinology. Within countries in WHO’s AFRO region, this is most commonly facilitated through National Immunisation Technical Advisory Groups (NITAGs). Issuance of high-quality evidence-based immunisation recommendations by NITAGs demands competency in scientific skills. Many NITAGs, particularly in low resourced settings, lack optimal scientific skills to issue high-quality and timely evidence-based immunisation recommendations. Sustainable mechanisms to support such technical healthcare groups with essential scientific skills are lacking. There is need to provide a sustainable scientific support to NITAGs and other healthcare groups that routinely access, synthesize and utilize research evidence for policy formulation. We propose establishment of an academic-based Regional Scientific Hub (RSH) to provide sustainable scientific support to NITAGs and other similar healthcare technical groups. This application proposes to conduct a 4 months scoping exercise to inform the establishment of a RSH for the WHO-Africa (WHO-AFRO) region. </p>
|
| 30/09/2019 |
£19,879 |
|
UNIVERSITY OF OXFORD |
<p>The Ebola Data Platform (EDP) strengthens knowledge and capacity across the health, research and humanitarian communities to reduce the impact of Ebola through responsible data reuse. The Data Access Committee (DAC) is a key pillar of the Platform’s governance framework, facilitating access to data from the Platform for equitable research and to help tackle the most pressing challenges in the global response to Ebola.</p>
<p>IDDO and the Data Access Committee Chair seek to convene the full DAC membership in person for an inaugural meeting in West Africa later in 2019. Key outputs expected from the meeting:</p>
<ul>
<li>Develop Data Access Guidelines for the EDP and finalise the DAC Terms of Reference.</li>
<li>Strengthen the EDP plans to support research capacity across Ebola-affected countries.</li>
<li>Align the EDP data access policies with other initiatives across West Africa and the continent.</li>
<li>Provide feedback to the EDP Steering Committee on research priorities, issues in data access and promoting equity in data use.</li>
</ul>
<p>This application requests funding for travel, accommodation and subsistence during the two-day meeting for the 10 members of the DAC and two members of the Secretariat. The current DAC membership is mostly comprised of members from low-income countries, including those directly affected by Ebola.</p>
<p> </p>
|
| 30/09/2019 |
£348,810 |
|
WELLCOME TRUST SANGER INSTITUTE |
<p style="margin-left: 0cm; margin-right: 0cm">The Human Cell Atlas aims to understand cells at a fundamental level and what this means for health and disease. Our ambitious public engagement programme will explore fundamental questions embedded within the HCA research such as “What does it mean to be normal?” and “What influences peoples’ value and trust in research involving tissue donation and open access data?”</p>
<p style="margin-left: 0cm; margin-right: 0cm">We have identified audiences with whom engagement with HCA science has particular relevance. These are: 1) patient groups affected by conditions investigated as part of the HCA, 2) existing and potential organ donors, 3) communities not often represented in conversations around healthcare research and organ donation, and 4) education cohorts whose learning experience could be influenced by the research.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our vision through the engagement with our target communities is to improve outcomes related to the value and trust people place in research with consequent impact on willingness to donate tissue for research, share their data and help to identify areas of unmet need that the HCA could tackle. Our impact also extends to the global HCA consortium, where the methods and resources created and tested through our work will be made available to the wider community.</p>
|
| 30/09/2019 |
£25,001 |
|
NEW YORK ACADEMY OF MEDICINE |
<p>ICUH 2019 will be held in China, already a global leader in promoting healthy cities. The conference title is People Oriented Urbanisation: Transforming Cities for Health and Well-Being. Key themes for the conference are: integrated governance, resilience and health risk reduction; climate change and healthy cities; economy, trade, employment and social inclusion; emerging diseases, healthcare and public services; urban-rural recoupling, soil security and migration; liveable urban environments, and urban planning and design. These themes are aligned with Wellcome’s planetary health agenda and its commitment to strengthening the evidence base for urban health. The detailed program can be found at www.isuhconference.org. In recent conferences, we received as many as 1,346 abstracts from 80 countries. ICUH2018 was held in Kampala, Uganda, and 214 abstracts were accepted for oral and poster presentations, and 145 of those were from LMICs and thanks to the support of our sponsors, 59% of delegates were from the global South. We are happy that several conference subthemes are well aligned with Wellcome Trust's concerns for planetary health. As a sponsor you may choose to target your funds towards support of LMIC scholars whose abstracts are most closely related to your planetary and urban health areas of emphasis. </p>
|
| 30/09/2019 |
£499,992 |
|
GLAXOSMITHKLINE |
Chemoprevention efforts for malaria (IPTp, SMC) have had a major impact decreasing malaria
cases but have downsides (adherence to treatments, toxicity issues or parasite resistance among
others). GSK and PATH identified lgG's in GSK's candidate malaria vaccine RTS,S/AS01B
vaccinees (MAL071 study) that prevent malaria infection in animal models. In this project, several of
these mAbs will be evaluated and optimized for potency, pharmacokinetic properties, optimal
manufacturing stability and yields to have the required profile of a prophylactic mAb able to prevent
P. falciparum liver infection, with the ultimate goal of prevention of blood stage infection. The
molecules should have 3-4 months half-life and acceptable cost of goods, to overcome drawbacks
of the current prophylactic therapies. |
| 30/09/2019 |
£139,997 |
|
MONASH UNIVERSITY MALAYSIA |
<p style="margin-left: 0cm; margin-right: 0cm">Snakebite is a public health problem with substantial morbidity and mortality that affects an estimated 5.4 million people annually. The Association of South East Asia Nations (ASEAN) is recognised as having one of the highest regional burdens of snakebite, however, the true magnitude, especially the economic aspects remain unknown. The result is a lack of access to effective antivenom due to inadequate understanding of demand and supply in the antivenom market. This study will collect the Clinical and Antivenom Market data to provide a more accurate assessment of the burden of snakebite and project the clinical and economic implications of scenarios with various levels of antivenom availability in 7 ASEAN. This is a critical first step in the development of national and regional action plans to address the burden of snakebite.</p>
|
| 30/09/2019 |
£60,000 |
|
ZINC |
<p><strong>This project will demonstrate the benefits of collaborative, problem-led user research among entrepreneurs and researchers. Zinc’s core business focuses on the translation of secondary research. With the support of this Award, Zinc is well placed to also run a high-profile experimental approach to user engagement. </strong></p>
<p>Zinc’s third mission brings together 50 entrepreneurs to build new, scalable businesses that improve the quality of later life, in areas such as disease prevention, neglected health conditions, social isolation and care-giving. This project represents a new approach to problem-led user research, integrating the currently separate R&D approaches to user-engagement of early stage entrepreneurs and researchers into a new, joined-up and replicable model. The new approach will be tested with 1500 users, 15 new businesses and 15-20 researchers. It will be widely disseminated across the public, private and third sectors.</p>
<p>The project takes the shape of a 12-month Public Engagement Fellowship, that runs alongside Zinc’s third mission. The Fellow’s role would be to: (1) create innovative opportunities to engage with a diverse group of users to gain a comprehensive understanding of their needs and contexts; (2) disseminate learnings about users and the new process through a range of creative channels and formats.</p>
|
| 30/09/2019 |
£750,858 |
|
UNIVERSITY OF CAMBRIDGE |
<p>Our project will use genomic data and a detailed understanding of pathogen evolution to<br>
deliver a robust, rapid, accurate and cost-effective pathogen detection kit for use in the field.</p>
<p>Current methods are unsuitable for detection as they are slow, inaccurate and cannot be<br>
field deployed. Our work has already changed the basic understanding of how cholera<br>
spreads and identified high and low epidemic risks that are the cornerstones of disease<br>
prevention. By making robust molecular indicator kits adapted to field settings we are able to<br>
rapidly probe the likely behaviour of cholera strains and provide actionable data that can<br>
make a direct contribution to a major human health challenge.</p> |
| 30/09/2019 |
£748,053 |
|
UNIVERSITY OF MARYLAND |
Non-typhoidal Salmonella (NTS) such as Salmonella Typhimurium and Salmonella
Enteritidis generally cause self-limiting gastroenteritis. However, in sub-Saharan Africa,
clones of these Salmonella serovars cause invasive disease particularly in infants and
toddlers. Our overall goal is to develop vaccines to provide broad protection against
invasive non-typhoidal Salmonella (iNTS) disease. The main goal of the project is to
show that we can develop live oral Salmonella vaccines with improved safety due to
reduced transmission, designated here as Live Attenuated Non-Transmissible (LANT)
vaccines. We will complete pre-clinical safety and efficacy studies assessing the in vivo
persistence, immunogenicity, and protective efficacy of candidate S. Typhimurium and
S. Enteritidis LANT vaccines in mice. At the conclusion of this project, we anticipate
demonstrating that iNTS LANT vaccines are only shed in feces for a short duration but
are still immunogenic and can protect animals against challenge with wild-type iNTS. If
we are successful, these results will pave the way for initiating future Phase I clinical
trials using safe, live attenuated Salmonella Typhimurium and Salmonella Enteritidis
vaccines. |
| 30/09/2019 |
£4,906,388 |
|
UNIVERSITY OF DUNDEE |
The University of Dundee Mode of Action(MoA)group works on finding and confirming the molecular targets of compounds that have biological activity against a variety of different pathogens. The MoA group hasa toolbox of multipleorthogonaltechnologiesto undertake this work. They will be working with the Wellcome Trust HIT-NTD Flagship to determine the mode of action of compounds coming from the drug discovery programmes supported by Flagship, includingthose inleishmaniasis, Chagas’ disease, cryptosporidiosis and schistosomiasis. In addition,they will undertake some work on characterising novel molecular targets identified through this work. The project will be led by Dr Susan Wyllie and Prof Ian Gilbert and colleagues in Dundee. The Dundee MoA team will work in collaboration with Prof Karl Hoffmann at the University of Aberystwyth and Prof Rolf Muller at the Helmholtz Institute in Saarbruken." |
| 30/09/2019 |
£317,928 |
|
AFRICAN ACADEMY OF SCIENCES |
<p style="margin-left: 0cm; margin-right: 0cm">Over the next 23 months, we will continue to focus on;</p>
<ol>
<li>Strengthening CPE capacity among our DELTAS and H3A consortia,</li>
<li>Embedding engagement in routine AAS ST&I programmes and practices and,</li>
<li>Advocating the value of CPE across various AAS’ stakeholders. </li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">The second strategic objective cuts across all AAS programmes, hence will not be addressed within this discretionary award application. This application seeks support for strategic objective 1 and 3</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our Proposal is to;</p>
<ol>
<li>Conduct 2 CPE F2F capacity strengthening workshops to cover;
<ol style="list-style-type: lower-alpha">
<li>Grant writing</li>
<li>Monitoring, Evaluation & Learning</li>
</ol>
</li>
<li>Schedule virtual on-going support for CPE implementers </li>
<li>Cross-sharing and learning of best practice through the MESH Platform</li>
<li>Conduct 5 site visits to 5 DELTAS grantees over the grant duration </li>
<li>Conduct 2 inception meetings for the DFID/WT/AAS DELTAS Seed Fund (CPE & Gender Equity)</li>
<li>Strengthen Monitoring, Evaluation & Learning for the DELTAS CPE Seed Fund and wider DELTAS Consortia </li>
<li>Attend at least 5 DELTAS consortium specific AGMs to advocate the value of CPE. Its on these that site visits will be piggy-backed</li>
<li>Establish a continental CPE advisory group</li>
<li>Establish a CPE programmatic board</li>
<li>Undertake staff development – at least 2 networking and/or learning meetings of relevance to CPE over the grant duration</li>
</ol>
|
| 30/09/2019 |
£1,133,897 |
|
BRIGHAM & WOMEN'S HOSPITAL |
The objective of this study is to test the safety and immunogenicity of HaitiV – a novel
live-attenuated cholera vaccine. Pre-clinical data suggest that HaitiV can provide rapid
(within a day), single-dose, long-lived protection from cholera. The key goals of the
study are 1) creation of a GMP lot of HaitiV for use in human studies and development
and approval of an investigator sponsored Investigational New Drug application to
conduct a first-inhuman Phase I trial of HaitiV; 2) determination of the maximum
tolerated dose and safety profile of HaitiV; and 3) identification of the most
immunogenic HaitiV dose. These studies will provide the pivotal data required for future
development of this vaccine, including human challenge studies and field trials in
cholera endemic regions. |
| 30/09/2019 |
£8,304 |
|
UNIVERSITY OF LIMERICK |
Not available |
| 30/09/2019 |
£8,304 |
|
UNIVERSITY COLLEGE DUBLIN |
Not available |
| 30/09/2019 |
£8,304 |
|
ROYAL COLLEGE OF SURGEONS IN IRELAND |
Not available |
| 30/09/2019 |
£15,917 |
|
NATIONAL UNIVERSITY OF IRELAND GALWAY |
Not available |
| 30/09/2019 |
£5,536 |
|
UNIVERSITY OF YORK |
<p>Vacation Scholarships 2019 - University of York</p> |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF THE WEST OF ENGLAND |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF SURREY |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF STIRLING |
<p>NA</p> |
| 30/09/2019 |
£11,072 |
|
UNIVERSITY OF ST ANDREWS |
<p>NA</p> |
| 30/09/2019 |
£8,304 |
|
UNIVERSITY OF SOUTHAMPTON |
Not available |
| 30/09/2019 |
£15,916 |
|
UNIVERSITY OF SHEFFIELD |
<p>Vacation Scholarships 2019 - University of Sheffield</p> |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF READING |
<p>Vacation Scholarships 2019 - University of Reading</p> |
| 30/09/2019 |
£12,456 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£10,380 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 30/09/2019 |
£13,840 |
|
UNIVERSITY OF NORTHAMPTON |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 30/09/2019 |
£10,380 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2019 |
£11,072 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 30/09/2019 |
£24,566 |
|
UNIVERSITY OF LEEDS |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF KENT |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF HULL |
Not available |
| 30/09/2019 |
£15,224 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2019 |
£17,992 |
|
UNIVERSITY OF EDINBURGH |
<p>Vacation Scholarships 2019 - University of Edinburgh</p> |
| 30/09/2019 |
£10,380 |
|
UNIVERSITY OF EAST ANGLIA |
Not available |
| 30/09/2019 |
£11,072 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2019 |
£26,988 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 30/09/2019 |
£5,536 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 30/09/2019 |
£2,768 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 30/09/2019 |
£58,474 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2019 |
£8,304 |
|
ULSTER UNIVERSITY |
<p>NA</p> |
| 30/09/2019 |
£2,768 |
|
SHEFFIELD HALLAM UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
ROYAL HOLLOWAY, UNIVERSITY OF LONDON |
<p>Vacation Scholarships 2019 - Royal Holloway, University of London</p> |
| 30/09/2019 |
£2,768 |
|
ROEHAMPTON UNIVERSITY |
Not available |
| 30/09/2019 |
£5,536 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 30/09/2019 |
£2,768 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p>Vacation Scholarships 2019 - Queen Mary University of London</p> |
| 30/09/2019 |
£28,372 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
MEDICAL RESEARCH COUNCIL |
Not available |
| 30/09/2019 |
£2,768 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£2,768 |
|
LIVERPOOL JOHN MOORES UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
LANCASTER UNIVERSITY |
Not available |
| 30/09/2019 |
£15,916 |
|
KING'S COLLEGE LONDON |
<p>NA</p> |
| 30/09/2019 |
£2,768 |
|
INSTITUTE OF CANCER RESEARCH |
Not available |
| 30/09/2019 |
£13,840 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2019 |
£2,768 |
|
GOLDSMITHS, UNIVERSITY OF LONDON |
<p>NA</p> |
| 30/09/2019 |
£2,768 |
|
GLASGOW CALEDONIAN UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
COVENTRY UNIVERSITY |
<p>NA</p> |
| 30/09/2019 |
£2,768 |
|
CARDIFF UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
BRUNEL UNIVERSITY |
Not available |
| 30/09/2019 |
£2,768 |
|
BANGOR UNIVERSITY |
<p>Vacation Scholarships 2019 - Bangor University</p> |
| 30/09/2019 |
£2,768 |
|
BABRAHAM INSTITUTE |
Not available |
| 30/09/2019 |
£5,536 |
|
ANGLIA RUSKIN UNIVERSITY |
Not available |
| 30/09/2019 |
£51,571 |
|
HARVARD UNIVERSITY |
<p style="margin-left: 0in; margin-right: 0in">The third Planetary Health Annual Meeting will be held on September 4-6, 2019 at Stanford University and co-organized by the Planetary Health Alliance and Stanford University. The objective of this year's conference is to catalyze efforts towards resolving the great planetary health crises of our time by: 1) strengthening the scientific case for planetary health framing; 2) learning from efforts to solve planetary health problems – both failures and successes; and 3) convening stakeholders from academia, the private sector, civil society and government to support catalytic conversations to address these crises. Emphasizing the involvement of voices that are currently underrepresented in the field of planetary health is integral to our vision of a successful Planetary Health Annual Meeting. The Planetary Health Annual Meeting Travel Scholarship Program competitively awards students and early-career professionals from low- and middle-income countries to participate in the Annual Meeting. Awardees lead poster and oral presentations, engage with mentors during a mentorship lunch, and write post-conference blog posts on how they will integrate planetary health in their work. Of past travel scholar cohorts, many have become advocates for planetary health at their home institutions. Travel scholarships cover registration, accommodations, and economy-class travel.</p>
|
| 30/09/2019 |
£752,983 |
|
UNIVERSITY COLLEGE LONDON |
<p>Navigation to improve outcome of epilepsy surgery', Principal Investigator- Professor John<br>
Duncan (UCL). The successful neurosurgical treatment of epilepsy depends on complete<br>
removal of the part of the brain that gives rise to epileptic seizures, and in avoiding damage<br>
to brain areas and pathways critical for functions such as vision, language, sensation and<br>
motor control. Achieving these goals requires accurate 30 planning of the surgical approach<br>
and resection and real time feedback during the course of surgery. This project builds upon<br>
our EpiNA V platform to visualize brain structures that need to be removed to cure epilepsy,<br>
and those that need to be spared, in order to avoid adverse effects. This anatomical<br>
guidance will be displayed to the surgeon via a neurosurgical navigation interface so that<br>
brain tissue removal is optimised, in terms of maximising the chances of remission of the<br>
epilepsy and avoiding complications such a loss of part of the field of vision and of language<br>
abilities.</p> |
| 30/09/2019 |
£332,231 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p style="margin-left: 0in; margin-right: 0in">The WHO Global Health Ethics team is investigating the scientific, ethical, social and legal challenges associated with human genome editing. As part of this work, WHO has established a global, multi-disciplinary expert panel to examine the scientific, ethical, social and legal challenges associated with human genome editing (both somatic and germ cell), with a view to advising and making recommendations on appropriate governance mechanisms for human gene editing. </p>
<p style="margin-left: 0in; margin-right: 0in">The Committee will build on pre-existing initiatives, and work in a consultative manner. It will have the following core functions:</p>
<ul>
<li>To review the current activities and literature on human gene editing in order to understand and advise the Secretariat and WHO Director General on the state of the research and its applications, its potential usages and societal attitudes towards the different uses of this technology;</li>
<li>To advise the Secretariat and WHO Director General on potential oversight mechanisms for research into, and application of, human gene editing technology going forward; and</li>
<li>To make recommendations to the Secretariat and WHO Director General on global governance structures for the research into, and potential application of, human genome editing.</li>
</ul>
<p> </p>
|
| 30/09/2019 |
£241,840 |
|
NATIONAL ACADEMY OF SCIENCES, AMERICA (NAS) |
<p>The U.S. National Academies of Sciences and Medicine and the Royal Society will convene an international commission of experts to conduct a study that will develop principles, criteria, and standards for the clinical use of genome editing of the human germline. At the conclusion of the study, the commission will issue a consensus report with findings and recommendations at a public release event.</p>
<p>Overseeing the commission will be an international oversight board (IOB) comprised of leaders from public and private sectors including representative leadership of academies of sciences and medicine. The IOB will approve the commission slate, statement of task, workplan, and reviewer slate and ensure that the commission's report is rigorously peer reviewed prior to publication. It will operate virtually via conference calls and email communication.</p>
<p>The commission will hold three meetings and an international workshop. After the first meeting a call for public input will be issued. The results will inform the second meeting and the international workshop. The third meeting will be used to develop the commission’s findings and recommendations. In general, the commission will follow the policies and procedures of the US National Academies regarding consensus studies including conflicts of interest, independence, and external report review. </p>
|
| 30/09/2019 |
£884,134 |
|
KATHOLIEKE UNIVERSITEIT LEUVEN |
<p>KU Leuven, according to Reuters Europe's most innovative university already for 4<br>
consecutive years, has a long tradition in translational research. Over the years KU Leuven<br>
has established a broad and professional framework for supporting translational activities.<br>
Nonetheless, significant barriers are still existing which all too often prevent translation of<br>
excellent research (especially in biomedical sciences), such as regulatory affairs intelligence<br>
and specific entrepreneurial management support. To complement the existing framework,<br>
KU Leuven and Wei/come Trust are setting up a partnership, unique on the European<br>
mainland, that is geared to overcome these barriers.<br>
Both partners will commit to setting up a comprehensive network of expertise and resources<br>
that allows to swiftly and professionally de-risk the KU Leuven translational portfolio (focused<br>
on biomedical sciences) to the point where they can be taken up by either industry or<br>
venture capital players. By making the right expertise available at the right point in time, both<br>
partners are convinced that this will result in a higher overall quality of KU Leuven's<br>
translational research portfolio, a shorter time to market per project and more efficient use of<br>
(public) resources.</p> |
| 30/09/2019 |
£120,000 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">The African Academy of Sciences (AAS) is strengthening financial management of grants by developing a good financial grant ecosystem, that whilst developed in Africa is applicable to the Global Grant Community. By being applicable across borders, geographical regions and sectors, it will help ensure buy in and adoption by global funding agencies and grantors.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Wellcome have supported the development of the Global Grant Community – Good Financial Grant Practice by providing the initial £0.5m funding, which catalysed GFGP and additional funding from other funders of circa £3m and supporting Genny to provide advisory and operational support to AAS, Michael Kilpatrick who is based in Nairobi at the AAS and the initiative, initially for one day a week, while Genny was seconded to Sanger as their CFO and for the past year on a full time basis.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The requested funding will enable Genny to continue to work with the AAS in the development of this initiative alongside the new role as CFO of the OUCRU as an employee of Oxford University.</p>
|
| 30/09/2019 |
£158,263 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p>Human Challenge Studies are trials in which participants are deliberately infected with an infectious disease pathogen. Whilst this may sound at odds with modern ethical principles, they have been instrumental in the development of vaccines, including against smallpox, and are currently being used to fast track and facilitate vaccine development. Clearly these studies raise a plethora of ethical issues and the fact that there is growing interest in their usage in low and middle income and endemic settings, raises a whole suite of new challenges for which specific ethical guidance is needed. Given this and the current lack of global ethical guidance in this area, WHO</p>
|
| 30/09/2019 |
£1,000,000 |
|
CHARITé - UNIVERSITäTSMEDIZIN BERLIN |
<p>The ultimate aim of the Wei/come Trust- Charite/81H Translational Partnership is to<br>
maximize the translational potential at the Charite/81H via the stimulation and subsequent<br>
implementation of a comprehensive and all-pervading value-based culture change within the<br>
Charite/81H research ecosystem. In doing so, a more sustainable, efficient and patient<br>
orientated translational research ethos will be established, enabling the Charite/81H to more<br>
efficiently fulfil its translational potential. This proposal for widespread institutional culture<br>
change is based on the premise that translational excellence can only be achieved by<br>
tailoring the institutional infrastructure and related services to ensure that value and quality<br>
of research is maintained throughout the process of scientific investigation.<br>
C9</p> |
| 30/09/2019 |
£753,490 |
|
UNIVERSITY OF DUNDEE |
<p>Difficulties in establishing diagnosis of small bowel (SB) disorders, prevented<br>
effective treatment. This problem was resolved by rigid wireless capsule endoscopy<br>
(WCE), which rapidly became the gold standard SB investigation in routine clinical<br>
practice. Patients are required to swallow the WCE pill, which tumbles down and<br>
provides imaging of the inside of the SB. Despite their benefit, WCE has several<br>
limitations: the lack of active locomotion can result in incomplete examination,<br>
capsule retention and impaction within strictures. The SOFTIE project aims to<br>
replace the rigid WCE with a soft segmented narrower mini-robot (easier to swallow)<br>
with intrinsic locomotion produced by vibrating motors. SOFTIE will be equipped with<br>
HD CMOS camera imaging system with LED-lighting, enabling full and complete<br>
enteroscopy. In the small bowel SOFTIE will rely on its on-board power supply and<br>
RF communication with a wireless external portable console. SOFTIE will avoid all<br>
the documented complications of WCE devices. Prof Sir Alfred Cuschieri and his<br>
engineering team at the Institute for Medical Science and Technology (IMSaT),<br>
assisted by two clinical colleagues at Ninewells Hospital, Dundee (Mr Afshin Alijani<br>
and Dr Craig Mowat) will produce a proof of concept working prototype which will<br>
undergo testing by experiments in an in-vitro porcine small bowel model'</p> |
| 30/09/2019 |
£4,649,780 |
|
WELLCOME TRUST SANGER INSTITUTE |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£141,048 |
|
UNIVERSITY OF EDINBURGH |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£271,098 |
|
ROYAL BOTANIC GARDEN EDINBURGH |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£728,182 |
|
EARLHAM INSTITUTE |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£576,482 |
|
MARINE BIOLOGICAL ASSOCIATION |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£762,584 |
|
UNIVERSITY OF OXFORD |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£868,764 |
|
NATURAL HISTORY MUSEUM |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£313,996 |
|
KEW ROYAL BOTANIC GARDENS |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£784,478 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£264,009 |
|
UNIVERSITY OF CAMBRIDGE |
<p>Life has evolved from a single origin to generate >1.5 million eukaryotic species. Sequencing all species will provide an inventory of life, transform understanding of evolution, catalogue eukaryotic gene toolkits for biology and biotechnology, and enable monitoring of ecosystems under increasing stress. The Darwin Tree of Life (DToL) is a new initiative that will exploit long read technologies to sequence all 60000 species in the British Isles and play a leading role in the Earth BioGenome Project. This data resource will underpin bioscience for the coming century.</p>
<p>We are a consortium of partners who will build and prove an end-to-end pipeline of sample collection, sequencing, genome assembly, annotation and data dissemination that can deliver this visionary project. We will:</p>
<ul>
<li>
<p>Establish sample collection networks (to collect, record and voucher ~8000 species)</p>
</li>
<li>
<p>Put in place large-scale sequencing and analytic processes (including for single cells and small-bodied taxa)</p>
</li>
<li>
<p>Generate reference quality, deeply annotated genome assemblies for 2000 species</p>
</li>
<li>
<p>Develop portals to disseminate the reference genomes, empowering wider scientific communities to embrace genomics in their future endeavours</p>
</li>
<li>
<p>Share expertise in protocol development and informatics among the Darwin Tree of Life partners to strengthen institutional capacities across the consortium, and with the global EBP.</p>
</li>
</ul>
|
| 30/09/2019 |
£2,734,774 |
|
INTERNATIONAL VACCINE INSTITUTE |
<p style="margin-left: 0cm; margin-right: 0cm">This funding will build upon the IVI internal investment and will accelerate the process that would otherwise be conducted serially after successful completion of the initial IVI funded portion and after securing additional funding. Support from the Welcome Trust will expedite the development of this vaccine through the preclinical toxicology stage and anticipate its use in Phase I human clinical trials. The long-term aim of this project is to develop a trivalent vaccine through efficacy, in-country licensure (marketing authorization in the country of manufacture), World Health Organization prequalification (WHO PQ), and any necessary policy recommendations from SAGE and national technical advisory groups. WHO PQ will pave the way for this vaccine to be purchased through Gavi/ UNICEF funding.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£1,060,379 |
|
UNIVERSITY OF MELBOURNE |
Early identification and inteNention for schizophrenia and other psychoses is a
key focus in psychiatry. It remains unclear what the core disturbances of
schizophrenia are, which hampers early identification and inteNention strategies.
Findings from recent phenomenological, neurocognitive and neuroscience
research converge around the concept of disturbed basic self-awareness as a
core feature of schizophrenia spectrum disorders. This refers to a disruption in the
automatic, implicit sense of ownership of one's experience and sense of agency,
expressed in a range of anomalous cognitive, bodily and interpersonal
experiences. Although the phenomenological, neurocognitive and neuroscience
research findings have been highly congruent, the link between these domains
with regard to basic self-disturbance has not yet been directly tested.
The current study will be the first to directly empirically test this integrated
neurophenomeno/ogica/ self-disturbance model. The study will assess the
relationship between phenomenological, neurocognitive and neurophysiological
measures of basic self-disturbance in three samples: 1. Patients at high risk of
psychosis (N=400), 2. Patients with non-psychotic disorders (N=100), 3. Healthy
control participants (N=50). The relationship between these measures will be
analysed as well as their prognostic implications in the high risk for psychosis
sample. The research will enhance understanding of core cross-domain features
of schizophrenia, result in a clinical tool for improved identification of young people
at high risk of progressing to psychotic disorders, and point towards mechanism-based
treatment targets. |
| 30/09/2019 |
£500,000 |
|
NOVARTIS INSTITUTE FOR BIOMEDICAL RESEARCH |
<p>Dengue disease is on the World Health Organization (WHO) list of "10 threats to global<br>
health in 2019". The virus infects an estimated 50-100 million people per year, causing<br>
22,000 deaths. There is no drug available to treat dengue, so patients are given supportive<br>
therapy with fluid replacement. At the Novartis Institute for Tropical Diseases (NITD), more<br>
than a decade of research has yielded a first-in-class dengue virus inhibitor. The novel<br>
compound directly blocks viral replication and demonstrates efficacy against all four<br>
serotypes of dengue virus in cultured cells, as well as in infected mice. It also shows a good<br>
safety profile in preliminary rat and dog studies. With the support of a Wellcome Trust<br>
Innovator grant, we propose to progress the compound into advanced preclinical safety<br>
testing. These key studies should enable the compound to enter clinical trials, and potentially<br>
deliver the first oral drug for dengue virus.</p> |
| 30/09/2019 |
£190,167 |
|
AFRICAN ACADEMY OF SCIENCES |
<p style="margin-left: 0cm; margin-right: 0cm"><strong>The AAS Research Management Programme in Africa (ReMPro Africa) </strong></p>
<p style="margin-left: 0cm; margin-right: 0cm">The Programme is a response to the critical gaps that were identified in building the continent’s research and development ecosystems that support a vibrant research culture and leadership.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Research management is a core component of the African research ecosystem. However, there is limited skill-sets and capacities in many African institutions of higher learning and research. The lack of specialist research management threatens the integrity and quality of research coming out of African institutions. There is, therefore, an urgent need to develop research management in order to drive the research enterprise and improve research productivity. In other words, research management is a catalyst for the research enterprise.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Research management is defined as; ‘<em>all administrative, operational and management functions and activities an institution undertakes to support the output of its researchers, other than the conducting of the research itself<strong>[1]</strong>.’</em> Investing in the transformation of research management in Africa will have a catalytic impact on the quality, quantity and impact of research undertaken.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The AAS, and partners, seek to enshrine research management at the heart of the research support system, supporting institutions and their researchers by delivering a coordinated programme to nudge its transformation.</p>
<p> </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£20,000 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p>The Agriculture, Nutrition & Health (ANH) Academy will be organising the 4th Annual ANH Academy Week from 24-28 June 2019 in Hyderabad, India. This follows three successful ANH Academy Weeks in Addis Ababa (2016), Kathmandu (2017) and Accra (2018)</p>
<p>The ANH Academy Week is an annual event open to the global research community, organised through the UK Aid funded Innovative Methods and Metrics for Agriculture and Nutrition Actions (IMMANA) programme. In order to maintain the scale, high quality and inclusive nature of the annual ANH Academy Week we are seeking funds to support specific elements of this year’s event. In particular, we are committed to bringing participants together from across the world and to providing spaces for networking and meaningful interaction. </p>
<p style="margin-left: 0px; margin-right: 0px">We would like to extend the participation of more presenters from developing countries, especially early career researchers. In light of this, we would like to request £20,000 which would be used to provide bursaries to selected early career researchers from low income countries, as well as going towards the costs of organising a networking event.</p>
|
| 30/09/2019 |
£15,258 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p style="margin-left: 0in; margin-right: 0in">This proposal is to request support to launch the WHO Snakebite Envenoming (SBE) Roadmap on the side of the World Health Assembly (WHA), on 23 May 2019. The event will have high level participation from countries, WHO Senior Management, Non-State Actors and antivenom manufacturers.</p>
<p style="margin-left: 0in; margin-right: 0in">In May 2018, the WHA adopted a resolution to address the snakebite envenoming that was led by Costa Rica and co-sponsored by 31 additional Member States.</p>
<p style="margin-left: 0in; margin-right: 0in">A SBE Roadmap has been developed with multi-stakeholders providing a clear plan of action and aligns with targets set WHO’s 13<sup>th</sup> General Programme of Work and the Sustainable Development Goals.</p>
<p style="margin-left: 0in; margin-right: 0in">Dr Mike Turner is a member of the WHO SBE working group and Wellcome Trust has been engaged in the process since the beginning and made it possible to host a small drafting group in Geneva, and the complete SBE WG in London in June 2018 that produced the zero draft. WT contribution goes beyond financial support but would contribute directly to the roadmap's implementation through reviving and stabilizing the market for effective antivenoms; accelerating research and innovation to improve existing antivenoms; developing alternatives and working with funders, researchers, policymakers and industry to accelerate progress.</p>
<p> </p>
|
| 30/09/2019 |
£829,430 |
|
UNIVERSITY OF OXFORD |
<p>None provided </p> |
| 30/09/2019 |
£47,104 |
|
UNIVERSITY OF NOTTINGHAM |
<p>This pilot research will lay the foundation for a larger project examining the experiences of Latin American women who are forced to travel across borders for abortion care due to barriers preventing them from receiving care close to home. This wider project will be exploring the barriers that prevent women from receiving safe, legal abortions in three countries in Latin America (Mexico, Peru, and Guatemala) and the strategies they devise to resist these barriers to seek reproductive healthcare through travel.</p>
<p>With this pilot research I will travel to Peru and Mexico (across a total of three trips) to set up my contacts with sexual health and activist organisations. This will ensure that I have the network to make my future research on this topic a success and I will conduct some pilot interviews to help me refine my research area and explore what the barriers to access are. This work will be supported by a research assistant in Mexico. When in the UK I will be strengthening my relationships with my ReproGeog research group and with policy practitioners and abortion organisations that are based in the UK but have an international reach beyond my study sites.</p>
<p> </p>
|
| 30/09/2019 |
£51,580 |
|
INSTITUT PASTEUR |
<p>Request for a financial support for an International Course on Antibiotics and Resistance </p>
<p>Held on a yearly basis ( 2019 will be the 4th edition)</p>
<p>bringing together leaders in academics and industry (40) with trained scientists (40) who seek state-of-the-art notions on resistance mechanisms and new antibiotic discovery</p>
<p>The course takes place at Fondation Mérieux (Annecy, France) for 9 days, allowing close interactions between students and teachers to build an international cadre of collaborative, well networked, and highly trained specialists.</p>
|
| 30/09/2019 |
£50,047 |
|
GLASGOW CALEDONIAN UNIVERSITY |
<p style="margin-left: 0cm; margin-right: 0cm">One of the biggest issues in the UK is the stubbornness of health inequalities. Despite years of attention, health gaps between best and worst-off are actually widening. Implementing a health-in-all-policies (HiAP) approach can help to challenge health inequalities. This relies on political will and implies resource shifts across sectors – a politically contentious issue. We do not know how UK intersectoral policymaking on health inequalities occurs or what public preferences are for related policy proposals.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The primary purpose of this funding is to develop my thinking around: a HiAP approach to tackling health inequalities; how to elicit public preferences for policies that impact on health inequalities; and, the wider implications of how evidence of public preferences could inform intersectoral priority setting decisions on health inequalities. Research development work will be undertaken using a mixture of desk-based research and qualitative interviews that ultimately will be used to inform a Fellowship application. This work will focus on: </p>
<ol>
<li>Developing arguments for why public preferences for policies that impact on health inequalities are needed</li>
<li>Network building</li>
<li>Identifying candidate non-health sector policies that impact on health inequalities</li>
<li>Understanding intersectoral priority setting in relation to health inequalities</li>
</ol>
|
| 30/09/2019 |
£112,276 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p>This proposal is designed to undertake the work that is essential to prepare for a potential clinical trial of snakebite treatment in eSwatini. It will evaluate the burden and clinical pattern of disease, assess feasibility from a logistic and governance perspective and undertake pre-clinical efficacy studies of selected antivenoms to inform the choice of antivenoms to study. </p>
<p>Key goals are: </p>
<ol>
<li>Determination of the number and location of eSwatini snakebite victims that could be enrolled into a trial</li>
<li>Assessment of the clinical, logistic and governance capacity for potential clinical trials</li>
<li>Identification of the most appropriate antivenoms for a clinical trial based upon preclinical efficacy</li>
<li>Assessment of the natural history of venom-induced necrosis and determination of most appropriate potential outcome measures in a prospective clinical observation study of patients envenomed by spitting cobras</li>
</ol>
|
| 30/09/2019 |
£925,102 |
|
UNIVERSITY OF OXFORD |
<p>The MORU, a Wellcome Africa Asia Programme (APP), is a strategic partner of Wellcome Innovations flagship “Innovation for impact in LMICs” undertaking a number of translational research projects related to this flagship portfolio. The flagship translational resource supports common infrastructural and discipline capacity needed to support the Flagship programmes.</p> |
| 30/09/2019 |
£52,363 |
|
UNIVERSITY OF OXFORD |
<p>The MORU, a Wellcome Africa Asia Programme (APP), is a strategic partner of Wellcome Innovations flagship “Innovation for impact in LMICs” undertaking a number of translational research projects related to this flagship portfolio. The flagship translational resource supports common infrastructural and discipline capacity needed to support the Flagship programmes.</p> |
| 30/09/2019 |
£2,000,000 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p><strong>Background:</strong> The tenth epidemic of EVD in the Democratic Republic of the Congo, affecting the provinces of North Kivu and Ituri, was declared by the Ministry of Health on 1 August 2018. The initial strategic response plan (SRP-1) covering the period up to in October 2018 and then PSR-2 for the period from October 2018 to January 2019 facilitated the deployment of the important resources of the Congolese Government and its partners.<br>
<br>
Despite the complexity of this epidemic (dense and mobile population, insecurity, community resistance and risk of spread at the national and regional levels), the implementation of the interventions made it possible to significantly reduce the spread of the outbreak in the initial epicentres of Mangina / Mandima and Beni and stopped transmission in some secondary foci like Tchomia, Masereka and Mutwanga.<br>
Nevertheless, since the beginning of December a significant increase in the incidence of new cases has been observed particularly along the corridor towards the large urban center of Butembo (health zones of Butembo and Katwa) and beyond in the zone of Kayna health center located about 150 km from Goma. In addition, active outbreaks have emerged to the north, particularly in the health zones of Komanda and Oicha.<br>
<br>
<strong>The main objective for the current response efforts is to</strong>: Interrupt the transmission of Ebola virus disease in North Kivu and Ituri Provinces and prevent its spread to other provinces of the Democratic Republic of the Congo and neighbouring countries.<br>
</p> |
| 30/09/2019 |
£764,647 |
|
TRANSFORMATIVE AI LIMITED |
Transformative creates artificially intelligent algorithms to predict acute
outcomes of chronic diseases. Using advanced AI and statistical analysis, our
algorithms detect minute changes in patient physiology and predict the imminent
risk of serious arrhythmia. Our initial focus is on ventricular and atrial fibrillation.
The former is the leading cause of Sudden Cardiac Arrest while the latter is
responsible for stroke among elderly patients. Our ultimate mission is to deploy
predictive analytics for a wide range of medical conditions. With Wellcome Trust
funding, we aim to optimise the algorithms through data obtained in partnerships
with hospitals, expand our team of data scientists to accelerate development,
and hire software developers to build accompanying software for the algorithms |
| 30/09/2019 |
£134,200 |
|
MEDICINES DISCOVERY CATAPULT |
<p>In the context of the PC, successful academic engagement will need to be underpinned by effective and coordinated outreach efforts from MDC, as the leading organisations, and the PC Partners.</p>
<p><br>
The work proposed for funding from the Wellcome Trust has been informed by discussions with the PC Partners, including 2 Charities and 6 Pharma, and the Wellcome Trust, and developed by MDC PR and Marketing team. This work will enhance the PC’s overall impact in psychiatry disease, and complement the consortium’s main focus, by creating and strengthening the links between academia and industry in the area, consolidating the networks of exchange that sit outside the consortium, and by creating a longer-term appetite for more collaboration to advance drug discovery, ultimately enabling a robust drug-discovery pipeline.</p>
<p>The activities proposed will aim to achieve the following outcomes, with a focus on an academic audience nationally and internationally: PC promotion & awareness within the academic community; academic engagement and training; scouting of opportunities; sourcing of high-value projects for the PC.</p>
<p>The main activities proposed will include: website development and marketing via online platforms; business development through conferences; engagement events such as webinars and workshops. Detailed information is provided in the proposal.</p>
|
| 30/09/2019 |
£387,458 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p>Work is good for mental health but a negative working environment can lead to physical and mental health problems. Depression and anxiety have a significant economic impact; the estimated cost to the global economy is US$ 1 trillion per year in lost productivity. Harassment and bullying at work are commonly reported problems, and can have a substantial adverse impact on mental health. There are many effective actions that organizations can take to address mental health in the workplace; such actions may also benefit productivity. WHO will produce evidence-based guidelines on this and will seek to do this in collaboration with ILO.</p>
|
| 30/09/2019 |
£500,000 |
|
UNIVERSITY OF GLASGOW |
<p>The Scottish Public Engagement Network proposes a collaborative pilot scheme to allocate Wellcome Research Enrichment for Public Engagement funding in Scotland between July 2019 and July 2020. The universities of Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews will form a steering group, with financial and administrative processes co-ordinated by the University of Glasgow. ScotPEN has an established profile, communication channels and collaborative relationships across the public engagement sector. Combined with our local institutional expertise, this will help us raise awareness, tailor support to researchers’ needs and broker productive partnerships. Based on identified need, we plan to share training opportunities and provide bespoke mentoring workshops. A separate assessment panel, chaired by Paul Manners (NCCPE) and including academic and community partners, will ensure independent and transparent decision-making. We will hold two funding calls (deadlines in September and March) offering awards of up to 5% of a researcher’s main Wellcome grant, or £100,000. We anticipate this pilot will have synergistic effects on institutional capacity and ScotPEN through shared learning and strengthened relationships. This should improve quality of projects and increase engaged research. Progress will be examined in interim and end reports and opportunities to capture longer term impact will be explored with Wellcome.<br>
</p>
|
| 30/09/2019 |
£500,000 |
|
UNIVERSITY OF OXFORD |
<p>We will pilot a new way of encouraging, supporting and awarding Wellcome Public Engagement (PE) Enrichment grants through a devolved funding model and an internal collaborative and creative approach, together with a robust decision-making process. Two levels of funding will be offered: <strong>Small Awards</strong> and<strong> Large Awards</strong>.</p>
<p>We will reach out to and provide pre-application support to all Wellcome-funded researchers to develop their ideas and project plans through workshops and one-to-one surgeries. The post-award support programme will also provide Public Engagement with Research (PER) and evaluation advice and guidance to all awardees. We will also pilot a new PER grant application and decision-making process focused on effective project planning and enabling discussion between the applicants and the panel before the funding recommendations are made.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The key aims of this programme are to encourage a diverse range of researchers to apply, including those that are new to public engagement, and to enhance the quality of the proposals and the impact of the funded activities. Evaluation will be an important aspect of this pilot and we will gather evidence and data on the outcomes and impacts of the funded projects and the challenges and successes of running the programme in this way.</p>
|
| 30/09/2019 |
£2,929,772 |
|
UNIVERSITY OF ANTWERP |
<p> <br>
The purpose of VALUE-Dx is to facilitate and accelerate the rigorous assessment and implementation of (new) diagnostic technologies into healthcare settings, by establishing the infrastructure, methods, processes and approaches needed to understand, evaluate, assess, and demonstrate the multi-faceted value of diagnostics and overcome the associated barriers to their widespread adoption and use.<br>
<br>
The project intends to transform clinical practice, improve patient outcomes, and combat AMR, through the widespread use of clinical and cost-effective innovative diagnostics strategies to achieve more personalised, evidence-based antibiotic prescription and use in community care settings.</p>
|
| 30/09/2019 |
£199,914 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">This project aims to address the problem that the sheer number of outbreak events around the world prevents experts involved in outbreak detection and response from analysing and reflecting on the lessons learned from previous outbreaks because they are so busy responding to the latest emergency. This knowledge is critical to improving our understanding of emerging infections and bringing them under control. We propose to extend an existing sucessful collaborative project between the World Health Organization Health Emergencies Department (WHE) and the London School of Hygiene & Tropical Medicine (LSHTM) to provide dedicated expertise to support WHE and others to publish data on outbreaks.Jillian Murray a Research Fellow at LSHTM, with support from Jimmy Whitworth (LSHTM) and Oliver Morgan (WHE), will spend substantial time working with WHO in Geneva, the regional WHO offices, and where practical, with the relevant country offices. She will collaborate with WHO, Ministries of Health, and other relevant partners, to analyse data available following disease outbreak responses, and work to develop peer-reviewed publications and other scientific summaries of the epidemiology and control response to important outbreaks of infectious diseases globally. </p>
|
| 30/09/2019 |
£690,687 |
|
UNITED NATIONS |
<p>In 2018, the health team in the Executive Office of the Secretary-General focused on positioning global health as a priority within the UN Secretary-General’s and Deputy Secretary-General’s programme of work, pivoting the UN system from vertical action for health issues to a more holistic effort for the healthy societies, and ensuring high political profile within intergovernmental and global events. This centred around the identification of key global health issues that the UN Secretary-General will champion and is articulated in his Global Health Engagement Strategy. In order to support these efforts, this proposal focuses on following areas of work from 2019 to 2021:</p>
<ol>
<li>Operationalize the Secretary-General’s Global Health Engagement Strategy, fully leveraging the Secretary-General’s and Deputy Secretary-General’s unique voices and platform</li>
<li>Strengthen the UN’s work on mental health to inform a coordinated response that addresses key gaps and raises ambition for greater investments in mental health</li>
<li>Continue to position antimicrobial resistance (AMR) within the political discourse and SDG implementation and review. Including, providing strategic support to the Inter-Agency Coordination Group on AMR (IACG) as it finalizes a set of recommendations for the Secretary-General in Spring 2019.</li>
<li>Encourage greater cross-sectoral linkages to improve health outcomes, particularly in the context of climate change.</li>
</ol>
|
| 30/09/2019 |
£50,500 |
|
UNIVERSITY OF OXFORD |
<p>Antimicrobial resistance (AMR) is one of the greatest public health emergencies of our time. Many governments are becoming increasingly concerned about AMR and are aware that urgent measures are needed. In the UK, in particular, the 2016 O’Neill AMR Review, government expert reports like the 2018 Parliamentary Office of Science and Technology on AMR and Immunisation, and efforts of the UK’s Chief Medical Officer indicate the high level of current political concern about antibiotic stewardship. But AMR is not a problem that can be fully mitigated at the national level: tackling AMR requires global and multi-sectoral action. Recent UK leadership on AMR is an important step in the right direction but will not be enough. For international stewardship efforts to be truly effective, what is needed is a lasting international agreement – a grand bargain – on how we collectively manage the antimicrobial commons in order to ensure sustainable access to these life-saving medicines over the long-term for everyone’s benefit. We propose to support dialogue on the necessary components of such a grand bargain by organising two meetings of experts and policy makers to discuss, design, and promote a possible grand bargain on AMR.</p>
|
| 30/09/2019 |
£50,000 |
|
JISC |
<p>Support for a one-year employment of a licensing manager to negotiate transformative agreements that meet the requirements of the Wellcome Trust OA policy.</p> |
| 30/09/2019 |
£984,615 |
|
UNICEF UK |
<p>Despite the availability of inexpensive treatments for conditions such as pneumonia, malaria, diarrhoea and neonatal sepsis, children are still dying due to lack of access to antibiotics for these conditions. While a large proportion of deaths caused by infections could be averted by access to timely and appropriate antimicrobial treatment, this needs to be done under well-managed conditions, since inappropriate use can contribute to the accelerated spread of resistance. In this project, Unicef will work with in-country practitioners and researcher in Cambodia, China and Vietnam, Tanzania and South Africa to identify the key challenges that inhibit access to off-patent antibiotics, undertake research regarding their use and stewardship in resource-constrained settings, and support the development of practical tools that help close avoidable access gaps whilst reducing inappropriate use of antibiotics. All countries will have government approved national action plans for AMR.<br>
The key goals are:</p>
<ul>
<li>5 in-country stakeholder workshops to map the context and identify research priorities</li>
<li>One call for letters of intent solicited</li>
<li>Up to 10 projects funded</li>
<li>2 regional protocol development workshops held, resulting in up to 10 research project protocols</li>
<li>2 regional interpretation and dissemination workshops organised</li>
<li>Up to 10 publications to peer reviewed journals submitted</li>
</ul>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£9,599,726 |
|
UNIVERSITY COLLEGE LONDON |
<p><br>
Understanding the neural circuit basis of behaviour is one of the great challenges in biology. Yet no single laboratory can study the many brain regions, connections, and cell types working together o coordinate decision-making. There is thus a disparity between the capacity of individual laboratories and the complexity of problems being addressed. The International Brain Laboratory orchestrates the efforts of 21 experimental and theoretical laboratories to understand a single behavior. By standardizing experimental procedures and data pipelines, we enable the data acquired by different laboratories to be assembled into a large combined dataset. Our mouse decision-making task requires valuation of different choices based on sensory evidence, choice selection based on this valuation, and integration of prior experience to update a model of the world. We seek a comprehensive understanding of the neural mechanisms underlying these functions, at scales ranging from single neurons to local microcircuits to inter-area communication. To do so we will harness powerful electrophysiological, optical, and genetic tools, and exploit the rich set of theories and analytical approaches developed in recent years. This large-scale effort will provide the first end-to-end “standard model” of a complex mammalian behavior, and inspire new ways to collaborate on difficult problems in neuroscience. <br>
</p>
|
| 30/09/2019 |
£464,668 |
|
PATH |
The goal of the project is to develop a novel oral, inactivated whole-cell, cross-protective vaccine against Shigella, a major cause of diarrhea among children in low-resource settings. The vaccine candidate, the Shigella truncated mutant (STM), will be delivered with a mucosal adjuvant, which can improve immune responses. The vaccine candidate’s inactivated Shigella flexneri 2a whole cell strain is genetically engineered to maximally expose conserved surface antigens by shortening O-polysaccharide sidechains (O-PS), which typically mask certain, often conserved, antigens on the cell surface. The unmasking of surface antigens could allow the STM to also express and maximally present antigens of other pathogens. Therefore, the project will also assess this property of the STM using a novel conserved heptasaccharide antigen of Campylobacter jejuni, another leading cause of diarrhea." |
| 30/09/2019 |
£3,853,752 |
|
UNIVERSITY OF MELBOURNE |
Significant progress has been made over the last twenty-five years in adopting strategies for reducing the rate of progression to psychosis in people with subthreshold symptoms at clinical risk/ultra-high risk (UHR) of psychosis. However, more effective treatments are still required to further improve short and longer-term outcomes. This is especially true during the at-risk stage of a psychotic disorder.
The Cannabidiol study aims to answer an important clinical question: can subthreshold psychotic manifestations be treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa? Cannabidiol is a promising treatment for testing due to its encouraging safety and tolerability profiles and strong preliminary evidence for its ability to reduce psychotic symptoms. We will test CBD for the first time in the UHR phase of psychotic disorder.
The study design encompasses a three-arm randomised controlled trial (RCT) – with a placebo arm and 2 discreet drug doses. Participants will be recruited from eight recruitment sites across 4 states of Australia utilising a nationwide network of early psychosis services and related research network.
The primary outcome of the study is the Improvement of positive psychotic symptoms on the Comprehensive Assessment of At-Risk Mental States (CAARMS) at 12 weeks. Secondary outcomes include the following: Improvement of other domains of psychopathology (negative symptoms, depression and anxiety); distress associated with positive psychotic symptoms; transition to psychotic disorder; overall clinical improvement (CGI); social and occupational functioning; quality of life; safety and tolerability at 12 weeks; cost-effectiveness.
The primary hypothesis is that the CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. Predictive biomarkers will also be collected from blood and urine parameters of cannabinoids; inflammatory cytokines and oxidative stress measures from plasma. Levels of hair cortisol will also be examined.
The key deliverable outcome in this project is to provide a novel biological treatment for young people at UHR of psychosis that can be used in a wide variety of settings, from primary care to specialist, and be easily extended and translated to longer-term treatment
|
| 30/09/2019 |
£250,000 |
|
CARNEGIE UK TRUST |
<p>This proposal is for a one-year £500k joint funded grants scheme between Wolfson Foundation, Wellcome Trust and Carnegie UK Trust. The scheme will support public libraries across the UK to deliver public engagement with research in the fields of science, humanities and the arts.</p>
<p><br>
Public libraries will be supported with access to funding (<£25k), a grants plus programme with opportunities for networking and learning, and support with evaluating the impact of their work. The funding scheme is for year one of a potential three-year opportunity. The grant will be led and administered on behalf of the funders by Carnegie UK Trust.</p> |
| 30/09/2019 |
£52,920 |
|
DIAMOND LIGHT SOURCE LTD |
<p>Diamond Phase III Capital</p> |
| 30/09/2019 |
£2,430,465 |
|
DIAMOND LIGHT SOURCE LTD |
<p>Diamond Operating Capital</p> |
| 30/09/2019 |
£728,598 |
|
SURGIBOX INC |
<p>18 million lives and GBP 1. 1 trillion GOP are lost annually to surgical<br>
conditions, ranging from obstructed labor and appendicitis to cancer and<br>
trauma. Disasters further destroy established surgical infrastructure. Even<br>
when available, austere surgery is fraught with high infection risks to<br>
patients and providers alike. Most bacteria in deep wound infections<br>
originate from the intraoperative air or skin. 70% of surgical and<br>
obstetrical/gynecological providers globally are exposed to bodily fluid<br>
splashes during procedures each year, infecting 85,000 providers each year<br>
with HIV and hepatitis. SurgiBox aims to provide state-of-the-art levels of<br>
protection through a system that simplifies logistics. Teams operate through<br>
ports in a plastic bubble sealed via antimicrobial incise drape to the patient's<br>
skin. The bubble is kept clean through an advanced airflow system and<br>
protects teams from fluid splashes. Everything runs off batteries and<br>
components that fit into a typical backpack.</p> |
| 30/09/2019 |
£508,763 |
|
UNIVERSITY COLLEGE LONDON |
<p>Cytomegalovirus (CMV) affects 50-80% of UK adults and is of limited significance in<br>
healthy individuals. However: following stem-cell-transplantation (allo-SCT), CMV can be<br>
life-threatening. Despite advances, drug treatments are unsatisfactory due to severe<br>
toxicities, viral resistance, high costs and prolonged hospitalisation. An alternative<br>
approach is to harness the immune-system to target CMV. Clinical trials of CMV T-ee//<br>
immunotherapies in allo-SCT patients appear to control CMV with minimal side-effects.<br>
However, al/o-SCT patients at highest risk for CMV are those with graft-versus-hostdisease<br>
(GvHD), a devastating condition requiring treatment with immunesuppressing<br>
drugs including glucocorticoids. Glucocorticoids improve GvHD, but kill CMV T-ee/Is,<br>
worsening CMV infection and making patients ineligible for CMV immunotherapy trials. To<br>
address this unmet need, we will engineer CMV-specific T-ee/Is in the laboratory to be<br>
glucocorticoid-resistant in order to bring CMV immunotherapy to patients with GvHD<br>
requiring glucocorticoids, hoping to reduce CMV-related morbidity, mortality, antiviral drug<br>
use and hospitalisation in this population."</p> |
| 30/09/2019 |
£495,385 |
|
OSIVAX |
<p>"Every year, -10% of global population suffer symptomatic flu, leading to -5<br>
million severe cases and >650,000 deaths. Seasonal influenza remains a<br>
devastating disease and pandemic flu a major threat that would cause >30<br>
million deaths within the first 6 months. Current vaccines target highly variable,<br>
strain-specific surface viral antigens restricting duration of protection to a specific<br>
season and limiting efficacy (41% on average, 25% in elderly). We will<br>
circumvent the need for annual vaccine updates by 1) targeting the intraviral<br>
nucleoprotein (NP), highly conserved across influenza strains, 2) transforming<br>
NP into a highly immunogenic antigen triggering robust immune responses. By<br>
targeting the full-length NP antigen, our universal flu vaccine could be a best-inclass<br>
candidate in terms of population and flu strains coverage. With a nonadjuvanted,<br>
highly purified recombinant protein composition and a scalable<br>
manufacturing process, the vaccine has a leading safety and cost profile.</p> |
| 30/09/2019 |
£763,346 |
|
IMPERIAL COLLEGE LONDON |
<p>Conventional MRI cannot accurately diagnose tissues such as ligaments, tendons and<br>
cartilage. Patients, who suffer chronic pain and seek cure, often undergo arthroscopy, a form<br>
of keyhole surgery, often without much certainty about their value. We have developed an<br>
entirely new type of MRI scanner, which enables us to obtain non-invasively detailed new<br>
information about microscopic properties, potentially providing new and safe methods for<br>
diagnosing disease or injury in joints. This scanner is open and very comfortable for<br>
claustrophobic patients. It is also significantly cheaper, very compact and much easier to<br>
install than those normally found in hospitals. In this project we will provide the evidence<br>
needed to adopt the new methods in practice, by conducting trials, first with healthy<br>
volunteers, and then with selected patients already undergoing treatment. This could lead to rapid and accurate MRI imaging as a new standard technique for diagnosing injury or<br>
disease of joints.</p> |
| 30/09/2019 |
£4,592,577 |
|
PROKARIUM |
<p>to be confirmed finalising information that can be shared</p> |
| 30/09/2019 |
£249,884 |
|
UNIVERSITY COLLEGE LONDON |
<p>Global Health 50/50 seeks to advance action and accountability for gender equality in global health. Co-led by Professor Sarah Hawkes and Dr Kent Buse and hosted by the UCL Centre for Gender and Global Health, GH5050 has three key assets: the groundbreaking 2018 GH5050 report, a review of the gender policies and practices of 140 organisations active in health, its high powered Advisory Council whose members engage their networks to influence global health policy and practice, and a team of dedicated strategists, researchers and gender experts.</p>
<p>GH5050 has three strategic objectives:</p>
<ol>
<li>
<p>Shaping ideas: Increase knowledge and awareness on and reframe gender equality in global health to shift gender norms</p>
</li>
<li>
<p>Driving institutional change: Advocate and track progress to drive accountability for gender equality in global health</p>
</li>
<li>
<p>Shifting interests: Develop a policy community to advance gender equality in global health</p>
</li>
</ol>
<p>Under this grant, GH5050 will work to achieve these objectives through a range of activities, including publication and dissemination of its 2019 and 2020 reports, implementation of systematic policy engagement strategies and tracking organisational change. GH5050 also plans to adapt its model in several countries by strengthening the capacity of diverse policy collectives and linking them to policy makers.</p>
|
| 30/09/2019 |
£27,746 |
|
UNIVERSITY OF STELLENBOSCH |
<p>Provoked and inspired by contemporary debates around engagement, epistemic justice, and the decolonization of science, the proposed project aims to begin to build a critically engaged global health studies in (and from) Africa and the global South. What might ‘global’ health become, the project asks, if the power to shape it shifted to the South, into the hands of those often positioned as the objects of its interventions? Through critical dialogues and collaborative processes of participatory knowledge exchange, we hope to create space for new forms of critique and engagement to emerge from this more proximate positionality. </p>
<p>The proposed project is structured into three stages, which explore the past, present, and future of global health in Africa. In the first stage, through critical reading and direct exchanges with prominent figures in the field, we will focus on understanding the ‘genealogy’ of global health in Africa. In the second stage, we will look to the present moment, asking how postcolonial politics and critical social theory might disturb how we think about global health. The final stage will develop a collaborative vision for the future of critical global health studies in Africa and the global South.</p>
|
| 30/09/2019 |
£22,741 |
|
UNIVERSITY OF CENTRAL LANCASHIRE |
<p>Violence has far-reaching impacts for people’s lives. Being subject to violence causes physical and/or psychological health and wellbeing harms that lead to some degree of health loss, functional capacity loss and/or disability and which often endure across people’s lives. The type of violence - its severity, whether it has a sexual element to it and the relationship between the victim and perpetrator will affect the scope of harms suffered and the health and wellbeing changes experienced. Research investment in violence as a public health issue over the last two decades means that there is a growing body of research about harms and altered health and wellbeing experiences associated with violence. This exploratory research project involves a systematic scoping review to identify, collate, chart and summarise the extent of our current knowledge of the harms and altered health and wellbeing experiences associated with contextually different types of violence. This new outline of the violence, health and wellbeing knowledge landscape will be shared with key stakeholder groups to shape and prioritise future directions of research and innovation to extend our knowledge so that victim/survivors receive the most appropriate care and intervention. </p>
|
| 30/09/2019 |
£351,475 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">Existing antimicrobial resistance (AMR) surveillance systems are based mostly on diagnostic microbiology laboratory antimicrobial susceptibility testing results alone, which limits direct assessment and subsequent modelling of the clinically relevant impacts and burden of drug resistant infections (DRI). Tools to capture and analyse AMR data in LMICs are scarce, which hinders engagement with and utilisation of available data.</p>
<p style="margin-left: 0cm; margin-right: 0cm">To fill these gaps, the major aim of this project is to develop and test a comprehensive data capture system for patient-focussed AMR surveillance in LMIC settings. Data collected will expand on the pathogen-focussed WHO Global Antimicrobial Resistance Surveillance System to enable accurate classification of infection syndromes and outcomes. These data will be of critical importance to estimate syndromic and/or pathogen outcomes and associated costs: <em>i.e.</em> how many people die from DRIs and how much does it cost?</p>
<p style="margin-left: 0cm; margin-right: 0cm">Project objectives are to:</p>
<ul>
<li>Establish a framework for patient-focussed DRI surveillance tailored to LMIC settings;</li>
<li>Develop and refine tools for AMR data capture, verification, and interactive visualisation;</li>
<li>Produce comprehensive diagnostic stewardship and surveillance training materials;</li>
<li>Pilot surveillance at two sites in Southeast Asia;</li>
<li>Prepare for wider roll out of surveillance at sites across the Wellcome Asia Programme network and beyond.</li>
</ul>
|
| 30/09/2019 |
£923,235 |
|
UNIVERSITY OF STRATHCLYDE |
<p>The programme of exchange and networking proposed here aims to build on preliminary experiences of connecting and co-working between UK and Chinese institutions in order to:</p>
<p> </p>
<p style="margin-left: 0cm; margin-right: 0cm">i. Drive the Medical Humanities as a mature disciplinary field in China.</p>
<p style="margin-left: 0cm; margin-right: 0cm">ii. Grow collaborative working between an expanding number of Chinese institutions and UK universities in the Medical Humanities.</p>
<p style="margin-left: 0cm; margin-right: 0cm">iii. Establish a generation of scholars in the Medical Humanities with experience of research, training and teaching in both academic cultures and the capacity to build the field in China and elsewhere.</p>
<p style="margin-left: 0cm; margin-right: 0cm">iv. Equip graduates of the programme with Medical Humanities knowledge and perspectives to enable them to engage in fresh ways with human health problems and challenges as they enter careers and sectors beyond academe around the world.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm">It will connect the partners at the institutions above as they work together to enable:</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm">i. 18 M.Sc. students from SHU, SASS and Fudan to complete Masters degrees at the CSHHH Glasgow and the CHSTM at Manchester University.</p>
<p style="margin-left: 0cm; margin-right: 0cm">ii. 9 one-year Early Career Researcher (ECR) Medical Humanities Fellowships at SHU, SASS and Fudan University.</p>
<p style="margin-left: 0cm; margin-right: 0cm">iii. 6 Medical Humanities events (3 workshops in UK and 3 conferences in China) to showcase the network.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£49,954 |
|
KING'S COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Severe growth faltering leading to stunting and undernutrition remains highly prevalent in low- and middle-income countries (LMICs) and is estimated to play a role in 45% of under-5 deaths. However, despite many decades of research, the precise aetiology of this growth faltering remains obscure. The <u>D</u>iet <u>o</u>n <u>M</u>icrobiome interactions for better <u>I</u>mmu<u>n</u>e <u>O</u>utcomes (DoMInO) consortium brings together multidisciplinary research scientists with expertise in nutrition, breast-milk bioactives, gut microbiome and immunity to:</p>
<ol>
<li>Advance our understanding of the interactions between diet, gut microbiome and human immunity, especially in LMIC settings.</li>
<li>Conduct a small study (20 mother-infant pairs) to:</li>
</ol>
<ol style="list-style-type: lower-roman">
<li>Test systems and methods for the detailed assessment of diet on microbiome interactions and infant vaccine responses, as a proxy for infant immune responses.</li>
<li>Develop a package of robust methods and assessment protocols for integration into future research proposals.</li>
<li>Obtain variance metrics from all assays to be used as a basis of power calculations for a substantive future study.</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">Together, this work will underpin the development of future large research grant applications led by the DoMInO consortium.</p>
|
| 30/09/2019 |
£49,412 |
|
UNIVERSITY OF SOUTHAMPTON |
<p>Disease and under-nutrition in children can exert profound effects on growth and development and have adverse later effects that continue into adulthood. The treatments used in the management of disease can also exert effects which although curative have immediate short-term effects on nutritional state and metabolism but also persist into later life with increased morbidity and mortality. At the heart of many of these disease and treatment-induced changes in metabolic regulation and control are attributable to a limited number of cellular processes relating to cellular bioenergetics, redox/antioxidant state and inflammation. Within this paradigm, we seek support to develop a program of work to better understand how these processes contribute to an overt example of accelerated ageing/metabolic dysregulation seen in Children, teenagers and young adults(CTYA) surviving Acute Lymphoblastic Leukaemia(ALL) treated with allogeneic haematopoietic stem cell transplantation(HSCT) and intervene through targeted nutritional and exercise interventions. Our key goals are to i) build a multi-disciplinary team with complimentary capabilities to explore and explain the clinical and biological consequences of HSCT from the molecular to the whole body level, ii) synthesise the available evidence and case-identification, and iii) develop methodology, to work together to construct a high quality research program application for follow-on funding. </p>
|
| 30/09/2019 |
£653,308 |
|
INTERNATIONAL AIDS VACCINE INITIATIVE |
<p>An improved understanding of Lassa virus (LASV) seroprevalence and incidence is critical for proper design of LASV vaccine studies in humans. The current understanding of LASV epidemiology and circulating LASV genotypes is limited and based on small studies conducted several decades ago. The lead applicant has significant experience with large-scale epidemiology studies, and the participating investigators maintain a strong presence in Sierra Leone with extensive experience with Lassa field studies, including cross sectional studies and advanced LASV clinical laboratory capacity. The cross-sectional visits and surveillance for Lassa fever cases is conducted by teams of outreach workers, and the overall project team is well-versed in epidemiological survey methods, questionnaire administration, informed consent and collection of blood in community settings. We are seeking Wellcome Trust funding to determine incidence and genotypes of LASV in various hotspots in Sierra Leone to inform rationale vaccine trial design and trial site selection. To this end, we propose enrolling 8,000 volunteers from 40 villages (20 of which have participated in the initial cross sectional study and 20 are new study villages) for two visits to determine LASV incidence. Support for epidemiological research will strengthen our partner sites and develop local investigators’ capacity to conduct clinical trials.</p>
|
| 30/09/2019 |
£50,000 |
|
UNIVERSITY OF READING |
<p>Our aim is to develop a research proposal addressing the nutritional value of weaning foods across the entire food pathway; from crop variation to individual effects on metabolism and the microbiome. In order to achieve this, some method development and preliminary data will need to be generated. The key objectives for this pump priming funding are to:</p>
<ol>
<li>Identify potential sources of staple food crops that are commonly available in developing countries, for the purpose of weaning infants</li>
<li>Explore cooking and processing methods that exist within communities</li>
<li>Research and develop analytical methods for identification and quantification of key phytonutrient and anti-nutrient compounds in the crops of interest (maize, rice, cassava)</li>
<li>Develop <em>in vitro </em>model protocols for assessment of gut microbiome composition and immunology</li>
<li>Scout for possible cohort communities within developing countries</li>
<li>Arrange a collaborative sandpit meeting to bring together additional expertise, and host a workshop to develop ideas for a follow-on application</li>
</ol>
|
| 30/09/2019 |
£49,948 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0cm; margin-right: 0cm">Sarcopenia, defined as a loss of muscle mass and function, develops in the context of many disease states. Malnutrition in early childhood, which is still highly prevalent in low- and middle-income countries (LIMC), is associated with a loss of muscle mass; similarly, in the elderly and, interestingly, obesity has also been found to be related to sarcopenia. The study of the mechanisms to reverse muscle wasting is key in treating sarcopenia. There is a lack of understanding of the mechanisms that can drive the reverse of muscle wasting.</p>
<p style="margin-left: 0cm; margin-right: 0cm">An obvious approach to understand muscle homeostasis would be to use a myriad of ‘omics technologies, often called “deep-phenotyping”. However, deep-phenotyping based on one sample per participant is very noisy and challenging to interpret. This makes it difficult to apply in malnutrition. It is imperative that we have a paradigm shift in deep-phenotyping. We propose serial –omics analyses with an actual perturbation of metabolic homeostasis. These perturbations or “nudges” as defined by short acute metabolic challenges allow us to study the adaptability in muscle loss and regeneration in various sarcopenic populations.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We will organise two workshops, one on methods for evidence synthesis and one closed to develop a large collaborative proposal.</p>
|
| 30/09/2019 |
£243,591 |
|
INTERNATIONAL AIDS VACCINE INITIATIVE |
<p>Monoclonal antibodies (mAbs) are safe, effective treatments for many chronic<br>
diseases and have had a transformational impact on human health and<br>
medicine. However, access to mAb products is limited mostly to developed<br>
countries and/or private retail markets. In parallel, the potential for mAbs has<br>
expanded to passive immunization and therapy for infectious diseases. Many<br>
antibody-based candidates are being tested in clinical studies, but they have an<br>
unclear path to broad, affordable global access. The Wellcome Trust has<br>
commissioned the International AIDS Vaccine Initiative (lA VI) to prepare a landscape<br>
report on the challenges and investment opportunities for affordable global access to<br>
mAbs for prevention and therapy in low- and middle-income countries, with an<br>
analysis of opportunities to broaden access in high-income countries as a secondary<br>
goal. This report will include case studies for marketed antibodies and an application<br>
of these learnings to antibodies in development for multiple diseases, including<br>
infectious diseases.</p> |
| 30/09/2019 |
£29,885 |
|
ASHOKA UNIVERSITY |
<p style="margin-left: 0cm; margin-right: 0cm">The proposal is to build a substantive, international research agenda, delving into several, hitherto under-researched, dimensions of health outcomes through the creation and consolidation of a network of active researchers with a specific Southern focus. The proposed research agenda on economic and social determinants of health and morbidity will fill several knowledge gaps, as well as contribute specific inputs into policy and advocacy. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The team is interested in developing a research agenda along the following broad themes. The research would either be cross-national or focus on a specific country; however, the issues are broad enough to have wide ranging international implications. The broad themes are: </p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>1. Socioeconomic Status, Stigma and Health: Racial and Caste Disparities </strong> </p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>2. Women’s Health: Son Preference, Breastfeeding and Participation in Paid Work</strong></p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>3. The Origins of Health Disparities: The Importance of Early Childhood</strong></p>
<p style="margin-left: 0cm; margin-right: 0cm">4. <strong>Intersecting Identities: Gender, Caste and Class</strong></p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>5. Improving Measurement and Policy: Understanding Demand and Supply of Health Services</strong></p>
<p style="margin-left: 0cm; margin-right: 0cm">The plan is for the core researchers to participate in three closed-door workshops of 2-3 days each over 12 months. At the end of this period, we hope to be successful in building a coherent proposal for a research programme subsuming multiple linked projects. </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£30,000 |
|
BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL (BBSRC) |
<p>Development of a national network to support Imaging Scientists to enable to UK to remain at the forefront of biomedical research.</p> |
| 30/09/2019 |
£106,895 |
|
GLOBAL CAMPAIGN FOR MENTAL HEALTH |
<p style="margin-left: 0cm; margin-right: 0cm">This proposal is to complement and build on the work United for Global Mental Health (United GMH) is currently undertaking as part of a Wellcome grant. It aims to deliver a plan of action for the first four months of 2019 to shift the scale of ambition and sustain lasting activity on mental health.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The proposal plans activities covering four streams:</p>
<ol>
<li><strong>Catalysing commitment at Davos 2019</strong>: spurring greater action within the growing global movement and launching WEF’s new programme area</li>
<li><strong>Further amplification of the Lancet Report</strong> to new audiences</li>
<li><strong>Maintaining the Drumbeat </strong>using the Friendship Bench</li>
<li><strong>Sustaining work of the Blue Print Group</strong> through to the end of April 2019</li>
<li><strong>Operational support</strong> for United for Global Mental Health</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">The United GMH team will leverage support from Wellcome to mobilise partners, and the wider global mental health community, to maintain the momentum built since July to raise mental health further up the global political agenda in 2019. We are requesting £106,895 from Wellcome to further this work.</p>
|
| 30/09/2019 |
£714,682 |
|
UNIVERSITY OF CAMBRIDGE |
<p>"Medical imaging is routinely used for diagnosis and treatment monitoring of patients<br>
with solid tumours and is currently the only available technique for non-invasive<br>
assessment of treatment response. Currently, image segmentation and evaluation are<br>
mostly performed manually and semiquantitatively.<br>
We will develop an image analysis workflow that is automated, robust, capable of<br>
continuous learning and, more importantly, integrated in patient's clinical pathway. Our<br>
initial target population is patients with advanced ovarian cancer undergoing<br>
neoadjuvant chemotherapy, where current methods for evaluation of treatment<br>
response are suboptimal.<br>
In the longer term, we expect to integrate our tool in the clinical workflow for all cancer<br>
patients. The tool will also enable analysis of multi-centre clinical trials and multi-<br>
"Medical imaging is routinely used for diagnosis and treatment monitoring of patients<br>
with solid tumours and is currently the only available technique for non-invasive<br>
assessment of treatment response. Currently, image segmentation and evaluation are<br>
mostly performed manually and semiquantitatively.<br>
We will develop an image analysis workflow that is automated, robust, capable of<br>
continuous learning and, more importantly, integrated in patient's clinical pathway. Our<br>
initial target population is patients with advanced ovarian cancer undergoing<br>
neoadjuvant chemotherapy, where current methods for evaluation of treatment<br>
response are suboptimal.<br>
In the longer term, we expect to integrate our tool in the clinical workflow for all cancer<br>
patients. The tool will also enable analysis of multi-centre clinical trials and multi-<br>
"Medical imaging is routinely used for diagnosis and treatment monitoring of patients<br>
with solid tumours and is currently the only available technique for non-invasive<br>
assessment of treatment response. Currently, image segmentation and evaluation are<br>
mostly performed manually and semiquantitatively.<br>
We will develop an image analysis workflow that is automated, robust, capable of<br>
continuous learning and, more importantly, integrated in patient's clinical pathway. Our<br>
initial target population is patients with advanced ovarian cancer undergoing<br>
neoadjuvant chemotherapy, where current methods for evaluation of treatment<br>
response are suboptimal.<br>
In the longer term, we expect to integrate our tool in the clinical workflow for all cancer<br>
patients. The tool will also enable analysis of multi-centre clinical trials and multi-institutional CT datasets that so far have been hard to quantitatively evaluate due to heterogeneous image acquisition and reconstruction."</p> |
| 30/09/2019 |
£1,821,198 |
|
INSTITUT PASTEUR |
<p>Diarrheal diseases are the second leading cause of death in children under five years<br>
old, and are responsible for killing around 525,000 children every year. 80% of the<br>
deaths occur in south Asia and sub-Saharan Africa, with a burden cost of more than 7<br>
million Disability-Adjusted Life Years (DAL YS). Over the last 20 years, WHO, UNICEF<br>
and more recently the Wei/come trust (WT) and the Bill and Melinda Gates Foundation<br>
(BMGF) have supported many possible prevention measures, including vaccination.<br>
lnstitut Pasteur has developed a monovalent vaccine candidate against Shigella.<br>
flexneri 2a (SF2a), one of the most prevalent S. flexneri serotypes worldwide. The<br>
candidate, named SF2a-TT15, is a synthetic carbohydrate-based conjugate vaccine<br>
incorporating a functional oligosaccharide (OS) mimic of the 0-antigen (0-Ag), the<br>
bacterial outer membrane polysaccharide, coupled to tetanus toxoid (TT). The SF2aTT15<br>
vaccine candidate was shown to be safe and highly immunogenic in a Phase I<br>
clinical trial, performed in healthy Israeli adult volunteers (NCT02797236, Cohen eta/.<br>
manuscript in preparation). Based on these results, BMGF and WT have decided to<br>
support a Phase 2a age descending study (ADS), which aims at making the proof of<br>
concept of safety and immunogenicity of SF2a-TT15 in the target population. Basically,<br>
parenteral injection of the SF2a-TT15 vaccine candidate will proceed by starting with<br>
a first adult cohort, then a 2-5 yr-old children cohort, and eventually a 9mo-o/d infant<br>
cohort. Moving from one cohort to the other will be based on safety data and /DMC<br>
approval. The doses of the vaccine and the use of alum as an adjuvant will follow the<br>
study design of the phase 1 clinical trial, which showed no safety or tolerability issues.<br>
lnstitut Pasteur is sponsor for this ADS and the Kenya Medical Research Institute<br>
(KEMRI) I Kericho Field Station is the investigator site with Prof Fredrick Sawe being<br>
the principal investigator. This clinical study combined to the ongoing controlled human<br>
infection model (CHIM) study to provide the proof of concept of protection induced by<br>
SF2a-TT15 will give rise to a "GO-NO GO" decision for further development of a 4-<br>
va/ent conjugate Shigella vaccine based on the use of synthetic OS mimics.</p> |
| 30/09/2019 |
£14,856 |
|
UNIVERSITY OF YORK |
<p>Post-human approaches in social science are destabilising traditional barriers between humans and non-human animals through acknowledging complex interspecies relationships within contemporary society. The concept of 'interspecies entanglement' has recently been used within sociological studies of biomedicine and healthcare; illuminating how scientific advancement and the increasing significance of pets within families are creating new spaces for the study of heath.</p>
<p>Previous research has used the veterinary treatment of pets as an empirical space from which to access unique accounts of experiences, frustrations and preferences related to the medical treatment of humans. This proposal seeks to apply the concept of interspecies entanglement to the development of a new stream of social scientific research; utilising the disparities and growing similarities between veterinary and medical healthcare approaches to create a unique and novel environment for end of life care research.</p>
<p>This grant will bring together healthcare professionals from the medical and veterinary settings to share their experiences of 'interspecies entanglement' during end of life care. Sociologists and medical ethicists will explore how such interspecies entanglements offer opportunities to connect existing streams of research and create new interdisciplinary spaces. Regulators will be invited to consider how such research might contribute to future policy discussion .</p>
<p> </p>
<p> </p>
<p> </p>
|
| 30/09/2019 |
£834,100 |
|
UNIVERSITY OF BRITISH COLUMBIA |
<p>Sepsis is the leading cause of death and disability in children, every hour of delay in<br>
treatment is associated with greater organ damage and ultimately death. The challenges,<br>
especially in poor countries, are the delays in diagnosis and the inability to identify children<br>
in urgent need of treatment. To circumvent these challenges, we propose the<br>
implementation and evaluation of a trigger tool that will reduce the time to diagnosis and<br>
prompt the timely initiation of life-saving treatment. The key innovations are 1) a data-driven<br>
approach to rapid diagnosis of sepsis severity and 2) a low-cost digital tagging system to<br>
track the time to treatment. The tool will require minimal cost, clinical expertise and training<br>
or time to use. The tool will identify high risk children and reduce time to treatment. Our<br>
mobile platform (mobile device and dashboard) will create a low-cost, highly scalable<br>
solution for children with sepsis.</p> |
| 30/09/2019 |
£8,333,000 |
|
ACADEMY OF MEDICAL SCIENCES |
<p>This request is to support an extension of funding of Wellcome's partnership schemes with the Academy of Medical Sciences, specifically the Springboard, Starter Grants for Clinical Lecturers (SGCL), Daniel Turnberg and INSPIRE schemes until 31 December 2020.<br>
As a reminder:<br>
• SGCL offers up to £30k over 1-2 years for research consumables for Clinical Lecturers<br>
• Springboard offers up to £100k over 2 years towards direct research costs, including research staff, for biomedical or social science/medical humanities researchers in their first independent post (or equivalent).<br>
• Daniel Turnberg Travel Fellowships offer £3,500 or £9,000 for 1 or 3 month exchange visits (respectively) of biomedical researchers between the UK and Middle East.<br>
• INSPIRE is an initiative to engage and inform UK medical, dental and veterinary undergraduates about research opportunities.</p>
|
| 30/09/2019 |
£761,887 |
|
IMPERIAL COLLEGE LONDON |
Each year there are 50-100 million cases of dengue worldwide, and 40% of the world’s
population live in affected areas. There is an urgent need for diagnostic tools able to
accurately identify dengue infections at the point-of-care to ensure timely and targeted
clinical management. This is especially important in lower-middle income countries,
including Thailand, where access to healthcare facilities is limited. We will deliver a
novel portable device that can rapidly diagnose dengue from blood and identify its
serotype with very high accuracy, whilst using a cloud connected mobile phone to map
the location of infection. The technology, which utilises microchip based chemical
sensors, will be validated as part of a diagnostic evaluation within Thai healthcare
settings. To ensure the technology is appropriate for end user requirements it will be codesigned
by healthcare workers in Thailand, with guidance from the Ministry of Public
Health and the Village Health Volunteer system." |
| 30/09/2019 |
£30,000 |
|
NO ORGANISATION |
<p>2018 Wellcome Screenwriting Fellowship in partnership with BFI and Film4</p> |
| 30/09/2019 |
£5,382,687 |
|
UNIVERSITY OF OXFORD |
<p>This Project will establish the Sowth and Southeast Asian Community-based Trials Network<br>
(SEACTN), which in the first instance will be used for monitoring the incidence, causes and<br>
outcomes of febrile illness in rural communities in the region. The SEACTN infrastructure will be used in later projects for the trialling of interventions delivered by village health workers<br>
(VHWs) and rural clinics to improve the management of febrile illness.<br>
During the initial three-year funding period the SEACTN infrastructure will be built up across<br>
750 villages in three South and Southeast Asian countries, facilitating the capturing of over<br>
100,000 episodes and outcomes of febrile illness in remote and underserved communities.<br>
Key activities include the provision of mobile devices with data collection applications to VHWs<br>
and health facility staff for them to record the incidence of patients presenting with febrile<br>
illness. They will then be prompted to follow patients up to record the outcomes of the illness<br>
episodes. Samples from febrile patients will also be taken for aetiological investigations ·to<br>
better understand the causes and spatiotemporal heterogeneity of fever, and to investigate<br>
whether host biomarkers of severe illness can predict which patients are most likely to require<br>
referral from the community to higher level facilities. Health seeking behaviour surveys will<br>
also be carried out, and health facilities and services in the region will be mapped.<br>
The findings will provide an unprecedented account of the incidence and associated morbidity<br>
and mortality of febrile illness in rural settings in South and Southeast Asia, home to hundreds<br>
of millions of people with restricted access to healthcare. More importantly, the findings will be<br>
used to develop and deploy bespoke, spatially-explicit, electronic decision-support tools<br>
incorporating point-of-care tests for the management of febrile illnesses. The impact of these<br>
and other interventions on improving outcomes for patients with febrile illness will be evaluated<br>
in follow-on projects using pragmatic cluster-randomised trials across the SEACTN villages<br>
and health facilities."<br>
</p> |
| 30/09/2019 |
£1,183,016 |
|
UNIVERSITY OF OXFORD |
<p>The project is the second in a portfolio of joint projects with Wei/come and Oxford<br>
Tropical Network that aim to reduce mortality and morbidity from critical illness. This<br>
project's primary objective in phase 1 is to network a large number of ICUs in the<br>
Southeast and South Asia regions by implementing a setting-adapted, real-time,<br>
clinician-led electronic registry. The information captured through the registry will directly<br>
benefit patient care by evaluating the quality of care currently delivered in each ICU (and<br>
enable recognition of the bottlenecks to quality care delivery) and provide a platform for<br>
quality improvement interventions and clinical trials within the network. (phase 2). This<br>
project unites with the proposal led by OUCRU to evaluate technology innovations in<br>
critical care. Collaborating countries include: Bangladesh, India, Laos, Malaysia, Nepal,<br>
Pakistan, Sri Lanka, Thailand and Vietnam. The resulting internationaiiCU network will<br>
enable high impact multi-site evaluation of setting-adapted interventions to improve<br>
critical care delivery and patient outcomes.</p> |
| 30/09/2019 |
£3,802,345 |
|
UNIVERSITY OF OXFORD |
<p>The project is the second in a portfolio of joint projects with Wei/come and Oxford<br>
Tropical Network that aim to reduce mortality and morbidity from critical illness. This<br>
project's primary objective in phase 1 is to network a large number of ICUs in the<br>
Southeast and South Asia regions by implementing a setting-adapted, real-time,<br>
clinician-led electronic registry. The information captured through the registry will directly<br>
benefit patient care by evaluating the quality of care currently delivered in each ICU (and<br>
enable recognition of the bottlenecks to quality care delivery) and provide a platform for<br>
quality improvement interventions and clinical trials within the network. (phase 2). This<br>
project unites with the proposal led by OUCRU to evaluate technology innovations in<br>
critical care. Collaborating countries include: Bangladesh, India, Laos, Malaysia, Nepal,<br>
Pakistan, Sri Lanka, Thailand and Vietnam. The resulting international ICU network will<br>
enable high impact multi-site evaluation of setting-adapted interventions to improve<br>
critical care delivery and patient outcomes.</p> |
| 30/09/2019 |
£34,948 |
|
UNIVERSITY OF STRATHCLYDE |
<p style="margin-left: 0cm; margin-right: 0cm">This project builds on Seed Awards held by Smith and Spandler, and will lead to a future Collaborative Award (CA) application on Sport and Mental Health involving all three collaborators. Events will include:</p>
<ol style="list-style-type: upper-alpha">
<li>The Age of Athl-Ethics: History, Society and Modern Athletes</li>
<li>Troubling Sport: A Postgraduate Conference and Career Development Workshop</li>
<li>Gender and Sport at the Crossroads: A Workshop for Academics and Activists</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">These events will allow us to:</p>
<ol>
<li>Deepen and broaden our understanding of the complex and often ambiguous relationship between sport and health by critically examining issues related to ethics, gender and the purpose of sport.</li>
<li>Clarify research questions and project structure for CA project.</li>
<li>Recruit interdisciplinary academic collaborators for CA project (eg. for co-writing and PhD supervision).</li>
<li>Cultivate relationships with non-academic partners (including athletes, journalists, sporting officials, activists and policy makers) in order to develop the public engagement activities planned for CA project.</li>
<li>Identify early career researchers (especially at the postgraduate event) who can work either directly (as named researchers) or indirectly (by collaborating on publications and outreach) on CA project.</li>
<li>Situate physical and mental health within the emergent field of critical sport studies.</li>
<li>Publish an edited volume based on the best papers presented at the events.</li>
</ol>
|
| 30/09/2019 |
£600,000 |
|
AFRICAN ACADEMY OF SCIENCES |
<p style="margin-left: 0in; margin-right: 0in">We propose an initiative spanning over thirty (30) months with two broad goals. </p>
<p style="margin-left: 0in; margin-right: 0in"><strong>Goal 1:</strong> Build and/or strengthen CPE capacity within the DELTAS Africa programme with specific focus on DELTAS Doctoral Trainees (i.e. PhD and Post Doctoral),</p>
<p style="margin-left: 0in; margin-right: 0in"><strong>Goal 2:</strong> Implement a themed strategy on Gender Equity in Science. </p>
<p style="margin-left: 0in; margin-right: 0in">The purpose is to;</p>
<ol>
<li>Enable DELTAS doctoral trainees to develop and implement engagement plans in line with their research projects,</li>
<li>Improve DELTAS doctoral trainees' knowledge translation capacity and practice,</li>
<li>Provide a practical CPE training platform for DELTAS consortia engagement staff, </li>
<li>Provide a platform for piloting programmes of activity to promote societal impact of DELTAS research and move towards people-centred approaches,</li>
<li>Contribute towards enhancing gender equitable progression in science careers on the continent. </li>
</ol>
<p style="margin-left: 0in; margin-right: 0in">We will implement the initiative as a grant call for proposals with two (2) rounds. Round 1 will respond to Goal 1 and Round 2 will respond to Goal 2. They will be launched End of November 2018 and May 2019 respectively. </p>
<p style="margin-left: 0in; margin-right: 0in">The initiative will align with the outcomes around the DELTAS Learning Research Programme and the DELTAS Theory of Change. DELTAS will act as a pilot project before AAS and partners can launch similar opportunities more broadly in future. </p>
<p style="margin-left: 0in; margin-right: 0in"> </p>
|
| 30/09/2019 |
£1,765,496 |
|
INTERNATIONAL VACCINE INSTITUTE |
<p style="margin-left: 0cm; margin-right: 0cm">The Group A streptococcus (GAS), <em>Streptococcus pyogenes</em> causes 500,000 annual deaths. RHD is a late immunological consequence of untreated GAS infections of childhood, causing death in the 3d or 4<sup>th</sup> decades of life in roughly 320,000 persons per year, Invasive GAS infection of the skin and soft tissue kills 150,000 annually. RHD has nearly disappeared from high income countries (HIC) as a result of access to treatment for acute GAS pharyngitis but remains common in low and middle income countries (LMIC). WHO prioritized GAS vaccine development in 2014; in 2018 the World Health Assembly articulated the need for a GAS vaccine. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The enormity of this problem stands in contrast with resources available for vaccine development. We propose a Consortium that will provide leadership, advocacy, and organization around GAS vaccine development. The Consortium will (1) advocate for, mobilize and coordinate funding for gaps identified in the GAS Roadmap and (2) develop a full Public Health Value Proposition (FPHVP) inclusive of business and global health investment cases. By the end of the proposal, in addition to the FPHVP, the Consortium will have identifed vaccine manufacturers, increased GAS funding, and raised awareness of GAS as a global health problem.</p>
|
| 30/09/2019 |
£40,187 |
|
OSWALDO CRUZ FOUNDATION |
<p>There is a need to know if the duration of immunity of the 17DD yellow fever vaccine, developed by Bio-Manguinhos, induced by smaller doses is maintained for at least 10 years. We did a study in 2017 where we verified that immunity to yellow fever on reduced doses was maintained for 8 years, when there is primary seroconversion and immunity is maintained for 10 months, without significant differences among groups. This is a Phase IV cohort clinical trial with a total of 300 research participants male subjects, adults, healthy that participated on the 2017 study "17DD yellow fever vaccine - A double-blind, randomized clinical trial of immunogenicity and safety on a dose-response study", meeting the study eligibility criteria.</p>
<p> </p>
|
| 30/09/2019 |
£3,378,475 |
|
KING'S COLLEGE LONDON |
<p>A VA TAR therapy is a brief intervention aimed at reducing the frequency of<br>
auditory verbal hallucinations (A VH, henceforth 'voices'). It involves the use of a<br>
digital simulation (avatar) of the entity the person believes is the source of the<br>
voice in a three-way discussion between participant, avatar and therapist,<br>
focussing initially on managing anxiety and helping the participant to stand up to<br>
the avatar (phase 1) followed by a realistic enactment of the ascribed character of<br>
the voice, targeting processes that are specific to an individualised formulation<br>
(phase 2). The first fully powered RCT found AVATAR therapy resulted in a rapid<br>
and substantial fall in frequency and associated distress of voices that was<br>
superior to a supportive counselling control condition at 12 weeks. In the current<br>
study we have four main goals. First, a multicentre RCT to examine the effects of<br>
high and low intensity A VA TAR therapy (where high intensity involves both phases<br>
and low intensity only phase 1) by comparing each to a treatment as usual<br>
comparator, and to identify who would be likely to benefit from the high intensity<br>
therapy versus those for whom low intensity alone would be sufficient. Second, to<br>
examine the relative cost-effectiveness of the two levels of A VA TAR therapy and routine treatment. Third, to broaden the availability of AVATAR therapy by<br>
expanding the number of staff trained in geographically dispersed NHS settings.<br>
Finally, to provide the evidence on effects and cost-effectiveness necessary to<br>
take AVAVAR therapy to recommendation by guideline bodies such as NICE.</p> |
| 30/09/2019 |
£85,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£28,500 |
|
UNIVERSITY OF MALAYA |
<p style="margin-left: 0in; margin-right: 0in">Antimicrobial resistance (AMR) has emerged as a major public health problem all over the world. Infections caused by AMR microorganisms fail to respond to treatment, resulting in prolonged illness and greater risk of death. Due to the increased usage of antimicrobials in the human, animal and the environmental sectors globally, AMR is recognised as an OneHealth challenge. Antibiotics are used as growth enhancers, metaphylactics, and prophylactics in human health and animal husbandry, and transmitted in the environment through irrigation using wastewater. Influencing human behaviour on antibiotic usage is a complex process which includes factors like knowledge, attitudes, social norms, socio-economic conditions, peer pressure, experiences, and bio-physical and socio-behavioural environment. In medical practices and farms in high- and middle-income countries, numerous Antibiotic Stewardship policies have been designed and implemented. However, these remain underexplored in lower and middle income countries such as Malaysia. Understanding these aspects on the utilisation of antimicrobial drugs among the different sectors in Southeast Asia is essential to develop and implement policies to halt and curb AMR development and transmission that cut-across all sectors within the OneHealth consortium. This study will enable the development of standardised protocols for the import and export of food products within the region.</p>
|
| 30/09/2019 |
£13,372 |
|
UNIVERSITY OF KENT |
<p style="margin-left: 0cm; margin-right: 0cm">There has been lively inquiry over decades into the history and sociology of medical measurement and diagnosis. <em>Living Assessments </em>is distinctive in bringing medical humanities approaches in a mutually generative and critical dialogue with policy and practice. We are interested in the health aspects of two important assessments of children: attempts to measure the support requirements of disabled children and their families; and to measure threats of harm to children’s health and development in the context of their families. These cases represent the two faces of health within reactive welfare provision: questions of care needs and questions of harm. Together they constitute a barometer for following the changing position and stakes of health-and-social-care as a domain of governance, and the calibration of thresholds for state intervention, support and protection in the shifting zone between the ‘health’ and ‘social’ needs of children and their families. We will examine the history and current utilisation of the ‘threshold for services’ to understand the qualities and quantities of the minds and bodies of child subjects and of families deserving or undeserving of intervention. We will explore the reciprocal relationship between practices and the experiences of assessors and assessed, including health implications of assessments themselves. </p>
|
| 30/09/2019 |
£120,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£150,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£50,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£50,000 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2019 |
£66,146 |
|
UNIVERSITY OF CAMBRIDGE |
<p>The Centre for Trophoblast Research holds two unique collections of histological material pertaining to placental research, and is keen to preserve these for future generations and to make them freely available to the wider community through digitisation. The material is in the form of histological sections of placenta-in-situ specimens. These specimens were collected in the 1950’s through to the 1970’s, when obstetric practice was very different to that of today, and pregnant hysterectomy was a more common procedure. The sections are therefore irreplaceable. Despite their age, the staining characteristics are still excellent. The specimens range across gestation, from 6 weeks of pregnancy to 32 weeks, but predominantly cover the first and second trimesters when the critical events of placental development take place. Because the placenta is still attached to the uterine wall, these sections provide unique insights into not only placental development but also how the relationships between the placenta and uterus change during pregnancy. The sections have been crucial to interpreting contemporary imaging and physiological data that have led to recent paradigm shifts in our understanding of early pregnancy, and as we move into the era of single cell sequencing it is likely they will be even more important.</p>
|
| 30/09/2019 |
£27,160 |
|
UNIVERSITY OF ST ANDREWS |
<p style="margin-left: 0cm; margin-right: 0cm">The UK is home to experts in menstruation across many disciplines and institutions: the sciences and humanities, NGO work and activism, the arts, industry and the NHS. Through a programme of three workshops and the establishment of a website, the proposed project will create the first UK-wide menstruation research network. This is a timely suggestion, due to the contemporary policies and measures to tackle menstrual poverty in Scotland and the current public interest in fertility apps and related issues. The establishment of a menstruation network will empower professionals, activists and academics to gain an overview over the state of the field, knowledge and cultural representation, set research agendas together, and plan future collaborative work. While the programme of events will be hosted by Scottish institutions, to reflect the historic roll-out of menstrual policy there, it will also bring together researchers, NGOs, medical professionals, educators and artists from across the UK. Its sustainability is ensured through the range of interested parties, the central node of administration and intellectual leadership, the inclusion of further grant applications in its stated aims and a public-facing internet profile that will allow it to function as a centre of expertise for media enquiries and policy work.</p>
|
| 30/09/2019 |
£37,247 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£52,691 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 30/09/2019 |
£3,099,568 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">The International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) is a federation of clinical research networks whose aim is to prevent illness and deaths from infectious diseases outbreaks. This aim is supported by two key objectives: (i) To generate and disseminate clinical research evidence for outbreak-prone infectious diseases, whenever and wherever they occur; (ii) A global federation of clinical research networks, providing a proficient, coordinated, and agile research response to outbreak-prone infectious diseases. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The first objective will be achieved by implementing collaborative, multi-member, inter-epidemic research projects on severe acute respiratory infections, Lassa fever, and plague; and ‘pre-positioning’ clinical trial protocols for MERS-CoV and Nipah virus. In addition, the ISARIC Global Support Centre and the ISARIC membership will provide technical and operational support to other ISARIC members and stakeholders wishing to conduct research in preparation for or in response to outbreaks. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The second objective will be achieved both through the process of developing and implementing collaborative clinical studies and through a programme of membership engagement and capacity development activities that includes scientific seminars, fellowships, and training in clinical research methods.</p>
<p style="margin-left: 0cm; margin-right: 0cm">To ensure ISARIC is a truly global asset, the programme will be implemented in close partnership with WHO and others.</p>
|
| 30/09/2019 |
£53,473 |
|
UNIVERSITY OF YORK |
Not available |
| 30/09/2019 |
£18,802 |
|
ST GEORGE'S UNIVERSITY OF LONDON |
Not available |
| 30/09/2019 |
£35,973 |
|
UNIVERSITY OF EXETER |
Not available |
| 30/09/2019 |
£10,000 |
|
ROYAL VETERINARY COLLEGE |
Not available |
| 30/09/2019 |
£6,440 |
|
UNIVERSITY OF BATH |
Not available |
| 30/09/2019 |
£36,687 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 30/09/2019 |
£225,000 |
|
SICK OF THE FRINGE LTD |
<p>To support the core running costs of The Sick of the Fringe for 3 years.</p> |
| 30/09/2019 |
£29,833 |
|
UNIVERSITY OF SYDNEY |
<p style="margin-left: 0cm; margin-right: 0cm">The Oceania region comprises Melanesia, Micronesia, Polynesia and Australasia, spans more than 100 million square kilometres of the Pacific Ocean, and is home for about 40 million people. The health and wellbeing of the people of Oceania, and future generations, is currently threatened by human population growth, urbanization, forest loss, overfishing and climate change. Although the case for a planetary health approach has become compelling for regional leaders, clear pathways for policy and action at the ecology–health nexus are yet to be defined. Building on the Healthy Islands ideal first advanced in Oceania more than 20 years ago, the International Union for Conservation of Nature (IUCN) Oceania Regional Office and the University of Sydney Planetary Health Platform will jointly convene an inaugural Oceania Planetary Health Forum during 5-6 November 2018 in Nadi, Fiji. The Forum will bring together more than 50 regional stakeholders to (1) share case studies of planetary health good practice, (2) develop a planetary health research framework, (3) establish a planetary health network, and (4) draft a communiqué for regional and global policy dialogue. The requested funding will be used for travel bursaries to enable participation in the Forum by LMIC stakeholders from across the region. </p>
|
| 30/09/2019 |
£50,048 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/09/2019 |
£776,642 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2019 |
£59,084 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 30/09/2019 |
£22,221 |
|
UNIVERSITY OF STRATHCLYDE |
Not available |
| 30/09/2019 |
£22,339 |
|
UNIVERSITY OF ST ANDREWS |
Not available |
| 30/09/2019 |
£86,647 |
|
UNIVERSITY OF SOUTHAMPTON |
Not available |
| 30/09/2019 |
£82,464 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2019 |
£162,384 |
|
QUEEN MARY UNIVERSITY OF LONDON |
Not available |
| 30/09/2019 |
£1,171,479 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£50,335 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 30/09/2019 |
£171,733 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 30/09/2019 |
£279,901 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 30/09/2019 |
£170,178 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£84,434 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2019 |
£62,657 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 30/09/2019 |
£131,596 |
|
UNIVERSITY OF LEEDS |
Not available |
| 30/09/2019 |
£366,979 |
|
KING'S COLLEGE LONDON |
Not available |
| 30/09/2019 |
£20,775 |
|
KEELE UNIVERSITY |
Not available |
| 30/09/2019 |
£299,953 |
|
INSTITUTE OF CANCER RESEARCH |
Not available |
| 30/09/2019 |
£436,751 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2019 |
£219,718 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2019 |
£435,246 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 30/09/2019 |
£206,517 |
|
UNIVERSITY OF DUNDEE |
Not available |
| 30/09/2019 |
£132,562 |
|
CARDIFF UNIVERSITY |
Not available |
| 30/09/2019 |
£1,016,251 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2019 |
£167,738 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 30/09/2019 |
£179,692 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 30/09/2019 |
£21,956 |
|
BIRKBECK UNIVERSITY OF LONDON |
Not available |
| 30/09/2019 |
£99,632 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">The London School of Hygiene & Tropical Medicine and World Resources Institute propose to engage key stakeholders and co-host a transdisciplinary workshop with the Wellcome Trust to design and advance the development of a Planetary Health Watch (PHW). This system is aimed at the integrated monitoring of factors relating to the health impacts of environmental change at multiple geographical and temporal scales, the drivers of change, and policy responses so as to protect health. PHW will harness emerging technological opportunities and facilitate harmonisation and integration of existing monitoring efforts to allow for evidence-informed responses to complex threats posed by the transgression of planetary boundaries.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The aim of the engagement and workshop is to agree on the scientific design, operational and governance characteristics of such a PHW system, to maximize its utility in monitoring risks to planetary health and supporting protective actions. Our proposed approach is based on engagement through an introductory webinar and online surveys eliciting world-leading expert opinion and decision-maker and other practitioner needs in relation to PHW. The workshop will serve as the key point of transdisciplinary consolidation of expert and practitioner perspectives, identifying vital strategic directions and critical design aspects for the successful development of PHW.</p>
|
| 30/09/2019 |
£2,526,611 |
|
UNIVERSITY OF OXFORD |
<p>Our project’s primary objective is to provide proof-of-principle that new technology can help improve the care of critically ill patients with infectious diseases in resource-limited settings. To achieve this objective we will develop a new inter-disciplinary ‘innovations for critical care’ team within Oxford University Clinical Research Unit (OUCRU), a Wellcome Africa Asia Programme in Vietnam. The team will consist of Vietnamese and International clinicians, biomedical engineers, and computational scientists in OUCRU, linked to biomedical engineering groups at Oxford University, King’s College London, Imperial College London, and Eidgenössische Technische Hochschule, Zurich.<br>
The team will develop and test technology with the potential to save lives and prevent disability from the common causes of critical illness in Asia. We will also investigate whether novel technologies can improve rehabilitation and long-term outcomes in survivors from critical illness.<br>
We have 4 key goals:<br>
1: To develop new devices, or test existing devices, including point-of-care ultrasound, that will enable lost-cost capture and monitoring of key clinical and physiological variables in critically ill patients<br>
2: To use artificial intelligence and computer-assisted and machine learning to devise clinical decision-support systems from clinical, physiological, and imaging data<br>
3: To investigate whether interventions such as in-bed cycling and rectus femoris ultrasound can aid physical rehabilitation, and whether low-cost wearable devices can promote and predict better functional recovery after critical illness<br>
4: To determine the current costs of critical illness care in Vietnam and to assess the potential acceptability, affordability and cost-effectiveness of the technology tested in Vietnam and similar settings.</p> |
| 30/09/2019 |
£1,503,910 |
|
UNIVERSITY OF OXFORD |
<p>Our project’s primary objective is to provide proof-of-principle that new technology can help improve the care of critically ill patients with infectious diseases in resource-limited settings. To achieve this objective we will develop a new inter-disciplinary ‘innovations for critical care’ team within Oxford University Clinical Research Unit (OUCRU), a Wellcome Africa Asia Programme in Vietnam. The team will consist of Vietnamese and International clinicians, biomedical engineers, and computational scientists in OUCRU, linked to biomedical engineering groups at Oxford University, King’s College London, Imperial College London, and Eidgenössische Technische Hochschule, Zurich.<br>
The team will develop and test technology with the potential to save lives and prevent disability from the common causes of critical illness in Asia. We will also investigate whether novel technologies can improve rehabilitation and long-term outcomes in survivors from critical illness.<br>
We have 4 key goals:<br>
1: To develop new devices, or test existing devices, including point-of-care ultrasound, that will enable lost-cost capture and monitoring of key clinical and physiological variables in critically ill patients<br>
2: To use artificial intelligence and computer-assisted and machine learning to devise clinical decision-support systems from clinical, physiological, and imaging data<br>
3: To investigate whether interventions such as in-bed cycling and rectus femoris ultrasound can aid physical rehabilitation, and whether low-cost wearable devices can promote and predict better functional recovery after critical illness<br>
4: To determine the current costs of critical illness care in Vietnam and to assess the potential acceptability, affordability and cost-effectiveness of the technology tested in Vietnam and similar settings.</p> |
| 30/09/2019 |
£50,000 |
|
WORLD HEALTH ORGANIZATION, SWITZERLAND |
<p style="margin-left: 0cm; margin-right: 0cm">WHO is convening the First Global Conference on Air Pollution and Health, aimed at enhancing the global response to prevent air pollution and related diseases, while at the same time achieving a wide range of health, climate and sustainability co-benefits. The conference was requested by the <em>World Health Assembly Resolution on Addressing the Health Impacts of Air Pollution</em>, and health and the related <em>Road Map for an Enhanced Global Response to the Adverse Health Effects of Air Pollution</em>, adopted in 2015 and 2016 respectively.</p>
|
| 30/09/2019 |
£29,595 |
|
BIOTECHNOLOGY INDUSTRY RESEARCH ASSISTANCE COUNCIL |
<p>On request - Diana Tay</p> |
| 30/09/2019 |
£785,731 |
|
BIOTECHNOLOGY INDUSTRY RESEARCH ASSISTANCE COUNCIL |
<p>On request - Diana Tay</p> |
| 30/09/2019 |
£5,201,550 |
|
KING'S COLLEGE LONDON |
<p>The Wei/come Trust is funding a unique manufacturing facility for complex<br>
medical devices. The new facility will be fully staffed, equipped and certified to<br>
build Class II & Ill medical devices for use in clinical studies. This will facilitate the<br>
translation of research to patients, and allow academic research supported by<br>
innovation funding to develop and deliver life-saving technologies. This will<br>
promote the reputation of UK Academic research worldwide</p> |
| 30/09/2019 |
£871,672 |
|
UNIVERSITY OF MINNESOTA |
<p style="margin-left: 0in; margin-right: 0in">CIDRAP will lead the collaborative development of an R&D roadmap for accelerating progress toward universal influenza vaccines. We will work closely throughout the project with partners at Wellcome Trust and the Global Funders Consortium for Universal Influenza Vaccine Development, as well as global stakeholders and subject-matter experts in government, academia, industry, philanthropy, and nongovernmental organizations. The roadmap will provide a valuable tool to develop consensus on high-priority research strategies, coordinate research and funding efforts, and stimulate overall investment in influenza vaccine R&D. The scope of R&D includes incremental improvements in seasonal (HA head) influenza vaccines as well as transformational innovations in vaccine technology to enable broader and more durable immunity against antigenically diverse strains, including novel pandemic influenza viruses. </p>
|
| 30/09/2019 |
£31,346 |
|
IMPERIAL COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">This project supports HIC-Vac's aims by developing a community of practice for human challenge researchers on the Global Health Network platform. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The Global Health Network (https://tghn.org/) is a facility to support and enhance clinical research in developing countries. They have attracted 11,000 users comprising research staff from 56 developing countries – many of whom are research nurses. It has 37 different communities of practice operating, has had over 10 million views and 300,000 site memberships. Hundreds of thousands of research documents have been downloaded and over 400,000 online courses taken. The site has been successful because it is developed with simple, user-friendly technology and is perceived as an open and trusted space independent of any single institution. This website has proved there is demand for professional networking for researchers in Global Health alongside a trusted source of valid and comprehensive resources, training, tools and guidance.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Imperial will create, populate and maintain a dedicated webspace on TGHN for global volunteer infection studies.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£622,407 |
|
WORLD ECONOMIC FORUM |
<p>Strategic partnership with WEF, renewed annually.</p> |
| 30/09/2019 |
£1,523,437 |
|
UNIVERSITY OF OXFORD |
<p>Vivax malaria remains a major global health problem. Because of the existence of a hypnozoite stage and the clinical relapses this causes, elimination strategies are more difficult to design and implement successfully than for falciparum malaria. Vaccines and new well-tolerated anti-relapse drugs are badly needed. To accelerate vaccine development, we will develop and assess the feasibility of conducting <em>Plasmodium vivax</em> volunteer infection studies in Thailand, recruiting semi-immune volunteers from endemic areas representative of target populations for vaccine deployment. We will draw on the participating institutions' expertise in clinical malaria, immunology, entomology, parasitology, volunteer infection studies, and vaccine development.</p>
<p>We plan to develop vivax controlled human vivax malaria infection models able to test protective efficacy of the pre-erythocytic and blood stage vivax malaria vaccines currently in development. During this programme we plan to conduct six volunteer infection studies, determine immunological correlates of protection, and test four vaccine candidates. The programme will lay the groundwork for developing models to test future transmission blocking vaccines and new anti-relapse drugs for radical cure.</p>
<p>The volunteer infection studies will be accompanied by a programme of social science and empirical ethics research to assess their acceptability and the understanding of volunteers, patients, researchers and policy-makers.</p>
|
| 30/09/2019 |
£56,155 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2019 |
£22,846 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Over the twentieth century, the Court of Protection was responsible for adults in England & Wales who were found ‘incapable of managing their own affairs’. Tens of thousands of people, including individuals with learning disabilities, mental illness, and the elderly were in this position by the 1920s, and their numbers were growing. Despite its considerable power over so many, and current controversies over mental capacity assessments and legislation, the role of the Court of Protection is little understood.
In this project, I will engage with adults in England & Wales with and without experience of incapacitating conditions, to explore how decisions about an individual’s capacity have been, are, and could be made. This project will involve three workshops involving people affected by dementia, using archival material from the Court of Protection to explore past decisions about mental incapacity and the issues they raise. This will generate an interactive play based on historical case studies, in which audiences are invited to say how they would respond to actual past events, and to discuss present policies and hypothetical futures. A version of the play will also be filmed, to expand and continue the discussion in new settings.
This will connect my historical research with contemporary opinions and concerns, providing insight into current perceptions of mental incapacity and its associated legal mechanisms, past and present. It will also increase public understanding of the Court of Protection, helping me and my audiences to think about legal and social responses to infirmity and vulnerability.
|
| 30/09/2019 |
£11,232 |
|
UNIVERSITY OF YORK |
<p>Many traditional and ancient crafts produce great amounts of pollutants, in the form of fine dust particles, which can be very detrimental to health. It is now becoming possible for archaeologists to retrieve a range of microscopic pollutants from the ‘mouth’ of ancient individuals, as they can become entombed in their dental tartar, thanks to cutting edge research involving Archaeology, Environmental and Physics Material Sciences. From early summer 2020 to early summer 2021 two consecutive exhibitions will be held at ‘The King’s Manor’ (home of the Department of Archaeology) and at ‘DIG: an archaeological adventure’- run by the York Archaeological Trust (YAT). The exhibitions will communicate, to an audience of families and schools, that mainly experiences the past in the form of buildings and artefacts, the importance of air quality by engaging the audience with the ‘dust’ and airborne particles from craft activities, effectively moving the focus of attention from the object to the crafters and their health. The public will be able to view large high resolution images of pollutants retrieved from skeletal remains (King's Manor) of ancient crafters, as well as directly 'connecting' with 'pollutants' via a tactile experience (DIG), while learning about oral health. The tactile experience at DIG will provide the opportunity to feel the 'weight' of the pollutants generated over time during pottery/textile work. The exhibitions will elucidate the health experiences of both ancient and modern artisans, and create awareness of the importance of air quality to health through archaeology. <strong>Keywords pollution, archaeology, crafters, health</strong></p>
|
| 30/09/2019 |
£16,000 |
|
UNIVERSITY COLLEGE LONDON |
<p>We will have achieved a comprehensive understanding of not only the most appropriate ways and times to discuss inclusion in a SUDIC registry with bereaved families but how we can better inform and support them through the death of their child and the multi-disciplinary investigation that follows a sudden death. We will have established:</p>
<ul>
<li>What families understand now about the process that takes place when a child dies suddenly and unexpectedly </li>
<li>How/if they received sign-posting information </li>
<li>Where there are major gaps in information </li>
<li>What support professionals and charities may require to improve this </li>
<li>What information families would like to receive regarding the registry, when and how. </li>
</ul>
<p>As a result of this engagement with a wide range of stakeholders we will have collectively designed multiple formats for sharing information, research outputs and sign-posting to ensure all partners are fully engaged. These will include: Web-based resources including links to short animations and/or videos, downloadable electronic/pdf versions of leaflets, contact details including telephone/email/website for support, written leaflets, flowcharts, infographs, text messaging and social media templates.</p>
<p>The created resources will include but not necessarily be limited to topics such as:</p>
<ul>
<li>What happens after a child dies suddenly including mandatory requirements that families can expect to be met for review meetings</li>
<li>Who they can contact for support e.g. appointed paediatrician, key worker, charity befrienders</li>
<li>What the registry is and what tissues will be retained in the biobank</li>
<li>What the registry hopes to achieve, how families can influence and benefit from this</li>
<li>Consent options and processes</li>
</ul>
|
| 30/09/2019 |
£191,955 |
|
UNIVERSITY OF BIRMINGHAM |
<p style="margin-left: 0cm; margin-right: 0cm">Typically diagnosed in early adulthood, polycystic ovary syndrome (PCOS) disproportionally affects South-Asian women, who often experience additional healthcare barriers. Therefore, our project will build visible PCOS leadership in Birmingham’s large South-Asian and university/college communities, aiming to reduce health inequality. Novel training will equip 24 women with relevant skills/confidence to become experts in their own condition and advocate others alongside researchers on the nature of PCOS as a lifelong metabolic disease, thereby reducing the ‘reproductive disorder’ stigma. Charity ‘Cysters’ will support our South-Asian recruitment and connect us to existing Youth Ambassadors who promote women’s health/wellbeing. Together we will better understand PCOS community needs whilst mitigating cultural/youth barriers to co-craft culturally and contemporary-relevant public engagement (PE) that speaks to target audiences (South-Asians – including underserved/youth; university/college students). Twelve ‘Share’ events will promote two-way exchange in community settings (e.g. temples, Fresher events). ‘Pop-Ups’ will tour festivals targeting South-Asians and/or young people, creatively exhibiting PCOS lived experience to enhance public awareness and empathy. Two city-centre ‘Showcases’ during the PCOS Awareness Month will capitalize on media interest, engaging a wider Birmingham demographic through unveiling provocative public artwork created via crowdsourced contributions from women motivated to share personal PCOS stories. Active community-level advocacy will reduce health inequality longer-term, providing a leadership template for other health conditions. Robust evaluation will directly shape our future PE ambitions, with project report and learning shared online and at key events e.g. Engage Conference.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Key words:</strong>Polycystic ovary syndrome; PCOS; metabolic disease; ethnic diversity; community engagement; women’s health; public engagement; leadership; youth </p>
|
| 30/09/2019 |
£21,192 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p>Working closely with Akwaaba (https://akwaaba.org.uk), an anti-racist migrant befriending centre in East London, our project will support six creative writing workshops, follow-up events, and a summative performance and exhibition. Bringing in BME artists to facilitate creative workshops, we will support diverse practitioners, who will in turn mentor members of the storytelling group at Akwaaba.<br>
<br>
These workshops will offer users at Akwaaba the means for telling their stories using varied literary forms, in a supportive environment. In dialogue with our partner organization, we have chosen creative writing and storytelling as the project’s means of engagement with questions of race and migration, because stories can function as a safe and agential way of communicating experience, allowing for various ways of processing, externalizing and sharing experience, as well as addressing the urgent need, at this moment, for countering cruel narratives about migrants and refugees.<br>
<br>
Members of the storytelling group and the BME practitioners supported through this project will be invited to join the ‘Pathologies of Solitude’ research network, and will hold workshops for the PI and postdoctoral researchers that help inform the main project of the ways in which race and migration shape experiences of solitude. Finally, the work of the project will be disseminated through zines made with workshop participants, workshops with academics facilitated by Queen Mary’s Centre for Public Engagement, an inclusive exhibition and performance, and a toolkit for other academic projects interested in carrying out similar activities. Ongoing participatory evaluation through photography and journaling will contribute to the final exhibition.<br>
</p>
|
| 30/09/2019 |
£180,129 |
|
UNIVERSITY OF MANCHESTER |
<p style="margin-left: 0cm; margin-right: 0cm">Animal research remains a controversial public issue. Engagement is too often orientated toward the resolution of a polarized for/against debate taking the form of linear provision of information from specialist to non-specialist. Our programme, which draws on humanities and social sciences approaches to understanding animal research, challenges polarization to create new dynamic cultures of communication. Alongside our <strong>academic</strong> research, we bring together the diverse <strong>stakeholder</strong> community, <strong>patient</strong> groups and <strong>publics</strong>, to work in partnership with <strong>arts and engagement professionals</strong> to co-create evolving activities and events which share the complexities and consequences of animal research. Our work is structured around two complementary pathways:</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong><em>1. Everyday Interventions. </em></strong>Short, mobile, and material activities transported into existing spaces like festivals, museums, and classrooms, provide accessible engagement with animal research. Playful reflection and discussion is engendered through commonplace practices (e.g. games and crafting) to disrupt preconceptions about animal research, prompt conversations, and engage ethical issues. Familiar tactile activities allow animal research to be encountered as relatable ‘everyday’ work without high levels of knowledge (see <u>https://vimeo.com/346172368</u>).</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong><em>2. Immersive experiences: </em></strong>Bespoke immersive theatre allows participants to enter the world of animal research as the decision makers in an unfolding narrative, guided by actors, to experience the challenges and choices that shape the practice of animal research. The interactive structure allows participant to explore, through group interaction and learning, how scientific and social concerns inform governance and practice of animal research without requiring the need for high level specialist knowledge or necessitating a universal for/against choice (see <u>https://vimeo.com/346172464</u>).</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/09/2019 |
£400,000 |
|
UK BIOBANK LTD |
<p>This proposal outlines the need for research support for the new UK Biobank Ethics Advisory Committee (UKB EAC), including the appointment of a senior research fellow (SRF). Located within a centre of excellence for clinical ethics and law research, the SRF will build the previous work of the Ethics and Governance Council (EGC), and undertake detailed empirical and conceptual research to support the research led arm of the new UKB EAC. The SRF will report to the UKB EAC and (indirectly) to UKB board and be supervised, and supported, by members of the EAC. This new research led service will ensure that advice, or position statements, from UKB EAC is evidence based and responsive to ethical issues as they arise, and that UKB will continue to maintain its robust ethical justification for current and future activity. In this way we envisage that that the UKB EAC will provide an ethical benchmark for existing cohort studies, as well as to new studies such as the new 5 million advance disease detection cohort.</p>
|
| 30/09/2019 |
£1,000,000 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF EXETER |
Not available |
| 30/09/2019 |
£1,000,000 |
|
UNIVERSITY OF BIRMINGHAM |
Not available |
| 30/09/2019 |
£2,000,000 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2019 |
£400,000 |
|
UNIVERSITY COLLEGE DUBLIN |
Not available |
| 30/09/2019 |
£200,000 |
|
UNIVERSITY OF NOTTINGHAM |
Not available |
| 30/09/2019 |
£400,000 |
|
UNIVERSITY OF WARWICK |
Not available |
| 30/09/2019 |
£2,000,000 |
|
UNIVERSITY COLLEGE LONDON |
Not available |
| 30/09/2019 |
£240,000 |
|
QUEEN'S UNIVERSITY BELFAST |
Not available |
| 30/09/2019 |
£2,000,000 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF SUSSEX |
Not available |
| 30/09/2019 |
£1,000,000 |
|
UNIVERSITY OF YORK |
Not available |
| 30/09/2019 |
£2,000,000 |
|
UNIVERSITY OF OXFORD |
Not available |
| 30/09/2019 |
£500,000 |
|
UNIVERSITY OF LEEDS |
Not available |
| 30/09/2019 |
£1,400,000 |
|
CARDIFF UNIVERSITY |
Not available |
| 30/09/2019 |
£2,000,000 |
|
KING'S COLLEGE LONDON |
Not available |
| 30/09/2019 |
£1,000,000 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2019 |
£500,000 |
|
UNIVERSITY OF ST ANDREWS |
Not available |
| 30/09/2019 |
£1,500,000 |
|
UNIVERSITY OF GLASGOW |
Not available |
| 30/09/2019 |
£1,500,000 |
|
UNIVERSITY OF DUNDEE |
Not available |
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF ABERDEEN |
Not available |
| 30/09/2019 |
£400,000 |
|
TRINITY COLLEGE DUBLIN |
Not available |
| 30/09/2019 |
£1,500,000 |
|
UNIVERSITY OF BRISTOL |
Not available |
| 30/09/2019 |
£400,000 |
|
ST GEORGE'S UNIVERSITY OF LONDON |
Not available |
| 30/09/2019 |
£400,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
Not available |
| 30/09/2019 |
£1,500,000 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 30/09/2019 |
£600,000 |
|
UNIVERSITY OF LEICESTER |
Not available |
| 30/09/2019 |
£1,000,000 |
|
UNIVERSITY OF MANCHESTER |
Not available |
| 30/09/2019 |
£1,500,000 |
|
NEWCASTLE UNIVERSITY |
Not available |
| 30/09/2019 |
£600,000 |
|
BIRKBECK UNIVERSITY OF LONDON |
Not available |
| 30/09/2019 |
£20,000 |
|
UNIVERSITY OF OXFORD |
<p>In chronobiology and sleep research, a significant proportion of past research studies examining the effects of light on the acute suppression of melatonin and on circadian photoentrainment have exclusively examined male participants, or naturally cycling female participants. The basis for this bias in participant recruitment is empirical evidence that the production of melatonin may be modulated by the menstrual cycle and, in this context, also by the use of hormonal contraceptives. To avoid these potentially "confounding" effects, exclusion criteria are typically used to exclude women who use hormonal contraceptives, thereby ignoring a large proportion of the population.</p>
<p>The goal of this <em>Diversity & Inclusion</em> activity is to increase our knowledge on sex-based biases in the scientific literature on the non-visual effects of light. To this end, the project has two main objectives:</p>
<ul>
<li>(1) Developing the<strong> first systematic survey of sex representation in research studies on the non-visual effects of light</strong>. This will be accomplished using a pre-registered systematic review, using a well-defined database search strategy and standardised information extraction methods regarding the recruitment of men and women in these studies (sample size, proportion of female subjects, hormonal status).</li>
<li>(2) Developing an <strong>open-access toolkit for researchers on addressing sex biases in participant recruitment in chronobiology and sleep studies</strong>, outlining the problem as well as practical solutions. This will be accomplished using a small round-table workshop of diverse invited junior and senior researchers in the field of chronobiology.</li>
</ul>
|
| 30/09/2019 |
£595,277 |
|
MERCK SHARP & DOHME |
Malaria is one of the world's most devastating diseases of humans and results
in over 450,000 deaths annually. Novel therapies are urgently required to
populate the antimalarial clinical portfolio, as the current therapeutics that treat
this disease are becoming less effective due to emerging resistance.
A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA
(known as MSD outside the US and Canada) and Professor Alan Cowman from
the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria
aspartyl protease enzymes are an attractive drug target, as they perform
essential functions for survival in blood, sexual and liver stages of the parasite
life cycle.
Through screening aspartyl protease inhibitor libraries, the collaboration has
identified novel drug-/ike hit compounds that are potently active against the
malaria parasite. The proposed research aims to increase potency against the
parasite whilst maintaining selectivity, progressing to a lead optimisation stage
discovery program." |
| 30/09/2019 |
£595,277 |
|
WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH |
Malaria is one of the world's most devastating diseases of humans and results
in over 450,000 deaths annually. Novel therapies are urgently required to
populate the antimalarial clinical portfolio, as the current therapeutics that treat
this disease are becoming less effective due to emerging resistance.
A collaboration between Dr David Olsen from Merck & Co., Kenilworth, NJ USA
(known as MSD outside the US and Canada) and Professor Alan Cowman from
the Walter and Eliza Hall Institute (WEHI), has demonstrated that malaria
aspartyl protease enzymes are an attractive drug target, as they perform
essential functions for survival in blood, sexual and liver stages of the parasite
life cycle.
Through screening aspartyl protease inhibitor libraries, the collaboration has
identified novel drug-/ike hit compounds that are potently active against the
malaria parasite. The proposed research aims to increase potency against the
parasite whilst maintaining selectivity, progressing to a lead optimisation stage
discovery program." |
| 30/09/2019 |
£1,301,608 |
|
EXONATE LIMITED |
Exudative age-related macular degeneration (wAMD) and diabetic macular
oedema (DME) are the leading causes of blindness in the Western world.
wAMD affects 1.3 per cent of people over 50 years old with a global incidence
of 1. 5 million. Diabetes affects 382 million people worldwide, expected to
increase to 592 million by 2035 and is the leading cause of severe vision loss
in working age adults. Diabetic macular oedema is the major cause of visual
loss in diabetic patients. Approximately 14% of diabetes patients develop
DME and the prevalence increases to 29% (696, 000) for patients using insulin
for more than 20 years.
Current treatment options for these conditions are limited. Anti-Vascular
Endothelial Growth Factor (VEGF) agents improve vision in some patients
and slow its deterioration in most, but they must be administered by regular
intravitreal injections and non-specifically block both pro-angiogenic and antiangiogenic
isoforms of VEGF. There is therefore an incentive to develop a
non-invasive therapeutic modality with efficacious and safe agents.
Exonate has developed small molecules that inhibit production of proangiogenic
VEGF through selective inhibition of Serine/threonine-protein
kinase 1 (SRPK1)-mediated VEGF splicing. These inhibitors have already
demonstrated superior efficacy as topical agents in preclinical models of
wAMD.
Thanks to the support of the Wei/come Trust, Exonate will take several of
these inhibitors into an optimisation programme culminating in the nomination
of a preclinical candidate drug with optimal characteristics for clinical
development. The funded project will also involve the assessment of the
candidate in regulatory toxicology and safety pharmacology studies to support
an application to the regulatory authorities for clinical evaluation at the end of
the funding. Exonate expects to reach this milestone and enter the clinic in
early 2020. |
| 30/09/2019 |
£711,492 |
|
QUEEN'S UNIVERSITY BELFAST |
<p>In most organs and tissues, old cells are constantly dying and being replaced by new cells. This balance is critical for normal organ/tissue function and is maintained by a balance between new cells being created by cell division and old cells dying by a process known as "apoptosis". One of the key characteristics of cancers is that the old cells do not die efficiently by apoptosis and therefore accumulate giving rise to a tumour that ultimately disrupts organ function. This block in apoptosis is also a major problem when it comes to treating cancers as the effectiveness of chemotherapies and radiotherapies usually rely on their ability to activate this type of cell death. Dr Daniel Longley team at Queen's University of Belfast have identified an intra-cellular protein called "FLIP" that plays a critical role in preventing the death of cancer cells treated with chemotherapy and radiotherapy. This protein plays a prominent role in increasing the resistance to therapy in a number of types of cancer, including non-small cell lung cancer, which is a particularly drug-resistant cancer and is the focus of this proposal. The project team plan to generate drugs to block FLIP's function and thereby overcome drug resistance and improve the therapeutic management of patients with this disease.</p> |
| 30/09/2019 |
£371,234 |
|
QUEEN'S UNIVERSITY BELFAST |
In most organs and tissues, old cells are constantly dying and being replaced by new cells. This balance is critical for normal organ/tissue function and is maintained by a balance between new cells being created by cell division and old cells dying by a process known as "apoptosis".
One of the key characteristics of cancers is that the old cells do not die efficiently by apoptosis and therefore accumulate giving rise to a tumour that ultimately disrupts organ function. This block in apoptosis is also a major problem when it comes to treating cancers as the effectiveness of chemotherapies and radiotherapies usually rely on their ability to activate this type of cell death.
Dr Daniel longley's team at Queen's University of Belfast have identified an intra-cellular protein called "FLIP" that plays a critical role in preventing the death of cancer cells treated with chemotherapy and radiotherapy. This protein plays a prominent role in increasing the resistance to therapy in a number of types of cancer, including non-small cell lung cancer, which is a particularly drug-resistant cancer and is the focus of this proposal. The project team plan to generate drugs to block FLIP's function and thereby overcome drug resistance and improve the therapeutic management of patients with this disease. |
| 30/09/2019 |
£245,447 |
|
UNIVERSITY OF SHEFFIELD |
Not available |
| 30/09/2019 |
£189,728 |
|
THE FRANCIS CRICK INSTITUTE |
Not available |
| 30/09/2019 |
£20,000 |
|
UNIVERSITY OF EXETER |
<p>For researchers aspiring to building their own research group, most enter into doing so with no formal training on how to run and manage a research team. This is a particularly daunting prospect if there are few senior role models to relate to, and underrepresented groups are particularly likely to leave research as early career researchers. This highlights the need to support early career researchers in overcoming barriers to successfully establishing their own groups and long-term research careers.</p>
<p><br>
We will run a leadership workshop to provide early career researchers with the skills required to set up and manage an independent research group. The workshop will be used to identify the challenges facing early career researchers in our department and approaches to overcome these issues, in order to reduce the loss of underrepresented groups at these career stages.</p>
<p><br>
The knowledge and skills acquired will be used to develop resources to better enable individuals to overcome these barriers. Course participants will produce an open access toolkit to allow participants to share what they have learned with the wider research community. We will also produce a more bespoke guide to assist early career researchers setting up their own groups in our department, and will run workshops, support networks and a mentoring scheme for early career researchers establishing their own groups.</p>
|
| 30/09/2019 |
£79,764 |
|
UNIVERSITY OF NOTTINGHAM |
<p>Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy in adults. It is a highly debilitating condition affecting more than 100,000 patients in developed countries with an average life expectancy of 58 years. DM1 is primarily a neuromuscular disorder, which also affects a range of other systems including the heart, brain, endocrine and digestive systems. Patients may also show specific patterns of psychological dysfunction and personality traits, cognitive impairment/mental retardation and excessive daytime sleepiness. All features show an obvious deterioration with time and difficulty swallowing and sucking food into the lungs in the later stages of the disease contribute towards chest infections and represent a major cause of morbidity and mortality. There is no treatment for DM1. DM1 is caused by a repeat expansion mutation in the 3' untranslated region of the DMPK gene. Unaffected people have 5 to 30 copies of this sequence whereas patients may have hundreds or sometimes thousands of copies. When expressed the DMPK expansion transcripts remain in the nucleus where they form distinct spots or foci. Professors Chris Hayes and David Brook at the University of Nottingham developed an assay to screen for compounds that might provide a treatment for DM1. They identified small molecules that target a novel protein and destroy the spots in DM1 cells, thereby leading to a significant reduction in the faulty RNA and other molecular features of the disorder. Their drug discovery approach, in collaboration with Argenta, a Charles River company, is based on targeting this novel protein, by refining the chemical starting points to make them more selective and more suitable for oral administration to patients. The multisystem nature of DM1 provides particular challenges but Professors Hayes and Brook anticipate that a successful drug would target most/all features of the disease</p> |
| 30/09/2019 |
£263,623 |
|
UNIVERSITY OF EDINBURGH |
Not available |
| 30/09/2019 |
£173,706 |
|
UNIVERSITY OF LIVERPOOL |
Not available |
| 30/09/2019 |
£220,097 |
|
IMPERIAL COLLEGE LONDON |
Not available |
| 30/09/2019 |
£102,887 |
|
WISTAR INSTITUTE |
Epstein-Barr Virus (EBV) is estimated to be responsible for ~1% of all human cancers worldwide including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, gastric carcinoma, NK/T cell lymphoma, and lymphoproliferative disease in the immunosuppressed.The World Health Organisation classifies EBV as a type I carcinogen. Maintenance of latent EBV in infected cells depends on the continuous expression of one viral protein, EBNA1. The essential role of EBNA1 in cell proliferation, transformation and lymphomagenesis associated with EBV malignancies makes it an attractive target for drug discovery and development.Recently, the crystal structure of EBNA1 has been determined and revealed a druggable surface within its DNA binding domain. Exploiting this property, the team of Professor Lieberman at the Wistar Institute in Philadelphia completed a successful high-throughput screening campaign. Supported by a three year Seeding Drug Discovery award the team will now use medicinal chemistry and structure-based drug design methods to optimize promising starting points into small molecule inhibitors of EBNA1. The goal of this project is the development of a pre-clinical candidate ready to be taken into Phase 1 first in human clinical trials. This innovative project has the potential to deliver a completely novel anti-viral in a field of significant unmet medical need. |
| 30/09/2019 |
£231,654 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2019 |
£196,426 |
|
WELLCOME TRUST SANGER INSTITUTE |
Not available |
| 30/09/2019 |
£219,876 |
|
UNIVERSITY OF CAMBRIDGE |
Not available |
| 30/09/2019 |
£1,026,950 |
|
CARDIFF UNIVERSITY |
Around 1% of the population will suffer from schizophrenia at some point in their life. Symptoms such as paranoia and/or hearing voices can be reasonably well treated by existing medications.
However, these drugs have little effect on the other symptoms (lack of motivation and impaired social function) and impaired cognition, including difficulties with attention, memory and problem-solving that result in a “brain fog”. These largely untreated symptoms remain a huge barrier to the resumption of a fully functional, “normal” life for these individuals and are associated with an annual estimated cost in the UK alone of around £12 billion.
Professor Simon Ward from the University of Sussex has received a Seeding Drug Discovery Award to identify and develop drug which is a selective modulator of the AMPA receptor which has the potential to provide an innovative new treatment for patients with schizophrenia. If successful the team expect to have a compound ready for clinical evaluation in just over three years time.
Nerve cells (neurons) communicate with each other by releasing chemicals known as neurotransmitters that interact with proteins called receptors on adjacent neurons. Levels of the neurotransmitter glutamate, which is crucial for normal cognitive function, are altered in schizophrenia. A specific subtype of glutamate receptor, the AMPA receptor, is thought to be associated with cognition and therefore increasing AMPA receptor function should improve cognitive performance in schizophrenia and thereby addressing an unmet need and revolutionizing the functional outcome of this patient population. |
| 30/09/2019 |
£1,909,721 |
|
SAVE THE CHILDREN |
<p>NA</p> |
| 30/09/2019 |
£300,000 |
|
UNIVERSITY OF CAMBRIDGE |
<p>This proposal aims to explore further our surprising finding that a <em>Xenopus </em>oocyte can enormously prolong the residence time of a transcription factor that can control cell fate and stabilize its induced gene expression. The <em>Xenopus</em>oocyte is a cell that maintains its pattern of gene expression for months or years. The <em>Xenopus</em>oocyte can stabilize the induced expression and function of the factor for hours or days compared to the residence time of seconds or minutes described for other factors such as the glucocorticoid receptor and oestrogen. The assay we use, so far, has been carried out with a mammalian neurogenic transcription factor, Ascl1, acting on its mammalian specific chromatin binding site. This is provided in the assay either on a DNA plasmid or as the same DNA integrated into the chromosome of a mouse-cultured cell-line whose nuclei are transplanted to <em>Xenopus </em>oocytes. We propose to identify the stabilizing factors or mechanisms in the <em>Xenopus </em>oocyte by testing a selection of candidate components normally present in these oocytes. The possibility exists that the transcription factors and mechanisms used by oocytes could be applied to differentiating mammalian somatic cells and so reduce the likelihood of malfunction or cancer in these cells. </p>
|
| 30/09/2019 |
£69,032 |
|
MQ TRANSFORMING MENTAL HEALTH |
Not available |
| 30/09/2019 |
£8,339,626 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2019 |
£202,000 |
|
DIAMOND LIGHT SOURCE LTD |
Not available |
| 30/09/2019 |
£1,000,000 |
|
ETH ZURICH FOUNDATION |
Founded in 1855, ETH Zurich commits to supporting independent thinking, top performance
research, and entrepreneurial spirit. In order to increasingly pioneer effective solutions to the
global challenges of today and tomorrow, ETH also seeks to take down barriers that hinder
progress and development. Therefore, it is of strategic importance to increase translational
research through organizational and individual innovation. With the support of the
Translational Partnership Award from Wellcome, ETH will be able to massively strengthen
medical research and translation at ETH and make decisive progress towards its grand vision
of becoming a globally leading medicine research cluster in the heart of Europe. The Award
will be used to strengthen ties between translational researchers and clinicians through new
forms of research projects and additional scientific facilitators. Furthermore, the Award will
build on the entrepreneurial network at ETH. Ultimately, this partnership intends to create
numerous opportunities to bring new solutions for today's challenges and improve the quality
of life for many. |
| 30/09/2019 |
£1,498,362 |
|
UNIVERSITY OF MELBOURNE |
Psychotic illnesses such as schizophrenia and bipolar disorder are a major cause of
premature mortality and disability in Australia and globally. These disorders generally
have their onset in adolescence and young adulthood and often derail the normal
developmental course, leading to compromised social functioning, disability, vocational
strategy and in many cases premature death. Since the early 1990's there have been
concerted efforts to research and develop services for those in the early stages of a
psychotic illness. Although early intervention services for psychosis now have
Cochrane level 1 evidence for their effectiveness, outcomes for many young people
remain unsatisfactory. Trialling new interventions in early psychosis can be challenging
because of the innate heterogeneity of these disorders resulting in consort evaluations
where a high number of patients are required for eligibility screening in order to secure
a suitable study-specific clinical trial participation. As no trials networks have emerged
in early psychosis research, trials in this disease area remain relatively small in size
and any collaborations are hard to establish and reliant solely on existing relationships
and goodwill. A dedicated clinical registry and research network to facilitate, support
and conduct large clinical trials in this space is absent internationally and urgently
required.
The project involves creating a national platform for such a Clinical Registry (CR) and
Clinical Trial and Translation Network (CTTN) focusing on the critical early stages of
psychotic disorders in young people and emerging adults. In combination with a
number of key foundation member early psychosis clinical services nationwide, we aim
to create the Australian Early Psychosis Collaborative Consortium (AEPCC) network
and registry. The platform aims to catalyse, cohere and enhance the development,
evaluation and translation, across Australia and beyond, of new and existing treatment
strategies in early psychosis to improve key outcomes including, remission and
recovery.
Our specific key deliverables include the development of both the CR and CTTN
starting with seven large early psychosis services, including the organisational and
governance structures, and translational activities. Through the CTTN we aim to
facilitate the approval of up to 2 multicentre clinical trials in accordance with regulatory
requirements. |
| 30/09/2019 |
£18,712,060 |
|
SCRIPPS RESEARCH INSTITUTE |
As the drug discovery division of Scripps Research, Calibr has established a robust
infrastructure and experienced team, focused on the development of new medicines
for unmet medical needs. We propose to draw upon this expertise and infrastructure,
as well as a network of collaborators and prior investment of over $80million in global
health drug discovery, to create the Integrated Drug Discovery Consortium for
Neglected Tropical Diseases (IDDC-NTD). The IDDC-NTD will leverage innovative
approaches and enabling technologies to tackle some of the most challenging
neglected tropical diseases, aiming to create new drug candidates for
schistosomiasis, leishmaniasis, Chagas disease, cryptosporidiosis and dengue. By
exploring multiple parallel approaches, we aim to deliver several drug candidates that
could progress into patient studies, including the potential to accelerate such
development using a novel drug repurposing resource called ReFRAME. In
summary, by leveraging our considerable investment, scale, and momentum in
preclinical drug discovery, including significant expertise and enabling technologies in
global health, our IDDC-NTD is expected to have a major impact on the HIT NTD
flagship’s objectives toward creating new technologies and medicines to impact
NTDs. |
| 30/09/2019 |
£6,240,000 |
|
NOVARTIS PHARMA AG |
KAE609 is a novel antimalarial development program led by Novartis. It was
discovered through a joint research program with the Novartis Institute for Tropical
Diseases, Novartis Natural Products Research Group, the Genomics Institute of the
Novartis Research Foundation, and the Swiss Tropical and Public Health Institute.
Research was supported by the Wellcome Trust, the Singapore Economic
Development Board, and Medicines for Malaria Venture (MMV). Novartis is leading
the development of KAE609 in collaboration with MMV and with financial support from
the Wellcome Trust
Wellcome exists to improve health by helping great ideas to thrive. We support
researchers, we take on big health challenges, we campaign for better science,
and we help everyone get involved with science and health research. We are a
politically and financially independent foundation. https://wellcome.ac.uk/.
Novartis is reimagining medicine to improve and extend people’s lives. As a
leading global medicines company, we use innovative science and digital
technologies to create transformative treatments in areas of great medical need.
In our quest to find new medicines, we consistently rank among the world’s top
companies investing in research and development. Novartis products reach more
than 750 million people globally and we are finding innovative ways to expand
access to our latest treatments. About 109,000 people of more than 145
nationalities work at Novartis around the world. For more information visit
www.novartis.com." |
| 30/09/2019 |
£348,810 |
|
WELLCOME TRUST SANGER INSTITUTE |
The Human Cell Atlas aims to understand cells at a fundamental level and what this means for health and disease. Our ambitious public engagement programme will explore fundamental questions embedded within the HCA research such as "What does it mean to be normal?" and "What influences peoples’ value and trust in research involving tissue donation and open access data?"
We have identified audiences with whom engagement with HCA science has particular relevance. These are: 1) patient groups affected by conditions investigated as part of the HCA, 2) existing and potential organ donors, 3) communities not often represented in conversations around healthcare research and organ donation, and 4) education cohorts whose learning experience could be influenced by the research.
Our vision through the engagement with our target communities is to improve outcomes related to the value and trust people place in research with consequent impact on willingness to donate tissue for research, share their data and help to identify areas of unmet need that the HCA could tackle. Our impact also extends to the global HCA consortium, where the methods and resources created and tested through our work will be made available to the wider community.
|
| 30/09/2019 |
£5,400,000 |
|
WELLCOME TRUST SANGER INSTITUTE |
No Data Entered |
| 30/09/2019 |
£1,601,709 |
|
GLAXOSMITHKLINE BIOLOGICALS SA |
This Project advances the clinical development of an innovative vaccine
candidate targeting the most common Shigella serotypes causing moderate to
severe diarrhea in impoverished communities globally. The GSK Vaccines
Institute for Global Health (GVGH) is developing Sonflex1-2-3, under a
mandate from GlaxoSmithKline Biologicals SA (GSK BIO), a vaccine candidate
against Shigella based on the GMMA-technology. Successful completion of the
Project will allow selection of the most appropriate dose and schedule of the
vaccine in Kenyan adults and infants, and will further provide insight into the
human protective immune response following vaccination. |
| 12/09/2019 |
£233,879 |
|
VILLAGEREACH MOZAMBIQUE |
<p style="margin-left: 0in; margin-right: 0in">Immunizing children under the age of two is an extremely cost-effective public health intervention. However, in Mozambique, 32-percent of children aged 12-23 months have not completed the full vaccination program, leaving them at risk of vaccine preventable diseases. Several studies have uncovered surface-level barriers to full vaccination, however few studies have sought to fully understand these and other potential barriers, and design solutions from participatory approach.</p>
<p style="margin-left: 0in; margin-right: 0in">Bate-Papo Vacina! will train caregivers of children aged 12-23 to conduct community–driven participatory research and human-centered design (HCD) methods to collect primary data from Health Workers (HWs) and caregivers to answer the research question “<em>What are the barriers to caregivers fully vaccinating their children and what are potential solutions to address those barriers?</em>”<strong> </strong>By engaging HWs and caregivers as knowledgeable innovators and collaborators, our approach will generate richer, more relevant, and nuanced content, which will inform impactful solutions for addressing health system barriers and caregiver needs to fully vaccinating their children. In addition, by engaging HWs directly in the research through an HCD workshop, they will have the opportunity to challenge their own assumptions and hear directly from caregivers. </p>
|
| 12/09/2019 |
£256,211 |
|
AFRICAN POPULATION & HEALTH RESEARCH CENTRE, KENYA |
<p style="margin-left: 0in; margin-right: 0in">Ending hunger by 2030 is a core Sustainable Development Goals target. In Kenya, slum residents experience high levels of food and nutrition insecurity, with over 80% of their households being food insecure, close to half of children under five years being stunted and about a third of mothers being underweight. Despite this, the right to food is recognized in the Kenyan constitution. Through a public engagement fellowship funded by the Wellcome Trust, we piloted a model, working with community organized groups (COGs) from 10 Nairobi slums, to engage their communities on food and nutrition security concept and research evidence thereof, using participatory methodologies. We will scale this model to other Kenyan slums. We aim to empower people on food and nutrition security concept and the research evidence thereof, and obtain their views to shape further research and interventions, hence eventually bridge the gap between the lived experiences, future research and food security. We will also build capacity of COGs in public engagement, for greater effectiveness, success and sustainability. Our proposal aligns with Wellcome’s criteria in that it empowers communities to engage with and contribute to health research, making it people-centred; targets poor communities; and, builds on a piloted successful project.</p>
|
| 12/09/2019 |
£116,052 |
|
UNIVERSITY OF BIRMINGHAM |
<p style="margin-left: 0cm; margin-right: 0cm">How does collaboration in public engagement with research (PER) affect participants and audiences? Are assumptions about the value of different PER activities well-founded? How do we best develop great ideas into impactful PER outcomes? Unlike research, PER rarely compares different approaches side-by-side: essential if we want to know what works in what context, and why.</p>
<p style="margin-left: 0cm; margin-right: 0cm">‘The Exchange’, University of Birmingham’s forthcoming flagship city-centre engagement space will tackle global problems through the lens of local and civic challenges, providing an opportunity to consult with Birmingham’s diverse communities on their healthcare needs and how together we might more effectively address them through PER. CREDiBLE is a novel PER ‘experiment’, testing four different combinations of expertise, activity type and development across researchers and community representatives, with the advantage that we can carefully measure and evaluate each combination, at every stage of project development.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The four resulting PER activities, “outputs”, will be linked to current Wellcome-funded research in Birmingham. The ultimate outcomes will be to empower key communities to better navigate their healthcare challenges through meaningful engagement with research. Importantly, our novel approach will form a basis on which to programme purposeful activity for The Exchange that is replicable for other cities and settings.</p>
|
| 12/09/2019 |
£74,336 |
|
CHILDREN'S TRUST TADWORTH |
<p>Research in childhood Acquired Brain Injury (ABI) and neurodisability is lacking. As the major provider of paediatric neurorehabilitation, The Children’s Trust is well positioned to empower young people and families to be involved in health research, using their lived experience to shape the future neurodisability research agenda and use health research for their benefit. Specifically, the project will increase public engagement and involvement by working alongside children and families to co-produce 80% of our research projects by 2023.<br>
It aims to:<br>
• Build a co-production model which engages and empowers involvement in research by parents and children with brain injury. <br>
• Improve connectivity using locally inspired and driven approaches to neurodisability and brain injury research.<br>
• Reach a broader public audience by bridging the knowledge gap and making research more accessible to more people.<br>
<br>
Families have demonstrated an appetite to engage in and influence each step of the research process. Through these activities they will feel empowered and connected to the research agenda. This creative and adaptive approach will encourage shared decision making by building confidence and increasing knowledge.</p>
<p><br>
In turn, families will advocate more confidently for improved practice and make the most of their lives.<br>
</p>
|
| 12/09/2019 |
£91,450 |
|
BARBICAN CENTRE TRUST |
<p>Following the success of Barbican’s first annual theme in 2018, <em>The Art of Change</em>, and the ongoing evaluation of 2019’s Wellcome-supported <em>Life Rewired</em>, we are planning the 2020 theme. <em>Inner Visions</em> (working title), will explore how artists pioneer new ways to express their inner lives, and how their work can help us communicate who we are, interrogating themes such as authenticity and identity.</p>
<p>Central to <em>Inner Visions</em> is a thread of projects dealing with neuroscience, neurodiversity, and how we can better understand ourselves and our experience of the world, making space for dialogue between audiences and important ideas.</p>
<p>These projects will creatively engage over 16,000 people through a year-long series of health-related arts and culture, including a cinema season considering how neurodiverse people are portrayed in film, and music-based performances exploring scientific and analytic responses to loss, melancholy and botanical and pharmaceutical remedies.</p>
<p>We will empower diverse audiences to think critically about health and get involved through activities including an event exploring the arts and mental health with brain injury charity, Headway East; a research project with Autistica looking at our offering for Autistic people; and a public project exploring the health impacts of sound on those living in cities.</p>
|
| 12/09/2019 |
£64,614 |
|
UNIVERSITY OF NORTHAMPTON |
<p style="margin-left: 0cm; margin-right: 0cm">The DEFIN-YD project (Dementia Experts For Involvement Network for Younger people with Dementia) project aims to (1) raise awareness of YOD (2) make the local communities and people affected by YOD (in the north, midlands and south of England) aware of the existing research into young onset dementia care and (3) create a strong and stable regional public and patient involvement forum network to inform YOD research and policy.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Three one day events across the country will take place in the north, midlands and south of England, which provide a platform for younger people living with dementia to get involved in the design of dementia research activities. Following the event, a national network with three regional hubs, specific for younger people living with dementia, will be created and supported. Members will receive PPI training, and meet on three separate occasions to inform research. A “one year on …” event will take place in Northampton in May 2021 to highlight the great work that the network has achieved and to potentially recruit more PPI members onboard. The project will provide platform for people with YOD to get involved in research, through being experts by experience.</p>
|
| 12/09/2019 |
£50,300 |
|
THE INVOLVE FOUNDATION |
<p>The sharing of H&SC data both between public service providers and with the public is expected to bring significant benefits across the H&SC system. However, sharing is not happening at the rate and extent needed. One significant block is concerns about the extent to which the public support sharing both in principle and in individual contexts.<br>
<br>
This project will pilot a new methodology to distribute deliberative dialogue across communities within two locations, NW London and North Lanarkshire. The pilot will build deliberative capacity within each community. By providing expertise and resources, the project will support community groups, which between them involve a diverse range of publics, to have an informed deliberative discussion about the relevance and implications of H&SC data sharing for them and service provision within the community.<br>
<br>
In doing this, the dialogue will empower people to access and use their own H&SC data and support them to think critically about the role that such data plays in the delivery of, and innovation in, the H&SC system. It will also directly inform policy and practice in the two locations. If successful it will support the development of an effective and sustainable network of engagement in the two locations.</p>
|
| 12/09/2019 |
£97,428 |
|
UNIVERSITY OF GLASGOW |
<p style="margin-left: 36pt; margin-right: 0cm">Air pollution is a global health priority, leading to reduced life expectancy and increased respiratory disease. Air pollution is high in major cities, with residents of informal settlements particularly badly affected. A previous project, AIR Network, successfully used innovative creative methods to raise air pollution awareness in Mukuru, an informal settlement in Nairobi, Kenya. The current project, which emerged from community consultations, will extend AIR Network methods into community sensitisation to increase residents’ (including children/youth) knowledge of air pollution and lung health in Mukuru and a neighbouring higher-income area, Buruburu, and empower them to engage equitably in child lung health research (the forthcoming Tupumue study). We aim to: raise air pollution and lung health awareness and promote local knowledge-sharing/advocacy; support community input to the Tupumue fieldwork design; and build children/youth’s confidence about becoming Tupumue participants/citizen scientists. To do this, we will hold community workshops to co-develop participatory, creative sensitisation strategies, and train community members to implement them in strategic locations to maximise diversity in engaging local children/youth/parents/teachers/youth workers. AIR Network findings that creative methods successfully build trust and break down barriers make us confident of achieving sustainable impact in air pollution and lung health awareness-raising and equal health research partnership-building. </p>
|
| 12/09/2019 |
£166,802 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">How people think about vaccines is a global concern<u><sup>1</sup></u>. <em>‘One for All?’</em> asks: “How does engagement with herd immunity influence attitudes to immunisation?”. By working in close partnership with communities, researchers, artists, healthcare professionals, experts by experience, policy-makers and creative engagement practitioners in Africa and the UK, we will co-create a range of graphic-based, online and print resources focused on herd immunity. Developing, testing, evaluating and sharing <em>‘One for All?’</em> resources will</p>
<ul>
<li>Empower people who make decisions about immunisation (e.g. parents, guardians, community leaders, influencers, older children) to:
<ul style="list-style-type: circle">
<li>Make informed choices about vaccination, informed by a set of resources based on robust research, common concerns and in context;</li>
<li>Contribute actively and meaningfully to future research.</li>
</ul>
</li>
<li>Enable researchers, fieldworkers, practitioners, policy-makers and healthcare professionals to ‘do’ engagement with vaccines, based around concepts of herd immunity through the use of our creative, accessible and transferable resources;</li>
<li>Inform research and engagement practice by testing and evaluating our central question and sharing our learning;</li>
<li>Potentially reach further global audiences through strategic branding, campaigning and stakeholder engagement.</li>
</ul>
<p style="margin-left: 0cm; margin-right: 0cm"><em>‘One for All?’</em> ultimately contributes to the goal of decreasing vaccine hesitancy and increasing vaccine uptake by contributing to the learning and practice of engagement with immunisation.</p>
|
| 12/09/2019 |
£79,000 |
|
TINNITUS HUB |
<p>This project aims to promote patient-driven tinnitus research.</p>
<p><br>
The project will combine direct patient-researcher interaction with the creative use of online tools to bring insights from patients around the world. We will have tinnitus patients discuss and vote online on the most promising recent publications in the field of tinnitus. We will deliver those insights to researchers. Over time, a core panel of patients will develop sufficient expertise to formulate recommendations for how tinnitus research can become more patient-centred. Finally, we’d like to see at least one study being funded that explicitly follows these recommendations.</p>
<p><br>
This project will build on:</p>
<ul>
<li>Tinnitus Hub’s experience with facilitating patient peer-to-peer interaction and patient-researcher interaction;</li>
<li>Our online engagement tools, including our support forum;</li>
<li>Our connections with tinnitus researchers and our own research experience (including several academic publications).</li>
</ul>
<p><br>
Ultimately, we hope to see tinnitus researchers develop an enhanced understanding of the needs of tinnitus patients, and for these needs to inform and shape their research questions and methods. And we would like tinnitus patients to have the knowledge and means to steer research in a direction that is beneficial for them.</p>
|
| 12/09/2019 |
£87,075 |
|
NO ORGANISATION |
<p>My Extinction is a documentary investigating the rise in neo-eugenic ideology, and the ethics around the CRISPR Gene editing technology. It is told through the lens of David Proud a Spina Bifida film maker contemplating Pre Implantation Genetic Diagnosis, to eliminate passing a disability onto his child. As David and wife Amy battle with one of the biggest decisions of their lives we see how the greater existential questions expand from their personal situation. </p>
<p><br>
The documentary will hopefully spark a greater debate on the ethics of future gene editing technology. Scientific techniques such as CRISPR can be hard for an audience to connect with. Through David’s emotional story we make reproductive technology accessible for a wider audience. It also helps to build trust and in the scientific community, and to discuss how efforts are made to push the boundaries of medical innovation in an ethically responsible way. </p>
<p>With the disabled community feeling critically undervalued in society and science playing into this by making them sound like an error to be fixed, or made extinct, this piece of work is both timely and crucial to start the conversation, hopefully ensuring correct decisions can be made in future reproductive technology. </p>
<p> </p>
<p> </p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p> </p>
<p> </p>
|
| 12/09/2019 |
£98,549 |
|
UNIVERSITY OF BRISTOL |
<p style="margin-left: 0px; margin-right: 0px">Grief affects everyone, yet remains taboo, with bereaved people often unsupported and isolated. We will hold a city-wide festival on grief and bereavement in Bristol in May 2020 (Good Grief, Bristol), focussed on engaging disadvantaged young people and members of BME communities, who access bereavement support less than other groups.</p>
<p style="margin-left: 0px; margin-right: 0px">The festival will involve three main strands, developed via consultation with community partners:</p>
<ol style="list-style-type: lower-roman">
<li>A Creative Grief competition supported by practical Grief & Arts workshops for young people and schools outreach;</li>
<li>An art project (This Grief Thing) proven to engage socioeconomically deprived communities;</li>
<li>High-profile cultural events, followed by panel and public discussions.</li>
</ol>
<p style="margin-left: 0px; margin-right: 0px"><br>
Funded community consultation to further develop the festival begins summer 2019.</p>
<p style="margin-left: 0px; margin-right: 0px">Primary outcomes are empowering >2500 community members to access and respond to grief and bereavement research; comparing three methods of public engagement (i-iii) to provide actionable research data relevant to other sensitive topics; and recruiting a diverse group of ≥30 members of the public to a public involvement and engagement panel to inform research across the South West.</p>
<p style="margin-left: 0px; margin-right: 0px">Our team includes major cultural venues and expertise in health research, evaluation, the arts, community engagement, bereavement support and event management. High-profile contributors have also confirmed their participation. </p>
|
| 12/09/2019 |
£59,895 |
|
MUSLIM WOMEN'S COUNCIL |
<p>The way we do research to inform policy isn't working. Today, most community based/‘led’ research is done through collaborations between large science or specialist research institutes partnering with local organisations beyond their institutions. Whilst this is an attempt to enrich the quality of research and of bringing wider social benefits, it still lacks the true representation of the communities they are trying to help. Where such partnerships are formed the experiences are not always productive or conducive to drawing on the knowledge and expertise of all participants, as they remain the subject not the co-authors of the research.<br>
There is a need for a process that places these individuals and communities as the authors of research that considers the issues they face; and develops practical responses and recommendations from the ground up. There is a need for a radical shift and movement in how authentic data and insights are collected from women of Black and Minority Ethnic backgrounds.<br>
In response, MWC wants to develop an approach that focuses on the delivery of authentic and appropriate research to create better policy and practice that drive practical solutions that address women’s health and wellbeing.<br>
</p>
|
| 12/09/2019 |
£124,866 |
|
MENTAL HEALTH FOUNDATION |
<p style="margin-left: 0cm; margin-right: 0cm">It is clear that there is not enough research being done on fathers’ perinatal mental health, which is reflected in the lack of services for fathers. It has also become clear that health researchers recognise a need for incorporating the public voice in their work – and have difficulty accessing the perspectives and experiences of a wide range of fathers. Engagement with football club fans has shown to be fertile area for behaviour change, with initiatives such as the highly successful <em>Football Fans in Training</em> (promoting health in fans – now Europe wide), and <em>The Changing Room</em> in Scotland (to encourage men to take action on mental health). We are proposing an 18 month pilot project using participation in football as a means to attract new fathers to participate in facilitated peer support groups, connect them to other new fathers and be engaged with research on perinatal wellbeing. There will be a "kick-off" event to facilitate co-creation of tools for engaging fathers. There were also be 2 events at Cardiff City Stadium to ensure inclusion of fathers not attending the peer support groups. The Project will also facilitate the creation of a Research Consortium on fathers' perinatal mental health. </p>
|
| 31/08/2019 |
£35,791 |
|
UNIVERSITY OF WARWICK |
<p style="margin-left: 0px; margin-right: 0px">This project will develop a forum for interdisciplinary collaborations and collective imagination on the socioethical implications of genomics, using live data-sharing as a spring board to theoretical and conceptual enhancement, and future research agenda development.</p>
<p style="margin-left: 0px; margin-right: 0px">The project will bring together academics, researchers, clinicians, policy-makers and doctoral students working on, or alongside, the socioethical implications of genomics, for four focused workshops over 24 months, informed by the input of a patient/public advisory group. These workshops will provide otherwise non-existent opportunities for collaboration through the presentation and collective curation of current research data and emergent analyses, presented along axes of core cross-cutting themes (e.g. risk/genetic responsibility). The workshops will highlight areas of interdisciplinary resonance for further development, with the ultimate goal of enhancing the theoretical robustness and transferability of underlying concepts, and illuminating pathways for future research. </p>
<p style="margin-left: 0px; margin-right: 0px">It is anticipated that the emergent network of researchers/academics/clinicians/policy-makers interested in socioethical genomics will continue beyond the lifetime of the project, providing an open space for sustained interdisciplinary data-sharing and collaborative analysis, to ultimately enhance the quality and robustness of research in this area, as well as highlighting new directions for the translation of research into policy and practice. </p>
|
| 31/08/2019 |
£29,320 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">Population-level research governance is at a critical juncture. Traditional governance tools, like informed consent and expert committee review processes, have been stretched beyond their ability to function in an effort to accommodate research at scale. While consensus on the importance of involving the public in governance exists, there is little agreement on what such involvement means in practice, when it should be undertaken, and what the primary justifications for it are. There is also little understanding of how involvement approaches integrate with other legal and regulatory structures to effectively inform governance.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Primary aims:</p>
<ul>
<li>Conduct scoping work which examines:</li>
</ul>
<ol>
<li>How should we characterise the range of governance and regulatory challenges that confront us with respect to population-level biomedical research?</li>
<li>
<p style="margin-left: 0cm; margin-right: 0cm">What approaches are currently being used to address these challenges and how, if at all, do these techniques incorporate elements of public involvement?</p>
</li>
<li>
<p style="margin-left: 0cm; margin-right: 0cm">Where are potential areas that public involvement might be introduced to meet these governance challenges?</p>
</li>
</ol>
<ul>
<li>Build an international network which focuses on the intersection of governance and societal involvement in the context of population-level biomedical research</li>
<li>Develop a larger research proposal that will address the role of societal involvement in governance challenges in this context.</li>
</ul>
|
| 31/08/2019 |
£29,525 |
|
ASTON UNIVERSITY |
<p style="margin-left: 0cm; margin-right: 0cm">There is a clear need to focus on the role of transnational companies involved in manufacturing and marketing unhealthy products (e.g. alcohol, processed food and tobacco), which represent leading risk factors in noncommunicable diseases.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The grant will support a two-day workshop in Cape Town, South Africa aimed at furthering research into the commercial determinants of health and its translation into public health advocacy and policy through the GECI-PH network ((The Governance, Ethics and Conflicts of Interest in Public Health), which is unique in terms of its geographic spread and breadth of expertise covered by its membership. The primary aim of the workshop is to push the boundaries of research on the commercial determinants of health and cultivate collaboration and knowledge exchange between scholars and civil society actors.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The workshop will: a) expand the number of scholars and professionals in the network from the global south (key to capacity building); b) expand the range of disciplines represented within the network (key to developing new mixed, interdisciplinary methods to addressing the role of commercial activities on health and health inequalities); c) forge new modes of interdisciplinary collaboration; d) increase the representation of civil society actors within the network (key to research translation).</p>
|
| 31/08/2019 |
£26,922 |
|
UNIVERSITY OF LEEDS |
<p>This project aims to establish foundations for a comparative study of social reciprocity and exclusion in the expanding blood economy. Building on an emergent collaboration among researchers in the UK and East Asia, this project sets out to ask how the donation and circulation of blood (from whole blood to various blood components) across social boundaries intersects with local histories of ‘othering’, such as conceptions of race/ethnicity, caste/class, and sex/gender/sexuality. The project combines scoping activities and networking events to enhance our comparative understanding of social challenges in the increasingly interconnected global blood economy. It has three main goals:<br>
1) To create a new international research network to promote a comparative understanding of the social dynamics of inclusion and exclusion in the global blood economy.<br>
2) To publish two peer-reviewed publications that draw on exploratory research and international exchanges.<br>
3) To develop joint funding applications for public engagement and collaborative research. </p>
|
| 31/08/2019 |
£30,723 |
|
UNIVERSITY OF THE WITWATERSRAND |
<p style="margin-left: 0cm; margin-right: 0cm">There has been growing interest in developing and shaping Medical and Health Humanities (MHH) in Africa. While still a nascent field on the continent, in the last six years, through conferences and meetings, the increasing visibility of MHH has resulted in discussions about what the field is; how it can shape understandings, provision, and research related to health; and how artists, academics, activists, and health care seekers and providers based in Africa can contribute to its local development and international evolution. Our project seeks to support existing, local MHH networks; foster the growth of new regional networks; and connect regional networks through the creation of a MHH Africa hub and working group.</p>
<p>Starting with southern and east Africa, this project will build a community of MHH researchers and practitioners and bring together people to collectively identify future projects, and to strengthen and develop formal, collaborative MHH structures. The intention is to foster a community of people involved in MHH and actively engage them in contributing to the future of the field and the network on the continent. Our vision is to build a south-led, south-to-south collaboration, which by 2025 will be an internationally recognised MHH Africa hub and working group.</p>
|
| 31/08/2019 |
£29,210 |
|
UNIVERSITY OF BIRMINGHAM |
<p style="margin-left: 0cm; margin-right: 0cm">Qualitative research is important in health and social care research but there is considerable evidence that it is often a-theoretical and of poor quality. The aim is to bring together prominent researchers from across the humanities, health and social sciences and establish an expert group on theory use and methodological clarity in qualitative research. We will work with the expert group to develop and revise existing resources developed by the team so that they can have greater impact on the quality of reporting in qualitative research.</p>
<p style="margin-left: 0cm; margin-right: 0cm">To achieve this we plan a two-day workshop and through a process of Concept Mapping, the experts will work with, and revise the previous resources. We will work with a graphic designer/artist in preparing a high quality report and visual materials to showcase the work of ‘QUANTUM’ (The QUAlitative research Network for Theory Use and Methodology) and to launch QUANTUM as a new network for qualitative research.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Planned outcomes are: 1) To produce resources that can drive up quality of reporting in qualitative research; 2) To establish QUANTUM as a new network to support rather than duplicate, the work of EQUATOR, COREQ and QUESTS, particularly by emphasising the place of theory in qualitative research. </p>
|
| 31/08/2019 |
£25,003 |
|
UNIVERSITY OF KENT |
<p>Medical Humanities is a healthy interdisciplinary programme in Britain, yet there is potential to stimulate further collaboration across a range of disciplines to integrate the social sciences and sciences to transcend traditional boundaries. This application offers a series of workshops to explore the potential for more transdisciplinarity in a series of themed workshops. Two workshops explore the potential for collaboration with the social sciences and sciences, and is followed up by third workshop on international transdisciplinarity. The international workshop will extend the reach of Medical Humanities scholars in the UK to participate with international scholars to engage, share, and offer the potential for collaboration across disciplines with colleagues in the future. Overall the workshops will contribute to the network of Medical Humanities scholars in the UK, offering a space to explore ideas surrounding transdisciplinarity with the Social Sciences and Sciences. <br>
In addition, three Engagement Workshops will examine ways that Medical Humanities offer opportunities in research, teaching, new digital technology, public engagement and grant applications. There may be scope for these workshops to explore the potential for transdisciplinarity through cross-fertilisation with the social sciences and sciences. These Engagement Workshops are aimed at a broad audience of scholars, students, and health professionals. </p>
|
| 31/08/2019 |
£23,754 |
|
UNIVERSITY OF LIVERPOOL |
<p style="margin-left: 0cm; margin-right: 0cm">This interdisciplinary project aims to establish a robust network of collaborators from Humanities, Health and Social Sciences to examine ancient and modern corporeal relational dynamics, i.e. conceptions of the relational dynamic of the body with its constituent parts. It draws on recent theoretical approaches (‘ontological turn’, new materialisms, ‘corporeal turn’) and advances in disability studies, and examines a variety of processes of bodily fragmentation, fusion, and trans-formation with an extra focus on gender, socio-cultural status and religious belief.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Historical conceptions of corporeal relational dynamics will be contrasted with contemporary biomedical views and collaborators are encouraged to reflect on their own discipline and practice. The aim is to foreground the body as a composite structure, dialectically shaped by individuals and cultures, and open to debate. Thus we can deepen our understanding of the fluidity between the ‘ancient’ and ‘modern’/’post-modern’, ‘real’/‘physical’ and the ‘imaginary’/‘represented’ body and body parts. </p>
<p style="margin-left: 0cm; margin-right: 0cm">Three distinct but thematically related workshops, a) <strong>Fragmentation and Fusion</strong>, b) <strong>Focus and Frontiers</strong>, c) <strong>Trans-Formation</strong>, will bring together researchers in the humanities and disability studies experts with researchers of medical humanities and/or social scientists. These will enable participants to interact, build on, and develop their current approaches to and understanding of their evidence.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 31/08/2019 |
£10,865 |
|
SWANSEA UNIVERSITY |
<p>The biennial conference for the Society for the Social History of Medicine (SSHM) attracts a regular international audience. Each conference has a broad, inclusive theme. The 2020 conference at Swansea University celebrates the 50<sup>th</sup> anniversary of the SSHM with the theme of ‘Resilience’. As interest in resilience has grown, the conference presents an important opportunity to bring together researchers from across the humanities, health sciences, medicine and cognate fields to share approaches to resilience and to explore new research networks and collaborations. </p>
<p>Since 2006, the Society for the Social History of Medicine conference has brought together scholars from Britain and overseas. It is the largest and single most important meeting in the field to take place in Britain on a regular basis, attracting between 150 and 250 participants across all areas of the social history of medicine. Particular attention is paid to allowing younger scholars the opportunity to present their research.</p>
<p>The Wellcome Trust has a long association with the SSHM, having funded all previous conferences. We request similar support for 2020, specifically for an evening reception, a public engagement activity, a linked ECR workshop, and a subvention for students and non-waged participants.</p>
|
| 31/08/2019 |
£33,315 |
|
UNIVERSITY OF GHANA |
<p>The increasing demand for good sustainable health care and the need to reduce medical errors in Africa calls for the implementation of appropriate bioethical training for health care professionals. However, the available tools today are mostly generated in a Western context that relies on a framework and a language that do not fully resonate with the local cultural values, resulting in a normative and motivational gap. This project brings together an international interdisciplinary team to explore ways of closing this gap with the aim of producing professional educational tools for health care professionals. The project will<br>
a) carry out five focus group discussion meetings to explore and publish findings on motivations and attitudes towards clinical bioethics;<br>
b) organize three workshops in Ghana to analyse findings and to discuss (i) adequate frameworks, (ii) culturally grounded motivational tools, (iii) contextualized pedagogical tools;<br>
d) organize a dissemination conference for regional stakeholders on clinical bioethics.<br>
A major output will be a draft version of an African handbook for clinical bioethics that will be piloted in schools of health sciences and by professional bodies. The project network will also constitute the basis for scaling up this project to serve the West African sub-Region.</p>
|
| 31/08/2019 |
£23,935 |
|
UNIVERSITY COLLEGE DUBLIN |
<p style="margin-left: 0cm; margin-right: 0cm"><br>
Child sexual abuse (CSA) is a major public-health issue directly affecting up to one in five people worldwide, with serious mental and physical health consequences. While CSA is well-researched from psychology, social science and medical perspectives, cultural approaches to it are notably lacking. This means that representations of CSA in cultural works like novels, films and TV series remain seriously under-explored, leaving key gaps in cultural and wider scholarship.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Cultural approaches are vital because cultural works collectively provide a key lens through which issues are viewed. They thus form a major overlooked source potentially informing social understandings of CSA, and these in turn affect prevention and survivors’ health outcomes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The project’s key goals therefore are to build a research agenda around cultural approaches to CSA and to develop a professional network to support it. The network will connect cultural scholars interested in the area with other relevant humanities, social science and medical scholars, CSA-survivor experts-by-experience, and healthcare practitioners through an integrated programme of activities.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This will allow the most effective cultural approaches to be determined, and build research capacity for exploring this important, neglected theme in contemporary cultural production and transforming understandings of how social views of CSA are formed.<br>
</p>
|
| 31/08/2019 |
£29,575 |
|
KING'S COLLEGE LONDON |
<p>In the Muslim Middle East, the growth of assisted reproductive technologies (ARTs) has not been accompanied by the creation of comprehensive guidelines and regulations. In this region, any method of medically reproductive assistance is consistently governed by Islamic law. Given divergent sectarian perspectives among Sunni and Shi’a Muslims, there are various approaches to ARTs. Sunni religious authorities banned all forms of ARTs involving third-party donors, due to their strict faith regarding incest and biological lineage. Nevertheless, Shi’a Muslims hold more progressive opinions on gametes and embryo donation, and gestational surrogacy. Despite this conflict of beliefs, two Shi’a dominant countries, Iran and Lebanon, supply the donor technology for infertile couples from both Shi’a and Sunni sectors in the Middle East.</p>
<p>This project aims to build an international network of humanities scholars, social scientists, bioethicists, policy-makers, regulators, scientists, and other stakeholders, to understand the key debates on the ethics and governance of ARTs in this region.</p>
<p>Moreover, it will lay the groundwork for a future large grant application by building an international and collaborative network to explore the global and regional perspectives about how to develop more authoritative and efficient ethical governance of the new ARTs in this geo-politically far-reaching region.</p>
|
| 31/08/2019 |
£30,300 |
|
BIRKBECK UNIVERSITY OF LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">We are a group of historians located at the intersection of the history of medicine and science, medical humanities and international relations. With the help of this grant we would like to throw light on the social and political infrastructures, practices and organisations that have shaped ‘medical internationalism’ in practice in the course of the 19<sup>th</sup> and 20<sup>th</sup> centuries. ‘Internationalism’ can refer to very different ideas and practices, from the search for intergovernmental agreements to the practice of international assembly and the transfer of ideas, objects or people across borders. We are seeking to make explicit the infrastructures, organisations and networks that have shaped how medically-trained professionals have understood their place in the world. Our main goal is to create a network of researchers with expertise in medical and scientific internationalism and the internationalisation of academic institutions. This grant would enable us to define a new and shared research agenda, and to anchor our enquiries within the broader scholarships on internationalism and international relations which have hitherto frequently ignored the roles played by medicine.</p>
|
| 31/08/2019 |
£30,603 |
|
UNIVERSITY COLLEGE DUBLIN |
<p>Archiving the 8th is a research and networking project that arose in the immediate aftermath of the referendum on the 8th amendment of the Irish Constitution in 2018, which overturned the constitutional ban on abortion in Ireland. Its purpose is to support and coordinate nationwide efforts to archive, collect, and research the referendum and related outputs concerning women's reproductive health and rights. These include political ephemera, organisational records, websites and digital material, photography, visual and material culture, and oral histories. This project is a non-partisan and voluntary network with open membership, and currently includes more than 50 nationwide academic, archivist, and academic members, led by a steering group. I am the coordinator of the Network.</p>
<p>This application seeks support to expand and enhance the research agenda of the Archiving the 8th Network. The key goals of this proposal are to share knowledge and improve researcher/archivist practices in the field of rapid response collecting in women's health and reproductive rights; enhance the research agenda of the Network through conferences, bibliographic development, and supporting future funding bids; and to create/disseminate outputs of value to external partners (eg the collecting/archiving guides to be made available to community groups; individuals; and small/independent archives).</p>
|
| 31/08/2019 |
£30,300 |
|
UNIVERSITY OF MANCHESTER |
<p>This proposal brings together health practitioners and academic researchers to establish a new, qualitative, medical humanitarian research agenda focused on how emerging healthcare management technologies are deployed among vulnerable populations. </p>
<p>Despite hopes that technology would serve as a force for human liberation, emerging information communication technologies generate unintended consequences that can serve to replicate existing health and human inequalities. This potential may be especially grave where existing health vulnerabilities are already acute. Emerging digital health technologies may help to combat medical and humanitarian crises, yet enthusiasm must be tempered with an awareness of how these technologies might work among vulnerable people or in local, historically particular and often fragile settings.</p>
<p>This agenda will unite clinicians, technologists, aid workers and academics over a period of 18 months to establish a network and new research agenda to examine these dilemmas from both academic and practitioner perspectives. Starting online, and working towards a face-to-face symposium in the summer of 2020 at the University of Manchester, this project will gather heretofore separate research streams in digital health, humanitarian mapping, and bioethics, with the intention of generating theoretical, ethical and practical outcomes for the use of medical humanitarian data technologies.</p>
|
| 31/08/2019 |
£29,985 |
|
LANCASTER UNIVERSITY |
<p>This project will foster an international network of social scientists, healthcare practitioners and civil society stakeholders to explore grassroots advocacy and healthcare interventions addressing the needs of migrants, refugees and other mobile populations. Past decades have seen growing numbers of health practitioners crossing international borders to care for the world’s most disadvantaged populations. Yet most doctors do not work <em>without</em>, but rather <em>within</em> borders. They practice medicine in domestic settings where healthcare is channeled through national systems designed to treat settled populations. However, the 2008 financial crisis, austerity policies, conflicts and migratory movements in the European neighbourhood have challenged healthcare systems in the European area (WHO 2018). Without traveling overseas, practitioners increasingly care for migrants, refugees and other mobile populations who (a) present with health problems associated with displacement and poverty; (b) lack regular legal status and/or permanent address, complicating access to care. We gathered preliminary evidence showing how these developments prompted some medical practitioners to seek practical avenues for addressing the needs of mobile patients and to advocate for those groups’ human right to health. This network will develop a research agenda in health and mobilities, aiming for a framework to understand the human, socio-political and medical issues involved.</p>
|
| 31/08/2019 |
£26,792 |
|
UNIVERSITY COLLEGE DUBLIN |
<p>Stammering is a complex, fascinating phenomenon that involves 70 million speakers worldwide, with a ratio of approx. 4 men to 1 woman (<em>Stuttering Foundation</em>). Attended by a history of problematic medical/clinical intervention (Shell 2005; Eagle 2014), it continues to challenge neuroscientists exploring its causes (Per Alm 2006), clinicians developing treatments, and (most of all) the individuals who stammer across the borders of class, culture and ethnicity.</p>
<p>Despite the profound significance of cultural responses to the experience of dyslfuency and its expression, the humanities have remained sidelined from mainstream scientific/clinical practice (e.g., Oxford Dysfluency Conference 2017). The present project proposes the first humanities-led network in the area, one in dynamic conversation with clinical/scientific voices around concepts of 'normal' speech and the tenacious alignment of fluency with social 'health' and cultural authority. Building upon presentations/discussions from the recent 'Metaphoric Stammers' conference (2018), three workshops (Clinical, Cultural and Creative) will identify a shared agenda and a series of key objectives, along with the practical structures necessary for delivery.</p>
<p>Overall aim: development of a transformative approach to dysfluency with the interdisciplinarity and flexibility necessary to respond to its complex, highly individualised nature, ultimately informing and reshaping public debate/policy around clinical practice and resourcing.</p>
|
| 31/08/2019 |
£27,800 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">Viral hepatitis is a global health threat that contributes to more annual deaths than HIV or malaria. Hepatitis B virus can be prevented by early vaccination or treated with antiviral drugs and hepatitis C virus can be cured safely and effectively with direct acting antivirals, yet screening, diagnosis and treatment remain low on a global scale. The way hepatitis is experienced and managed is context specific, making public health programmes dependent on an understanding of local knowledge and practices. Despite this, viral hepatitis is, generally, underfunded and understudied from a social science perspective.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The goal of this specific application is two-fold. First, to build upon an international platform of social science researchers working on research related to infectious disease threats to include a specific working group focused on viral hepatitis. Second, to create a core team of researchers from multiple contexts in East Africa, West Africa, and Southeast Asia to develop and prepare a larger collaborative research agenda<strong> </strong>related to viral hepatitis that will be implemented in low- and middle-income countries. We will host two meetings: one to discuss past and ongoing research and the second to develop a protocol for submission for a collaborative award.</p>
|
| 31/08/2019 |
£29,968 |
|
BIRKBECK UNIVERSITY OF LONDON |
<p>This project brings together an international network of leading HIV scholars, activists, artists, policymakers and practitioners in 5 Fast Track Cities (FTC) – Delhi (India), Brighton (UK), New York (US), Nairobi (Kenya) and Havana (Cuba) to develop an innovative research programme that foregrounds the body in relation to stigma, HIV treatment and prevention encompassing intimate, public and globally comparative perspectives. The UN FTC partnership is a global initiative inviting municipalities in the Global South and North to commit to arresting HIV transmission by improving access to health services and reducing stigma. This focus on the eradication of stigma to facilitate access to HIV biomedicines for treatment and/as prevention, neglects how people affected by HIV live their bodies in respect of localised socio-economic contexts, sexual cultures and HIV bio-technologies - crucial for understanding how stigma operates. During 5 workshops structured following the arts-based methodology Embodied Mapping, we will develop innovative epistemological and methodological approaches for assembling situated knowledges about HIV stigma; investigate how visual methods open up new trajectories for HIV stigma research; and explore how the body in relation to HIV and stigma is understood differently between sectors and urban locations and how this multiplicity is negotiated in practice. </p>
|
| 31/08/2019 |
£29,019 |
|
UNIVERSITY OF NOTTINGHAM |
<p>This project will fund the activities of the Mental Diversity Law Network, a developing network of (currently) approximately 150 academics, service users, professionals and policy-makers from a variety of fields across the UK. The funding will go towards the next two biennial conferences of the Network (2020 and 2022), and a variety of smaller events between these conferences.</p>
<p>The considerable bulk of the grant will fund the involvement of people with lived experience of mental distress in the Network's activities. The Network's policy is that at least 20 per cent of delegates to our events should be people with lived experience; the grant will ensure that this is possible.</p>
<p>The additional events are designed to engage with people in cognate areas (eg., housing law, criminal law) for whom mental disability law is relevant, but who have not engaged with that subject. Since these will be outreach events, we need to keep user costs of those events down. The grant will allow us to do that. It will also fund post-graduate and early career researcher events between the biennial conferences.</p>
<p>A small amount of the grant will also go towards funding of major international speakers for the biennial conferences. </p>
|
| 31/08/2019 |
£21,978 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">There is a resurgence of interest in African population history. The past 2 years have seen the start of several large projects, PhDs and development of undergraduate curricula on the subject, and the field has been strengthened by the development of new technologies for extracting, linking and showcasing historical population microdata. This is important for African history as population change is a critical indicator of wider historical forces; it is also vital for understanding contemporary demographic regimes and influencing future population growth in Africa. </p>
<p style="margin-left: 0cm; margin-right: 0cm">With this grant, I aim to foster collaboration and communication between scholars working in the field of African population history through establishing the African Population History Network (APHN). I aim to raise the profile of African population history through two international workshops. The first will enable scholars to showcase new work and data and will lead to the publication of an edited volume. The second will focus on future comparative projects and will lead to a collaborative grant application. I establish a web presence and newsletter for the APHN to facilitate ongoing communication about members’ activities and seek funding to sustain the network in the future.</p>
|
| 31/08/2019 |
£29,994 |
|
UNIVERSITY OF SUSSEX |
<p>The aim of the project is to strengthen collaboration of public health and political science communities, particularly in low- and middle-income countries (LMICs), to improve capacities for analysing the politics of global health security.</p>
<p>Despite increasing attention to the ‘political determinants’ of health and frequent reference to the ‘need for political will’ to improve global health security, political analysis is not often integrated into global health research and practice. Such perspectives are needed, however, to understand how interests, power and institutions affect health policies and outcomes.</p>
<p>Where political analyses of global health are emerging, they originate mostly from researchers based in high-income countries. This is problematic not only from an equity perspective, but also because global health policy implementation happens largely in LMICs. In many ways, politics are local, reflecting local interests, power relations and institutions. Effective political analysis and engagement, therefore, requires local experts. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The project: (1) brings together researchers with a background in the biomedical sciences, public health, and political analysis based in Tanzania and the UK; (2) supports a series of workshops to facilitate cross-disciplinary engagement and capacity building, and (3) seeks to develop a common research agenda on the politics of health security in Tanzania/East Africa.</p>
|
| 31/08/2019 |
£27,294 |
|
GLASGOW CALEDONIAN UNIVERSITY |
<p style="margin-left: 0in; margin-right: 0in">A century old global wealth disparity remains surrounding expectant mothers’ engagement with biomedicine, even in western countries where vast amounts of money is spent on healthcare. How can we account for such disparity, especially in wealthy western countries? This project will build international academic networks, and practitioner and third sector linkages in the United States and developing countries to provide the historic and contemporary context for facilitating a patient-centred research agenda that seeks to understand this antenatal crisis. Three key goals will help realize this:</p>
<ul>
<li>To grow an international network of medical humanities researchers interested in low-income, pregnancy and biomedicine.</li>
<li>To build collaborative networks with healthcare practitioners and third-sector agencies currently addressing poverty, pregnancy and healthcare in different national contexts.</li>
<li>To advance a patient-centred research agenda, with routes for impact, by engaging with healthcare practitioners and third-sector partners.</li>
</ul>
<p style="margin-left: 0in; margin-right: 0in">Together, these goals will develop an international network and research agenda to progress a research vision that includes modern input into patient-centred historical research questions surrounding low-income, maternity and prevention.</p>
|
| 31/08/2019 |
£52,386 |
|
UNIVERSITY OF LINCOLN |
<p>This project develops a collaborative, interdisciplinary network of researchers to advance new tools and a framework to map, anatomise and begin to interpret the relationships between two features central to UK higher education: (i) the complex network of sectoral, para-sectoral and private organisations reshaping the operations—and the occupational and pedagogical characteristics—of the twenty-first century university; (ii) the growing preoccupation with and interventions relating to university student and staff mental health.</p>
<p>Our specific goal is to produce the first systems/network analysis to map actors/organisations with significant influence on mental health and well-being in UK universities. The network allows structures of power and influence to be visualised. In tandem, we will collectively assess policies and documents surrounding university staff and student mental health. Where do they locate causes of mental ill-health and poor well-being? What approaches (e.g. whole system; mindfulness; different therapies) are being used in attempts to ameliorate the situation? Who is being contracted to deliver them? Which kinds of expertise are foregrounded in relation to university staff and student mental health? </p>
<p>We will host two collaborator workshops to build and share methodological and substantive expertise, an interdisciplinary conference panel, and a public-facing event bringing together academics, policymakers, and other stakeholders.</p>
|
| 31/08/2019 |
£29,317 |
|
KING'S COLLEGE LONDON |
<p><em>Healthy Scepticism </em>aims to examine and find sense in the cloud of doubt, suspicion, cynicism, and distrust that has surrounded medical practice from the mid-20<sup>th </sup>century to the present. Rather than dismiss sceptics of medicine as outliers of our cultures of expertise, the project will engage them in search of critical insight into medicine’s political, social and epistemological status past and present.Thinking through the species of medical scepticism will form the basis for a taxonomy of how and why medical scepticism functions, ranging as it does in use from the medical laboratory as a guarantor of scientific validity, the clinic as a correction for an over-reliance on judgment and instinct, and the public, where its roles run the gambit from structural to personal critique and everything in between. Investigating scepticism about health is an intentional exercise, in getting to know medicine better, getting to know what our expectations for medicine are, and how, when, where, and why they have or have not been met. But <em>Healthy Scepticism </em>is at the same time intended to offer critical perspective on the position – the health - of scepticism itself, as a form of critical engagement in and for our uniquely sceptical age.<br>
</p>
|
| 31/08/2019 |
£16,409 |
|
UNIVERSITY OF ESSEX |
<p style="margin-left: 0cm; margin-right: 0cm">Our series '<strong>The Body of Work' </strong> will enrich our understanding of embodied experiences associated with work, and of practices that marginalise the bodies of certain groups. Although underrepresented in organisation studies, knowledge of how the body affects one's work is crucial to shape inclusive polices, practices and career pathways. </p>
<p style="margin-left: 0cm; margin-right: 0cm">Our key goals are:</p>
<p style="margin-left: 0cm; margin-right: 0cm">1) to reach a wide audience to advance knowledge and foster discussions on under-explored or silenced bodily experiences in organisations.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This will be carried out through a collaborative approach between scholars and industry experts, and will be implemented through dissemination of research and the creation of brief guidelines for change in organisations (in the form of a flyer including ten points from each event, available as a shareable PDF on the website).</p>
<p style="margin-left: 0cm; margin-right: 0cm">2) to create a network of people that will serve as a platform not only connecting isolated scholars working on these issues to one another, but also NGOs and charitable organisations outside of academia (e.g. The Miscarriage Association; Sands; The Red Box Project; Endometriosis UK; Rethink; Mind; reMEmber; Daughters of Eve). </p>
<p style="margin-left: 0cm; margin-right: 0cm">3) to create an online space that will support the durability of the network, and facilitate its growth beyond the series.</p>
|
| 31/08/2019 |
£30,000 |
|
UNIVERSITY OF THE WEST OF SCOTLAND |
<p>Dementia is one of the most significant global challenges of the 21st century; yet, since the late 18th century our understandings of dementia have been based upon <em>mono-species </em>worldviews, in which the impact of neurocognitive disease upon indivisible human subjects has been the primary focus of investigation. Drawing on cutting-edge research from across the humanities, social sciences and biological sciences, this project will chart the contours of an alternative (multi-species<em>) </em>perspective, in which relations between human and non-human bodies becomes the primary lens for understanding dementia and its affects. We will build on the success of an initial multi-disciplinary workshop, held at UWS in May 2019 (and funded by the British Society of Gerontology), to establish a new, international and multi-disciplinary network of researchers. We will facilitate three meetings of the network over the lifetime of the project. Meetings will be informed by Jabereen's (2009) eight-phased process for building a shared conceptual framework. We will produce a detailed proposal, and draft chapters, for a path-breaking edited collection ('Dementia: A Multi-Species Perspective') based on members' research and the network's emergent, shared conceptual framework. In so doing, the project will stimulate new ways of understanding and cultivating multi-species approaches to dementia.</p>
|
| 31/08/2019 |
£23,809 |
|
UNIVERSITY COLLEGE CORK |
<p style="margin-left: 0cm; margin-right: 0cm">The proposal is to establish the Ethics, Law and Pregnancy in Ireland Network (ELPIN), to facilitate understandings of the pregnant subject in a way that highlights the centrality of agency, autonomy and dignity. This interdisciplinary network will include ethicists; lawyers; medical professionals; midwives/directors of midwifery; philosophers; sociologists; and women’s health/reproductive rights advocates. The interdisciplinary nature of the network allows for more complex understandings of the pregnant subject. ELPIN will also facilitate the development of critical competencies among researchers around ethical and legal issues in pregnancy and childbirth in the new (medical/legal/social/ethical) environment post repeal of the Eighth Amendment to the Constitution of Ireland in May 2018. ELPIN will also empower women’s health advocates, pregnant people, and the general public by providing clear and accessible information about rights/interests in pregnancy and childbirth. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The foundation for the network will be established through three workshops. The first will re-imagine the framing of the pregnant subject post repeal; the second will address issues of agency, choice and communication in pregnancy and childbirth; the third will examine experiences of harm in pregnancy/childbirth. ELPIN will be supported by a website containing resources for researchers as well as ‘explainers’ aimed at women’s health advocates/pregnant subjects/the general public. </p>
|
| 31/08/2019 |
£12,630 |
|
QUEEN'S UNIVERSITY BELFAST |
<p>It is a time of political, economic and social change on the island of Ireland. In the Republic of Ireland, there has been strong economic growth and significant social reform in areas such as abortion and marriage equality. Devolution has stalled in Northern Ireland and there are rising political and population divisions over Brexit. Healthcare is one of the key policy sectors affected by these developments, with any change in the relationship between the United Kingdom and the European Union likely to have a significant impact on cross-border healthcare provision. Bringing together researchers, practitioners and other stakeholders from Northern Ireland and the Republic of Ireland, a series of workshops will be held to examine key healthcare topics such as reproduction, patient safety and end of life care. The goals of the project are to establish a cross-border research network on healthcare law, policy and ethics for the first time and to identify a research agenda that will facilitate interdisciplinary research collaborations and outputs in the future.</p>
|
| 31/08/2019 |
£24,992 |
|
BRUNEL UNIVERSITY |
<p style="margin-left: 0px; margin-right: 0px">Four workshops will address how novel forms of medicines and other products increasingly entail integrating complex living tissues. While some tissue-based products are envisaged at vast scales, others are tailored for personalised use. No longer merely source-materials for R&D, cells are increasingly seen as the end-product itself, meaning they must be designed for specific markets, and modified to suit scaled-up or scaled-down manufacturing processes. Consequently, new infrastructures, fabrication, data, and oversight practices evolve.</p>
<p style="margin-left: 0px; margin-right: 0px">Novel social science conceptual analysis will be developed to capture and assess these changes. They beg questions of what it means to alter and scale-up living human and animal tissue to mass quantities, or to scale-down to personalized approaches. Both socially and economically disruptive, there are significant implications for the ontology of tissue, normative policy and ethical oversight, and clinical and consumer use.</p>
<p style="margin-left: 0px; margin-right: 0px">A core group of social scientists (Faulkner, Hinterberger, Hogle, Martin, Meskus, Morrison, Stephens) will attend all workshops. The first three feature topic-specific guest contributors (life sciences, policymakers, industry) and focus on:</p>
<p style="margin-left: 0px; margin-right: 0px">1) New infrastructures</p>
<p style="margin-left: 0px; margin-right: 0px">2) Interactional complexity through industrialisation</p>
<p style="margin-left: 0px; margin-right: 0px">3) Business models and valuations</p>
<p style="margin-left: 0px; margin-right: 0px">The fourth workshop consolidates findings, designs dissemination activities (policy and academic) and future collaboration plans (research networks and grant development).</p>
|
| 31/08/2019 |
£27,202 |
|
CANTERBURY CHRIST CHURCH UNIVERSITY |
<p>Generations are increasingly central to public discussions about health and wellbeing. Claims about intergenerational (un)fairness imagine younger and older generations in a zero-sum competition over health, social care, and educational resources, especially within ageing societies. Policymakers are increasingly interested in understanding how intergenerational relationships can both improve, and adversely affect, the wellbeing of individuals and communities. Our project will examine how these can benefit from an improved understanding of what exactly is passed down through generations, how generational identities coalesce and function, and how commitment and care between the generations can be strengthened and supported by public policy.</p>
<p>This proposal seeks funding to develop a network of academics and Third Sector organisations actively working with ‘generation’, to map how this concept can best be used, and to improve understanding of the relationship between generations, wellbeing, and public policy. The network aims to transform the ways that generation is discussed among scholars, where there is currently little dialogue between disciplinary fields using the concept in parallel but separate and contradictory ways, and between academics and policy-facing organisations. It further aims to transform the way that ‘generation’ is used in media and public policy discussions, promoting a more nuanced and constructive understanding.<br>
</p>
|
| 31/08/2019 |
£26,746 |
|
ROEHAMPTON UNIVERSITY |
<p>Visual cues like graphic warning labels and generic packaging are increasingly seen as important weapons against unhealthy forms of consumption – especially in the areas of tobacco control, and, increasingly, alcohol reduction and obesity prevention. However, public health interventions tend to ignore the physical qualities of packaging in favour of its visual attributes as a marketing tool, which may limit the effectiveness of such legislation based on misplaced assumptions about how people engage with it. A thriving array of studies in the social sciences on the material politics of packaging therefore offer new analytic directions for conceptualising its relationship with the everyday activities of eating, drinking and smoking by drawing attention to its powerful material role in shaping the circulation of goods and the meanings they hold. Accordingly, this project has three objectives: 1) to map how packaging has been conceptualised within the public health and social science literature; 2) to develop new methodological approaches and original empirical data on the relationship between drinking patterns and the containerisation of alcohol; and 3) to assemble a network of scholars interested in developing new approaches to studies of packaging and public health.</p>
|
| 31/08/2019 |
£25,481 |
|
UNIVERSIDAD DE GUANAJUATO |
<p style="margin-left: 0cm; margin-right: 0cm">The aim of the project is to ask how scientific and non-scientific communities of knowledge production in Latin America have historically perceived ethical concerns regarding human genome editing, stem cell and embryonic research. The project will explore how current regulations, frameworks and discourses in the United States and Europe engage with (or contradict) those in Latin America. The grant will help support a multidisciplinary research network that will meet to discuss the implications of a geographical and discursive distance between those places where bioethical frameworks are produced (global north) and those where the actual practice of human genome editing (research and trials) could be potentially happening. The grant will allow the organization of a workshop and other meetings with key stakeholders from the few countries in the region with some level of regulation on human genome editing and/or stem cell research (i.e. Ecuador, Chile, Panamá). These encounters will aid the development a regional approach to human genome editing and the conditions for further research on bioethics and clinical trials/applications.</p>
|
| 31/08/2019 |
£24,532 |
|
UNIVERSITY COLLEGE DUBLIN |
<p style="margin-left: 0cm; margin-right: 0cm">Healthcare, sociology, psychology and the growing field of ‘cultural gerontology’ have begun to interrogate the complexity of ageing. Despite this welcome development, there is little methodological dialogue between the humanities and gerontology. This project therefore aims to explore methodological cross-pollination through two collaborative UCD/TCD-led workshops. Entitled “Framing Ageing: A Clinical, Cultural and Social Dialogue”, our project recognises that society is a web of signs subject to shifting meanings and contested interpretations. This insight has far-reaching epistemological and methodological consequences: it de-essentialises the notions of biological matter, of the body and bodily change, of mind and matter, and of the ‘natural’ chronology from birth to death. Drawing on research expertise in the two institutions and beyond, the workshops bring together gerontologists, who deal with ageing from clinical, psychological and social perspectives, social scientists who work with quantitative data, and humanities researchers, who investigate ageing in cultural and historical perspectives, as well as art practitioners and NGOs. A key aim is to create a transdisciplinary network that liberates the field from the constraints of pathological models of ageing by exploring an entanglement between the biopsychosocial and the interpretive, the empirical and the aesthetic, the historical and the contemporary, and research and practice.</p>
|
| 30/07/2019 |
£990,164 |
|
UNIVERSITY OF ST ANDREWS |
<p>The project will draw the global history of a foundational but historically neglected process in the development of scientific approaches of zoonosis: the global war against the rat (1898-1948). The project will examine the scientific study of the rat and the public health practices developed and deployed for its control and eradication in the wake of understanding its role in the transmission of infectious diseases. It will explore the synergies between knowledge acquired through scientific studies of the rat, with knowledge acquired during the development and application of practical, public health measures of vector-control: rat-proofing, rat-catching and rat-poisoning. By examining for the first time the <strong>epistemological, architectural, social, and chemical histories of rat control</strong> from a global, comparative perspective, the project will engage in an analysis of how new forms of epidemiological knowledge and reasoning arose centred on the epistemic object of the rat. The project will address two key research questions:</p>
<ol>
<li>In which ways did the global war against the rat contribute to the emergence, development and consolidation of zoonosis as a scientific category?</li>
<li>What was the role of the global war against the rat in establishing animal-human contact as a pivot of epidemiological reasoning and public health intervention?</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
|
| 30/07/2019 |
£886,718 |
|
UNIVERSITY OF CAMBRIDGE |
<p>Many experts agree that crop genetic diversity is essential to agricultural productivity, present and future, and therefore an important determinant of human health and well-being. Yet the routes through which this diversity is made valuable in agriculture, for example in breeding more disease-resistant or nutritious crops, remain underexplored. The dominant narrative credits plant breeders alone with generating value from crop diversity and has enabled breeders and seed companies to claim ownership over plant varieties. This in turn has encouraged a dramatic consolidation of the seed industry that many consider a threat to global food security.</p>
<p><br>
The narrative of breeder-generated value must be assessed and challenged. Through four historical case studies and a synthetic account, this project argues for a more encompassing view of how diverse materials give rise to the crops eaten around the world. It documents the contributions of researchers engaged in plant exploration, introduction, conservation, and utilisation. It charts efforts to locate disease-resistant varieties, prevent the spread of crop pathogens, ensure access to dietary diversity, and locate the genes that give rise to nutrient-rich varieties. By following neglected actors and methods, the project changes our understanding of how and by whom modern agricultural crops have been made.</p>
|
| 30/07/2019 |
£739,506 |
|
UNIVERSITY OF EXETER |
<p>Shame is a powerful force in the everyday experiences of patients, medical students and healthcare practitioners. For patients, shame has been associated with treatment avoidance, increased burden of illness, and negative health outcomes, while also being recognised as a force that can sometimes motivate positive changes to lifestyle and health. Shame can influence how healthcare practitioners perform, interact with patients and other professionals, and cope with adversity. In addition, shame has been identified as a negative, yet frequently present, aspect of medical education. Despite the prevalence and significance of shame within various aspects of healthcare, at present, our understanding of the impact of shame, its many varieties, and other related negative self-conscious emotions, within medical contexts is incomplete. <em>Shame and Medicine </em>engages an interdisciplinary team working across medicine, medical humanities, and social sciences, in order to investigate shame, and related experiences, within healthcare. We aim produce new evidence on the experiential basis of shame, cultures of shame, and to investigate differential experiences of shame due to race, ethnicity, class and gender. <em>Shame and Medicine </em>is a ground-breaking interdisciplinary project that will propose new opportunities to improve the quality of healthcare delivery within a more responsive and effective health service.<br>
</p>
|
| 30/07/2019 |
£728,994 |
|
UNIVERSITY OF BIRMINGHAM |
<p>Shame is a powerful force in the everyday experiences of patients, medical students and healthcare practitioners. For patients, shame has been associated with treatment avoidance, increased burden of illness, and negative health outcomes, while also being recognised as a force that can sometimes motivate positive changes to lifestyle and health. Shame can influence how healthcare practitioners perform, interact with patients and other professionals, and cope with adversity. In addition, shame has been identified as a negative, yet frequently present, aspect of medical education. Despite the prevalence and significance of shame within various aspects of healthcare, at present, our understanding of the impact of shame, its many varieties, and other related negative self-conscious emotions, within medical contexts is incomplete. <em>Shame and Medicine </em>engages an interdisciplinary team working across medicine, medical humanities, and social sciences, in order to investigate shame, and related experiences, within healthcare. We aim produce new evidence on the experiential basis of shame, cultures of shame, and to investigate differential experiences of shame due to race, ethnicity, class and gender. <em>Shame and Medicine </em>is a ground-breaking interdisciplinary project that will propose new opportunities to improve the quality of healthcare delivery within a more responsive and effective health service.<br>
</p>
|
| 30/07/2019 |
£389,846 |
|
ROYAL HOLLOWAY, UNIVERSITY OF LONDON |
<p>We propose an innovative interdisciplinary approach to identifying pharmaceutical ingredients cited in ancient or medieval manuscripts in Indo-European and Semitic languages. We will conduct a case study (John the Physician’s <em>Therapeutics,</em> vernacular version) from late 13th century Cyprus, and run comparative and analytical studies on other scholarly and non-scholarly texts.</p>
<p>Our main goal is to develop a new, documented and transferable methodology to address a key, unresolved challenge when working with such texts, how to identify with confidence the individual ingredients (primarily plants and minerals) cited, and how to assign a confidence level. This is an essential step in analysis of pharmaceutical practices. Ingredients identified will be mapped onto their current pharmaceutical uses thus exploring potential interest to pharmacological research. Our multidisciplinary team consists of experts from the field of philology, botany, ethnopharmacology and geology from Royal Holloway, University of London, Royal Botanic Gardens, Kew, Zurich and Haifa. Our output and data will be made available open access to maximise impact and reach. Two workshops will enable us to test our methodology and results among experts outside our team, and help promote their use by others.</p>
|
| 30/07/2019 |
£759,145 |
|
KING'S COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">This project will make a fundamental contribution to explaining the epidemiological transition in nineteenth and early twentieth-century Britain by analysing patterns of ill health derived from approximately 30,000 pension records of General Post Office (GPO) workers. Most postal workers in this period, particularly in London and large cities, retired early because of ill health. Sickness rates were higher in these places and rose over the period. We will use information on sickness and the reason for retirement to identify and explain spatial and temporal variations in ill health between 1859 and 1908. We will map ill health in different areas and in different types of places by analysing variations in sickness, taking into account geography, age, gender and occupation. We will use record linkage to identify the post-retirement life course for a sample of workers, providing an insight to the relationships between morbidity and mortality. We will examine policy responses relating to occupational health including medical provision, the design of workplaces, management of labour processes, and the implementation of technology. We will engage the public through an exhibition, website and freely available database that will be of major importance to family historians.</p>
|
| 24/07/2019 |
£5,503,191 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p>The availability, scale and depth of data collected in the course of health care, by or about patients - combined with data-driven approaches to its analysis – is creating a paradigm shift in health care and its delivery. Machine learning and other automated methods of analysis will only succeed in providing useful insights for health and care if we understand health data in practice: how data is actually generated, interpreted and used. </p>
<p>Human-centred data science operates ‘at the intersection of human-computer interaction, computer-supported cooperative work, human computation, and statistical and computational techniques of data science’ while preserving ‘ the richness associated with traditional methods while utilising the power of large data sets.’ We adapt this concept to the 'health data in practice' doctoral programme with the goal of developing highly skilled future scientific leaders able to apply interdisciplinary perspectives to research and innovations in health data science for the benefit of patients, the public, health care systems and society.</p>
<p>Our training programme will introduce students to a wider context for their science, enabling them to draw on a range of concepts, disciplines and sciences underpinning algorithmic designs, human-interactions, evaluation and decision-making, in real-world settings across diverse populations. </p>
|
| 24/07/2019 |
£6,066,810 |
|
UNIVERSITY COLLEGE LONDON |
<p>The ‘Optical Biology’ PhD programme will train future research leaders to answer fundamental questions in biology by exploiting and developing state-of-the-art optical techniques. The programme brings together life scientists, physicists, chemists and computational scientists at UCL, with world-leading industrial and academic partners, to deliver an integrated training programme in the most advanced optical methods and analysis tools. This would be the first UK PhD programme offering multidisciplinary training in the major advanced light-based methods that are transforming all areas of biomedical research. The programme will be based at UCL, a world-leading environment where many major advances in optical techniques for biology have been developed, including ultra-fast 3D 2-photon microscopy, targeted 2-photon optogenetics, low power super-resolution imaging and whole-brain optical mapping. It will also offer students outstanding opportunities to undertake internships and training with our industrial and academic partners, promoting their career development and providing them with attractive post-PhD prospects. <br>
<br>
<em>Key programme goals:</em><br>
<br>
1. To train researchers capable of developing and using state-of-the-art optical methods and associated analysis techniques.<br>
<br>
2. To train researchers to use these methods to address fundamental biological problems.<br>
<br>
3. To create researchers who engage, communicate and collaborate effectively with both industry and academia across disciplinary boundaries.</p>
|
| 24/07/2019 |
£6,005,246 |
|
HEALTH DATA RESEARCH UK |
This four-year programme in Health Data Science includes one year of foundational training followed by a three-year thesis project. It will contribute to much-need capacity-building in health data science by bringing quantitative methods graduates into the health research sphere. Its underlying philosophy is that health data science requires a combination of expertise spanning three fundamental areas: statistical, computational and health sciences. This goes beyond the capacity of any single individual; impactful progress can only be made through highly collaborative communities led by resilient leaders who can challenge and overcome restrictive paradigms. Health data scientists must therefore be trained to operate in multi-disciplinary teams with each member an expert in one of the fundamental areas but conversant in all three.
The proposed programme will have a UK-wide reach, drawing on the combined research expertise of two national research institutions. Each student will be co-supervised by at least one expert in quantitative methods and one in substantive health research. Co-funded projects with non-academic partners will include a third supervisor drawn from the partner organisation. Topic selection will be informed by exposure during year 1 to a wide range of problems and methodologies, with flexibility to switch topic and location for years 2-4.
|
| 24/07/2019 |
£5,488,462 |
|
UNIVERSITY OF DUNDEE |
<p>The proposed programme reflects the vision of University of Dundee to drive social change locally and transform lives globally through the creation, sharing and application of knowledge. A diverse cohort of students will flourish in a culture of excellence, developing research skills and attaining competencies in leadership, management and communication. They will experience world-leading life sciences research in a first-class training environment, with excellent core facilities and well-funded research groups, whilst enhancing research outputs with their energy and innovation. Students will participate in multidisciplinary research in Cellular Regulation, Protein Modification, Infection and Immunity and Drug Discovery and Translation. The flexible PhD programme will provide structured training in experimental design, data handling and processing, basic bio-computational skills and ethical standards in scientific research. By the end of year 1, students will have selected their research project and will have 3 years to consolidate their core bioscience skills, carrying out and documenting their research. There is the option for a career enhancement placement in year 3, while year 4 will support students in career choices and thesis submission. After thesis submission, flexible funding may be used to facilitate paper writing/completion or allow students to undertake a project in our Drug Discovery Unit.<br>
</p>
|
| 24/07/2019 |
£5,488,462 |
|
UNIVERSITY OF GLASGOW |
<p>The mission of the proposed IIB Programme is to inspire the next generation of innovative world-class researchers to tackle global infection challenges. We will achieve this by shaping excellent PhD projects that build synergistic collaborations across the University of Glasgow and our partner institutes. Our aim is to give all students an exceptional experience, driving them to build their careers with the ability, confidence and integrity to make transformative contributions to global health. Our principles are promoting inquisitive and rigorous science, imparting technological and analytical skills, and reinforcing personal well-being. Our graduates will be ‘Scientists without Boundaries’ at ease with the implementation of far-reaching interdisciplinary concepts on the local and global stage. </p>
<p>The IIB Programme is integrated around Glasgow’s core of global excellence across infectious disease research, including pathogen biology, pathogen-host interaction, epidemiology, ecology and transmission control, encompassing >25 Wellcome Trust-funded investigators. We have partnered with key institutions in Europe and Africa, to offer PhD students exceptional opportunities in all areas of infection biology. UoG funding will add 2 students from Africa each year, making 7 altogether. Students will select projects after laboratory rotations and be fully mentored through to a ‘PhD-Plus Year’ fostering the transition to their post-doctoral career. </p>
|
| 24/07/2019 |
£5,685,862 |
|
UNIVERSITY OF OXFORD |
<p>This Programme will provide unique training for a new generation of scientists focusing on the quantification of biologically-important molecular interactions in physiologically-relevant settings. It is currently impossible to accurately and directly quantify interactions of molecules, and their consequences, in the complex physiological settings relevant to diagnosis and treatment of disease. To address this unmet need, we will harness physical science-based approaches to develop technologies that will underpin research across the spectrum of cell biology and biomedical science<br>
<br>
Scientific goals:</p>
<ul>
<li>Collaborative research outputs (papers, patents) using innovative approaches to provide new insights into biomedicine.</li>
<li>Adoption of our technologies by the broad biomedical research community to study fundamental biology/diseases including Alzheimer’s, schizophrenia and cancer.</li>
</ul>
<p><br>
We have developed an innovative framework for our training programme, promoting a diverse and positive research culture change that we aim to propagate across Oxford and the UK.<br>
<br>
Culture-change goals:</p>
<ul>
<li>Promotion of a positive research culture in Oxford demonstrated by uptake of our practices across the University.</li>
<li>Communication of our strategies <em>via </em>lectures on graduate education and publications in educational journals. </li>
</ul>
<p><br>
These ambitious goals provide an exceptional basis for a multidisciplinary programme that trains scientist equipped as problem solvers for a diverse range of 21<sup>st</sup>century workplaces. </p>
|
| 24/07/2019 |
£5,488,462 |
|
UNIVERSITY OF BRISTOL |
<p style="margin-left: 0cm; margin-right: 0cm">Identifying disease-associated genes, mutations and perturbed expression is only the first stage towards understanding human disease and the development of therapeutics. In Bristol we aspire to understand gene function and the proteins they encode across spatial scales, from the molecular level through to functional studies in cells, tissues and organisms. Since proteins, cells and tissues are all dynamic, wherever possible these processes need to be studied through multiple timescales. Advances in spatial and temporal resolution of microscopy provide opportunities to study processes at an unprecedented level across molecular and cellular scales. Only by combining these approaches will we truly understand organismal-level health, the pathoetiology of diseases and provide rational therapeutic routes to relieve them. This relies on biologists operating at the interface between molecular and cell biology. Our Wellcome programme will recruit, support and train a new generation of PhD students in Biomedical Research, with a broad base and understanding of molecular cell biology techniques coupled with world-class expertise in their PhD topic. These students will be trained to become future leaders in a wide range of careers, founded upon a holistic and rounded personal and professional development, which incorporates the best practice in PhD training. <br>
<br>
</p>
|
| 24/07/2019 |
£5,153,712 |
|
UNIVERSITY OF LEICESTER |
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Key goals</strong></p>
<p style="margin-left: 0cm; margin-right: 0cm">This transformative programme will train professionals able to address key public health research needs including: </p>
<ul>
<li>Improved healthcare through genetically-driven drug discovery, genetic prediction of disease progression and drug response; </li>
<li>Equal representation of minority ethnic and non-European ancestry individuals in genetic research; </li>
</ul>
<ul>
<li>The needs of deprived communities who have disproportionate environmental or lifestyle exposures with consequences that are better understood using genomic information; </li>
<li>Advancing the benefits of developments in genomics for hard-to-reach communities and; </li>
<li>Understanding the implications of genomics for healthcare professionals and policy-makers. </li>
</ul>
<p style="margin-left: 0cm; margin-right: 0cm">We will achieve these goals through<strong> </strong>an <strong>agile, flexible trainee-centred programme </strong>designed using feedback from PhD trainees and early career researchers, including WTISSF Fellows, and from UoL Biomedical and Humanities DTPs, WTISSF best practice models and the Wellcome Trust Review on PhD Training.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Our innovative programme will deliver:</strong> </p>
<ul>
<li>Skills development in priority areas of statistics, data science, computer programming, epidemiology, genomics and social science, medical law and ethics, and public health; </li>
<li>Trainee-centred development of inter-disciplinary skills and perspectives that enable success in different workplaces; </li>
<li>Opportunities for research placements in industry or that address the priorities of LMICs; </li>
<li>The development of trainee track-records of high-quality, visible research outputs; </li>
<li>Preparation for career transitions throughout trainees’ journeys. </li>
</ul>
<p style="margin-left: 0px; margin-right: 0px"> </p>
|
| 24/07/2019 |
£5,757,810 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Mental illness is a major public health problem, with poorly understood causes and highly variable treatment outcomes. While mental health research training has strength within disciplines, these typically operate in parallel, greatly impeding progress in improving clinical outcomes. The <strong>UCL Wellcome 4-Year PhD in Mental Health Science</strong> is an interdisciplinary, student-centred programme, which aims to train the next generation of research and policy leaders to succeed within mental health research fields, and foster greater cross-disciplinarity in future researchers. It leverages UCL’s outstanding mental health research environment across three broad Themes: Mechanism, Population Mental Health, and Intervention. In Year 1, students will obtain experience in these different Themes through short rotation projects and courses, including areas outside their academic background; through this they will be exposed to new concepts and techniques, learn to “speak the language” of the different disciplines, and spot the synergistic connections between them. For the main PhD project in Years 2-4, students will select a supervisory team and Thesis Committee across all three Themes, enabling interdisciplinary mentorship. A strong emphasis will be placed on developing a distinct and supportive cohort identity, with continual skills development and preparation for transition following the Programme, whether within or outside academia.</p>
|
| 24/07/2019 |
£5,153,712 |
|
UNIVERSITY OF BRISTOL |
<p>It is our overarching ambition that the 4-year PhD programme in Molecular, Genetic and Lifecourse Epidemiology will be a pioneer in developing and sharing best practice for supporting and training PhD students in Population Health Sciences. We will recruit, train and support the next generation of professional leaders in this field, with a strong inter-disciplinary foundation. They will be advocates of robust, reproducible research, expertly equipped for careers and impact, whether in academia or in other organisations. We will continue to refine a student-led PhD journey, informed by continual review and evidence-based iteration to meet the needs of both the student body and supervisors in executing their roles. We will leverage the characteristics of Population Health Sciences at Bristol University where methodological innovation is tightly linked to applied research of population and public health benefit, in a culture of open, intellectually generous, high quality scientific endeavour. This, alongside the strong institutional support and contributing infrastructure, creates our unique training environment and allows us to realise our vision of delivering outstanding postgraduate research training in partnership with Wellcome.</p>
|
| 24/07/2019 |
£5,509,212 |
|
UNIVERSITY OF EDINBURGH |
<p>Three years ago we established an innovative and successful 4-year Translational Neuroscience PhD Programme (‘TN1’) designed to address the fundamental problems in translating advances in discovery neuroscience to the clinic. We are equipping cohorts of outstanding students with the means to resolve these problems by providing rigorous, cross-disciplinary, cutting-edge training in the neuroscience of brain disorders across the lifespan. Demand has proved enormous. In TN2, we shall continue the key aim of TN1 by leveraging the opportunities offered by the highly collaborative Edinburgh Neuroscience community of world-leading clinical and fundamental scientists. This community has been substantially enhanced by recent key strategic developments that massively expand our portfolio of neuroscience research, including new opportunities in data science driven by a £250M CityDeal and new translational expertise introduced by our £23M Dementia Research Institute, our $20M Simons Initiative for the Developing Brain and our £50M Institute for Regeneration and Repair. By also incorporating lessons learnt from our TN1 cohorts and from relevant stakeholders to enhance student welfare, diversity and career options, our programme will provide exceptional training in translational neuroscience, key skills for research and other careers worldwide, and be a beacon of best practise in student development.</p>
|
| 24/07/2019 |
£5,509,212 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 31.85pt">To solve the problems of neglected and emerging diseases an integrated approach to infectious disease biology is needed. We must understand the biology of the pathogen and its interaction with the host, immune mechanisms that contribute to disease outcome, and the ecological and epidemiological factors that determine disease spread. If the future leaders in global health are to exploit knowledge of the full range of pathogen and host interactions, from core molecular processes to understanding host-pathogen interactions in the field, including co-infections, zoonoses and evolutionary dynamics, coupled with an appreciation of the wider societal context, we must prepare them from the outset of their PhD.</p>
<p style="margin-left: 0cm; margin-right: 31.85pt">Since establishment in 2016 the Wellcome Trust “Hosts, Pathogens and Global Health” programme has developed a unique interdisciplinary and international research training structure providing expertise spanning infectious disease biology from molecular to evolutionary and epidemiological scales. Our key goals are:<br>
</p>
<ul>
<li>To train a cadre of infection biologists skilled in interdisciplinary approaches to disease control and well versed in the opportunities of quantitative, theoretical and experimental approaches.</li>
<li>Use the community and mentorship ethos within Edinburgh and between our international partners to build a life-long supportive network of next-generation researchers working across disciplines to combat infectious disease.</li>
</ul>
|
| 24/07/2019 |
£5,488,462 |
|
UNIVERSITY OF MANCHESTER |
<p>Immune and inflammatory processes underlie virtually all major human diseases we now face. Similarly, dysregulation of the extracellular matrix (ECM) is a central process in the pathogenesis of chronic diseases. The molecular, physical and mechanical properties of the ECM regulate immune cell mobility, survival and function. In turn, the immune system is required to maintain and regulate healthy matrix and restore matrix integrity following injury. Together, the ECM and the immune system define tissue health, with failure leading to disease. However, matrix biology and immunology are typically studied independently and progress in understanding and treating disease is hindered by both immune system and tissue complexity. Our goal is thus to train a new generation of scientists to embrace tissue and disease complexity. By understanding the inter-connectivity between matrix and immune function they will make discoveries that help unravel complex disease. <br>
<br>
The programme will:<br>
1) Provide an intensive taught component of immunomatrix, tissue complexity and multimorbidity<br>
2) Deliver a bespoke training programme in bioinformatics<br>
3) Offer intellectually challenging cross-disciplinary PhD projects utilising state-of-the art technology<br>
4) Enrich student experience through optional "Silo Switches" into allied careers<br>
5) Provide active mentoring, and the experience of mentoring others<br>
</p>
|
| 24/07/2019 |
£5,685,862 |
|
UNIVERSITY OF OXFORD |
<p>Genomic Medicine and Statistics (GMS) is a four-year doctoral training programme at the University of Oxford, established in 2008. Over the next 5-year funding period our goal is to train future leaders in the application of genomics to advance human health, equipping them with skills sets spanning experimental and analytical genomic science to address current roadblocks by innovating and realising the potential of genomics. We will do this through a cross-disciplinary approach addressing core themes including genomic and -omic technologies, functional genomics, genome biology, population genetics, evolution, pathogen genomics, genomics of disease, genomic analysis, and application of genomics for drug development, diagnostics, precision medicine and therapy. We will recruit students from diverse backgrounds with a track record of academic excellence and enthusiasm for this field. The first year will provide necessary core skills through taught modules with a minimum of two three-month rotations to gain exposure and training in different research environments prior to deciding on the topic of doctoral research, with additional training tailored to the needs of individual students. We will build a strong cohort, deliver a student-focused training experience with world-class training, supervision and pastoral support and actively manage student transitions including established internships with partner organisations.</p>
|
| 24/07/2019 |
£5,685,862 |
|
UNIVERSITY OF OXFORD |
<p>Structural biology continues to provide one of the most important toolsets for molecular biosciences. It also underlies many crucial industries, supporting biomedical advances in drug and vaccine development and molecular engineering. It continues to develop at pace. The recent electron cryo-microscopy revolution has been transformative and advances in tomographic methods prove likely to soon bridge the gap between molecular and cellular levels. It is essential that we train cohorts of students with these tools. <br>
<br>
We aim to provide outstanding broad training in structural biology methods, while students conduct exciting research projects. We expect these cohorts to contain future academic research leaders, who apply structural biology to important cellular systems and/or contribute to development of methodologies. We aim to train future leaders of industry, equipping them for research and development. Our program will also prepare students for a wide range of other future careers, providing project management experience, programming skills, and the experience of working in a precise and numerically rigorous scientific field. We will equip and support our students to transition to careers in academia, industry and beyond, while ensuring that we train a cohort to continue to apply and to develop structural biology into the future.</p>
|
| 24/07/2019 |
£6,051,821 |
|
UNIVERSITY OF CAMBRIDGE |
<p>Specialist post-graduate training in Stem Cell Biology and Medicine is essential to produce a stream of highly skilled and innovative investigators equipped with a deep understanding of stem cell science and its significance for future medicine. In this context, the Wellcome PhD Programme in Stem Cell Biology and Medicine is unique in the UK in focus and scope. The enduring popularity of the programme, which receives on average 200 applications per year, and the quality of research outputs and next destinations are testament to both the calibre of students we are able to recruit and to the high-quality training they receive. Our programme provides an environment that is intellectually rigorous and personally supportive for students, enabling them to set and attain research objectives. The programme is designed to develop analytical and critically-minded individuals. Since its inception in 2008, the PhD Programme has evolved in response to the expressed needs of students and continuous developments in modern Stem Cell Biology. Our overarching goal is to produce well-trained and rounded PhD graduates who have generated significant and original research findings and are fully prepared for an ambitious and challenging career, whether continuing in stem cell science or moving to another profession.<br>
</p>
|
| 24/07/2019 |
£5,328,962 |
|
UNIVERSITY OF EDINBURGH |
<p><br>
Technological advances in genome editing and animal bioscience have potential for huge societal impact, and are opening up opportunities for the design of new ‘One Health’ models of neurodegenerative, cardiovascular, developmental, and infectious diseases of humans and animals. Such models can transform our approach to understanding pathogenesis, facilitating the development of therapies or preventive measures. However, there is little or no opportunity for graduate student training in relevant state-of-the-art techniques at world-class, purpose-built facilities by leading scientific innovators at the intersection of human and veterinary medicine. Moreover, scientists require training in bioethics and social science to allow them to appreciate the ethical and societal implications of these powerful new approaches. To address this need, we propose a PhD programme in “One Health Models of Disease: Science, Ethics and Society”. This innovative, and versatile programme will combine core training in relevant experimental techniques, bioethics and social sciences relating to One Health, rotation research projects, and internships with academic, industrial, policy and stakeholder organisations, alongside the main PhD project. Students will be supervised by world-leading life scientists addressing important diseases of humans and animals, and social scientists and bioethicists conducting cutting-edge research into the social and ethical dimensions of 21<sup>st</sup> century science.</p>
|
| 24/07/2019 |
£5,328,962 |
|
UNIVERSITY OF EDINBURGH |
<p>Technological advances in cell biology enable biological mechanisms, developmental processes and disease states to be probed in unprecedented detail, generating complex and multi-dimensional datasets that demand a step change in PhD level training. iCM will develop:<br>
<strong>Training</strong>; a new generation of broad-thinking scientists to use innovative approaches in quantitative research to understand the workings of distinct cell types in different settings.<br>
<strong>Cross-disciplinary research</strong>; promoted through supervisory teams pairing quantitative scientists, drawn from the physical sciences, informatics and quantitative biology, in equal partnership with cell biologists, to develop pioneering collaborative projects that uncover key cellular mechanisms relevant to health and disease.<br>
<strong>Diversity in recruitment</strong>; student cohorts with a broad spectrum of national, ethnic, social and educational backgrounds.<br>
<strong>Supportive environment</strong>; nurturing an <em>esprit de corps</em>within and between cohorts allowing them to learn from each other and become conversant in cutting edge approaches for data generation, analysis, management and reuse.<br>
<strong>Research culture</strong>; recognising student’s wellbeing as being paramount for their success; ensures students comprehend and adhere to the principles of good research practice, especially the importance of maintaining research record integrity including appropriately documenting, managing and presenting data; treats all students and supervisors equitably and respectfully; does not tolerate bullying or harassment.</p>
|
| 24/07/2019 |
£5,308,212 |
|
UNIVERSITY OF EAST ANGLIA |
<p style="margin-left: 0cm; margin-right: 0cm">In an era where preventive medicine is increasingly important due to an ageing population and rising obesity, optimised diets are key to improving health and reducing risk of ill health.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The EDESIA PhD programme will focus on investigating plant-based nutrition and health, from crop to clinic, drawing on the world-class interdisciplinary research expertise of institutions based on the Norwich Research Park (UEA, John Innes Centre, Quadram Institute, Earlham Institute, and Norfolk & Norwich University Hospital).</p>
<p style="margin-left: 0cm; margin-right: 0cm">Through a rotation-based programme, EDESIA PhD students will train in a wide range of disciplines across the translational pathway of nutrition research, including assessment of nutritional bioactives, biochemical, genetic, cell biological and functional analyses of plant metabolites, <em>in vitro</em> analyses in tissue and cell cultures, investigation of efficacy in animal models of disease, investigation of effects on composition and functioning of the microbiota, human intervention studies and analyses of epidemiological datasets.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This comprehensive PhD training programme allows the translation of science into guidelines for healthy eating and the production of nutritionally improved food crops, leading to innovative food products, particularly for prevention and treatment of chronic diseases where age is a major risk.</p>
|
| 24/07/2019 |
£4,457,720 |
|
UNIVERSITY OF NOTTINGHAM |
<p>This programme focuses on the application of a multidisciplinary <em>Team Science</em> approach to develop novel approaches and technologies involving the physical, biological and medical sciences to study membrane receptors in the right cell type and tissue. The programme embraces colleagues from UoN, pharmaceutical companies, SMEs and learned societies to develop a training programme that has the student at its centre but which engenders a collaborative multidisciplinary approach within a cohort-based programme of research. Each entry of four students will study one of the following disease-related themes: (a) cancer angiogenesis; (b) pain and addition; (c) respiratory diseases; (d) immune-oncology and (e) inflammation. Each cohort will tackle their given disease theme as a multidisciplinary team, with each student working in one of four key experimental areas: (a) Target engagement; (b) cellular environment; (c) in vivo and ex vivo models and (d) mathematical modelling and systems biology. The key programme goals will address: (1) the major skills gaps identified by ABPI in complex <em>in vivo</em> experimental models and <em>in vitro</em> pharmacological analytical approaches; (2) the need for multidisciplinary programmes, industrial/transitional placements and the provision of training in ‘translational’ skills such as communication, leadership and entrepreneurship; and (3) the need for supportive training environments.<br>
</p>
|
| 24/07/2019 |
£5,249,785 |
|
UNIVERSITY OF SHEFFIELD |
<p style="margin-left: 0cm; margin-right: 0cm">With ever scarcer resources for public health policies and programmes, high-quality scientific evidence on the cost-effectiveness and long-term benefits of alternative public health intervention options will become increasingly important for future decision-making.</p>
<p style="margin-left: 0cm; margin-right: 0cm">To our knowledge, PHEDS is one of just a handful of Doctoral Training Centres dedicated to Public Health Economics and Decision Science in the world. Wellcome Trust investment will allow us to grow, focus and strengthen ScHARR’s doctoral training in this area, broadening its scientific remit from health behaviours to also include research into the cost-effectiveness of policy options that address the social determinants of health (e.g. economic conditions, housing, employment) to reduce NCD and tackle health inequalities. Through the synergy of several cohorts of PhD researchers conducting cutting-edge research into these challenges at the same time with expert supervision, the programme aims to substantially increase the momentum of scientific discovery.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Equipped with 4 years of experience in interdisciplinary collaborative working environments and with strong analytic skills, our graduates will be excellently placed to forge influential careers as leaders in academia and governmental and non-governmental organisations promoting evidence-based decisions about resource allocation in public health and tackling disease burden in the UK and beyond.</p>
|
| 24/07/2019 |
£5,958,810 |
|
KING'S COLLEGE LONDON |
<p>The goal of the programme is to train a new generation of researchers in the advanced therapies that underpin regenerative medicine, including cell transplantation, gene therapy and endogenous tissue repair. At the heart of this young field is the importance of translating laboratory-based studies to patient benefit. Thus, students will gain knowledge of the underpinning discovery science, and clinical and commercial applications. Moreover, to foster translation we will bring together researchers in different disciplines, so that the students appreciate the creative possibilities of working at the interface between different fields. Supervisors are drawn from across King’s College London, spanning clinical, nonclinical, early, mid-career and senior researchers. The first year comprises three rotations, combined with taught courses and master classes, leading to the award of an MRes. This is followed by three years of focused research. Partner organisations and secondments provide additional training opportunities. From the outset, the programme emphasizes growing as a scientist, exploring post-PhD opportunities, and the scientist in society. Students and their supervisors are seen as partners in a journey, with a special focus on fostering mutual respect and understanding.</p>
|
| 24/07/2019 |
£6,293,560 |
|
KING'S COLLEGE LONDON |
<p>Cross-talk between the nervous and immune systems is critical for survival, and disrupted neuro-immune communication is observed in many debilitating conditions, including chronic inflammatory, neurodegenerative and psychiatric diseases. Yet, research and training in neuro-immune interactions is generally conducted in discipline-specific silos. We propose to <strong>accelerate ground-breaking interdisciplinary research and knowledge sharing by instituting a unique PhD training programme in Neuro-Immune Interactions in Health and Disease. </strong><br>
<br>
We will deliver:</p>
<ul>
<li>World-class scientific training, provided in a flexible, student-led fashion, by internationally<strong> </strong>leading investigators, using state-of-the-art technologies, cutting-edge science and supervision methods (Assessment, Feedback and Development (AFD)<strong> </strong>meetings, PhD Progress Committees).</li>
<li>Extensive skills training to transition students in and out of the Programme – individually tailored and formalised in a personal development plan (PDP).</li>
<li>A diverse<strong> </strong>and<strong> </strong>inclusive training environment, reflected in our Programme Management Board (PMB), supervisors, recruitment and partnership plans.</li>
<li>An open and positive research culture, including training in research integrity, data sharing, bespoke<strong> </strong>mental health provisions and zero-tolerance of bullying and harassment.</li>
<li>A new generation of scientists with the knowledge, skills and networks to drive world-leading neuro-immune research, who can excel equally in academic and non-academic professions.<br>
</li>
</ul>
<p><em>Searchable keywords: share, sharing, world-class, flexible, positive, diverse, inclusive, skills training, mental health</em></p>
|
| 23/07/2019 |
£154,318 |
|
UNIVERSITY OF WARWICK |
<p style="margin-left: 0cm; margin-right: 0cm">What made vegetarianism the dominant trope for understanding India’s diet, given that the majority of Indians are meat-eaters? I address this puzzle through an investigation of popular literature on diet and nutrition published in India between 1900 and 1960. Given the pre-eminence of Western Indian—particularly Marathi—publishing on dietetics, I focus on this region’s publications as a case study to gain insight into the rise and consolidation of the idea of India as ‘naturally’ vegetarian. In particular, I investigate how debates on what constituted a scientific diet for India both informed and were informed by contemporary social and political debates about something apparently unrelated: the Indian caste system.</p>
<p style="margin-left: 0cm; margin-right: 0cm">I will ask: to what degree were Indian dietetics’ re-framing of ‘scientific’ and ‘natural’ food practices instrumental in sustaining a caste-based social order? And to what extent did meat, milk, fasting and eating a ‘balanced diet’ come to function as wider discursive technologies of cultural governance?</p>
<p style="margin-left: 0cm; margin-right: 0cm">By situating Marathi dietary modernity within the broader context of the global rise of ‘nutrition’, I will explore if, and how, the emergence of nutritionism in India simultaneously made the everyday act of eating into an assertion of social power.</p>
|
| 23/07/2019 |
£214,062 |
|
UNIVERSITY OF EDINBURGH |
<p>Immunotherapy has been heralded as a therapeutic revolution as it utilises the patient's own body to treat cancer: (re)invigorating the personalisation agenda in cancer. Clinical concerns have however, been raised regarding long-term treatment side-effects, predicting response and prognosis, and management of patients’ hopes and expectations. Drawing upon interviews and ethnography conducted in two clinical sites implementing immunotherapy treatments as standard of care or in experimental trials, this project asks:</p>
<p><br>
(1) How are developments in immunology shifting conceptualisations of what cancer is and how it is treated?<br>
(2) How are patients’ experiences and subjectivities configured by immunological developments in cancer treatment?<br>
(3) How is immunity in cancer constituted through the material practices of scientists, clinicians and patients within the context of personalised cancer medicine?</p>
<p style="margin-left: 0cm; margin-right: 0cm"><br>
This project will extend existing debates concerning the societal implications of biomedical developments in oncology with a particular focus on the unfolding practices and everyday experiences of immunotherapy treatments. Empirically it will be one of the first in Medical Sociology and Science and Technology Studies to consider immunotherapy as an emerging technology for treating cancer and will yield novel theoretical findings relating to the implications of this approach for shaping how cancer is understood, practised and experienced.</p>
|
| 23/07/2019 |
£181,207 |
|
BATH SPA UNIVERSITY |
<p>My key goal is to identify meanings of environmental wellbeing within a broad sample of life writing by autistic adults and conventional medical and cultural representations of environmental wellbeing, to produce a more nuanced understanding of how this idea might be used in public health measures. I will combine functional, cultural and sociological narrative study with ecocritical and phenomenological readings, interviews and historical research. Narrative analysis is particularly relevant to the ambiguity and complexity of constructions of wellbeing, and my own position as an autistic researcher. A supplementary aim of this project is to develop understanding of autistic wellbeing in particular. As part of this, I will focus on particular thematic areas that are prominent in autistic life writing, including cross-species relations and affective relations between humans and other entities. <br>
<br>
Interpreting and disseminating stories provides a framework for elaborating on the social, cultural and material components of wellbeing and environmental wellbeing in the face of environmental threats. This will provide evidence in favour of the validity of the critical medical humanities, showing that language and literary structures can illustrate the multiple cultural, material and social locations of health without suggesting that these need be arranged in a hierarchical order.</p>
|
| 23/07/2019 |
£173,334 |
|
UNIVERSITY OF STRATHCLYDE |
<p>The Harvard Project on the Soviet Social System (HPSSS) was an initiative funded by the US Air Force which saw American social scientists and psychologists interview nearly a thousand Soviet émigrés in West Germany and the USA in 1950 and 1951 to understand the Soviet system ‘from within’. This project will expand upon an emerging body of scholarship, which seeks to nuance existing understandings of the history of mental health and the psy' disciplines during the Cold War, by emphasising forms of exchange across the iron curtain that shaped American psy' professionals’ approaches to mental health. The project has two key goals:</p>
<ol>
<li>To ask, through four key thematic strands that shaped the HPSSS – ideology, nationality, displacement/migration, and trauma – whether the Harvard psychologists' universalist assumptions about mental health in theory (which were in tune with prevailing medical paradigms in the West) were complicated in practice by the cultural and political differences that were the focus of this study</li>
<li>To demonstrate how the HPSSS’s official aim of consolidating animosity and division between the USA and the USSR were challenged by the Harvard psychologists’ interpersonal encounters with Soviet people in the clinical situation</li>
</ol>
|
| 23/07/2019 |
£346,772 |
|
UNIVERSITY COLLEGE DUBLIN |
<p><em>Enslaved Viruses </em>is a pioneering account of modern medicine, molecular biology, and microbiology that is written through the lens of the typing technologies used to create knowledge about infectious disease and the microbial environment.</p>
<p>The technology at the heart of the project is bacteriophage-typing. Described by Nobel Laureate André Lwoff as ‘enslaving’ viruses (1963), interwar researchers used standardised sets of bacteriophages (‘bacteria eating’ viruses) to identify and combat bacterial infections. Located in hubs of imperial and Cold War power, centralised reference laboratories became nodes of an international network of laboratory-based pathogen surveillance and molecular biology. Phage-typing influenced hospital designs, drug guidelines, and international health campaigns.</p>
<p><em>Enslaved Viruses</em> uses the history of bacteriophage-typing to:</p>
<ol>
<li>Reconstruct the 'mangle of practice' by which carefully curated typing sets changed ways of knowing viruses, bacteria, and infectious disease.</li>
<li>Analyse the influence of laboratory-based surveillance on international infection control and drug regulation.</li>
<li>Study geographically biased surveillance networks' impacts on infection control in low-income settings.</li>
<li>Explore type collections’ biological history and technological recycling by the biotech sector.</li>
</ol>
<p> </p>
<p>The project's joint analysis of phage-typing's entangled laboratory, epidemiological, and clinical guises will produce an authoritative account of the biomedical 'mangle of practice' at the heart of modern infection control.</p>
|
| 23/07/2019 |
£180,707 |
|
UNIVERSITY OF GLASGOW |
<p>Policy interventions addressing the social determinants of health such as income are most likely to address health inequalities. Policy modelling studies based on real-world data facilitate exploration of complex interventions and are increasingly influential in public health policy-making; however, existing studies focus mainly on policies aimed at individual health behaviours. A model evaluating societal-level, ‘upstream’ interventions would have significant potential to influence policy and reduce inequalities. I will create a model which predicts the impacts of proposed income and welfare policies on population mental health and health inequalities in the UK population.<br>
<br>
I will use a microsimulation modelling approach, first building a simulated representative UK population and integrating into this causal effects of changes in income and employment status on individual mental health outcomes. The income-mental health model will then be integrated with the EUROMOD tax-benefit microsimulation model, which can calculate expected changes in income for UK households under proposed new income/welfare policies. To test the model, I will use it to predict the effects of introducing a Universal Basic Income (UBI) on mental health outcomes and inequalities in the UK. The advisory group will include key stakeholders, to actively engage policymakers considering UBI and similar policies in the research.</p>
|
| 23/07/2019 |
£259,395 |
|
UNIVERSITY OF READING |
<p style="margin-left: 0cm; margin-right: 0cm">Early modern people deliberately wounded themselves surprisingly often and in numerous ways, from stabbing to castration. This project aims to find out how such phenomena grew from and potentially disrupted the cultural and social discourses of the period. It also seeks to explore how we can work across different kinds of text - plays, ballads, and medical treatises - to trace the multiple meanings of self-wounding.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The goals of the project include:.</p>
<ul>
<li>Transform our understanding of early modern social attitudes by unravelling why people wounded themselves, and what emotional and practical responses this provoked</li>
<li>Explore how self-wounding acts related to contemporary debates about selfhood and self-ownership</li>
<li>Develop a methodology which works across different kinds of early modern text to show how one phenomenon might be read in numerous, interrelated ways.</li>
<li>Inspire new research into wounding and other non-professional bodily practices, in the early modern period and beyond.</li>
</ul>
<p>This project will be the first sustained investigation into self-wounding in early modern England. It will provide contextualised analysis of some of the most compelling moments in the early modern dramatic canon, and will show how representations of self-wounding from across literary cultures contributed to contemporary notions of embodiment, morality, and self-expression</p>
|
| 23/07/2019 |
£216,078 |
|
UNIVERSITY OF SOUTHAMPTON |
<p>My research will investigate how patients, clinicians and scientists navigate the outputs from genomic technologies. Today’s technologies have great power to diagnose, but provide far more information than previous targeted testing could. Genomic tests identify around 100,000 rare genetic variants per person, but the clinical significance of these variants will fluctuate with respect to multiple parameters including: the current state of scientific knowledge; the person’s age; their medical and family history; their genetic background; and environmental exposures. I will examine how, why, and when scientists, clinicians and patients conceptualise variants from genomic data as clinical results.</p>
<p>I will adopt an empirical ethics approach drawing on grounded moral analysis. I will observe clinic appointments to examine how outputs from genomic tests are described in practice. I will interview patients and families having genomic tests, and conduct focus groups with clinicians and scientists who request, provide, or communicate outcomes from genomic tests. I aim to elicit perspectives on the nature of genomic results, and the processes by which they are constructed. Current debates and policy development often focus on ‘management’ of genomic results; my research will contribute by questioning what genomic results should be, and how they might be arrived at.</p>
|
| 23/07/2019 |
£248,981 |
|
UNIVERSITY OF OXFORD |
<p>Global health security (GHS) comprises of the activities required to reduce vulnerability to acute public health events, commonly infectious disease outbreaks, that affect populations across international boundaries. One such public health threat was the 2014 West African Ebola outbreak, which revealed failings in the ability of the World Health Organization to adequately respond to outbreaks of this severity. A consequence of this was the expansion of state-led GHS programmes in countries including the US and UK. These programmes comprise of states’ actions abroad to improve national health security. As the key aims of these programmes are not just to aid the primarily low and lower-middle income countries in which they act, but to protect the states from infectious disease outbreaks that threaten their own populations, their activities can be ethically, socioculturally and politically challenging.</p>
<p>The research objective of this DPhil is to undertake a normative and empirical ethics account of state-led GHS programmes, focusing on the actions and stakeholders from the US and UK in the period after the 2014 West African Ebola outbreak. The project has three stages: A critical interpretative synthesis of literature, semi-structured interviews with key informants, and an empirical bioethics analysis and formation of recommendations. </p>
|
| 16/07/2019 |
£2,966,714 |
|
UNIVERSITY OF OXFORD |
Formaldehyde is a ubiquitous reactive aldehyde that is present in our environment. However, a significant amount of formaldehyde is produced in our bodies probably as a consequence of metabolism. We discovered that we possess a two-tier protection mechanism (aldehyde detoxification and DNA repair) that prevents this endogenous formaldehyde from causing lasting damage to our cells. We also discovered that the detoxification of formaldehyde creates a single carbon unit that the cell uses to make nucleotides. Other than this, we know very little about the biology of endogenous formaldehyde. The purpose of this research proposal is to address this, in the first instance we want to measure and detect endogenous formaldehyde in serum and in cells . We will also identify specific biomarkers for formaldehyde exposure in DNA. We will use CRISPR Cas9 genetic screens in cell lines to identify the metabolic sources of endogenous formaldehyde. Ultimately we want to further understand how endogenous formaldehyde damages vital cells like blood stem cells, liver, kidney and brain cells in mice. In addition we will use biased approaches that indicate that protection against formaldehyde is more complex than we thought and we will perform genetic screens to identify new formaldehyde protection mechanisms.
|
| 16/07/2019 |
£1,761,835 |
|
THE FRANCIS CRICK INSTITUTE |
<p>On the cusp of the era of precision medicine, data from the British population comprise the world’s most well-characterized resource linking human genomes and traits, with vast information already available from over half a million individuals in initiatives such as the UK Biobank. These resources are producing unparalleled insights into human biology, but the evolutionary processes that shaped human genomic variation—and continue to shape them in the future—can only be fully understood with direct data from the past. Cutting-edge ancient DNA technology now provides unprecedented possibilities to retrieve genome sequences from ancient populations, but few ancient whole genomes from Britain have been published.</p>
<p>I propose to undertake reconstruction of fine-scale human evolution by extending available genomic data from the British population into a third dimension—the sequencing of 1,000 ancient genomes. This project aims to:</p>
<p>1. Provide an enduring resource of more than 1,000 genomes from 4,500 years of the Britain's past, and information on sex, relatives, ancestry, and pathogen presence for additional ~2,000 samples.</p>
<p>2. Trace ancestry changes through 4,500 years, untangling present-day population stratification hampering medical genetics studies.</p>
<p>3. Characterise natural selection on single variants and polygenic traits through time, including in response to industrialization, epidemics, and environmental changes.</p>
|
| 16/07/2019 |
£1,924,975 |
|
UNIVERSITY OF GLASGOW |
<p>Bats are among the most important sources of emerging viral threats, responsible for Ebola, SARS and Nipah. We currently mitigate the impacts of bat viruses reactively, by treating humans or domestic animals after viruses emerge and cause disease. This fellowship proposes that deeper understanding of viral epidemiology, combined with new statistical and biological tools, could empower a strategic shift towards prevention. Using a tractable and important bat virus, vampire bat-transmitted rabies, I will first use routinely-collected surveillance data to develop models that rapidly forecast spatiotemporal emergence risk as epidemiological situations change, enabling use of life-saving human and animal vaccines prior to outbreaks. Next, field studies, experiments and viral genomics will allow individual-to-landscape epidemiological models to identify sensitive points in viral transmission cycles that could be exploited by interventions. Finally, I will explore whether revolutionary new approaches to vaccinology using self-spreading vaccines can reduce human and livestock mortality by controlling bat viruses at their source. This research delivers immediate translational benefits by mitigating health and economic costs from the most important bat virus in the Americas, strengthens international research capacity, and creates a biological and methodological toolbox to manage pathogens in bats, an historically intractable reservoir of zoonotic viruses.</p>
|
| 16/07/2019 |
£2,119,443 |
|
UNIVERSITY COLLEGE LONDON |
<p>Understanding how neurons translate extracellular cues into specific patterns of gene expression is amongst the major goals of modern neurobiology. Efforts to unravel the molecular basis of localised gene expression have mostly focused on transcriptional control and mRNA transport. However, post-transcriptional mRNA processing is increasingly recognised as an essential step in the propagation of genetic information. Importantly, incorrect processing and delivery of mRNA causes developmental defects and severe human neurological disorders. The overarching scope of this project is to investigate novel mechanisms of mRNA metabolism that are likely to be conserved in all mammalian cells and to provide new insights regarding how gene expression is regulated in neurons. The 3’ untranslated regions (3’UTRs) of RNA transcripts play a key role in mediating many steps of RNA metabolism, including splicing, nuclear export and localization. We performed 3’end-Seq screens of transcripts localised in sub-cellular compartments of sympathetic neurons and are uniquely positioned to tackle the question of how 3’UTRs regulate RNA metabolism in neurons.<br>
We will address the following questions:</p>
<ol style="list-style-type: upper-alpha">
<li><em>What determines the fate of a bifunctional mRNA? </em></li>
<li><em>Does the 3’UTR influence the proteome in sympathetic neurons?</em></li>
<li><em>Do 3’UTRs generate a new class of RNAs that regulate neuronal development?</em></li>
</ol>
|
| 16/07/2019 |
£2,781,976 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Decisions require integration of sensory evidence and prior knowledge before committing to a chosen action, but the neural mechanisms of decision-making remain poorly understood, partly because they involve the interaction of multiple brain structures and timescales. We have developed a change-detection task in mice, which separates covert antecedents of choices from motor-execution-related activity, to probe mechanisms of decision-making. Pilot data reveal that secondary motor cortex (MOs) is selectively and persistently activated by behaviourally-relevant sensory evidence when animals expect a stimulus change, and is the earliest cortical area recruited prior to executing a behavioural choice. We will determine how neural dynamics in MOs unfold as mice commit to a decision, map these dynamics on genetically and anatomically identified populations of neurons, and test their necessity for behaviour. We will identify how MOs representations are updated by sensory evidence and how this is influenced by temporal expectation. We will test specific hypothesis about circuit mechanisms that drive decision-related dynamics in MOs, using targeted optogenetic inactivations of multiple brain regions to assess their impact on behaviour. This work will identify the contribution of cortical and subcortical pathways to transforming sensory evidence into decision, and how temporal expectation influences this transformation.</p>
|
| 16/07/2019 |
£1,819,436 |
|
UNIVERSITY OF BIRMINGHAM |
<p>The protozoan parasite <em>Toxoplasma gondii </em>chronically resides in 30% of humans as infections cannot be cleared. Infection is often asymptomatic, with serious complications and death in immunocompromised and congenitally infected humans. It is unclear how normal immunocompetent individuals control <em>Toxoplasma</em> during acute infection. Multiple unknown unique and overlapping mechanisms of <em>Toxoplasma </em>defence must exist in different human cell types. Host defence acts directly at the membrane between the parasite and the cytoplasm. We have developed an artificial intelligence-driven image analysis pipeline to conduct high-throughput single-cell analysis of these defence mechanisms. We will combine this approach with mechanistic cellular studies and unbiased mass spectrometry approaches. Like this, we will systematically define and characterise the human intracellular host defence machinery targeting <em>Toxoplasma gondii </em>in endothelial cells and macrophages. </p>
<p><em>We will address the following aims:</em><br>
I. Elucidate mechanisms driving endo-lysosome-mediated control of <em>Toxoplasma </em>in endothelial cells.<br>
II. Define mechanisms of ubiquitin-dependent host defencetargeting <em>Toxoplasma </em>in macrophages<em>.</em><br>
III. Identify novel cellular networks targeting <em>Toxoplasma </em>employing host defence proteins as tools for discovery-based mass spectrometry. </p>
<p>By discovering the compendium of host defence machinery that operates at the human <em>Toxoplasma </em>host defence vacuole in two divergent cell lines, this research directly contributes to human health. </p>
|
| 16/07/2019 |
£2,444,366 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Down syndrome (DS) is a common genetic disorder resulting from an extra copy of human chromosome 21 (Hsa21). This gene dosage disorder is characterised by cognitive deficits and early-onset neurodegeneration. It causes significant impact on the quality and longevity of life. Presently, there are no therapies.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The key aim of our proposal is to establish the mechanisms by which trisomy 21 causes cognitive impairment in DS. By using a unique complement of segmental trisomy-containing mouse models and human DS induced pluripotent stem cell-derived neurons, together with cutting-edge genetics, biochemistry, imaging, electrophysiology, neural circuit tracing and systems neuroscience, we will identify the genes that cause neurological deficits in DS, define the cells that are affected, and discover the mechanisms that underlie dysfunctional neural communication. Identifying the responsible proteins and their roles in the brain will allow us to devise innovative pharmacological and gene-based therapeutic approaches to reverse the deleterious cognitive phenotypes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our research strategy is based upon a significant bank of preliminary data. By using the diverse but complementary research skills within our collaborative group, we have the potential to deliver greater understanding of, and life-changing therapies for, people with DS.</p>
|
| 16/07/2019 |
£577,042 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Down syndrome (DS) is a common genetic disorder resulting from an extra copy of human chromosome 21 (Hsa21). This gene dosage disorder is characterised by cognitive deficits and early-onset neurodegeneration. It causes significant impact on the quality and longevity of life. Presently, there are no therapies.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The key aim of our proposal is to establish the mechanisms by which trisomy 21 causes cognitive impairment in DS. By using a unique complement of segmental trisomy-containing mouse models and human DS induced pluripotent stem cell-derived neurons, together with cutting-edge genetics, biochemistry, imaging, electrophysiology, neural circuit tracing and systems neuroscience, we will identify the genes that cause neurological deficits in DS, define the cells that are affected, and discover the mechanisms that underlie dysfunctional neural communication. Identifying the responsible proteins and their roles in the brain will allow us to devise innovative pharmacological and gene-based therapeutic approaches to reverse the deleterious cognitive phenotypes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our research strategy is based upon a significant bank of preliminary data. By using the diverse but complementary research skills within our collaborative group, we have the potential to deliver greater understanding of, and life-changing therapies for, people with DS.</p>
|
| 16/07/2019 |
£954,742 |
|
THE FRANCIS CRICK INSTITUTE |
<p style="margin-left: 0cm; margin-right: 0cm">Down syndrome (DS) is a common genetic disorder resulting from an extra copy of human chromosome 21 (Hsa21). This gene dosage disorder is characterised by cognitive deficits and early-onset neurodegeneration. It causes significant impact on the quality and longevity of life. Presently, there are no therapies.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The key aim of our proposal is to establish the mechanisms by which trisomy 21 causes cognitive impairment in DS. By using a unique complement of segmental trisomy-containing mouse models and human DS induced pluripotent stem cell-derived neurons, together with cutting-edge genetics, biochemistry, imaging, electrophysiology, neural circuit tracing and systems neuroscience, we will identify the genes that cause neurological deficits in DS, define the cells that are affected, and discover the mechanisms that underlie dysfunctional neural communication. Identifying the responsible proteins and their roles in the brain will allow us to devise innovative pharmacological and gene-based therapeutic approaches to reverse the deleterious cognitive phenotypes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our research strategy is based upon a significant bank of preliminary data. By using the diverse but complementary research skills within our collaborative group, we have the potential to deliver greater understanding of, and life-changing therapies for, people with DS.</p>
|
| 16/07/2019 |
£1,947,516 |
|
UNIVERSITY OF DUNDEE |
<p>Specificity in the SUMO system appears to be achieved by modification of large groups of proteins by a PIAS E3 ligase mediated SUMO spray. Our aim is to define the mechanism by which PIAS E3 ligases select multiprotein complexes for modification. Proteomic identification of sites of SUMO modification and SUMO ChIPSeq analysis provide evidence that the SUMO spray functions in human induced pluripotent stem cells. Our objectives are to establish the role of the “SUMO spray” in maintaining pluripotency. We will deplete SUMO globally using the ML792 E1 inhibitor and will deplete SUMO locally at specific genomic loci using Cas9-SUMO protease fusions and at multiprotein complexes using nanobody-SUMO protease fusions. We will follow cell fate, changes in histone marks, chromatin accessibility, transcriptional output and the stability of multiprotein complexes. PIAS proteins can be recruited to substrates via DNA, SUMO and specific protein interactions. We will use structural, biochemical and single molecule approaches to describe PIAS mediated SUMO modification. Our ultimate goal is the structural determination of a ternary complex of DNA bound substrate, PIAS protein and SUMO loaded E2. This would be a first in its class structure and would reveal the mechanism of SUMO spray mediated substrate modification.<br>
</p>
|
| 16/07/2019 |
£2,740,933 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0in; margin-right: 0in">Viruses depend on cellular machinery to express and replicate their genes. Viral RNA must therefore be delivered or generated in the cytosol. Some viruses also deliver genomic DNA into the nucleus, for integration into the host cell genome. The cell’s principal innate defenses are to mount a potent inflammatory response upon sensing cytosolic viral RNA and to repress the transcription of integrated viral DNA. To be effective, these responses must be sensitive, specific and appropriately calibrated to minimize toxicity and autoinflammation. Our overarching goal is to gain a molecular understanding of how the cell recognizes cytosolic viral RNA and how it silences viral gene expression with the necessary sensitivity and specificity. In pursuit of this goal we are applying a complementary set of biophysical, biochemical and cell biological approaches, with a focus on using high-resolution structural information to obtain detailed mechanistic insights with atomic-level detail. <br>
<br>
<strong>Our key goals are to understand:</strong><br>
<br>
-how cells distinguish viral from endogenous nucleic acids;<br>
-how the immune response against double-stranded RNA is generated and amplified; <br>
-how cells recognize and silence integrated viral DNA;<br>
<br>
This will provide invaluable insights on fundamental principles of host-pathogen recognition, chromatin regulation and host-virus coevolution.</p>
|
| 16/07/2019 |
£2,086,031 |
|
NEWCASTLE UNIVERSITY |
<p style="margin-left: 0cm; margin-right: 0cm">The first two steps of gene expression are tightly coupled in both bacteria and eukaryotes, which largely determines outcomes of gene expression. Transcription-translation coupling in bacteria is essential for viability and virulence. Transcription-splicing coupling in eukaryotes is critical for development and differentiation, and its malfunction may lead to disease. However, little is known about the molecular details of these mechanisms, mainly due to the absence of tractable experimental systems. We developed a unique <em>in vitro</em> transcription-translation coupled system, which we will use to investigate interactions of RNA polymerase with ribosome, how transcription regulates initiation of translation, and how ribosome controls RNA polymerase activities, transcription pausing and resolves transcription events that compromise genomic integrity. By using the first <em>in vitro</em> transcription-splicing coupled system, we will study direct interactions of RNA polymerase II with spliceosome ribonucleoprotein particles, how transcription elongation regulates assembly of the spliceosome and alternative splicing, and regulation of elongation by spliceosomal complexes, which is critical for splicing efficiency.<em> In vitro</em> programme will be complemented by new NGS-based techniques and CryoEM analysis of transcription-translation and transcription-splicing coupled complexes. The results will enrich our understanding of basic molecular processes that underpin many human diseases, and may provide new targets for antibiotics.</p>
|
| 16/07/2019 |
£2,262,630 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">Malaria prevention relies heavily on insecticide-based interventions including Long Lasting Insecticidal Nets (LLINs). Unfortunately, insecticide resistance threatens these tools. Worryingly, an escalation of resistance in <em>Anopheles funestus, </em>major malaria vector<em>,</em> is inducing an extensive loss of efficacy of all pyrethroid-LLINs including the newly introduced PBO-pyrethroid nets. If such super-resistance spreads Africa-wide, insecticide-based interventions could be compromised with catastrophic consequences. This super-resistance is likely driven by a dramatic increase in metabolic resistance and/or the development of a reduced penetration in super-resistant mosquitoes allowing them to now survive exposure to even PBO-pyrethroid nets and potentially conferring cross-resistance to other insecticide classes. Unfortunately, the molecular drivers of this super-resistance remain unknown preventing the design of diagnostic assays to track it and assess its impact on malaria control. Therefore, to help mitigate the impact of super-resistance, I will pursue the following aims: <strong>Aim 1: </strong>detecting molecular markers of the increased metabolic resistance driving the resistance escalation to insecticides in <em>An. funestus</em>; <strong>Aim 2: </strong>detecting genetic variants of the reduced penetration mechanism contributing to super-resistance, cross-resistance and design DNA-based assays to track it; <strong>Aim 3: </strong>establishing the impact of the escalation of resistance on the effectiveness of insecticide-based interventions and malaria transmission using molecular markers.</p>
|
| 16/07/2019 |
£1,729,179 |
|
BIRKBECK UNIVERSITY OF LONDON |
<p>The goal of this proposal is to obtain mechanistic insight the microtubule-based transport system that enables cilia/flagella to assemble and perform essential functions in cell motility, signaling, and sensing. Strikingly, this process of intraflagellar transport (IFT) involves multi-megadalton polymers, termed IFT 'trains', which move under the power of oppositely-directed microtubule motors dynein-2 and kinesin Kif3. To address outstanding motor mechanisms of IFT, I propose a multi-disciplinary approach spanning three scales. At the scale of individual motors, we will determine structures of the dynein-2 and Kif3 complexes to elucidate how their subunits come together and enable regulated motor activity. At the scale of multi-motor assemblies, we will reconstitute IFT trains with purified proteins to dissect how they polymerize and coordinate bidirectional motility. At the scale of whole cilia, we will determine how dynein-2 powers IFT turnaround at the ciliary tip and define spatial regulators of dynein-2 in mammalian cells. To achieve these goals, we will use reconstitution and cryo-EM to determine structures, fluorescence microscopy to visualize dynamics, and genome editing to interrogate cellular factors. Together, these studies will illuminate the multi-scale mechanisms that cells use to build and signal through cilia/flagella, which I will integrate into a molecular movie.</p>
|
| 16/07/2019 |
£923,847 |
|
UNIVERSITY OF GLASGOW |
<p style="margin-left: 0in; margin-right: 0in">Apicomplexan parasites cause diseases, including toxoplasmosis and malaria, that require new drugs. Apicomplexan mitochondrial translation is critical for parasite survival. For example, we recently showed that depleting a <em>Toxoplasma</em> mitoribosomal protein results in parasite death. Apicomplexan mitochondrial translation shows striking differences from humans, as many short mitochondrial rRNAs are transcribed rather than two large rRNAs. Additionally, tRNAs are imported into mitochondria rather than mitochondrially encoded. How translation is performed under these conditions is not understood.</p>
<p style="margin-left: 0in; margin-right: 0in">Using the model apicomplexan <em>Toxoplasma, </em>we will pursue two aims: </p>
<p style="margin-left: 0in; margin-right: 0in">1.Study the mitoribosome composition, structure and function.<br>
1.1.Via proteomics and genetics, taking advantage of our cell-lines with tagged or regulated mitoribosomal proteins<br>
1.2.Via structural analysis, exploiting our new mitochondrial macromolecule enrichment protocol, and cryoEM collaboration. </p>
<p style="margin-left: 0in; margin-right: 0in">2.Dissect and functionally characterize the mitochondrial tRNA import pathway.<br>
2.1.Through functional analysis of mitochondrial tRNA interactors we have already identified<br>
2.2.tRNA import may occur directly from the nucleus. We will examine the role of novel nuclear-mitochondrial contact sites.</p>
<p style="margin-left: 0in; margin-right: 0in">This work will provide mechanistic understanding of divergent aspects of apicomplexan mitochondrial translation. The molecular and atomic insights into how mitoribosomes operate and what interactions facilitate tRNA import, may inform the design of new mitochondrial translation inhibitors, thus seeding drug development. </p>
|
| 16/07/2019 |
£2,423,363 |
|
UNIVERSITY OF CAMBRIDGE |
<p>To understand how the genome directs development, we need to know the cell-to-cell changes in genomic activity at individual loci and how changes are regulated. Advances in single-cell profiling provide a new ability to determine the regulatory configuration of individual cells genome-wide through profiling gene expression and chromatin accessibility. However, determining the connections between mother and daughter cells remains difficult. The invariant and known cell lineage of <em>C. elegans</em> solves this problem, making it possible with single-cell profiling to determine locus-specific activity in every cell from the zygote to the differentiated state. In Aim 1 we study the early events of genome quiescence, zygotic genome activation (ZGA), and lineage commitment by profiling all cells from the zygote to the 26-cell stage, and germ cells through their later ZGA. In Aim 2 we use the 20-cell intestine as a paradigm to study progression through a complete developmental trajectory. We will investigate mechanisms of key transitions and further study the relationship of activity patterns to genome 3D structure. In Aim 3, we focus on the impacts and regulation of active and PRC2/Polycomb chromatin domains. Our work will impact understanding of core principles of genome regulation relevant across animals. <br>
</p>
|
| 16/07/2019 |
£1,256,598 |
|
UNIVERSITY OF BRISTOL |
<p>A robust wound inflammatory response is critical for survival of most organisms. We propose analysing how innate immune cells - neutrophils and macrophages - respond to wound cues, and once they arrive at the wound what are their varied activities and functions at the wound site, both positive and negative. We will use a marriage of Drosophila and zebrafish studies to model wound inflammation and to determine, what are the earliest damage signals that draw inflammatory cells to wounds and how these cells dramatically change their phenotype during their recruitment and throughout the period of wound repair in response to the dynamic wound environment. These signals and phenotypic “switching” events will be determined by a combination of FACS, genetics and live imaging approaches which are considerably aided by the translucency of our fly and fish models. We also want to determine how inflammatory cells influence other cell lineages at the wound site including fibroblasts and melanocytes and adipocytes, to the benefit and detriment of the wound healing process, with a view to developing therapeutic interventions that might alter these influences to enhance positive instructions and dampen the negative consequences of wound inflammation including excessive scarring.<br>
</p>
|
| 16/07/2019 |
£2,275,853 |
|
UNIVERSITY OF EXETER |
<p style="margin-left: 0cm; margin-right: 0cm">I have established that C-type lectin receptors (CLRs) play a central role in antifungal immunity. In this proposal, I will capitalize on our exciting recent discoveries to address two questions that represent novel aspects of CLR biology:</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<ol style="list-style-type: upper-roman">
<li><strong>How do CLRs regulate antifungal adaptive immunity?</strong></li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">We discovered dendritic cell expressed CLRs, the KLRs, which regulate the development of adaptive immunity during fungal infection. Our objective is to determine the physiological role of the KLRs, elucidating their cellular expression and function, the nature of their T-cell ligand(s), their influence on T-cell immunity and their importance in anti-fungal immunity.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<ol start="2" style="list-style-type: upper-roman">
<li><strong>What is the impact of fungal secondary metabolite recognition by CLRs?</strong></li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">We identified two novel CLRs that recognise fungal secondary metabolites, including secreted toxins such as aflatoxin (a major clinically significant fungal-derived carcinogen). Our objective is to gain a definitive understanding of the functions of these receptors and the immunological and physiological impact of their ability to recognise these secreted fungal products.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Using a variety of <em>in vivo</em> and <em>in vitro</em> approaches, this research programme will significantly advance our knowledge of the underlying mechanisms of antifungal immunity, and will open new fields of investigation in the areas of adaptive immunity and medical mycology.</p>
|
| 16/07/2019 |
£1,647,968 |
|
UNIVERSITY COLLEGE LONDON |
<p>Although sleep is highly conserved and has a major impact on human health, the genetic and neuronal mechanisms that regulate the timing and amount of sleep remain poorly resolved. From a combination of whole-brain activity mapping, targeted gene editing, and behavioural analysis, we have discovered that neurons in the zebrafish preoptic area that express the neuropeptide Galanin become activated during rebound sleep and that proper sleep homeostasis requires functional Galanin. We will now use RNA sequencing, pharmacology, and mutant analysis to dissect the signals that converge onto Galanin-mediated sleep homeostasis. Second, we will leverage the optical translucency of the zebrafish brain and genetically encoded calcium indicators to image Galanin neurons’ activity in relation to known wake-promoting circuits, such as Hypocretin and Noradrenaline neurons, in vivo. Finally, we will use chemogenetic tools to manipulate the activity of Galanin neurons during and after normal and homeostatic rebound sleep to elucidate the functional role these neurons play in sleep regulation. </p>
|
| 16/07/2019 |
£1,706,361 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0in; margin-right: 0in">African trypanosomes have remarkable cell surfaces which mediate their interactions with the molecules of infected mammals. These surfaces are packed with a dense layer of the variant surface glycoprotein (VSG), allowing a population survival strategy based on antigenic variation. Within thisVSG coat operate receptors for mammalian ligands such as transferrin and haptoglobin-haemoglobin. We have shown how these receptors have evolved to bind ligands while minimising exposing of the trypanosome to the adaptive immune system. We have also shown that trypanosome receptors bind to complement components, identifying and characterising receptors for factor H and complement C3. This latter work validated a bioinformatics screen that identified a further 25 putative receptors. The aim of this proposal is to now identify the complete receptor repertoire used by <em>Trypanosoma brucei</em>to exploit and survive within its host. We will assess whether receptors are virulence factors and whether they represent new biology. We will understand the molecular basis for their action. We will also determine what causes the distribution and dynamics of different receptor types within the cell. This will produce detailed mechanistic insight into the cell and molecular biology of trypanosome receptors, yielding a greater understanding of both the trypanosome and the disease.</p>
|
| 16/07/2019 |
£3,687,583 |
|
UNIVERSITY OF BRISTOL |
<p style="margin-left: 0cm; margin-right: 0cm">Sub-Saharan African (SSA) already has twice the number of older adults than northern Europe, with life expectancy rising rapidly. Ageing exponentially increases fracture risk. The WHO have called for action to prevent and manage fragility fractures in SSA in the next decade; there is an urgent and compelling need for research to inform actions to improve healthcare provision. We will establish vertebral fracture prevalence (the commonest fragility fracture), hip fracture incidence (the most life-challenging fragility fracture) and, over 12-months, their impact on survival, disability and health costs. We will examine the contribution of risk factors of importance in the context of SSA, e.g. HIV, body composition. Ethnographic research will inform understanding of fracture care pathways, patient’s beliefs, patterns of health service delivery and factors influencing implementation of fracture services.</p>
<p style="margin-left: 0cm; margin-right: 0cm">To ensure success, our collaboration encompasses international expertise in epidemiology, health economics, anthropology/qualitative methodology, HIV medicine, orthopaedic surgery, gerontology, skeletal imaging, and country-specific research experience within Gambia, Zimbabwe and South Africa. This application builds on our recently-completed South African hip fracture incidence study. The myth that fragility fractures are not an African problem is out-dated; high-quality research is needed, to enable a response to the WHO’s call to be realised.</p>
|
| 16/07/2019 |
£4,016,242 |
|
KING'S COLLEGE LONDON |
PRECISE-DYAD will extend the ongoing PRECISE network study [PRECISEnetwork.org] of 6,000 pregnant women and their infants (dyads); it will provide a greater epidemiological and mechanistic understanding of health and disease pathways in the sub-Saharan African context (The Gambia and Kenya), following uncomplicated pregnancies and those complicated by pregnancy hypertension, fetal growth restriction, stillbirth, and/or preterm birth.
For women, we aim to determine if, and how, these pregnancy events identify those more likely to avoid complications in subsequent pregnancies, mental ill-health, or early onset of cardiometabolic diseases. For their children, we will assess the impact of these pregnancy disorders on their physical, mental, and neurodevelopmental health to 2-3 years of age. We will explore the consequences for maternal health trajectories of caring for children with moderate-to-severe neurodevelopmental delay resulting from complicated pregnancies, and will interrogate interactions with social determinants of health, including environmental exposures on maternal and infant health. We will develop a rich database and a large sample biorepository for future studies.
Thereby, PRECISE-DYAD aims to achieve an overarching understanding of the factors that contribute to optimal maternal and child health within these contexts. Ultimately, the goal is to design interventions to optimise health of mothers and their children.
|
| 16/07/2019 |
£509,382 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 0cm">The 3D organisation of the genome is a subject of intensive investigation internationally. In this proposal, we aim to understand what determines how heterochromatin is organised in the human nucleus. We recently discovered that a specific protein of the nuclear pore complex -TPR – is responsible for excluding heterochromatin from in front of nuclear pores and is essential for the heterochromatin re-organisation that occurs during oncogene-induced senescence. By manipulating TPR we are able to reversibly change the spatial organisation of heterochromatin from localisation along the nuclear periphery to clustering in internal foci. In this proposal our goals are to determine how this heterochromatin reorganisation occurs, and then to investigate the properties of TPR and how this large protein, located on the nuclear pore basket, excludes heterochromatin from pores. Finally, we will investigate what happens to gene expression and RNA processing when heterochromatin is allowed to occlude nuclear pores. </p>
<p style="margin-left: 0cm; margin-right: 0cm">Through this study we will gain new insights into the molecular mechanisms and dynamic properties underlying a fundamental feature of the 3D human genome – the organisation of heterochromatin.</p>
|
| 16/07/2019 |
£3,435,098 |
|
UNIVERSITY COLLEGE LONDON |
<p>We are pioneering the development and application of haematopoietic stem cell (HSC) gene therapy for rare disease, including primary immunodeficiency and inborn errors of metabolism. Remarkable progress has been made over the last two decades, with notable clinical success in a number of different diseases, and transfer of some into the commercial biotechnology sector. Our overall research aim is to create a flexible pipeline of research from gene discovery through disease biology to translation of novel gene and cell therapies. We will address the following areas. 1) enhancement of therapeutic translation for increased numbers of tractable disease targets 2) development of state-of-the-art manufacturing processes to ensure reliability of effect and safety, alongside use of novel technologies to increase efficiency 3) interrogation of haematological and immunological reconstitution in patients as a platform for understanding efficacy and underlying biological mechanisms 4) development of gene editing platforms for HSC modification where semi-random gene addition may be undesirable or ineffective 5) Development of new tools to enhance gene editing in HSC 6) evaluation of novel technologies for detecting on and off-target gene editing aberrations and pre-clinical/clinical assessment of safety 7) application of novel reduced toxicity conditioning strategies for HSC engraftment in gene therapy protocols.</p>
|
| 16/07/2019 |
£2,138,030 |
|
UNIVERSITY OF DUNDEE |
<p>Trypanosomes are divergent eukaryotic parasites and excellent models for investigating the diversity of gene regulatory mechanisms, including allelic exclusion, histone modification and post-transcriptional control. The variant surface glycoproteins (VSGs) are major virulence determinants and have provided starting-points for decoding regulatory mechanisms. I propose to build upon the following discoveries from my laboratory;</p>
<ul>
<li>A VSG <strong><em>allelic exclusion</em></strong> machinery that associates with the single active <em>VSG</em> and silences all other alleles. I propose a detailed dissection of the exclusion mechanism.</li>
<li>Characterisation of the <strong><em>histone acetyltransferases and deacetylases</em></strong>. I propose detailed characterisation of the essential nuclear enzymes, factors they associate with, histone residues they modify and impact on gene regulation.</li>
<li>Hundreds of <strong><em>post-transcriptional</em></strong> <strong><em>regulatory</em></strong> 3’-untranslated regions have been identified using a high-throughput genetic screen. I propose identification of regulatory RNA-binding proteins, the genes they regulate and the underpinning regulatory mechanisms.</li>
</ul>
<p>The proposed studies will fill major gaps in understanding, illuminating mechanisms of <em>VSG</em> allelic exclusion, chromatin-based control and post-transcriptional regulons. How eukaryotic cells express only one gene from the largest gene families, in particular, remains a major unresolved question. Potentially druggable targets that emerge will also present opportunities for further collaboration with colleagues in the Wellcome Trust Centre for Anti-Infectives Research.</p>
|
| 16/07/2019 |
£3,292,176 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0in; margin-right: 0in">The aim of my research is to understand the molecular mechanisms that control cytotoxic T lymphocyte (CTL) polarized secretion and killing. <br>
<br>
In a recent screen of single gene deletion mice we identified novel genes that are required for CTL killing and implicate important roles for organelles including mitochondria and peroxisomes. During the course of these studies we also developed advanced (high-throughput) assays for CTL killing and a detailed map of events leading to CTL secretion. <br>
<br>
Our specific aims over the next five years will be to<br>
<br>
(i) Identify the roles of the newly discovered genes, and the organelles they implicate, in CTL killing using a combination of biochemical, genetic and high-resolution imaging approaches. <br>
<br>
(ii) Determine how transcriptional control fine-tunes CTL killing, combining gene deletion and cell biological approaches (eg micro-patterning) with single cell transcriptomics to ask how CTL modulate their responses in order to modulate their killing.<br>
<br>
(iii) Broaden the range of genetic diseases for studying CTL function and make use of emerging genomic data to identify new causal genes in immunodeficiency.</p>
<p style="margin-left: 0in; margin-right: 0in">With the combination of genetic and cell biological approaches that we take, we aim to bridge the current gap between genes and function in CTL. </p>
|
| 16/07/2019 |
£910,424 |
|
UNIVERSITY OF MANCHESTER |
<p>Activity is required for correct development of neural circuits and emergence of appropriate behaviour. At early stages activity is spontaneously generated, and then superseded by patterned network activity as sensory afferents become active. A period of maximal plasticity, termed critical period, generally spans these two phases. Significantly, aberrant activity during neural circuit development, especially when occurring in the critical period, can lead to network errors that become ‘locked in’ and may contribute to neurological disorders in later life. Whilst a requirement for activity is universal for circuit development, important questions remain unanswered. We have identified a comparable requirement for activity in the development of the motor circuit of <em>Drosophila</em> larvae. Notably, perturbation of activity leads to permanent and significant errors in circuit function. This system is composed of identifiable, tractable neurons of defined connectivity. These advantages allow us to study fundamental questions in ways not possible in higher organisms. Exploiting this exceptional level of resolution, our overall goal is:</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>to generate detailed understanding of the cellular and molecular processes that underlie normal network tuning and lead to errors following early activity perturbation; further, to determine in this tractable circuit the capability of homeostatic mechanisms to compensate for early induced perturbations.</strong></p>
|
| 16/07/2019 |
£956,398 |
|
UNIVERSITY OF CAMBRIDGE |
<p>Activity is required for correct development of neural circuits and emergence of appropriate behaviour. At early stages activity is spontaneously generated, and then superseded by patterned network activity as sensory afferents become active. A period of maximal plasticity, termed critical period, generally spans these two phases. Significantly, aberrant activity during neural circuit development, especially when occurring in the critical period, can lead to network errors that become ‘locked in’ and may contribute to neurological disorders in later life. Whilst a requirement for activity is universal for circuit development, important questions remain unanswered. We have identified a comparable requirement for activity in the development of the motor circuit of <em>Drosophila</em> larvae. Notably, perturbation of activity leads to permanent and significant errors in circuit function. This system is composed of identifiable, tractable neurons of defined connectivity. These advantages allow us to study fundamental questions in ways not possible in higher organisms. Exploiting this exceptional level of resolution, our overall goal is:</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>to generate detailed understanding of the cellular and molecular processes that underlie normal network tuning and lead to errors following early activity perturbation; further, to determine in this tractable circuit the capability of homeostatic mechanisms to compensate for early induced perturbations.</strong></p>
|
| 16/07/2019 |
£2,275,897 |
|
UNIVERSITY OF GLASGOW |
<p style="margin-left: 0cm; margin-right: 0cm">Inflammatory chemokines, and their receptors, orchestrate leukocyte recruitment to inflamed sites. These molecules are fundamentally involved in immune/inflammatory diseases and thus represent important therapeutic targets. However no molecules targeting inflammatory chemokine receptors have yet been licensed for use in immune/inflammatory pathologies. We believe that this, in part, relates to the complex nature of chemokine regulation of inflammatory leukocyte recruitment which is, currently, poorly understood. We have a particular interest in four chemokine receptors: CCR1, CCR2, CCR3 and CCR5 (collectively, iCCRs), which occupy a single genomic locus and play essential, but complex, roles in inflammation. We have generated three unique mouse models to allow us to analyse the individual and combinatorial roles of the iCCRs in inflammatory leukocyte migration. These include mice with the entire iCCR locus deleted; reporter mice in which each of the iCCRs can be individually tracked and mice in which the iCCRs can be switched on individually, and thus essential functions defined. We will use combinations of transcriptomics, in vivo imaging and infection models to rigorously define roles for the iCCRs in inflammation. We propose that the data obtained will be key to both understanding basic inflammation, as well as to the development of novel anti-inflammatory therapeutics.</p>
|
| 16/07/2019 |
£2,590,352 |
|
BIRKBECK UNIVERSITY OF LONDON |
<p>Type 4 secretion (T4S) systems mediate transfer of DNA from one bacterium to another in a process called "bacterial conjugation". As a result, T4S systems are crucial players in the spread of antibiotic resistance among bacterial populations. They also mediate secretion and injection of protein effectors into eukaryotic host cells, and therefore, are important virulence factors in bacterial pathogenesis. This proposal focuses on conjugative T4S systems in Gram-negative bacteria. Conjugation starts with the processing of the DNA at a defined site called the origin of transfer (OriT). This processing step is executed by a large complex called the relaxosome, containing a protein called the "relaxase", and several accessory proteins. During processing, the relaxase nicks and covalently attaches to the DNA and it is this ssDNA-protein conjugate that is transported through the T4S system. Prior to transport, donor and recipient cells come together to form a conjugative junction. Our research goals are the following: i-determine the structure of the relaxosome bound to OriT; ii-trap the ssDNA-protein conjugate within the T4S machinery and solve the structure of this substrate-trapped system in order to elucidate the secretion path; iii- investigate the structure and architecture of conjugative junctions between donor and recipient cells.</p>
|
| 16/07/2019 |
£2,411,528 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">The Nurturing Care Framework (NCF) launched by WHO, UNICEF and the World Bank during the 2018 World Health Assembly argued that “Investing in early child development (ECD) is one of the best investments a country can make to boost economic growth, promote peaceful and sustainable societies, and eliminate extreme poverty and inequality.” </p>
<p style="margin-left: 0cm; margin-right: 0cm">250 million children under five in low and middle-income countries are at risk of not reaching their developmental potential with adverse consequences for their learning and adult prosperity. The NCF is a roadmap for action, focussing on pregnancy and the first 3 years of life as the foundation for wellbeing throughout the life-course. It includes interventions promoting responsive caregiving and early learning, known to improve ECD outcomes when delivered in face-to-face or group sessions with parents and children. However, doing this at the scale needed presents enormous challenges, as many health systems are over-stretched and under-resourced. Mass media may provide a more effective way forward.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We plan to explore this by developing a nurturing care radio campaign built on principles of <em>Saturation</em> and <em>Interactivity </em>informed by clinical psychology, behavioural science and epidemiologic evidence, and to evaluate the impact on ECD outcomes using a cluster randomised trial design.</p>
|
| 16/07/2019 |
£1,724,966 |
|
DEVELOPMENT MEDIA INTERNATIONAL |
<p style="margin-left: 0cm; margin-right: 0cm">The Nurturing Care Framework (NCF) launched by WHO, UNICEF and the World Bank during the 2018 World Health Assembly argued that “Investing in early child development (ECD) is one of the best investments a country can make to boost economic growth, promote peaceful and sustainable societies, and eliminate extreme poverty and inequality.” </p>
<p style="margin-left: 0cm; margin-right: 0cm">250 million children under five in low and middle-income countries are at risk of not reaching their developmental potential with adverse consequences for their learning and adult prosperity. The NCF is a roadmap for action, focussing on pregnancy and the first 3 years of life as the foundation for wellbeing throughout the life-course. It includes interventions promoting responsive caregiving and early learning, known to improve ECD outcomes when delivered in face-to-face or group sessions with parents and children. However, doing this at the scale needed presents enormous challenges, as many health systems are over-stretched and under-resourced. Mass media may provide a more effective way forward.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We plan to explore this by developing a nurturing care radio campaign built on principles of <em>Saturation</em> and <em>Interactivity </em>informed by clinical psychology, behavioural science and epidemiologic evidence, and to evaluate the impact on ECD outcomes using a cluster randomised trial design.</p>
|
| 09/07/2019 |
£1,048,211 |
|
FUNDAçãO DE DESENVOLVIMENTO DA PESQUISA |
<p>Over 400 million people are infected with hookworms, resulting in significant morbidity, mostly from chronic anemia.<strong> </strong>Our <strong>Controlled Human Hookworm Infection</strong> (CHHI) model could accelerate the development of a human hookworm vaccine (HHV) to prevent such infection. This CHHI model has been shown to be safe, well-tolerated, and reliably induce patent infection in hookworm-naïve adults infected with <em>Necator americanus</em> third-stage larvae (<em>Na</em>L3) produced at the Good Manufacturing Practice (GMP) facility at George Washington University. We propose to transfer <em>Na</em>L3 production technology to Brazil to conduct: (1) <strong><em>Necator</em> Donor Program</strong> for the continual production of <em>Na</em>L3 in Brazil; (2) <strong>Dose-escalation study</strong> in adults infected with<em> Necator </em>to determine a dose of <em>Na</em>L3 that is well-tolerated and reliably induces patent infection; (3) <strong>Hookworm vaccination-challenge trial</strong> of two lead HHV antigens: Glutathione S-transferase-1 (<em>Na</em>-GST-1) and Aspartic Protease-1 (<em>Na</em>-APR-1), which have proven safe, well-tolerated, and immunogenic in Phase 1 trials in the USA and <em>Necator-</em>endemic areas of Brazil and Gabon. Our proposal will establish a GMP facility in Brazil for production of <em>Na</em>L3 to conduct such controlled human infection studies. Importantly, this project establishes a platform for rapid assessment of vaccines, therapeutics and diagnostics for hookworm, in a population significantly affected by this helminth. </p>
|
| 09/07/2019 |
£640,968 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
Our goal is to establish a controlled human infection model for Schistosoma mansoni (CHI-S) in Uganda, to accelerate schistosome vaccine development. Schistosomiasis is second to malaria among parasitic causes of morbidity, and prioritised for vaccine development. Thirty percent of Ugandans are estimated to be Schistosoma-infected, 50% at risk.
Leiden co-applicants have developed a single-sex CHI-S, using male-only parasites, thereby avoiding egg-induced pathology. They recently obtained funding to explore a female-only model. Ugandan co-applicants have prepared for CHI-S by engaging stakeholders in ethical, logistical and risk deliberations.
We now propose to
Adapt and implement the Leiden CHI-S for an endemic, Ugandan population.
Utilise it to test preliminary efficacy of prime vaccine candidate Sm-p80+GLA/SE adjuvant (SchistoShield®) in schistosome naïve (Dutch) and endemic (Ugandan) communities
Explore correlates of protective immunity to schistosomes in naïve and endemic settings
Undertake, and evaluate approaches to, public engagement regarding CHI in Uganda.
Build sustainable capacity for CHI-S in Uganda
This work will advance schistosome vaccine development by establishing capacity for down-selection of candidate vaccines through preliminary efficacy testing in endemic populations; as well as for in-depth studies of immunity to schistosomes in endemic settings and for testing of candidate drugs.
|
| 09/07/2019 |
£120,000 |
|
INTERNATIONAL CENTRE OF INSECT PHYSIOLOGY AND ECOLOGY |
<p>Animal African trypanosomiasis (AAT) is a major livestock disease restricting economic development across Africa. AAT is caused by trypanosomes (<em>Trypanosoma</em> spp.), which are haemoparasites transmitted by blood-feeding flies; infection causes inflammatory anaemia, resulting in wastage and death if untreated. Prevention of infection depends on vector control and livestock management to minimise exposure. Therefore, improved epidemiological data are needed constantly to inform disease surveillance and intervention strategies. The role of sylvatic transmission to domestic animals from wildlife reservoirs is a key issue, which will be examined by tracking parasite genotypes across a national park boundary in southern Kenya. Using a third-generation DNA sequencing technology (Oxford Nanopore MinION), I will produce real-time transmission data with greater precision than ever before. I will produce transcriptomes for parasites isolated from vectors, wildlife and livestock over one year, extracting single nucleotide polymorphisms to track genotypes through space and time. This will test the hypothesis that sylvatic transmission from wildlife inside the park sustains AAT in livestock outside. This project will show how new sequencing technologies can enhance parasite epidemiology, while elucidating the importance of sylvatic transmission to AAT, so enabling animal health agencies to better manage disease risk and better localize and prioritize control strategies.<br>
</p>
|
| 09/07/2019 |
£120,000 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
<p style="margin-left: 0in; margin-right: 0in">The Kenya Community Health Strategy (CHS) is a plan of action to expand community access to health care using - amongst other measures - community health volunteers (CHVs). The CHS has had varying degrees of success with ongoing discussions on how to strengthen it.</p>
<p style="margin-left: 0in; margin-right: 0in">There is limited information on implementation of the CHS in urban informal settlements (‘slums’) such as those located in Nairobi, Kenya. This is despite such areas accounting for a high burden of disease.</p>
<p style="margin-left: 0in; margin-right: 0in">Focusing on four large slums within Nairobi County and utilizing a qualitative exploratory approach, this study seeks to understand what influences the performance of CHVs. Individual and group interviews will be conducted with various cadres of health staff at sub-national and community level. These will be supplemented with observations and document reviews. Data will be analysed using framework analysis. The findings from this work will have direct relevance on ongoing policy discussions and strategies on how to strengthen the role of CHVs to attain universal health coverage (UHC). Findings will also inform potential future intervention studies on the effectiveness of CHVs to support the recovery of ill children post hospital admission. </p>
|
| 09/07/2019 |
£120,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p>HIV is a major public health challenge in Sub Saharan Africa and lower respiratory tract infections (LRTIs) remains one of the leading causes of mortality and morbidity in HIV-infected individuals. A lot of studies focusing on peripheral blood have shown HIV-driven perturbations of B cells, however, there is paucity of data on impact of HIV on B cells in the airway. Recently, our group has shown that HIV infection leads to infiltration of B cells into the airway, but whether these B cells are functional is still unclear. My project aims to identify the phenotype, specificity and the functional capacity of the infiltrating B cells, and how this is impacted by antiretroviral therapy. Using flow cytometry, I will determine the phenotype and specificity of the infiltrating B cells, and using an ELISPOT assay I measure their functional potential. I hypothesise that chronic HIV infection alters airway B cell subsets, impairs airway B cell function and leads to recruitment of non HIV-specific B cells into the airway. A better understanding of airway B cell immunity is important for the development of novel therapeutic interventions targeted at reducing the high burden of LRTIs in this susceptible population.</p>
|
| 09/07/2019 |
£120,000 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
<p style="margin-left: 0in; margin-right: 0in">Clinical handovers involve transferring patient responsibility and accountability between outgoing and incoming healthcare providers across shifts and disciplines. It has been highlighted as the most vulnerable time in patient care. Communication failures during handovers have been linked to adverse events, jeopardizing patient safety. Many techniques have been used to improve handovers and communication in health care settings in High Income Countries (HICs) often focused on standardizing information transfer. The SBAR (Situation, Background, Assessment and Recommendation) structured handover approach is often regarded as a ‘best practice’ technique in critical care that has led to reductions of medical errors and enhanced safety culture. In LMICs, including Kenya interventions to improve handovers have not been implemented. In this study, focusing on neonatal ward care I propose: i) to systematically review tools used to improve and evaluate effects of handover interventions, ii) explore current Kenyan nurses’ handover practices and develop with them a contextually appropriate tool to improve and standardize handovers and, iii) to conduct a pilot implementation study using mixed methods (focus group discussions and a survey) to assess its potential effectiveness. This fellowship will then provide the preliminary evidence needed to inform the design future funding proposals for larger implementation studies.</p>
|
| 09/07/2019 |
£120,000 |
|
WITS HEALTH CONSORTIUM (PTY) LTD |
<p style="margin-left: 0cm; margin-right: 0cm">The goal of this study is to use economic analysis and disease modelling to determine the economic impact of non-communicable diseases (NCDs) in South Africa and to establish how to optimally allocate public-sector resources across NCD interventions.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Under this project I will construct a multi-disease health state transition model and use it to establish healthcare costs of and needs for different interventions (including preventative measures for distal risk factors such as smoking and alcohol intake) and packages of interventions targeted at the prevention, early detection and management of NCDs at baseline and over the next 20 years. Ingredients-based costing and micro-costing will be used to augment available data on intervention costs. Using an established epidemiological model parameterised to South Africa based on large surveys and routine data, I will then establish the incremental cost-effectiveness of individual interventions and intervention packages, allowing for downstream health benefits. Finally, I will test different combinations of interventions to identify the optimal package and service delivery platforms that will result in the most cost-effective programme to reach the country’s NCD policy goal, a reduction of premature mortality due to NCDs by 25%, under both the current budget and a budget increased by up to 50%.</p>
|
| 09/07/2019 |
£120,000 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p style="margin-left: 0in; margin-right: 0in">Early diagnosis of tuberculosis (TB) reduces transmission thus impacting TB incidence and prevalence. Research undertaken in developing countries shows that current TB diagnosis algorithms act as a barrier to poorer people seeking TB diagnosis and treatment. Patients accessing these services may incur catastrophic costs therefore hindering the achievement of WHO’s target of 0% incidence of catastrophic costs due to TB. This has led to concerted efforts to develop interventions that simplify TB diagnosis and treatment pathways. In Blantyre, Malawi, one such intervention based on computer-aided x-ray diagnosis (TB-CAD) is currently being investigated in the PROSPECT study, a randomised controlled trial.</p>
<p style="margin-left: 0in; margin-right: 0in">My research will investigate the public health benefits and cost-effectiveness, – from the health provider and societal perspective – of TB-CAD. By fitting statistical models using the PROSPECT study’s trial data, I will estimate the long-term impact on TB prevalence, incidence and mortality in Malawi, assuming that TB-CAD were to be scaled-up at country-level. I will additionally estimate whether the health benefits and reduction in costs are equally distributed between the poorest and the least poor in society. These data will provide policymakers with evidence for whether TB-CAD offers a cost-effective and equitable approach to reversing TB epidemics in Malawi.</p>
|
| 09/07/2019 |
£552,497 |
|
UNIVERSITY OF OXFORD |
This is a joint application that will leverage expertise spanning regulatory, ethical, clinical, and laboratory to establish Shigella human infection studies (HIS) at two sites in Kenya, Kericho and Kilifi. Shigella causes a high burden of disease in low-and-middle income countries (LMICs), where 70% of all cases occur in children under 5 years who form the target population for disease prevention through vaccination. However, there are no licensed Shigella vaccines in routine use with several candidates still in various stages of clinical development. Shigella human infection studies have played a key role in the vaccine development pathway to assess vaccine efficacy. Thus, the goal is to successfully establish Shigella HISs in Kenya. This will be achieved by: (a) conducting dose-finding and dose verification Shigella studies that safely and reproducibly induce ≥60% attack rates under the guidance of experienced clinicians and scientists; (b) assessing vaccine efficacy against a Shigella serotype that is impractical in more traditional field efficacy studies; and (c) explore the ethical and social implications of conducting these studies in a LMIC setting. Once established, the model will accelerate Shigella vaccine development by facilitating the early selection of the most promising vaccines for more extensive testing in LMICs.
|
| 04/07/2019 |
£263,119 |
|
INSTITUT PASTEUR CAMBODIA |
<p>We will purchase a FACS ARIA III (BD Biosciences) 4 laser flow cytometry cell sorter, with the capacity to sort cells in bulk and single cells in plates. The flexible system allows us to configure the sorter for our current needs, but can be easily expanded to future requirements, making it an ideal long-term investment. The ARIA III will be placed and maintained in the Immunology Unit, which is situated in a BSLII laboratory, and is accessible for <strong>all Institut Pasteur research Cambodia staff.</strong> In addition, through collaborations, the cell sorter will be available for <strong>all biomedical researchers in Cambodia outside of Institut Pasteur Cambodia.</strong> A dedicated and trained research engineer will operate the machine. This equipment will allow us to investigate complex pathogen-host interactions to the single cell level directly on site in a low/middle income country. A flow cytometry cell sorter is indispensable for projects such as the investigation of antibody responses to dengue virus, the understanding the mechanisms of P. vivax receptor-ligand interactions involved in reticulocyte invasion, and the monitoring of vaccine responses to avian and seasonal influenza and rabies virus. </p>
|
| 04/07/2019 |
£390,391 |
|
UNIVERSITY OF MANCHESTER |
<p style="margin-left: 0cm; margin-right: 0cm">Mass spectrometry-based proteomics has transformed our understanding of biological complexity. Tissues are regulated by elaborate cell-cell and cell-matrix interactions, and signalling pathways are propagated through numerous protein species in multiple proteoforms. The purchase of a <strong>Bruker TimsTOF Pro mass spectrometry system </strong>will provide a step change in our capacity to characterise physiological complexity. The instrument will address key experimental challenges: <strong>(1) </strong>Tissue characterisation requires analysis of complex mixtures of cells and matrix; patient-derived samples and spatial resolution also require the capacity to analyse very small volumes of material. The sensitivity of the TimsTOF will allow us to measure composition and heterogeneity within tumours, healthy and diseased organs. <strong>(2) </strong>Comprehensive understanding of cellular signalling pathways demands maximal detection of modified peptides with high sensitivity and confidence. The TimsTOF will enable enrichments from low volumes of material and will provide cleaner, more informative fragmentation spectra. This will accelerate research into the pathways that contribute to immune regulation, cancer and fibrosis. The equipment will be located in the Biological Mass Spectrometry (BioMS) facility, making a vital contribution to the missions of the Wellcome Centre for Cell-Matrix Research, the Lydia Becker Institute of Immunology and Inflammation and key projects within the wider research community.</p>
|
| 04/07/2019 |
£495,000 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 0cm">We propose to purchase the TIMS-TOF Pro, a state-of-the-art mass spectrometer (MS) combining the separation power of trapped ion mobility spectrometry (TIMS) with rapid time-of-flight (TOF) mass analysis. TIMS allows for ion mobility separation, which is not possible using current instruments in Edinburgh. Initial analyses, using our samples, confirm increased sensitivity, speed and accuracy from the TIMS-TOF Pro. We will exploit these to characterise the proteome of specific cell populations, understand key, medically relevant signalling pathways and identify precise sites of post translational protein modification and protein-RNA contacts. Housed in the Wellcome Centre for Cell Biology (WCB), the MS will be supported by two core-funded staff and managed by WCB group leaders. The TIMS-TOF Pro will greatly enhance the research of the co-Is, WCB, the School of Biological Sciences, and key collaborators, predominantly Wellcome-funded. We propose key method developments and provide examples of applications enabled by the TIMS-TOF Pro. These include: <br>
1) Unbiased analysis of RNA-protein interactions and their modulation in development and disease.<br>
2) The comprehensive proteomic analysis of rare and single cell populations.<br>
3) Deep phosphoproteomics to understand signalling control during meiosis, T cell activation and function, cellular quiescence in human epithelial cells and <em>T. brucei </em>quorum sensing.</p>
|
| 04/07/2019 |
£1,340,042 |
|
IMPERIAL COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">The Carbohydrate Microarray Facility at Imperial is an internationally leading operation providing collaborations for discoveries of glycan ligands to the biomedical community (<u>http://www.imperial.ac.uk/glycosciences/)</u>. Data accrued are making significant contributions to understanding the involvement of specific glycans in health, infections, inflammation, immune responses and cancer. <br>
<br>
This unique collaborative way of serving the community, with follow-through of data from screening analyses, has enabled substantial advances to be made in glycobiology.<br>
Access to ample amounts of glycans that is often required to corroborate assignments from screening analyses has largely depended so far on external collaborations with chemists. New links that we are forging with the Department of Chemistry to provide desired glycans are of fundamental value for the future of the Facility. <br>
<br>
We are seeking 4 years support to further integrate the new era of glycomics into biology and medicine. We will</p>
<ol>
<li>develop a unique human epithelial mucin/O-glycome resource for diverse recognition studies, in particular microbe-host interactions.</li>
<li>expand the ‘glycosaminoglycome’ and brain ‘gangliome’ library.</li>
<li>complement and diversify the library of glycan sequences with chemically and chemo-enzymatically synthesized glycans, guided from glycan array data.</li>
<li>introduce new software for integrated data management and data mining of glycome array analyses.</li>
</ol>
|
| 04/07/2019 |
£1,448,082 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
<p>Established in 1971, the Protein Data Bank (PDB), is the single global archive of macromolecular structures. It is managed by the Worldwide Protein Data Bank (wwPDB), currently consisting of four partner sites across Europe, Asia and the USA. The Protein Data Bank in Europe (PDBe) is a founding member of wwPDB and is an ELIXIR Core Data Resource and deposition database.</p>
<p>Structural biology is being transformed by rapid advances in structure-determination techniques (e.g. Electron Microscopy and Integrative/Hybrid Methods) and improved access to large-scale facilities that offer high-throughput methods (e.g. ligand and fragment screens). These developments lead to a continuous increase in the number, size and complexity of structures deposited to the PDB.</p>
<p>In this project we aim to address the challenges posed by these advances in structural biology through:</p>
<ol>
<li>
<p>Active engagement in worldwide data-archiving activities:</p>
<ol>
<li>
<p>Development of data-representation standards;</p>
</li>
<li>
<p>Further development of the wwPDB deposition, validation, and biocuration system (OneDep) to accommodate new structure-determination modalities;</p>
</li>
<li>
<p>Interoperability with specialist archives for experimental structural biology data.</p>
</li>
</ol>
</li>
<li>
<p>Maintaining data quality and integrity by fulfilling PDBe’s responsibility to curate all structures produced in Europe and Africa.</p>
</li>
<li>
<p>Development of data-analysis and dissemination tools for improved accessibility.</p>
</li>
<li>
<p>Conducting training, outreach, and public-engagement activities.</p>
</li>
</ol>
|
| 04/07/2019 |
£939,339 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
<p>RNAcentral and Rfam are complementary resources for non-coding RNA (ncRNA) biology developed at EMBL-EBI that capture and analyse primary research outputs and propagate annotations to large numbers of RNA sequences, analogous to UniProt and InterPro for proteins. Rfam is a database containing >3,000 ncRNA families represented by manually curated multiple sequence alignments, consensus secondary structures, and computational models that are used to annotate related RNAs in novel genomes. RNAcentral is a database of ncRNA sequences that provides unified access to data integrated from >30 specialist databases representing all ncRNA types from a broad range of species. Driven by scientific demand, we will further develop and enhance both resources by:</p>
<ol>
<li>introducing a new gene-centric data organisation to remove redundancy and facilitate new types of functional annotations across the taxonomic diversity;</li>
<li>semi-automatically connecting ncRNA genes, sequences, and families to the latest findings in the scientific literature; and</li>
<li>facilitating exploration of regulatory ncRNAs in metagenomic datasets, including biomedically significant environments, such as the human gut.</li>
</ol>
<p>RNAcentral and Rfam are perfectly positioned to deliver on these objectives in a cost-effective manner by harnessing the team’s expertise and an extensive network of collaborations with the RNA community.</p>
|
| 04/07/2019 |
£479,450 |
|
UNIVERSITY OF CAMBRIDGE |
<p><strong>Provision of cutting edge cell-sorter, with class II biocontainment to allow flexible workflows as applied to a broad range of studies within the Cambridge biomedical research community.</strong></p>
<p>The acquisition of a CL2 high-parameter cell-sorter will provide critical ability to purify live-cell populations. This capability is desperately needed to match the explosive growth in high-parameter single-cell analysis in the Cambridge biomedical community (high-parameter flow-cytometry, CyTOF mass-spec, single-cell (sc)-RNA-seq). Parallel cell-sorting capacity of mouse and human live-cells is crucial for validation of findings, and in-depth exploration of the biology of highly purified cell populations. Currently, there is no capacity in Cambridge for high-parameter CL2-designated cell-sorting. This Wellcome Trust multi-user equipment grant application will provide a critical resource to the Cancer Research UK, Cambridge Institute (CRUK-CI), and wider Cambridge biomedical community.</p>
|
| 04/07/2019 |
£237,247 |
|
UNIVERSITY OF EDINBURGH |
<p>We will determine protein co-regulation scores (ProCos) to aid the functional annotation of proteins. For this we will leverage the power of machine-learning to mine large amounts of public proteomics data. The results will be disseminated through STRING, the EBI’s PSICQUIC portal and on our website together with powerful, web-based analysis tools.</p>
<p>We have previously shown that protein co-regulation is an accurate indicator for protein function, strongly outperforming associations derived from mRNA coexpression data. Our prototype analysis uncovered around 60,000 interactions between 5,000 human proteins. Since 2019 these are available to thousands of daily users of STRING in the form of a specially created protein co-regulation channel.</p>
<p>We will expand this compendium by adding hundreds of experiments that have become publicly available recently. We will achieve comprehensive ProCos coverage of the human proteome and extend the approach to other species. Our prototype platform for ProCos-based protein function prediction (www.proteomeHD.net) will be improved and consolidated, in order to support biomedical research in an open, sustainable and permanent manner.</p>
<p>We request resources to support the salary of one full-time researcher at the University of Edinburgh for three years, and to purchase a server for data processing and dissemination.</p>
|
| 04/07/2019 |
£1,329,193 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 0cm">We will create the first atlas of the human brain showing the location, molecular composition and physical features of trillions of single synapses at the whole-brain scale. The Human Synaptome Atlas will reveal the distribution of excitatory and inhibitory synapse subtypes in all major areas of the brain in three normal individuals and in the prefrontal cortex of 100 normal individuals (20-80 years of age). </p>
<p style="margin-left: 0cm; margin-right: 0cm">Toward this, we have reported a breakthrough technology pipeline enabling mapping of billions of individual synapses to generate the mouse brain synaptome (PMC6117470). To address the challenges and opportunities presented by the human brain, we will:</p>
<p style="margin-left: 0cm; margin-right: 0cm">1. Establish the next-generation synaptome mapping pipeline – SYNSTAR – scalable to the size and complexity of the human synaptome.</p>
<p style="margin-left: 0cm; margin-right: 0cm">2. Generate novel reference resources and tools for analysis and interactive visualisation of human synaptomes. </p>
<p style="margin-left: 0cm; margin-right: 0cm">3. Integrate the atlas with international strategic programmes mapping human brain anatomy and function from the molecular and cellular scale to whole-brain networks. </p>
<p style="margin-left: 0cm; margin-right: 0cm">The Human Synaptome Atlas and SYNSTAR will provide a foundation for the study of the normal and diseased brain including the many genetic disorders, neurodegenerative conditions and brain injuries that damage synapses.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm">Keywords: Human, Brain, Synapse, Synaptome, Postsynaptic, Proteome, Atlas</p>
|
| 04/07/2019 |
£1,192,228 |
|
UNIVERSITY OF LIVERPOOL |
<p>The exponential increase and availability of large-scale Omic and other datasets (including associated metadata) has revolutionised our understanding of organismal biology. For maximum value, these data must be effectively integrated and made widely accessible. The TriTryDB database (<u>http://TriTrypDB.org/</u>) provides access to datasets and information on kinetoplastid species, leveraging infrastructure from the EuPathDB Bioinformatics Resource Center (NIH HHSN272201400030C), successive funding from Wellcome (WT099198MA; 2012 & WT108443MA; 2015), the Gates Foundation and others. The resulting web resources are widely viewed as <em>essential</em> for kinetoplastid research, providing functional genomics datasets, integrated with the latest reference assemblies and annotations, in a flexible, extensible and queryable framework to expedite discovery research and translational application. TriTrypDB was visited by an average of 5,694 unique users/month in 2018 (22% UK, 20% US, 34% endemic countries, incl. 12% Brazil). This Resource Grant will ensure continued and updated availability to the global research community. We propose to:</p>
<ol>
<li>Provide state-of-the-art web resources supporting diverse kinetoplastida, including non-pathogenic and free-living relatives.</li>
<li>Ensure sustainable mechanisms for capturing and representing available annotation, incorporating expert community knowledge. </li>
<li>Break down silos, through the integration of epidemiological data, host/vector-pathogen interaction datasets, and other systems-level information. </li>
<li>Deliver educational and training services.</li>
</ol>
|
| 04/07/2019 |
£887,602 |
|
UNIVERSITY OF BIRMINGHAM |
<p>This bid will support molecular histology infrastructure at UoB, addressing major technical challenges and limited capacity in this expanding area to create a nationally leading molecular histology facility.<strong> </strong>Building on existing infrastructure and expertise, it leverages a wide user-base, featuring an expanding portfolio of fundamental and clinically-facing biomedical science. It will stimulate three strategically important and overlapping UoB scientific themes: Immune Regulation, Metabolism, and, aligning with our WT-CRF, Immunotherapy Development, catalysing our understanding of the role of specific cell types and processes within highly defined tissue microenvironments. The synergistic platforms requested collectively represent a step-change in digital histology capability. A new multispectral immunofluorescence platform (the Vectra-Polaris), builds on our ‘Key Opinion Leader’ status for this approach. Secondly, two Leica platforms will increase capacity in multiplex staining and IHC scanning. Finally, we request a Nanostring-GeoMx ‘digital spatial profiler’ and associated nCounter, a potentially game-changing platform allowing highly multiplexed, spatially resolved analyses of RNA/protein markers in tissues. Funding will support UoB’s place on Nanostring's early access scheme for this technology, one of only 25 sites globally. A successful bid will establish a cutting-edge Birmingham Molecular Histology Facility catalysing fundamental scientific and clinical advances, yielding novel hypotheses, publications, stratification approaches, and clinical trials.</p>
<p> </p>
<p> </p>
|
| 04/07/2019 |
£1,009,816 |
|
KING'S COLLEGE LONDON |
<p>We request support for equipment and staffing of a new multi-user mock interventional suite managed by King’s College London and located within St Thomas’ hospital. Our ambition is to accelerate the development, evaluation, clinical translation and downstream commercialisation of interventional medical devices developed within the UK academic sector. This can only be done through developing an ambitious multi-user research infrastructure serving cross-disciplinary research teams engaging with MedTech companies.</p>
<p>King’s has committed £9.4M toward the creation of ~600m<sup>2 </sup>of multi-disciplinary, multi-user facilities for research in Surgical and Interventional Engineering (SIE). The mock interventional suite, forming the core of this space, has been designed to allow for cadaver studies, X-Ray imaging, and use of laser-based devices. Funding stemming from this proposal would support the procurement of state-of-the-art clinical-grade equipment to re-create modern interventional environments. This will be used to evaluate the performance of novel devices in realistic post-mortem studies. We request support for elements that are otherwise difficult to secure with discrete project-based funding: a range of interventional medical imaging devices (surgical microscopy, 3D X-Ray, ultrasound and photoacousics); shared compute and data storage capabilities; and technical staff support. Additional complimentary equipment funding (£1M) has already been secured from the Wolfson Foundation.</p>
|
| 04/07/2019 |
£1,000,000 |
|
MEDICAL RESEARCH COUNCIL |
<p>As cryo-electron microscopy and tomography (cryoEM, cryoET) methods develop, groups at MRC-LMB are studying increasingly ambitious samples. Identifying and optimizing the appropriate sample requires preparing and screening large numbers of cryoEM grids prior to final data collection. The capacity, quality, and properties of screening microscopes at the LMB currently limit how much screening is possible. We require an electron microscope capable of high-quality imaging for screening vitrified samples. It will be run in a highly automated, high-throughput manner, and allow selected grids to be transferred for data collection on a Titan Krios microscope. The microscope will overcome our severe bottleneck in screening, and allow us to develop new screening approaches that will permit new experimental directions and will be shared with the community.<br>
<br>
The microscope should have similar capabilities to the ThermoFisher Glacios CryoTEM for Life Sciences. It should be equipped with Field Emission Gun and Direct Electron Detector to obtain high quality images, a multi-specimen automatic grid transfer system to allow multiple samples to be screened in a single run, and the ability to run and adapt scripts for computer-controlled screening. The specimen holder must allow selected samples to be saved and directly transferred into existing Titan Krios microscopes.</p>
|
| 04/07/2019 |
£509,726 |
|
QUEEN'S UNIVERSITY BELFAST |
<p style="margin-left: 0in; margin-right: 0in">High-parameter flow cytometry is an innovative and powerful analytical tool that enables researchers to classify and analyse distinct cellular subtypes and phenotypes in the typically heterogeneous cell populations that make up normal and diseased tissues. The BD FACSymphony A5 is a state-of-the-art multi-parameter flow cytometer, which in its current typical set-up (5 lasers/31 parameters), is equipped with the UV, Violet, Blue, Yellow-Green and Red lasers, allowing simultaneous detection of two relative physical properties (forward and side scatter), as well as the analysis of up to 29 different colours.<br>
<br>
A distinct advantage of this instrument is the ease with which it allows investigators to identify rare cell populations through deep immune profiling with no loss of cellular information. This added depth will transform the studies of many research groups at Queen’s University Belfast and beyond. Furthermore, due to the similarity with existing, simpler flow cytometry platforms the BD FACSymphony A5 will make it easier for our current flow cytometry users to "scale-up" their existing panels compared to other new cytometric technologies (<em>e.g. </em>mass cytometry).</p>
|
| 04/07/2019 |
£333,750 |
|
UNIVERSITY COLLEGE LONDON |
<p>We seek funding for an array tomography scanning electron microscope (SEM) with ATLAS 5 software together with components to upgrade an associated light microscope, to enable 3D correlative light and electron microscopy (CLEM) of cells and tissues with nm resolution. Array tomography SEM allows for the detection, mapping and automated imaging of serial sections of resin embedded samples and is non-destructive technology. This technology is transformative and will enable high resolution 3D correlation of molecular machineries with cellular structure and specific cell and tissue processes. Using this new technology, our initial consortium of PIs will address the following specific objectives: </p>
<p style="margin-left: 0cm; margin-right: 0cm">1. To elucidate the mechanism of 3D patterning during organogenesis (Pichaud)</p>
<p style="margin-left: 0cm; margin-right: 0cm">2. To characterise the fundamental principle that regulate intracellular trafficking of cargoes and membrane, storage and lysosomal degradation (Brodsky, Futter and Schiavo)</p>
<p style="margin-left: 0cm; margin-right: 0cm">3. To determine the molecular basis for the interaction between the HIV virus and its host cells and tissues (Jolly and Marsh)</p>
<p>4. To elucidate the fundamental mechanisms of nuclear remodelling during passage through mitosis (Baum)<br>
<br>
5. To elucidate the connectivity underlying circuit function (Hausser and Wilson)</p>
<p>Altogether, our proposed studies will elucidate fundamental mechanisms of cell and tissue morphogenesis, homeostasis, function repair and infection.</p>
|
| 04/07/2019 |
£247,322 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">The requested Hamilton NGS Star automated liquid handling workstation enables high-throughput automated preparation of sequencing libraries which enables basic and clinical UCL researchers to process increasing sample numbers in a consistent, reproducible and timely manner. The proposed instrument and associated auxiliary equipment includes all the necessary hardware and software and is a fully walk-away system with a capability of processing up to 96 samples per run. Special features include air displacement pipetting using CO-RE (Compressed O-Ring Expansion) technology which provides superior measurement accuracy, precision and reproducibility without aerosol generation during pick-up and ejection, reducing the possibility of cross-contamination. Each aspirate and dispense step is dynamically tracked for confidence that the indexed and multiplexed samples are processed according to the workflow. The system also includes automated barcode reading to enable sample traceability, software with file handling capabilities and on-deck thermal cycling and cooling components for custom work flows to be fully automated. It is an open system which provides flexibility to customize workflows for specific NGS applications and develop new protocols and the scope to automate downstream processes on the same platform. The equipment will directly support £20M of Wellcome Trust-funded research through the generation of up to 15,000 NGS libraries.</p>
|
| 04/07/2019 |
£605,880 |
|
DIAMOND LIGHT SOURCE LTD |
<p>In this proposal we will enhance the robustness and usability of DIALS in synchrotron serial crystallography (SSX) and electron diffraction (ED) to help transition these fields from the domain of specialists into techniques easily accessible by all structural biologists. Building on recent scaling developments in DIALS, we will devise models that account for radiation damage and non-isomorphism between crystals based on prior knowledge from cluster-based methods and apply these to multicrystal and SSX data. Importantly, we will improve how unmerged data from scaling is best presented, without information loss, to downstream analysis for time-resolved, experimental phasing, molecular replacement and refinement applications. The integration of SSX data in DIALS will be further enhanced by implementing semi-empirical models of spot shape in reciprocal space to model pink-beam SSX data, building on the currently available pure physical models of reciprocal space spot shapes. For ED we will implement multicrystal and serial crystallography methods, in particular developing improved methods of indexing snapshot electron diffraction images. Finally, by analysing raw data streams in-memory we will address the technical challenge of providing real time feedback to users during serial crystallography experiments using the latest generation of detectors.</p>
|
| 04/07/2019 |
£451,991 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">Complex mathematical models are increasingly being used for research and decision making in academia, health and industry. However, the robust calibration and analysis of computationally intensive models is infeasible using currently accessible technologies, which limits the amount of information that can be extracted to inform decision making.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We have developed methods (history matching; HM) that can be used to robustly calibrate and analyse complex models, but implementation requires the full-time involvement of a trained statistician. The major hurdle preventing routine use of these methods by mathematical modelers is the lack of accessible and usable computer software to conduct the different components of HM, such as fitting emulators, drawing implausibility/optical density plots, and sampling designs for training points.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We will fill this technology gap by converting these specialist technologies into a comprehensive software package in R, accompanied by a series of ‘case studies’ demonstrating how these methods can be used by the academic, industry and health decision making communities. The technology will be created in a framework designed to sustain its use beyond the end of the project. This will improve the evidence available for academic, industry and health decision making communities; improve policy and practice; and, ultimately, save lives.</p>
|
| 04/07/2019 |
£1,000,000 |
|
UNIVERSITY OF DUNDEE |
<p style="margin-left: 0cm; margin-right: 0cm">The Jalview Resource is an open-source, GPL-licenced, graphical multiple sequence alignment editor and analysis workbench, first developed in 1996. It is installed on >57,000 computers in >130 countries and publications describing Jalview have been cited >5,600 times. In addition to sophisticated colouring, filtering, searching, alignment editing and annotation functions for DNA, RNA and Protein sequences, Jalview provides linked views of trees, three-dimensional structures and RNA secondary structure. Eight standard multiple alignment algorithms, four disorder predictors, seventeen conservation methods, the JPred protein secondary structure predictor and RNAalifold RNA structure predictor are freely available in Jalview. Users can interactively search PDBe and Uniprot, and retrieve alignments and genomic data from the Interpro and Ensembl data resources at the EMBL-EBI. Wellcome Trust investment since 2014 enabled improvements, including efficient handling of long genes with large numbers of annotations, a linked DNA/RNA/protein multiple alignment window, discovering and displaying genetic variation from Ensembl, extended querying against PDBe and Uniprot EMBL-EBI services and the development of >30 training videos that have received >50,000 views. Here we request support to extend the Jalview Resource to add sophisticated facilities for long RNA-read interpretation, reproducible data analysis, further links with EMBL-EBI, and a new web-friendly JavaScript version: JalviewJS.</p>
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| 04/07/2019 |
£616,706 |
|
UNIVERSITY OF EXETER |
<p style="margin-left: 0cm; margin-right: 0cm">We request funds to purchase an Illumina NovaSeq 6000 DNA Sequencing System. This will enable the University of Exeter to sequence DNA from humans and other species relevant to human health with the best possible efficiency, throughput, speed, and flexibility. Our current Illumina HiSeq 2500 system is approaching the end of its useful lifespan. Replacing it with the NovaSeq 6000 will reduce running costs by ~75%. Local accessibility to the most up-to-date DNA sequencing technology is critical to many researchers, especially those translating research into the NHS, and underpins several “flagship” Exeter research programmes.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The current equipment is routinely used by groups in the Medical School and Biosciences, and existing demand exceeds capacity. Local access to DNA sequencing has enabled Exeter researchers to drive world leading studies identifying the genetic basis of diseases including diabetes, obesity, dementia and schizophrenia, and enabled us to establish internationally-renowned projects in epigenomics and transcriptomics. The sequencer will be managed and operated as a Research Facility within the University, by an experienced sequencing team established more than 10 years ago, to provide a key resource for the biomedical research community in Exeter and beyond that is critical to our continued innovation and leadership in genomics.</p>
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| 04/07/2019 |
£808,928 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">As a result of a close collaboration with Thermo Fisher, and three visits to their factory in San Jose, modifications and designs have been iterated that have resulted in a modified Orbitrap Fusion Lumos tribrid mass spectrometer (MS). Critically this unique MS platform not only retains resolution at both high and low m/z ranges but also enables multiple rounds of tandem MS for state of the art lipidomics. Proof-of-principle data demonstrate that the instrument is capable of maintaining native membrane protein complexes and also, within the same experiment, characterising the lipids/ligands that regulate them. </p>
<p style="margin-left: 0cm; margin-right: 0cm">Our goals are to identify critical lipids/ligands through high resolution native MS of membrane protein assemblies as well as multiple rounds of MS/MS (MSn). Additional goals include developing fast fragmentation methods, such as UVPD, to define lipid binding sites within intact assemblies. Effectively this platform enables for the first time, top-down lipidomics directly from membrane protein assemblies. Importantly the direct link between the lipid and the parent protein-complex is maintained throughout the experiment providing a step change over current methods which involve separate lipid extraction and proteomics experiments. There is a high unmet need for this MS platform with multiple users and many exciting applications. </p>
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| 04/07/2019 |
£1,521,172 |
|
EUROPEAN BIOINFORMATICS INSTITUTE |
<p style="margin-left: 0in; margin-right: 0in">Drug discovery is a very challenging and expensive activity with a low success rate. Access to relevant, quality data is critical to enable the success of drug discovery projects which will deliver the new medicines that address unmet medical need. Large collections of data are also key to improving the overall drug discovery process, for example by developing computational models or understanding the causes of attrition. Traditionally, only those working in large pharmaceutical companies have had access to significant amounts of drug discovery data. That situation changed dramatically in 2008 when the Trust funded the development of the ChEMBL database as an open-access, public repository of data on bioactive molecules. This proposal aims to build upon the success of ChEMBL as a key community resource, with further goals of expanding our data coverage; improving the organisation of our data to ensure full FAIR compliance including improved disease annotations; enhanced data access via our web interface, workflows and tools; and improved sustainability of our infrastructure including a streamlined release process and open source software tools.</p>
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| 04/07/2019 |
£925,051 |
|
IMPERIAL COLLEGE LONDON |
<p>We are applying to support the enhancement, dissemination and application of the PhyreRisk/Phyre resource. PhyreRisk ( http://phyrerisk.bc.ic.ac.uk ) caters for researchers studying human genetic variation. Through PhyreRisk, a user can map DNA variants, from either genomic or proteomic coordinates, onto experimental and Phyre-predicted protein structures. The Phyre web-server (www.sbg.bio.ic.ac.uk/phyre2<u> </u>) is a widely-used (>90,000 distinct users in 2018) ELIXIR-UK resource to predict protein structure from sequence. Additionally, our program Missense3D (<u>http://www.sbg.bio.ic.ac.uk/~missense3d/</u> ) provides structure-based evidence for the effect of a missense variant.</p>
<p><br>
Funding will be used to develop the following new predictive features within Phyre for subsequent inclusion in PhyreRisk:<br>
(i) prediction of ligand/protein interactions,<br>
(ii) template-free tertiary structure prediction using contacts<br>
(iii) domain/domain packing.</p>
<p><br>
PhyreRisk will be markedly extended by:<br>
(i) increased structural coverage from Phyre and predicted complexes from our collaborator in Kansas<br>
(ii) enhancing Missense3D to include functional residues, protein/protein interactions and membrane-bound proteins to yield quantitative predictions<br>
(iii) the inclusion and subsequent analysis using Missense3D of genetic variants reported in major databases (e.g. gnomAD, ClinVar, COSMIC, Genomics England and UK-BioBank). <br>
(iv) linking PhyreRisk, particularly the structural data, to other resources including gnomAD.</p>
<p><br>
We will disseminate the resource via workshops, conference presentations and publications.</p>
|
| 04/07/2019 |
£1,200,000 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0cm; margin-right: 0cm">Because basic molecular mechanisms are shared universally, model organism databases are pivotal resources and drivers of research across species. We will enhance PomBase, the fission yeast model organism database, to place investigations using fission yeast in contexts that illuminate equivalent processes in other species, particularly human.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Through data stewardship, literature curation, and data integration, we will create emergent knowledge of eukaryotic cell biology, encompassing how proteins are connected into pathways, how pathways are connected to each other, what genes and pathways relate to human diseases, and what proteins remain unstudied across species.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We will develop generic open-source, modular, customisable tools to integrate diverse data types, thereby providing clear, user-responsive presentations of increasing volumes of complex data. We will continue to make substantial contributions to the development of shared infrastructures for semantic standardization of biology, supporting increased data propagation and re-use. We will engage closely with the research community through outreach activities.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our proposal addresses four interconnected key objectives:</p>
<p style="margin-left: 0cm; margin-right: 0cm">A1 Enabling fresh biological insights across organisms from quality-assured, standardised curation.</p>
<p style="margin-left: 0cm; margin-right: 0cm">A2 Improving core infrastructure and providing innovative tools.</p>
<p style="margin-left: 0cm; margin-right: 0cm">A3 Enhancing data acquisition, interoperability, and dissemination.</p>
<p style="margin-left: 0cm; margin-right: 0cm">A4 Increasing outreach, community curation and promoting the fission yeast model system.</p>
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| 04/07/2019 |
£1,200,000 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">Multilocus sequence typing (MLST) has been the principal approach to bacterial strain characterization for >20 years and is increasingly employed for whole genome sequence (WGS) analyses (whole genome and core-genome MLST). PubMLST (https://pubmlst.org) provides a major international resource for the storage, analysis, and dissemination of assembled microbial WGS data and hosts >100 databases that provide MLST nomenclature and link curated genetic, provenance, phenotype, and population data. The PubMLST resource, which has existed in various guises since 1998, operates from an Oxford-based web server and uses the open-source and open-access software platform BIGSdb, which was specifically developed for this purpose. PubMLST provides services to a wide variety of other resources, some of which employ the BIGSdb software. PubMLST also hosts the ribosomal MLST (rMLST) database, which enables bacterial species identification by cross-referencing >1.5M ribosomal allele sequences to a validated dataset of ~250,000 genomes representing 9500 bacterial species. Ongoing development of BIGSdb facilitates complex data querying and comparative analyses through a web interface. Data can also be retrieved and queried by other external (e.g. public health) databases via a programming interface. This application seeks to continue the operation and development of PubMLST, specifically enhancing the reuse of data is a major goal.</p>
|
| 18/06/2019 |
£145,832 |
|
CHARACTER COUNTS LTD. |
<p>Growing research from neuroscience and child development shows that significant gaps in children’s cognitive, social, and emotional development emerge in the first years of life, strongly influencing future mental health and educational outcomes (Marmot review into health inequalities, 2016). This makes parents and the home environment by far the most important influence on children’s development, and empowering parents a key priority for public health.</p>
<p>In 2015, we co-created ‘EasyPeasy’ with hundreds of parents from disadvantaged communities in south London through Guys & St Thomas’s & Design Council’s ‘Knee High Challenge’, generating ideas supporting the health and wellbeing of children from 2.5-5yo. Through collaborating with parents and experts we learned this scientific research hasn’t filtered into common knowledge, so we co-developed EasyPeasy to help parents understand the evidence base, and translate it into practical activities to support their child’s development.</p>
<p>In this project, we will work with parents to adapt and augment EasyPeasy for 0-2.5yo, co-creating new content with 20 families and then beta testing it with a larger group of 2,000 disadvantaged families. Our academic collaborator Professor Kathy Sylva (Oxford) will recruit experts to support with translation of research, and will embed learning and evaluation about our impact throughout.</p>
|
| 18/06/2019 |
£199,839 |
|
INFECTIOUS DISEASES INSTITUTE MAKERERE UNIVERSITY |
<p>We recently conducted a static exhibition entitled “Affected or Infected”: A History of HIV in Uganda at the Uganda National Museum, Kampala. The aim of the exhibition is to engage people in HIV response through reflection on the history of the HIV epidemic in Uganda, research undertaken, evolution in behavior change communication, and the journey towards scale-up of HIV treatment. Through stakeholder engagement we created an interactive exhibition that incorporated scientific papers, Information, Education and Communication materials, media outputs, paintings, sculpture, music, testimonies from survivors and leaders in the HIV response. It was visited by 2,202 people (40% aged<26 years), 377 were tested for HIV. For this grant we aim to produce a mobile exhibition that can be taken to six sites around Uganda and enriched with voices and content from a wider/more diverse demographic group. We will work with stakeholders to add content and local languages and then display in public places to encourage maximum visitors. We will specifically target and engage young people, who are at risk of HIV acquisition through community, school and religious groups. Free HIV counselling and testing services will be offered and those found to be HIV positive will be linked to care.<br>
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|
| 18/06/2019 |
£40,373 |
|
UNIVERSITY OF BRIGHTON |
<p style="margin-left: 0cm; margin-right: 0cm">Suicide is the single biggest killer of men aged under 45 in the UK, and young men are renowned for their reluctance to seek help and engage in traditional ‘talking’ therapies. The University of Brighton and Audioactive (a trusted grass roots music charity) are partnering to pilot this innovative health research project which will capture data from a demographic largely lost to standard forms of research. Over the course of a year, up to 30 young men from challenging circumstances aged 16 to 25 in East Sussex will work with professional rappers and spoken word artists to ‘get stuff off their chests’ in weekly workshops. Qualified support staff and researchers from the University will encourage the young men to co-produce a unique evaluative framework to enable the health data to be sensitively and creatively captured. The creative work produced from this will be showcased in public events at the end of the project. Presenting the research in creative forms such as an open-mic night aims to attract other young men in the same demographic, and engage them in thinking about their own well-being and how they could improve it. </p>
|
| 18/06/2019 |
£84,400 |
|
PODCAST AWARDS LTD |
<p>Using the reach and relationships of the British Podcast Awards, this is a scheme where podcasters can apply for small grants of between £3,000 and £7,000 to produce new, rigorous, health and science content that inspires their listeners to think differently. Concurrently, it will bring research practitioners into new environments, exposing them to different communities catered for by podcasters.</p>
<p>Podcasters will submit creative ideas for features and series to be a part of their existing podcasts. They will apply to the scheme with these ideas, alongside information about their podcast’s consumption and audiences. Our panel will review these applications and award up to ten grants of between £3,000 and £7,000.</p>
<p>Awarded podcasters will attend an immersion day to understand what is expected from them. They will then start by getting listeners to complete a pre-campaign questionnaire, whilst beginning their content creation. Mid-way through, we’ll work with them to feedback on their processes. After podcasting their series, listeners will complete a post-campaign questionnaire and our evaluation will continue.</p>
<p>Through the project we will have explored how small grants have benefited the podcasts, how listener thoughts and behaviour have changed and how researchers involved, have had their own understanding of audiences tested.</p>
|
| 18/06/2019 |
£86,456 |
|
UNIVERSITY OF SHEFFIELD |
<p>The process of deciding to give consent to the sharing and linking of our personal data for purposes beyond our direct care can be problematic for both patients and health professionals alike. The aim of our <strong>Tools for Life</strong> project is to engage patients in a participative process that a) understands the value, risks, and reasons that patients give for deciding whether or not to give their consent b) involves patients in the co-production of a set of publicly-accessible instruments for facilitating change in patient attitudes towards the sharing and linking of their personally-identifiable data i.e. a recorded theatre play, digital animation, information and advocacy tools iii) evaluates and tests the effectiveness of the instruments at Deliberation Days in the North and South of England. Our project involves patients, health and creative professionals, medical charities, and researchers in an effective collaboration seeking to facilitate and effect measurable change in patients’ attitudes towards to the sharing and linking of their personally-identifiable data. Via wide and visible dissemination of our tools, the project aims to empower patients to take informed and effective decisions about how the sharing and linking of personally-identifiable data can lead to improving public health.</p>
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| 18/06/2019 |
£98,343 |
|
GROUNDSWELL |
<p style="margin-left: 0cm; margin-right: 0cm">We are seeking to engage homeless people, NHS staff and homelessness support staff in health research to increase understanding of homeless health inequalities. This will be achieved through peer led health research on the experiences homeless people have when engaging with the healthcare system. Research will include collation of existing health research as well as focus groups in major UK cities to ensure good representation.</p>
<p style="margin-left: 0cm; margin-right: 0cm"> We will create a film to portray homeless people’s experiences within health, using humanity to engage people in health research. The film will be ‘toured’ at homelessness services in major UK cities with the aim of increasing understanding to trigger behavioural and systems change. Each screening will have a panel made up of people with lived experience, homeless and health professionals to encourage engagement and focus on solutions for change. Evaluation will measure people’s experiences and understanding of homeless health both before and after viewing with the goal of seeing how engagement will lead to change.</p>
|
| 18/06/2019 |
£110,000 |
|
ROLLING MARBLE |
<p><strong>'Locked-In' will be the first-ever long-form documentary that explores the neurological illness, Guillain-Barre Syndrome directed by a BAFTA nominated fimmaker who lives with a chronic form of the condition.</strong></p>
<p>Previously thought of as rare, it's now estimated that 1 in 1000 of us are likely to be affected by GBS in our lifetime. Yet the disease remains relatively unknown, despite having such a devastating impact on lives - at its nadir patients become so paralysed they are locked-in. Commissioned by BBC Storyville, the BBC's renowned international documentary strand, and with funding in place from the BFI, Locked-In will reach over 1 million viewers in its first year in the UK (and more if shown abroad). In addition there will be a targeted cinema release aimed at key, relevant medical and patient communities.</p>
<p>'Locked-In' will give a voice to people affected by and living with GBS. Elevating GBS into the public consciousness and empowering patients, it will give credence to their illness and help reveal the physical and psychological impact of living with it. We are working alongside key medical experts, at the frontline of GBS treatment and research to ensure that 'Locked-In' will show the urgent need for further research.</p>
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| 18/06/2019 |
£524,659 |
|
THE LIMINAL SPACE |
<p style="margin-left: 0cm; margin-right: 0cm">In 2018, The Liminal Space (LS) developed partnerships with industry and researchers to deliver <em>Night Club -</em> a unique interactive installation that engaged and empowered Co-Op's hard-to-reach night-shift workers on the economically and socially important topic of sleep health. 85% of the 150 workers reported learning useful new health information, and <em>Night Club</em> demonstrated a novel people-centered approach to health research.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><br>
As a result, Co-op reviewed their internal practices and Wellcome funded LS to scope how the project could be scaled-up and sustained. LS now proposes Night Club 2 to:<br>
1) establish a sustainable co-funding model for industry, academic and public engagement partnerships that deliver meaningful improvement for disadvantaged workers, whilst advancing academic research and industry practice.<br>
2) extend the impact of Night Club directly to 2,600 night-shift workers, reaching a minimum of 7,000 more workers through our cascading/dissemination tools and methods</p>
<p><br>
LS have already gained commitment from Co-op, John Lewis, and Thames Water to provide time, money, and Board-level support to deliver Night Club 2. We will also collaborate with leading sleep researchers to co-develop methods for embedding their research in future public engagement initiatives with an aim to improve wellbeing across the UK workforce through evidence-based practice change.</p>
|
| 18/06/2019 |
£260,000 |
|
INTERNATIONAL DOCUMENTARY FESTIVAL SHEFFIELD |
<p>The Exchange programme will bring together story forms across film, immersive content and debate on the theme of exploring a healthy planet. The Exchange will be free and open to all audiences, running in Sheffield in June 2019 and 2020, with an Exchange highlights programme tour taking place across three sites in Yorkshire, focusing on low-socio economic areas. Building on the impact of previous editions, we have set ambitious targets for maximum audience diveristy, and plan to expand successful audience initiatives, as well as develop new initiatives with the support of an audience development strategist. There will be a key focus on partnership development to ensure programme sustainability and impact. Broading the Exchange theme will enable us to tap into a diverse range of researchers spanning multiple disciplines. Research to be at the heart of the Exchange programme, as we will engage with health researchers, innovators and NGOs involved in the cultural sector producing relevant content. We will work with young programmers to curate a short film programme and create more video content to be live streamed across social media channels for greater digital presence and to grow younger audiences.</p>
|
| 18/06/2019 |
£728,291 |
|
LIVERPOOL SCHOOL OF TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm">One million people died of HIV in 2017 and an estimated 160 million Africans had active schistosomiasis, a cause of male and female genital lesions likely to increase risk and transmission of HIV. Control of both HIV and schistosomiasis relies mainly on treatment of active disease, with prior diagnosis essential for HIV but not schistosomiasis. For HIV, ~25% remains undiagnosed, concentrated in hard-to-reach groups, including men.<br>
<br>
Here I propose to adapt my previously successful secondary-distribution model for oral HIV self-test kits to pilot and trial peer-based approaches to increasing HIV testing care and prevention by fishermen, while also promoting presumptive praziquantel treatment for schistosomiasis. Both schistosomiasis (<em>S. haematobium</em>) and HIV are highly prevalent and poorly-controlled in fishing communities throughout Africa. The need to include adults in mass drug administration campaigns is recognised, but not yet well implemented, and likely to need different approaches for men and women. </p>
<p style="margin-left: 0cm; margin-right: 0cm">I will also use this opportunity to investigate how effectively peer-delivered strategies penetrate social and sexual networks, and to develop my skills in quantitative social network analysis and health economics modelling. Formative work will include exploring social networks before the trial allowing me to spend part of my first year developing methodologies.</p>
|
| 18/06/2019 |
£642,424 |
|
UNIVERSITY OF OXFORD |
<p>Melioidosis is a rapidly progressing and frequently fatal disease caused by a soil bacterium <em>Burkholderia pseudomallei </em>(Bp). Healthy individuals living in disease hotspots such as northeast Thailand develop serological evidence of exposure from early childhood. However, not all exposure leads to disease and infections can have variable outcomes, suggesting that there may be bacterial, host or environmental components that influence disease acquisition and severity. Our goals are: i) identify Bp genetic factors that determine disease severity; ii) identify host biomarkers associated with susceptibility to melioidosis and disease severity; and iii) construct models scoring Bp and host factors to predict disease outcome. As diabetes mellitus is a major predisposing risk factor for melioidosis, we will also test whether the factors in i) - ii) are modulated by host diabetic status. Building upon our previous collections, I propose to additionally collect and sequence or genotype 2,000 bacterial and 1,500 host samples. Studies of genome-wide association (GWAS), differential expression, and expression quantitative trait loci (eQTL), each of which will be conditioned on host diabetic status, will be performed to address aims i)-iii). A dual understanding of Bp and host factors leading to poor melioidosis outcomes could improve our ability to manage this disease.</p>
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| 18/06/2019 |
£215,699 |
|
WELLCOME TRUST SANGER INSTITUTE |
<p>Melioidosis is a rapidly progressing and frequently fatal disease caused by a soil bacterium <em>Burkholderia pseudomallei </em>(Bp). Healthy individuals living in disease hotspots such as northeast Thailand develop serological evidence of exposure from early childhood. However, not all exposure leads to disease and infections can have variable outcomes, suggesting that there may be bacterial, host or environmental components that influence disease acquisition and severity. Our goals are: i) identify Bp genetic factors that determine disease severity; ii) identify host biomarkers associated with susceptibility to melioidosis and disease severity; and iii) construct models scoring Bp and host factors to predict disease outcome. As diabetes mellitus is a major predisposing risk factor for melioidosis, we will also test whether the factors in i) - ii) are modulated by host diabetic status. Building upon our previous collections, I propose to additionally collect and sequence or genotype 2,000 bacterial and 1,500 host samples. Studies of genome-wide association (GWAS), differential expression, and expression quantitative trait loci (eQTL), each of which will be conditioned on host diabetic status, will be performed to address aims i)-iii). A dual understanding of Bp and host factors leading to poor melioidosis outcomes could improve our ability to manage this disease.</p>
|
| 18/06/2019 |
£304,066 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p>Most of our current understanding of the aetiological drivers, resultant phenotypes and treatment approaches of hypertension in native Africans are derived from studies in diaspora Africans. This is despite some evidence that the clinical manifestation of hypertension in native Africans differ from classical findings described elsewhere. The overall goal of this fellowship is to help decrease the substantial hypertension burden in sub-Saharan Africa. I will first use data from The Gambia National Eye Health Survey 2019 (GNEHS2019) to describe the prevalence of hypertension, its associated risk factors and comorbidities as well as demographic and socio-economic correlates. A sample of 500 individuals with hypertension as found in the GNEHS2019 with their age and sex-matched local controls will be re-examined to investigate the accuracy of using survey blood pressure measurements to classify individuals by hypertension status. I will then combine socio-demographic, clinical, laboratory, ECG, echocardiography and vascular function studies to explore whether hypertension phenotypes cluster into identifiable sub-groups that would better characterise the possible mechanism(s) of their hypertension. I will also investigate the burden, characteristics and associated factors of hypertension-mediated organ damage. Finally, I will validate the potential for AI-enabled ECG to screen for cardiac contractile dysfunction in low resource settings. </p>
|
| 18/06/2019 |
£343,006 |
|
IFAKARA HEALTH INSTITUTE |
<p style="margin-left: 0cm; margin-right: 0cm">Malaria burden in Tanzania has significantly declined following scale-up of long-lasting insecticide treated nets (LLINs)<sup>6</sup>. In some areas such as rural south-eastern Tanzania, <em>Anopheles gambiae</em> s.s, which was previously the number one vector has also disappeared under the intervention pressures. Unfortunately, a different vector species, <em>An. funestus</em> persists and now mediate >85% of ongoing malaria transmission despite their low densities<sup>2</sup>. These mosquitoes are also resistant to pyrethroids used on LLINs<sup>2,7</sup>, and require alternative control strategies.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Greater understanding of ecology of <em>An. funestus</em> will offer additional opportunities to achieve malaria elimination<sup>8</sup>. Swarming and mating behaviours, though often neglected, are particularly crucial. For the first time in Tanzania, our research has recently revealed that <em>An. funestus</em> (and <em>Anopheles arabiensis</em>) mate in swarms, which occur repeatedly in same locations and same time each day<sup>3,5</sup>. Targeting these behaviours may provide new opportunities to crash vector populations and drastically reduce malaria in areas where LLINs have achieved significant reductions but low-level transmission persists. Indeed, studies in Burkina-Faso have provided evidence that targeting swarms can reduce vector population by 80%<sup>9</sup>.</p>
<p style="margin-left: 0cm; margin-right: 0cm">I propose to demonstrate that <em>An. funestus</em> swarms can be identified, characterized and targeted for control with help from trained community members in selected Tanzanian villages.</p>
|
| 18/06/2019 |
£318,672 |
|
SEAMEO RECFON |
<p>A double-blind two-phase cluster randomized controlled trial will be conducted in West Java, Indonesia. Total 308 pregnant women will be recruited from 28 clusters (villages) in Sumedang district. Women who fulfil trial criteria will be randomly selected and invited into the trial. Clusters will be randomly assigned to receive placebo or micronutrient-enriched crackers (MEC) daily, distributed by cadres from 14 weeks to 5 months post-partum. Placebo and intervention crackers (recipe developed from chicken liver and eggshell by Food Scientists at University of Otago and pre-tested for acceptability) will be manufactured locally so they are identical in size, colour, and packaging, with a code known only by the local production manager who will not share the code until the primary outcome has been analysed statistically. Primary outcomes will be birth length and infant linear growth (attained and incremental). Secondary outcomes will be: (a) birth weight; (b) maternal haemoglobin at 37 weeks gestation; (c) volume and breastmilk micronutrient concentrations at 5 months post-partum; (d) maternal dietary intakes at 37 weeks and 5 months post-partum; (e) maternal micronutrient status at 37 weeks and 5 months post-partum; (f) micronutrient status of breastfeeding infants at aged 5 months. Analysis will be by intention to treat.</p>
|
| 18/06/2019 |
£299,706 |
|
KEMRI-WELLCOME TRUST RESEARCH PROGRAMME |
<p style="margin-left: 0in; margin-right: 0in">Recent high throughput studies have identified multiple human genetic polymorphisms associated with strong protection against severe and complicated <em>Plasmodium falciparum</em> malaria. Most of these are found in or near genes that are important for the structure and function of red blood cells (RBCs), the primary host cell for <em>P. falciparum</em> parasites in humans. Of particular interest is a novel structural polymorphism in the glycophorin (GYP) locus, a <em>GYPA</em> and <em>GYPB</em> gene rearrangement resulting in a hybrid gene encoding the Dantu blood group. Dantu is found at highest frequency on the East African coast of Kenya. Given the important functional role of the GYP proteins in the invasion of <em>P. falciparum </em>parasites into RBCs, and the strong protective effect of Dantu against severe malaria, developing a full understanding of the protective mechanism might enable the development of new interventions that inhibit invasion. Over the last two years I have established that Dantu impedes parasite invasion by impacting the RBC biophysical properties. I propose to elucidate the molecular mechanisms through which this is achieved, how <em>P. falciparum</em> adapts to the changing RBC environment, and the wider health consequences of Dantu that have driven its selection in East Africa.</p>
|
| 18/06/2019 |
£186,305 |
|
UNIVERSITY OF OXFORD |
<p>Antibiotic resistance is a major public health threat, mainly driven by (over)use of antibiotics, particularly in low- and middle-income countries (LMICs). In this fellowship I will evaluate the impact and cost-effectiveness of antibiotic stewardship programs (ASPs) in reducing the amount of inappropriate antibiotic use, improving patient outcomes and decreasing resistance levels in hospitals in Vietnam. Firstly, I will assess the impact of ASPs using an interrupted times-series design in three hospitals that have implemented the programme, using data on antibiotic use, mortality and resistance levels in 12 months before and after intervention. Secondly, I will collect the costs of implementing ASPs using the “time-driven activity-based costing” method. Both data on the actual impact and costs of the programme will be used to inform the economic evaluation model to identify under what circumstances ASPs are cost-effective in Vietnam. Finally, I will analyse existing datasets from the national resistance surveillance network to characterise trends, patterns and associations of antibiotic use and resistance in hospitals. This will provide a background understanding of antibiotic use and resistance and identify the possibilities for using surveillance data to inform the design and implementation of ASPs in Vietnam and other LMICs.<br>
</p>
|
| 12/06/2019 |
£1,211,464 |
|
UNIVERSITY OF MANCHESTER |
<p>Antibiotic resistance is one of the biggest public health challenges, causing over a million deaths annually. In order to slow down the emergence of resistance, there is a critical need for predictive approaches grounded in experiment. Knowing the effects of mutations and interactions between them (epistasis) is critical for predicting outcomes of selection. Unlike most studies, which are limited to <em>describing</em> these phenomena, my research aims to provide a <em>causal</em> understanding of how existing molecular mechanisms define the effects of mutations and epistasis. Without such causal understanding, predicting evolution is limited to those systems that have been fully experimentally characterized. My goal is to provide the first mechanistic genotype-phenotype map for two regulatory systems consisting of a protein and its DNA-binding site. Doing so would dramatically improve our ability to predict evolutionary outcomes for one of the major forms of resistance (multi-drug resistance through changes in transcriptional regulation of AcrAB-TolC efflux pump) by allowing predictions of DMEs and epistasis without the need to fully experimentally characterize them first. Being able to <strong>predict multiple antibiotic resistance evolution from first principles</strong>, before any patients take the drug, would improve treatment strategies, while also enabling better evaluations of novel drugs during their development.<br>
</p>
|
| 12/06/2019 |
£909,233 |
|
IMPERIAL COLLEGE LONDON |
<p>I aim to identify the mechanisms driving the emergence of enterovirus serotypes as a new cause of disease and their spatio-temporal patterns of spread using multiple data streams and mathematical and statistical models.</p>
<p>First, I will study the extent to which serotype-specific immunity explains the cyclical incidence of enteroviruses causing hand-foot-and-mouth disease, both by fitting transmission models to incidence data and exploring correlations with estimates of population immunity from serosurveys. Second, using cross-sectional seroprevalence and virus sequence data I will explore how gaps in population immunity and virus genotypic and phenotypic changes have led to the recent emergence of two new serotypes causing diseases (EV-D68 and CV-A6) following periods of low incidence of cases. Third, using phylogenetic and phylogeographic methods, I will characterise the geographical range of spread and global and regional patterns of viral movement of the three currently most important serotypes (EV-A71, EV-D68 and CV-A6), and I will explore how human mobility and other predictors drive these spatial patterns.</p>
<p>Understanding the mechanisms underlying the epidemiological dynamics of enteroviruses will help prioritise strategies to mitigate the morbidity associated to these infections by informing the serotypes that should be targeted by future vaccines, and optimise outbreak control and vaccination strategies.</p>
|
| 12/06/2019 |
£1,110,946 |
|
UNIVERSITY OF SHEFFIELD |
<p>In biomedical science, there is a growing realisation that the mechanisms of ageing underlie many major debilitating age-related diseases. Interventions in the ageing process therefore have the potential to make an immense impact on our healthspan. The most potent of these interventions is dietary restriction (DR) – decreasing dietary intake but avoiding malnutrition. Translation of DR to humans is impeded by our lack of knowledge on exact mechanisms and the optimal diet. DR is thought to result from a reduced intake of the macronutrient protein. Recent data in from my lab, however, suggests that restriction of micronutrients results in similar benefits to healthspan. I propose that by studying the restriction of micronutrients, translation is facilitated and more specific insight into mechanism is gained, as it provides a more precise intervention. I will elucidate the mechanisms of how dietary micronutrients affect ageing and disease using a systematic and comprehensive research program using the fly. I will screen for micronutrients that improve health and will test specific mechanisms based on my previous work connecting phosphate, copper and mitochondrial oxidative stress. Work in two disease models will complement these approaches, together providing key novel insight into the connections between diet, disease and ageing.</p>
|
| 12/06/2019 |
£1,464,550 |
|
BIRKBECK UNIVERSITY OF LONDON |
<p>Reactive oxygen species (ROS) are obligatory by-products of aerobic living conditions and important signalling molecules. Excessive amounts of ROS can be deleterious for cells: they can damage proteins, membranes and the DNA. They are the cause and consequence of multiple human diseases. Complex pathways have evolved to maintain the redox balance and, if necessary, trigger apoptosis to protect cells from damage accumulation.</p>
<p><br>
Despite their importance in human health and disease, the molecular mechanisms of ROS-regulated gene expression and cell survival decisions under oxidative conditions are poorly understood, with several key questions remaining. What are the molecular mechanisms underlying redox stress response in higher eukaryotes? What are the safety mechanisms that protect cells from thriving under oxidative stress and how are these mechanisms hijacked in pathological conditions? To answer these questions, I will elucidate the key steps in the redox stress response using a combination of biophysical and structural techniques. This work will focus on: i) the regulation of the major transcription factor implicated in the redox stress response; ii) the activation of the detoxification machinery; iii) the safety mechanisms that govern cell fate under oxidative stress.</p>
|
| 12/06/2019 |
£1,289,212 |
|
UNIVERSITY OF BRISTOL |
<p style="margin-left: 0cm; margin-right: 0cm"> Darwin was among the first to propose that animals probably use self-motion cues when navigating in featureless environments, a mode of navigation known as path integration. While an extensive literature supports the role of path integration in navigation, the cellular and circuit algorithms of this process remain unmapped. Such knowledge is critical for understanding one of the most fundamental features of our brain: representation of 'self' and 'surround'. </p>
<p style="margin-left: 0cm; margin-right: 0cm"> I will use a genetic screen in Drosophila to identify the neural circuit of path integration and characterise how the central complex neurons integrate self-motion cues. I will then test how olfactory and motion information streams are combined during olfactory navigation. Finally, I want to check whether transcription factors like FoxP act as 'behavioural toolkit' genes, subserving general roles in processes requiring that information is integrated at seconds to minutes timescales. I will address these questions in Drosophila using a combination of genetic screens, behavioural assays, functional imaging under virtual reality arena, whole-cell recordings and transcriptional profiling. My work will shed light on the neural basis of the 'sense of direction' and contribute to the wider questions of sensory coding and temporal integration.</p>
|
| 12/06/2019 |
£771,226 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0in; margin-right: 0in">For biological organisms, practice improves performance on any given task. Ultimately these behavioral improvements must be traceable to some change in the neuronal networks of the brain. Crossing these scales—linking learning to its neural basis—is a critical challenge facing theories of brain function. What changes at the neural level enable these behavioral improvements at the psychological level? And what principles govern the dynamics of the learning process? The goal of this project is to use mathematical analyses to develop a fundamental understanding of learning dynamics in artificial deep neural networks; to exploit this understanding to make testable predictions for experiments in psychology and neuroscience; and to critically test these hypotheses through close collaboration with experimental groups. This theory-experiment loop will help identify computational principles governing learning in the brain and mind. The proposal focuses on the dynamics of learning in complexly interconnected networks of brain areas; in settings where new knowledge must be incorporated alongside old (continual learning); and where there are nonlinear interactions between inputs and context. This research will furnish a new analytical toolkit for studying learning in neural networks, enabling a better understanding of how experience structures neural representations, and improved algorithms for artificial systems.</p>
|
| 12/06/2019 |
£1,105,056 |
|
KING'S COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">A key area of current immunological research are the mechanisms that control and adjust inflammation. In my previous work, I discovered an important role for neutrophil reactive oxygen species (ROS) localisation in tailoring inflammation to microbe size during bacterial and fungal lung infections: ROS suppressed cytokine production and immune cell recruitment in response to small pathogens. I plan to extend this work by studying <strong>ROS localisation in response to viral infection<em> </em></strong>and its impact on antiviral inflammation.<br>
In preliminary experiments, I observed that ROS are detrimental during influenza infection. Mice lacking ROS-producing NADPH oxidase Nox2 have a reduced viral load early after inoculation, increased numbers of lung-infiltrating immune cells and higher levels of proinflammatory cytokines, while the amount of type I and III interferons is reduced. The localisation of ROS during influenza infection is unknown. Neutrophils, major ROS-producing phagocytes, are recruited in great numbers during influenza infection. By elucidating ROS localisation and studying influenza infection in neutrophil-specific Nox2-deficient mice I will uncover ROS-affected signalling pathways and thus reveal <strong>how ROS control antiviral inflammation and virus clearance</strong>. Prospectively, these studies will enable the design of immunomodulators that control excessive immune responses and provide new avenues for the treatment of inflammatory diseases.</p>
|
| 12/06/2019 |
£1,066,222 |
|
UNIVERSITY OF CAMBRIDGE |
<p style="margin-left: 0cm; margin-right: 0cm">Peptide-loaded MHC-II (pMHC-II) is presented at the surface of antigen presenting cells and it has historically been assumed that pMHC-II is localised on the plasma membrane. However, immunofluorescence data reveals pMHC-II localised to patches rather than uniformly distributed. The loading of peptide onto MHC-II occurs within MVBs, specifically on ILVs. In order for pMHC-II to be subsequently incorporated into the plasma membrane, ILVs would be required to ‘back-fuse’ with the limiting membrane of the MVB. This back-fusion step represents an ambiguous fusion event. I have recently shown that exosomes can be physically tethered to the cell surface by tetherin. Tetherin is highly expressed in antigen presenting cells and these cells display clusters of exosomes at their surface. Using biochemistry, immuno-electron microscopy and functional assays I wish to test the hypothesis that surface-tethered exosomes present pMHC-II at the surface of antigen presenting cells.</p>
<p style="margin-left: 0cm; margin-right: 0cm">I will establish the molecular machinery which traffics tetherin to ILVs/exosomes, and define the residues on tetherin that are required for this trafficking. Finally, I will explore where and how exosomes fuse to recipient cells, and use a screening approach to identify molecules involved in exosomes – plasma membrane fusion.</p>
|
| 12/06/2019 |
£687,294 |
|
UNIVERSITY OF WARWICK |
<p><em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) is the causative agent of tuberculosis (TB) and is now the leading cause of death from a single infectious agent in the world, killing more people world-wide than HIV and malaria. With the escalation of drug-resistant TB infections we urgently need to develop novel strategies and interventions to control the growing TB global epidemic. To enable this, we need a more detailed understanding of the fundamental biology of <em>Mtb</em>. <em>Mtb</em> is an unusual pathogen that has the exceptional ability to survive within the human host for decades. However the energy sources that <em>Mtb</em> uses within this nutrient-poor environment and the mechanisms involved in their transport are poorly understood. The overarching aim of this project is to use a multidisciplinary approach combining chemistry, biochemistry and microbiology to determine i) which carbohydrates are (re)used by <em>Mtb</em>, ii) how they are (re)used and iii) the molecular mechanisms involved in these processes. This project will provide key insights into carbohydrate uptake/recycling and metabolism by <em>Mtb</em> and assign physiological function to the proteins involved. Altogether, these results will generate important mechanistic insights into the survival of this global pathogen and validate whether these pathways represent therapeutic/diagnostic targets.<br>
</p>
|
| 12/06/2019 |
£705,913 |
|
UNIVERSITY OF SUSSEX |
<p style="margin-left: 0cm; margin-right: 0cm">Chromosome segregation is essential for the accurate transmission of genetic material but is also a vulnerable process that can introduce genome instability. To segregate chromosomes perfectly, sister chromatids need to remain cohesed by the cohesin complex until stable spindle-kinetochore attachments are formed at the centromere to complete chromosome biorientation. Emerging evidence shows that to accurately disjoin sister chromatids following cohesin cleavage, cells require a specific chromatin modifying machinery comprising the PICH DNA translocase and the BLM helicase plus its partners. This complex resolves sister-DNA intertwinements that manifest as ultrafine DNA bridges (UFBs) in anaphase. Recently, we discovered that this machinery (named the UFB-complex) possesses a dechromatinisation activity that, when a key mitotic kinase, Polo-like kinase 1 (PLK1) is inactivated, can rupture centromeres during chromosome biorientation in metaphase. Since the UFB-complex is proposed to function during sister-chromatid disjunction, our findings imply that the UFB-complex is highly controlled to ensure centromere integrity throughout mitosis. In this proposal, I aim to elucidate the novel centromere-protection function of PLK1, particularly how it regulates the UFB-complex during mitosis. Additionally, I will investigate how the centromere damage caused by UFB-complex malfunction drives the evolution of whole-chromosome arm rearrangements and cellular transformation.<br>
</p>
|
| 12/06/2019 |
£711,403 |
|
IMPERIAL COLLEGE LONDON |
<p>Population genomics demonstrates many bacterial species are subdivided into distinct strains, changes in the prevalence of which are the primary drivers of many clinically-important trends, such as the global spread of multidrug-resistance and the emergence of vaccine-evading pathogens. During my fellowship, I have developed models of the evolutionary and epidemiological dynamics of <em>Streptococcus pneumoniae</em><em> </em>that presume they are driven by intragenomic conflict and competition between phenotypically-distinct strains. This extension will test these assumptions through experimental characterisation of clinical isolates and mutant genotypes, and panprotome-wide immunological data. The models’ applicability to two other naturally transformable respiratory pathogens, <em>Haemophilus influenzae</em> and <em>Moraxella catarrhalis</em>, will also be evaluated. Genome sequencing of isolates from systematic nasopharyngeal carriage surveys from two locations will enable comparisons with equivalent <em>S. pneumoniae</em> samples. Despite isolation from the same niche, these species vary in their population structure, antibiotic resistance profiles and responses to vaccination. Experiments and bioinformatic analyses will address whether this divergence is primarily driven by differences in recombination, epidemiology or ecology. These results will be used to improve models that explain the distribution of antibiotic resistance and post-vaccine changes in disease, with the aim of generating validated frameworks for aiding public health policy decisions using genomic data.</p>
|
| 12/06/2019 |
£572,964 |
|
UNIVERSITY OF OXFORD |
<p>Stroke recovery is a significant, largely unmet, clinical need. Novel therapies are urgently needed but the neurophysiological changes which underpin behavioural improvements are incompletely understood, making developing new approaches impossible. Here, I propose experiments in both rodents and humans to examine the neurophysiology of healthy motor plasticity as a model for stroke recovery. <br>
<br>
Decreases in local inhibition have been demonstrated during motor plasticity, and these have been related to the increases in network-level connectivity supporting motor improvements. However, the mechanism by this occurs is not clear. I will test the hypothesis that γ-activity is the linking mechanism and further that driving this emergent property is a powerful, specific method to improve motor learning in humans.<br>
<br>
The work has two aims: (1) to understand how the relationships between neurochemicals, γ-activity and functional connectivity are modulated to support functional improvements during human motor learning and (2) to exploit the cell-type and layer specificity afforded by mouse models to investigate the basis of γ-activity. This cross-species work will provide evidence necessary to develop novel adjunct therapies for stroke recovery, and position me strongly for my long-term aim of developing a cross-species platform to answer fundamental questions around the physiological changes during motor plasticity. <br>
</p>
|
| 12/06/2019 |
£1,019,605 |
|
UNIVERSITY COLLEGE LONDON |
<p>While we can deploy auditory spatial attention independently of gaze direction, we typically look at sound sources of interest. Our recent research suggests that when human listeners can see a visual stimulus whose size changes in time with amplitude changes of a sound source, this sound becomes easier to separate from competing sounds. Furthermore, listeners are more sensitive to changes in features of the sound that are not predicted by the visual stimulus, such as its timbre or pitch, suggesting that the visual and auditory streams are bound into an audiovisual object. We observed neural correlates of this effect in auditory cortex of ferrets, and identified a specific visual cortical field as providing critical input to auditory cortex. Here, we will address outstanding questions: Firstly, we will record neural activity simultaneously across multiple auditory cortical fields and the visual cortical fields that innervate them while ferrets perform the behavioural task our human listeners performed. I hypothesise that functional connectivity between early auditory and visual cortex is critical for audiovisual binding. Secondly, we will develop optogenetic approaches in the ferret animal model in order to dissect the neural circuit that underlies the integration of visual information in auditory cortex.<br>
</p>
|
| 11/06/2019 |
£13,435 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">My proposed secondment project will assess the situation and understanding of mental health in OECD countries. Health systems have not yet adequately responded to the burden of mental disorders, resulting in a wide gap between the need for treatment and its provision. The key goals are to: (1) summarise the different methods of measuring mental health across the 36 OECD member countries; (2) understand the drivers and social determinants of mental health over the life cycle, including prenatal, early years, working age and older age; (3) explore the poorly understood relationship between mental health and subjective wellbeing; (4) explore different treatment methods for mental health, both at the micro level including therapy, medication, and complementary and alternative therapies, and at the macro level including mental health resources, policies, programs and interventions available in OECD countries. </p>
<p style="margin-left: 0cm; margin-right: 0cm">This project will provide the most up to date and reliable qualitative and quantitative evidence on what is currently known about mental health and ways to effectively tackle its increasing burden. This will provide cross-country learning and sharing of best practices between OECD members and will be extremely useful to inform policy-making around the world.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Key words: mental health, determinants, measurements, treatments, well-being</p>
|
| 11/06/2019 |
£29,500 |
|
UNIVERSITY OF OXFORD |
<p>Uncertainty about causes of death and unregistered mortality patterns in low-middle income countries (LMICs) are limitations to planning and evaluation of health programmes. Funding bodies such as the Gates Foundation have advocated Minimally Invasive Autopsy (MIA) to address these important kinds of uncertainty and to minimise sensitivities. MIA involves using hollow needles to sample a number of organs without actually having to open the deceased body - as a possibly more acceptable alternative and less invasive to full autopsy.<br>
<br>
The conduct of MIA in practice presents a number of ethical and social challenges. While the global development and introduction of MIA is growing, little attention has been paid to these problems or to the development of global ethical norms. The World Health Organisation (WHO) – a key international actor in the context of global health - is particularly well placed to form global ethical norms on MIA.<br>
<br>
The aim of my project is to provide an overview of key ethical issues associated with designing and deploying MIA globally. I intend to develop a preparatory document for a WHO consultation meeting on establishing global ethical norms, with the aim to inform the development of MIA guideline.<br>
<br>
<strong>minimally invasive autopsy, ethics, WHO</strong><br>
</p>
|
| 11/06/2019 |
£19,249 |
|
GLASGOW CALEDONIAN UNIVERSITY |
<p style="margin-left: 0cm; margin-right: 0cm">The World Health Organisation (WHO) advocates the development of health policies on the basis of the best possible evidence. In addition to health data, the experience of policy-makers and peer-reviewed research, one of those sources of evidence is the views of citizens. A wide range of approaches to gathering and representing such views have been adopted across the world, integrating individuals and communities into the design and implementation of health policy through processes of ‘citizen engagement’.</p>
<p style="margin-left: 0cm; margin-right: 0cm">However, there is no comprehensive understanding of the nature and diversity of different citizen engagement mechanisms, and in what circumstances they may be best applied, with a recognition that the success of such initiatives is highly context-specific. This lack of understanding holds back efforts to advocate for, and operationalise, particular citizen engagement approaches within evidence-informed health policy-making in Europe.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The proposed project would review current approaches to citizen engagement in evidence-informed policy-making across the world, assessing context-specific considerations, examples of best practice and practical guidance on how they could be integrated within state structures. The findings of this work will contribute to the development of a strategy for citizen engagement in health policy-making, to be adopted by the Evidence-Informed Policy Network (EVIPNet) Europe.</p>
|
| 11/06/2019 |
£17,749 |
|
UNIVERSITY OF GLASGOW |
<p>An evidence brief for policy would be developed for country teams/Emergency Division working in concert with EVIPNet.</p>
<p>Following identification of health priority issues, the project would: </p>
<p>* develop searchable research questions and search strategies. Evidence will be retrieved, mapped and appraised for quality, and examined for local applicability. In this way the project will be fully relevant to local contexts and support the WHO values capacity building and empowerment.</p>
<p>* deliver a summary of packaged, relevant information i.e. an evidence brief for policy, to frame the policy priority issues, outline the evidence and the important governance, financial and delivery considerations. </p>
<p>* convene a deliberative dialogue for a fully collaborative process. </p>
<p>* support policy choice and implementation. </p>
<p>* allow for monitoring and evaluation. </p>
<p> </p>
<p> </p>
<p> </p>
|
| 11/06/2019 |
£28,796 |
|
UNIVERSITY OF EXETER |
<p style="margin-left: 0cm; margin-right: 0cm">This project considers the photographic practice of three contemporary artists who produce photograms, intimate close-ups of the natural world, asking: how do these artists portray humanity’s relationship with and responsibility for nature in the age of the Anthropocene? I will be working with a selection of material from the V&A Photography Collection to investigate the contemporary resonances of (and historical references to) the Victorian cyanotype photograms of Anna Atkins’, who pioneered nature photography in 1854. In particular, I will be looking at photograms produced by Barbara Baran (1956–) and Zafer Baran (1955–), Elaine Duigenan (1964–), and well-known photographer Garry Fabian Miller (1957–), as well as Anna Atkins’ cyanotypes. I will draw on the V&A’s previous exhibition “Shadow Catchers: Camera-less Photography” (13 October 2010 to 20 February 2011) and its associated publication <em>Shadow Catchers: Camera-less Photography</em> (2010), curated and written by Martin Barnes, Senior Curator of Photographs at the V&A. This project will look particularly at the ways in which contemporary artists utilise photogram technology to highlight an intimacy and proximity between humans and the natural world, and how this emphasis on intimacy and proximity poses a call to greater responsibility for the natural world.</p>
|
| 11/06/2019 |
£56,350 |
|
UNIVERSITY OF BRISTOL |
<p>This project explores curatorial practices at Japan’s Minpaku National Museum of Ethnology, which is also known as a “Universal Museum”. Coined by cultural historian and curator of tactile exhibits, Kojiro Hirose in 2006, this concept – and Minpaku as an institution – envision changing the museum and curating exhibitions in ways that enable <em>all</em> visitors to learn and enjoy their visit.</p>
<p>While most museums now recognise and work to remove barriers that people from all backgrounds may face when accessing museum collections and services, in practice they still pose multiple challenges for people with disabilities. Minpaku, where Hirose is based, is not only world-leading in anthropological thinking and practice on the Universal Museum, but also has significant practical expertise and experience in identifying and meeting these challenges.</p>
<p>This secondment, based at Minpaku, will allow me to contribute my combined academic and curatorial expertise to two forthcoming exhibitions there and to furthering Minpaku’s international collaborations and partnerships; simultaneously, it will enable me to achieve three key goals (1) exploring and enhancing the concept of Universal Museum Design<strong> </strong>(2) gaining skills to curate more inclusive, “universal” anthropological exhibits; (3) drawing theoretical insights and practical lessons to inform future, curatorial practices.<br>
</p>
|
| 11/06/2019 |
£16,954 |
|
UNIVERSITY OF OXFORD |
<p>The proposed project takes up the message of arts access charity Arts Emergency to ask 'is an arts emergency a health emergency?' and also to ask the question of who gets to access the arts from an interdisciplinary perspective.</p>
<p>Recent medical humanities research shows us that the arts have a critical role to play in health and wellbeing, both at an individual level and in terms of society as a whole. Meanwhile, government cuts mean that access to the arts —and therefore by extension interdisciplinary arts—are in danger of becoming an elite pursuit as value increases but public funding decreases.</p>
<p>There are two key strands to this work: </p>
<p>1. To use the findings of interdisciplinary research on the value of the arts to public and personal health to make the case for arts access & funding.</p>
<p>2. To investigate access to the medical humanities. What skill sets, mentoring, funding, and opportunities do school leavers from diverse and underprivileged need to pursue interdisciplinary projects? </p>
<p>This 6-month project aims to broaden access to the interdisciplinary arts, to establish a network of medical humanities mentors, and to design medical humanities skills training.</p>
<p> </p>
|
| 11/06/2019 |
£27,317 |
|
KING'S COLLEGE LONDON |
<p>With an ageing global population, questions of how we see older people are central to science, culture and the creative industries. Because of its importance, Age and Ageing is one of the current research themes that the V&A Research Institute (VARI), which brings together curators, academics, artists, designers and audiences, is seeking to investigate. The Museum is looking at it through a contemporary lens, considering today’s ageing population, its implications for our world, how we design it and our systems for living together, but also in terms of its connections to the past. The V&A seeks to explore different readings and conceptions of age, ageing and inter-generational relationships, from different historical periods and a range of cultures, in order to stimulate new thinking about creative solutions to today’s challenges. In undertaking the secondment, I will be moving across time and place to look at responses to the visible signs of age on the surface of the body: wrinkles, sagging skin, scars, pigmentation changes. In writing blogs, giving talks, and creating virtual collections of images and objects related to the ways in which we read bodily transformations over time, I will support the museum's aspirations to reach wider audiences. <br>
</p>
|
| 11/06/2019 |
£26,153 |
|
UNIVERSITY OF EXETER |
<p>This project will develop understanding of the use of horseshoe crabs in endotoxin testing as a complex scientific and societal issue, situated at the interface of human, animal, and environmental health. Bacterial endotoxins pose a serious public health concern, causing fever, inflammation, and death, meaning testing for endotoxins is vital for the safe production and use of injectable medicines and vaccines. </p>
<p>Endotoxin testing currently uses blood harvested from wild horseshoe crabs in the Limulus amoebocyte lysate (LAL) test. However, there are increasing concerns around the impact of capturing and bleeding ~500,000 crabs annually on animal welfare, coastal ecologies, and the sustainability of pharmaceutical supply. A synthetic substitute has been available since 2003, but uptake is slow, and there are many uncertainties and views on the future of endotoxin testing. </p>
<p>This project has been developed with the RSPCA. It will use social science methods to engage key stakeholders and understand their differing interests and perspectives on the biomedical, sustainability, animal welfare, commercial, and ecological risks around future horseshoe crab use. Goals are to use social science to understand the challenges to developing and embedding alternatives, and support dialogue around a currently invisible issue through stakeholder report, academic articles, and public-facing poster.</p>
<p> </p>
|
| 11/06/2019 |
£19,819 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Venezuelan-refugees are fleeing from the country’s political and economic crisis in what has been described as an exodus projected to eclipse that of Syria’s. To date, over half a million have arrived in Peru (second-largest intake). The Venezuelan medical-system is on the verge of collapse with an 85% pharmaceutical shortage, including vital HIV-medication and contraceptives. Those migrants arriving to recipient countries are in desperate need of the reproductive health services denied to them in Venezuela, to stem the spread of STIs and unplanned pregnancies.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Peru has offered a temporary-resident-permit-scheme (PTP) that ended in December 2018, inciting an influx of migrants towards the end of the year. The Peruvian medical-system (MINSA) offers free health care to those with citizenship; a bureaucratic hurdle that many Venezuelans are unable to jump for lack of appropriate documentation.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Working with the United Nations Population Fund (UNFPA-Peru), this project’s key goals are to: 1)Assess the situation of Venezuelan migrants’ access to reproductive health services in Lima, 2)Ascertain services that are lacking and/or in urgent need, 3)Make policy-recommendations and suggest necessary MINSA-worker training. Interviews, focus groups, and a survey will be undertaken. We will provide policy recommendations to the Peruvian government health-ministry (MINSA) based on the findings.</p>
|
| 11/06/2019 |
£26,597 |
|
UNIVERSITY OF SHEFFIELD |
<p style="margin-left: 0cm; margin-right: 0cm">The proposed project will explore youth drinking culture in England, how this has changed over time, and why this might be. Its primary output will be a policy briefing on this topic, informed by a critical review of the literature. A critical literature review involves a detailed examination and appraisal of <em>relevant</em> literature. Findings from the review will be written up as a briefing paper.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This work is necessary because, despite recent reductions in alcohol consumption across younger age groups in England which suggest that the place of alcohol in youth culture may be shifting over time, alcohol consumption remains the leading risk factor globally for mortality and morbidity among 15-49 year-olds. Youth drinking levels in England also remain high relative to many European nations. There is evidence that drinking practices established during adolescence influence alcohol consumption in later life, impacting substantially on future population health. The health benefits of reduced youth drinking cannot be fully realised unless such trends are furthered, continue into adulthood, and are replicated in future generations. There is a need, therefore, for public health decision makers, including parliamentarians, to understand the nature and drivers of youth alcohol trends in order to optimise their harm-reduction efforts.</p>
|
| 11/06/2019 |
£18,499 |
|
UNIVERSITY OF STRATHCLYDE |
<p style="margin-left: 0cm; margin-right: 0cm">Allowing countless individuals to avert rapid death since its first use in 1922, insulin therapy nevertheless only transmuted Type 1 Diabetes Mellitus (T1D) into its now familiar chronic form. By necessity investing final practical responsibility for therapeutic decision-making into the affected individual themselves, this encouraged unprecedented engagement with philosophical questions central to medicine as a profession. How should we incorporate concepts of <em>value</em> into healthcare? What should be done where professional expertise and lay-experience appear to contradict one another? In a very real sense, what is medicine<em> for</em>? This project will enhance the catalogue of T1D/insulin related objects in the possession of the Science Museum, with a particular emphasis on the reintroduction of the patient as a meaningful actor to a history often dominated by doctors, scientists, and other ‘great figures’. With the centenary of its discovery fast-approaching, this would be timely and important work.</p>
<p style="margin-left: 0cm; margin-right: 0cm">In summary, this project has four key goals:</p>
<ul>
<li>Engage in enhanced cataloguing of existing Science Museum collections related to the history of insulin/T1D.</li>
<li>Emphasise the socio-cultural context and ongoing relevance of identified objects.</li>
<li>Develop proposals for future acquisitions.</li>
<li>Produce an annotated bibliography of secondary material related to insulin/T1D.</li>
</ul>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Keywords: </strong>Insulin, diabetes, autonomy, expertise, paternalism</p>
|
| 01/06/2019 |
£20,000 |
|
CODE FOR SCIENCE AND SOCIETY |
<p>As part of this Research Enrichment activity, we plan to:</p>
<ol>
<li style="list-style-type: decimal"><strong>Understand specific workflows/needs of underrepresented groups. </strong>The funds will support two UX sprint events to help us understand the needs and workflows of key stakeholders from communities underrepresented in science and scholarly communication and involved in outbreak response.</li>
<li style="list-style-type: decimal"><strong>Design and distribute a survey</strong>. Based on what we learned during the sprints, we will design and distribute a survey to understand the needs of underrepresented groups in the outbreak science community world-wide.</li>
<li style="list-style-type: decimal"><strong>Incorporate feedback into Rapid PREreview</strong>.<strong> </strong>The feedback from the sprints and the survey will guide key decisions related to UI/UX design and development of the platform.</li>
<li style="list-style-type: decimal"><strong>Publish/open-source the process by which we designed for the inclusion of underrepresented groups</strong>. Because we are committed to open and transparent innovation and we want others to learn from our experience, we will publish our learnings as a series of blog posts, resources, and/or as a preprint, focusing on lessons learned and methodologies used.</li>
<li style="list-style-type: decimal"><strong>Form a project advisory committee with people from underrepresented groups</strong>. While we believe this work will help us build a platform that includes the voices and serves the needs of underrepresented groups, we think that is not enough. The sprints will help us develop connections that we intend to nurture and strengthen beyond the timeframe of the grant. We will invite people from underrepresented groups that have expressed an interest in this project to join our leadership.</li>
</ol>
|
| 01/06/2019 |
£59,500 |
|
KING'S COLLEGE LONDON |
<p>This programme will engage with those living with cardiac conditions to understand their stories and empower them to co-create a sensory and interactive journey through our heart. Together, we will deliver an immersive and interactive ‘inside the heart’ experience, an overall poetic and memorable experience for our target audiences to understand the power of the flow, and why blood flow is a major element determining our cardiovascular health. <br>
<br>
Building on our success of the “Big Heart Data” exhibition at Science Gallery London, the collaboration with designers, artists and charities will be the key to deliver this experience. We will collaborate with those living with cardiac conditions to help shape the exhibit and also our ideas on the future of healthcare enabled by computer models. We will inspire young students by illustrating the powerful role imaging and computer technologies play in improving heart healthcare.<br>
<br>
The finale of the collaboration will be an exhibit at the London Design Festival, followed by a touring of the exhibit alongside workshops with target audiences where they will get to discuss the exhibit and the science behind it with the scientists and designers themselves.<br>
<br>
This project will enable the research team led by Pablo Lamata to gain a better understanding of how heart patients think and feel about the research, plus establish a new perspective through working with Cellule studio. The team will further develop their public engagement practice and improve their confidence in engaging various audiences.<br>
</p>
|
| 01/06/2019 |
£248,615 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Three work streams will address participatory local action (outcomes 1-3), national media (outcome 4), and global communication (outcome 5). After two years, we will have stimulated local discussion and co-designed and implemented public engagement interventions for urban environmental sustainability and health – centred on waste management - with residents of informal settlements in Kisumu, will have equipped Kenyan journalists to increase and improve scientific reporting, and will have shared case studies and interactive models as the foundation of an ambitious web presence.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Outcome 1: Both quantity and quality of public discussion of urban health and environmental sustainability will have increased, led by residents of informal settlements, with mutual learning through visits by representatives of other partner cities.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Outcome 2: Local waste management solutions – benchmarked against scientific evidence and simulations - will have been co-developed by residents of informal settlements, community-based organisations, and researchers.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Outcome 3: Visual, audio, and text materials documenting activities and solutions will have been developed through participatory processes led by Kenyan researchers and creatives, and will be available to decision-makers and local and global publics as attractive, intelligible knowledge products.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Outcome 4: Media coverage around environment and health will have increased in quantity and verified scientific quality as a result of engagement with journalists.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Outcome 5: As a springboard for work in other cities, a set of case studies including art, narratives, infographics, and interactive simulations will be available and accessed through our website. The package will be a model for public engagement in other cities.</p>
|
| 01/06/2019 |
£55,032 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Children with epilepsy, their parents, play specialists, researchers and clinicians will have co-produced, and together feel ownership of, the design and implementation of new child-friendly wearable scanners, interactive games and tasks, and an engaging room interior.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Working alongside an artist and designer, we will have successfully run several diverse focus groups, workshops and interactive sessions for different cohorts of children and their families/carers. We will have used the feedback from these sessions to design and build prototype room interiors, interactive tasks and scanner helmets to be used in a clinical setting.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We will have demonstrated that, through engagement, this project has increased our ability to effectively scan very young children within a stimulating environment.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our success will be measured through compliance rate and typical scan duration achievable for the child patients in the new OPM system at Young Epilepsy. </p>
|
| 22/05/2019 |
£4,420,517 |
|
UNIVERSITY OF GLASGOW |
<p style="margin-left: 0cm; margin-right: 0cm">We aim<strong> to create an intergenerational longitudinal population study of chronic conditions in rural and urban Malawi,</strong> leveraging substantial existing research infrastructure, to address the <strong>lack of high-quality longitudinal-data on chronic conditions in low income sub-Saharan Africa</strong> (LI-SSA).</p>
<p style="margin-left: 0cm; margin-right: 0cm">Our prospective cohort data will provide age-specific incidence and survival estimates for multiple chronic conditions, and improve understanding of determinants (socioeconomic, psychological, nutritional, microbial and inflammatory) of health-related trajectories over the life-course, from poor pregnancy outcomes to multimorbidity in adulthood. Understanding how early-life exposures interact with later-life factors to mediate disease risk will indicate when and how to intervene effectively.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Within rural and urban populations (110,000 individuals) we hold detailed non-communicable disease risk factor and HIV-test data in adults, plus an extensive biorepository. Procedures for longitudinal tracking, community surveillance and birth capture are well-established in rural Karonga and have been piloted in urban Lilongwe. Wellcome LPS support will enable;</p>
<p style="margin-left: 0cm; margin-right: 0cm">1_Longitudinal tracking of 110,000 urban/ rural individuals.</p>
<p style="margin-left: 0cm; margin-right: 0cm">2_Repeat biomarker and clinical assessments of chronic conditions.</p>
<p style="margin-left: 0cm; margin-right: 0cm">3_Establish novel, effective migrancy tracking <em>within</em>/<em>between</em> rural/urban settings.</p>
<p style="margin-left: 0cm; margin-right: 0cm">4_Recruit/follow 7,500 nested families (grandparents-parents-siblings-pregnancy-<strong>birth</strong><strong>-cohort</strong>); pregnancy, early-life and intergenerational effects.</p>
<p style="margin-left: 0cm; margin-right: 0cm">5_Health facility linkage; low-cost longitudinal health-care/outcomes data.</p>
<p style="margin-left: 0cm; margin-right: 0cm">This resource will be shared with the global research community to best-practice guidelines.</p>
|
| 22/05/2019 |
£192,246 |
|
LANCASTER UNIVERSITY |
<p>We propose to develop statistical methodologies for the design and analysis of longitudinal population studies with high-dimensional molecular measurements. Currently there is a dearth of longitudinal statistical techniques that can be applied when the number of outcomes being studied is large. This is detrimental for population studies that measure molecular markers using high-throughput technologies. Our project will fill this gap by developing a set of highly scalable statistical tools that can be used to both effectively analyse high-dimensional data from longitudinal population studies, and to guide and improve the design of future studies. We will implement the design and analysis techniques as user-friendly software packages that are accessible to non-specialists. As a consequence, the value of existing studies will be enhanced because our methods will allow for the testing of more complex hypotheses, the extraction of additional information, and the detection of more subtle associations between clinically relevant molecular outcomes and observed covariates than would otherwise be feasible. Future longitudinal studies involving molecular measurements will additionally benefit from more efficient study designs, resulting in fewer participants or fewer follow-up visits needed.</p>
<p> </p>
<p> </p>
|
| 22/05/2019 |
£5,185,260 |
|
UNIVERSITY OF LIVERPOOL |
<p>Children Growing Up in LiverpooL (C-GULL) is a novel longitudinal research platform combining civic (CityLab) and birth (10,000 first-borns; triad design) cohorts. The scientific and civic aims share a need to better understand: non-communicable diseases trajectories, mental health and developmental/educational prosperity by focusing on connected determinants of child health in one of the UK’s most disadvantaged cities. We will identify early-life determinants and interventions for diseases including childhood/adult obesity, cardiovascular disease, asthma and mental health, and evaluate the impacts of systems change interventions to improve early years outcomes. The findings will be relevant for tackling health inequalities globally.</p>
<p><br>
Women will be recruited during the first trimester of pregnancy over a 42-month period at Liverpool Women’s Hospital. Extensive biological, biometric, socio-demographic and psychosocial information will be collected at two time points in pregnancy, at birth, 2–3 months, one year, two years and five years of age. The deep clinical, psychosocial and molecular phenotyping of this large cohort will be linked to routinely-collected data on the health & social care, education and welfare systems underpinning child health, lessening the burden on participants, and allowing the collection of additional data via emerging digital media that instrument behavioural, social and environmental factors.</p>
|
| 22/05/2019 |
£8,327,295 |
|
UNIVERSITY OF BRISTOL |
<p>ALSPAC is a multi-generation (G0/G1/G2), <em>prospective</em> <em>cohort</em> based in the UK [1-4] (<strong>supplementary information</strong>, Figure 1). This proposal seeks support to:<br>
<br>
- <strong>Maintain the </strong>existing samples and data resources.<br>
- <strong>Enhance visibility</strong> and access to data and samples.<br>
- <strong>Maximise linkage </strong>opportunities through broad and innovative use of administrative records.<br>
- <strong>Expand the resource</strong> by maximising recruitment and retention, and collecting new data and samples on original parents (G0), index participants (G1) and the next generation (G2).<br>
<br>
Work will be delivered via an efficient operational and governance infrastructure. We will deploy a combination of face-to-face assessment, biosample collection and analysis, remote data collection and administrative record linkage where the value of this activity is substantially enhanced by existing resources. All proposed work has been designed according to the overarching principles of (i) <u>scientific utility</u> and (ii) <u>engagement/recruitment/retention.</u> Study activities draw on experience from previous ALSPAC activity and consultation with participants and academics through bespoke workshops. Scientific focus reflects ALSPAC strengths and our <strong>target science areas</strong>, namely: The antecedents of cardiometabolic/cognitive/mental health, cross-generation contributions to health and era specific contributions to health, well-being and society.</p>
|
| 22/05/2019 |
£5,163,009 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0px; margin-right: 0px"><strong>Generation Scotland:NextGenScot</strong> <strong>(NextGenScot) </strong>builds upon the proven success and research value of <u><strong>Generation Scotland</strong></u><strong> (GS).</strong> We will extend the reach and relevance of GS through recruitment of additional members and younger relatives of current participants. Our <strong>vision</strong> is to transform GS from a cross-sectional, adult-only study into a <strong>longitudinal, multi-generational, life-course study</strong> that can address <strong>how genetic factors and environmental exposures influence disease risk, resilience and outcome</strong>.</p>
<p style="margin-left: 0px; margin-right: 0px"> </p>
<p style="margin-left: 0px; margin-right: 0px">As for GS, we will:</p>
<ul style="list-style-type: disc">
<li>engage with participants to shape the study objectives and seek broad consent for medically-relevant academic and commercial research,</li>
<li>seek consent to recontact for participation in follow-on enhancement studies, our proven mechanism to enrich the baseline data,</li>
<li>actively facilitate hypothesis and data-driven science by research users, openly sharing our research findings.</li>
</ul>
<p style="margin-left: 0px; margin-right: 0px"> </p>
<p style="margin-left: 0px; margin-right: 0px">NextGenScot expands GS to create an enhanced resource of scale (n=40,000), depth and rich annotation through:</p>
<ol start="1" style="list-style-type: decimal">
<li>self-report and serial remote data capture of health and lifestyle information;</li>
<li>e-HR linkage (from ‘birth-to-death’, updated annually); and</li>
<li>biological samples (collected at recruitment and longitudinally).</li>
</ol>
<p style="margin-left: 0px; margin-right: 0px"> </p>
<p style="margin-left: 0px; margin-right: 0px">NextGenScot would be the UK’s largest multi-generation study of clinical, biochemical, genetic, epigenetic and environmental health determinants, allowing estimation and determination of transgenerational effects (social, environmental and genetic) on disease risk and resilience.</p>
|
| 16/05/2019 |
£63,290 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">The main objective of the project is to sort, preserve and catalogue the administrative archive of the MRC National Survey of Health and Development (NSHD), held at UCL, to international standards and make it available to researchers.<strong> </strong>The project will be managed by the Head of Archives, UCL Special Collections, and the project archivist will be embedded in the management structure of that department. The NSHD archive will be housed with other specialist education archives at the UCL Institute of Education.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong> <strong>The aims of the project are:</strong></strong></p>
<ul>
<li>Removal, sorting and repackaging of archive material from the current storage</li>
<li>Appraisal of remaining archive material to remove duplicates and to agree retention</li>
<li>Repackaging of archive material into acid-free folders and boxes</li>
<li>Cataloguing of the archive using CALM, in line with international standards (ISAD(G) and ISAAR(CPF)). The catalogue will be added to the archive online catalogue (<u>http://archive.ioe.ac.uk/DServe</u>)</li>
<li>Conservation and digitisation of specified material in the archive</li>
<li>Creation of a records management plan to streamline future retention of material</li>
<li>Outreach and dissemination work relating to the archive collection in collaboration with staff at the MRC Unit for Lifelong and Ageing at UCL (LHA).</li>
</ul>
|
| 16/05/2019 |
£84,113 |
|
BRITAIN YEARLY MEETING |
<p style="margin-left: 0cm; margin-right: 0cm">This project will preserve and catalogue the archives of the Friends Ambulance Unit (1939-1947) and Friends Relief Service (1943-1948). These two bodies provided an alternative service during, and immediately after, World War II, for those who did not believe in fighting and saw humanitarian aid as a way to heal the wounds of war. The collections provide fascinating insight into some of the medical developments brought about by war: from the Hadfield Spears medical unit in North Africa, to the development of western medicine in areas of China cut off by the war. Both collections highlight the unique perspectives of pacifist aid workers, who saw relief work and post-war rehabilitation as implicitly linked to stopping future wars.</p>
<p style="margin-left: 0cm; margin-right: 0cm">We will carry out preservation activities such as stabilising and repackaging, catalogue the collection fully and make it searchable through our online catalogue, enable access for researchers, promote the collection to the academic community, and identify materials suitable for future digitisation projects. We also hope to engage local and family historians, schools (for example, through our peace education project), and other community groups and stakeholders. We hope these activities will broaden access to this collection and support new research.</p>
|
| 16/05/2019 |
£282,657 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 0cm">This is a collaborative, multidisciplinary project between Edinburgh University Library (EUL) and the Royal Zoological Society of Scotland (RZSS) to catalogue, preserve, selectively digitise and make available for innovative research three significant collections.These collections were identified because of intersections between research, evidence, and debate from different perspectives, human and animal health and well being. The archive collections are from animal protection charity OneKind, Royal (Dick) Veterinary College and Royal Zoological Society of Scotland (RZSS).</p>
<p style="margin-left: 0cm; margin-right: 0cm">The objectives are to:</p>
<ul>
<li>create interoperable standards-compliant digitally-online catalogues</li>
<li>ensure long-term preservation by rehousing collections in archival-quality enclosures;</li>
<li>carry out interventive conservation work on at-risk items;</li>
<li>digitise key illustrative material and make available through interactive technology for public and research access;</li>
<li>design and create a dynamic website for catalogues, providing contextual information for public engagement and research;</li>
<li>undertake interdisciplinary research using collections, including analysis of datasets;</li>
<li>engage research communities and wider public through social media, articles, talks, conferences, interventions and engagement events;</li>
<li>lay the foundations for further projects, funding for research and public engagement, scoping further related collections and forging partnerships with other institutions with related material.</li>
<li>Create a better understanding of the relationships between human and animal health and changing historical trends and ethical positions.</li>
</ul>
|
| 16/05/2019 |
£152,360 |
|
NEEDHAM RESEARCH INSTITUTE |
<p>The biochemist and historian, Joseph Needham, was given unprecedented access to medical and scientific institutions in China during World War II, and he was the only British scientist to visit China regularly between 1949 and 1978. His research while in China is recorded in photographs, notebooks, diaries and correspondence. He collected scientific and medical objects as well as cultural items, many now extremely rare. His wife Dorothy Needham, herself an eminent biochemist, joined him on these journeys and her journals provide additional insights into medical advances under challenging conditions.</p>
<p><br>
Needham wrote ‘If I have been the means of explaining the scientific, technological and medical achievements of the Chinese people to the rest of the world, I shall be more than satisfied.’</p>
<p><br>
This project will help to fulfil his vision by preserving and bringing a wealth of new resources online to researchers worldwide. The output of the project will be: a catalogue of the collection to international standards; the conservation and re-boxing of documents, photographs, glass plate slides and medical objects; the digitisation of photographs and notebooks. A programme of exhibitions and talks will raise awareness of this unique archive to students and scholars of all ages and the general public.</p>
|
| 05/05/2019 |
£98,620 |
|
UNIVERSITY COLLEGE LONDON |
<p>“Studies in Hypochondria” is an interdisciplinary, medical humanities project that charts changing conceptualisations of the relationship between health and illness through a literary and cultural history of the figure who troubles our ability to make that distinction: the hypochondriac. By reading medical and historical texts, I show how in the late nineteenth and early twentieth centuries, hypochondria lost its longstanding association with melancholy and hysteria, and took on its modern meaning as an excessive fear that one is suffering from disease. At this time the hypochondriac became the object of ridicule and scorn. I historicize these cultural shifts, arguing that, in its modern form, hypochondria arose in the late Victorian period as an anxious response to increased knowledge of disease and its diverse aetiologies. I argue that hypochondriacal doubt is constructed by the very medical discourses that it calls into question. Furthermore, through a series of literary “case studies” I examine hypochondria’s complex relationship with literature. By turning to three celebrated and self-described hypochondriac writers, I show how hypochondria has repeatedly been mobilized by artists and writers as a means of testing, often sceptically, the certainties of Enlightenment rationality and medicine.<br>
</p>
|
| 05/05/2019 |
£120,829 |
|
UNIVERSITY OF CAMBRIDGE |
<p>This research examines how (in)fertile couples, men in particular, can access and utilize assisted reproductive technologies (ARTs) in the socio-cultural, legal, religious and medical context of contemporary Iran. Iran is the only Muslim country in which ARTs, including the use of donor gametes and embryos, have been regulated by the state. Although the state partly subsidizes ARTs, they are not equally accessible to all. In Iran, infertility—a stigmatized condition—is considered a ‘woman’s problem’; male infertility is hardly recognized in families, society or in social science. This ethnographic study will yield insights into male infertility and the use of ARTs in Iran and how this relates to dominant notions of masculinity. It will build on four core theoretical notions—‘reproductive navigation’, ‘(Islamic) biopolitics’, ‘stratified reproduction’ and ‘emerging masculinities’—and take an intersectional perspective considering gender, class and religion. Conducted in Tehran and Yazd, the research methods will include: observation in hospitals and in the mundane lives of (in)fertile couples; interviews with couples and religious authorities, medical professionals and policymakers. This research will further our understanding of how gender, class and religion inform disparities in the use of and access to ARTs, and speak to reproduction policies in Iran and countries with similar conditions.</p>
|
| 05/05/2019 |
£86,431 |
|
UNIVERSITY OF EDINBURGH |
<p style="margin-left: 0cm; margin-right: 0cm">Antibiotics are vital to the successes of modern medicine and yet antimicrobial resistance (AMR) is escalating globally. The prevalence of militaristic language used to describe human-microbe relationships is significant. The human body is comprised to a large extent of microbiota such that our bodies are composed not of mass which is genetically ‘us’ but instead an ecosystem of microbial life. Although the microbiome is receiving greater scientific attention, AMR threatens to drastically change our modern medical and agricultural practices. Therefore, now is the time to reimagine our relationship with microbes using anthropological means. The project uses and contributes to a multispecies approach to ethnography. This in turn speaks to wider conversations the Anthropocene and the relationships between humans and non-humans.</p>
<p>This research uses ethnographic investigation of UK laboratories and artistic spaces whose work is concerned with the microbiome to examine the implications of these metaphors and explore the scope to reimagine them. By conducting this investigation in symmetry, using ‘the abject’ and Freud’s ‘uncanny’ as theoretical underpinnings, the impact of this research will contribute to wider interdisciplinary conversations and strategies to reduce the exacerbation of resistance and infection</p>
|
| 05/05/2019 |
£133,349 |
|
UNIVERSITY OF CAPE TOWN |
<p style="margin-left: 0cm; margin-right: 0cm">The 2014 West African Ebola crisis was the deadliest outbreak in this region. While the international response was delayed, eventually international actors, including scientists, clinicians, NGOs, and governments came to the aid of affected countries. What remains unclear is the impact of the international response on key African actors and institutions. This project will investigate the impact of the international response on the visibility, agency and capacity of African scientists, researchers and other key stakeholders. Through a social network analysis, using authorship and institutional affiliations, this project will map scholars contributing to the global discourse on Ebola. Additionally, a scoping review will be used to determine how the crisis of Ebola was framed. Combined, they may suggest the relative power African scientists had in shaping the scientific dialogue around this epidemic. This project will also conduct interviews with key stakeholders such as scientists, researchers, and policy makers in Nigeria, Sierra Leone and Liberia. Regional actors based at Africa CDC, will also be included. These interviews will provide important perspectives from key African actors about how the international response to the Ebola crisis, impacted on their agency, capacity and visibility during and after the crisis.</p>
|
| 05/05/2019 |
£89,369 |
|
UNIVERSITY OF YORK |
<p style="margin-left: 0cm; margin-right: 0cm">There has been much recent debates among global health scholars about WHO’s vital role in health crises and combating disease outbreak. These literatures seem to ignore the enormous material and human investments that the WHO has devoted to Africa, the longterm of the organization’s functionaries or the limited authority of the organization as a support and supplement to national health apparatus. The joint solution of health issues by WHO and national ministries of health in Africa has been given much less attention. A history of the WHO focusing on the patterns of health collaboration promises to deepen the knowledge of the organization and its national counterparts, of disease and cure in Africa. This research seeks to explore the significance and importance of local capacity and culture in achieving health goals through a historical study of international collaborative efforts between the WHO and local actors in Southern Nigeria in responding to health emergencies between independence and 2000. This study, using the examples of two case studies of international health campaigns(Smallpox and Guineaworm) will investigate how the operational strategies employed by indigenous actors complemented WHO’s goal to eradicate the outbreak of infectious diseases in the rural and urban areas in Southern Nigeria.</p>
|
| 05/05/2019 |
£83,088 |
|
UNIVERSITY OF MANCHESTER |
<p style="margin-left: 0cm; margin-right: 0cm">The NHS England Long Term Plan includes a commitment to champion ‘community approaches’ which aim to improve health and reduce demand on formal care services. Community approaches consist of two main elements:</p>
<ol>
<li>Social Prescribing - general practitioner referrals to local, non-clinical services to give them access to support in areas like employment, debt and physical activity.</li>
<li>Community assets - collective resources which individuals and communities have access to, like voluntary and community groups.</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>Aims</strong></p>
<ol>
<li>To what extent and in what populations would addressing debt improve health and reduce care utilisation?</li>
<li>To determine if there are inequalities in access to community assets, in terms of concentration and distance. If so, do these inequalities affect health and care utilisation?</li>
<li>To assess the effectiveness of a rollout of a social prescribing scheme at improving health and well-being in Greater Manchester.</li>
</ol>
<p style="margin-left: 0cm; margin-right: 0cm">The three aims will be achieved by applying econometric analysis to a combination of nationally representative datasets and a novel Greater Manchester specific dataset. The results will be used to inform policy makers of the effectiveness of community approaches. </p>
|
| 05/05/2019 |
£100,016 |
|
GOLDSMITHS, UNIVERSITY OF LONDON |
<p>This practice-based research engages with Uruguay’s ongoing deinstitutionalisation process bringing together spatial theories of coexistence and participatory art. It draws on critical human geography to chart deinstitutionalisation as a social and spatial process, with the understanding that the departure from the psychiatric asylum must be negotiated well beyond its walls. This project combines techniques from contemporary documentary filmmaking and pedagogies of Latin American Third Cinema to experiment with audio-visual practice as a device for witnessing difference and reimagining life together within difference.<br>
<br>
This research will promote encounters between people, between disciplines, and between practice and theory, engaging in transformative community-processes and the public discussion of topical issues. It will operate micro-politically, employing artistic practice to bring into conversation service users, professionals and staff of Uruguay’s mental health system, carers and relatives, and other members of society. By enabling dialogues outside traditional settings and roles and extending the conversations on mental health beyond the bounds of disciplinary discourses and established institutions, this research will contribute to the understanding of mental health in the context of mad studies and critical disability studies, and will advance the dialogical potential of audio-visual practice and its development as a research method. </p>
|
| 05/05/2019 |
£172,787 |
|
QUEEN MARY UNIVERSITY OF LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Qualitative research is proposed to examine how increasing persecution and hostility towards gay, bisexual and men who have sex with men (MSM) influence delivery of and access to HIV prevention and care services in Tanzania. By situating delivery and access to HIV services among MSM in a larger context, the study builds an appreciation of how the legal and policy environment influence the supply and demand sides of healthcare as well as the implementation of global health strategies to curb the HIV epidemic.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Data collection techniques will involve focus group discussion and in-depth interviews with MSM, and key informant interviews with regional AIDS control coordinators in participating regions, members of district health management teams, and healthcare providers in the non-governmental organizations and community-based organizations providing services to MSM. The study setting will be in Dar es Salaam and Shinyanga regions. </p>
<p>Results from this study can be used to inform various service delivery strategies and increasing access to HIV prevention and care services among MSM in contexts where homosexuality is criminalised. A workshop with relevant stakeholders will be arranged to discuss how the research findings can be translated into practical policy and health service delivery regarding HIV prevention and care.</p>
|
| 05/05/2019 |
£146,055 |
|
UNIVERSITY OF DURHAM |
<p style="margin-left: 0cm; margin-right: 0cm">This project proposes a comparative understanding of colonial era medical photographs taken in Malawi and Sudan through archival research, visual anthropology approaches, ethnographic methods and exhibitions. The archives relate to Dr John Brian Christopherson and Dr Hugh Stannus Stannus, colonial medical officers deployed in Sudan and Malawi, respectively. The first objective of this project is to explore how ideas about tropical medicine were conceptualised, visualised and rationalised against the backdrops of imperialism and colonialism. A second objective is to examine attitudes and responses of indigenous communities and health professionals to these images in contemporary settings. Taking an interdisciplinary approach will reshape conversations around historic medical photographs and draw out lessons about disease management and prevention applicable in present public health contexts. By connecting the photographs to contemporary communities the research will contribute to current debates on ways to engage with photographic archives and importantly it will incorporate responses from a diverse range of indigenous communities that will aid in identifying new public-driven questions.</p>
<p>Key words: Medical photography, disease outbreaks, anthropology,</p>
|
| 05/05/2019 |
£89,852 |
|
UNIVERSITY OF DURHAM |
<p>Persistent Physical Symptoms (PPS) is an umbrella term that groups together disparate symptoms by their collective lack of diagnosable pathology. PPS incur substantial costs to the NHS and economy and place a heavy burden on sufferers, the majority of whom are women. While the clinical literature acknowledges that shame<em> </em>is a ubiquitous feature of living with PPS, the dearth of critical attention to this affective experience represents a significant lacuna requiring immediate interdisciplinary attention. </p>
<p>This study has two interlinked goals: to explore the role of shame in women’s lived experiences of PPS, and to investigate its expression in narrative. Because shame is often hidden, these goals will be best achieved through a mixed-methods study combining literary, phenomenological and qualitative methods. Building on the work of Luna Dolezal, Havi Carel and J. Brooks Bouson, among others, this study will compare literary accounts and ‘direct’ patient testimony gathered through semi-structured interviews. These patient narratives will be analysed alongside contemporaneous medical and public discourses around PPS to examine the dialogic construction of shame. This research will break new ground methodologically, working towards longer-term goals of addressing the experiences of shame in PPS in healthcare policy and medical training. </p>
|
| 05/05/2019 |
£108,516 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0in; margin-right: 0in">This project seeks to shed light on experiences of pregnancy, childbirth, and maternity in carceral space in England – namely, within the women’s prison estate and the immigration removal estate. The extent, albeit limited, scholarship surrounding this area has focused almost exclusively on maternal incarceration and detention as it relates to child separation. This project would examine how motherhood itself – spanning pregnancy, childbirth, and maternity – is experienced and endured within these two types of custodial institutions. Empirically grounded, this project will consist of fieldwork in two women’s prisons, and two immigration removal centres. It will investigate how perinatal healthcare is administered within these spaces, and how custody is experienced and endured by pregnant and maternal subjects. Ethnographically oriented, it seeks to lend visibility and centrality to the women confined within these low-visibility spaces. Ultimately, this project seeks to develop answers to the following questions: how is perinatal healthcare experienced by women within the women’s prison estate and the immigration removal estate in England? What are the conceptual and practical implications for our understanding of dignity, agency, autonomy, and privacy? How do the experiences of pregnancy, childbirth, and maternity further our understanding of the gendered harms of custodial space?</p>
|
| 05/05/2019 |
£109,470 |
|
UNIVERSITY OF OXFORD |
<p style="margin-left: 0cm; margin-right: 0cm">Medical interventions used in pregnancy can affect the length and quality of life of both the woman and fetus. In cost-effectiveness analysis these effects are measured using quality-adjusted life years (QALYs), but fetal outcomes are rarely measured in QALYs, despite being an important clinical outcome. This exclusion will inevitably alter the perceived cost-effectiveness of interventions.</p>
<p>I propose QALYs should be used in this setting to support consistent decision making across healthcare, but that how fetal QALYs are valued may differ from the value used for other patients.</p>
<p>The aim of this doctoral studentship is to investigate whether QALYs could be applied to fetal outcomes when evaluating the cost-effectiveness of interventions in pregnancy, and how those QALYs should be valued. The project will take the preferences of pregnant women as its starting point, using secondary analysis of interviews with women experiencing high-risk pregnancies, qualitative focus groups, and a discrete choice experiment to first conceptualise and then quantify possible values that could be used in cost-effectiveness analysis.</p>
<p>The outcomes of the project will be a valuation based on maternal preferences, which could be used to make resource allocation decisions in pregnancy, while also opening the door to further research in this setting.</p>
|
| 05/05/2019 |
£87,054 |
|
UNIVERSITY OF STELLENBOSCH |
<p>In South Africa, state-funded social protection for disabled children has primarily been through the Care Dependency Grant (CDG). The CDG is distributed to the caregivers of these children and provides important financial assistance, but it is under-researched. Little is known about caregivers’ access and utilisation of the CDG, what the value of complementary interventions might be, how doctors assess need and deservingness, and how government agencies conceive of and communicate about the CDG. The proposed study will investigate these and other questions in a qualitative study using ethnographic and participatory methods, with a specific focus on the Cape Winelands district. Participants will include caregivers of children with disabilities, assessing doctors, South African Social Services Agency (SASSA) staff members, and organisations working with disabled children. Findings will be discussed with reference to broader debates around social protection, development, poverty alleviation, and access to health and education for disabled children. A better understanding of how this grant is conceived of, used, and distributed from the perspective of different stakeholders will build knowledge in this underdeveloped area. It will also produce important initial evidence for potential future interventions to improve the social protection of disabled children and their caregivers in South Africa.</p>
|
| 05/05/2019 |
£100,407 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0cm; margin-right: 0cm"> </p>
<p style="margin-left: 0cm; margin-right: 0cm">This <strong>ethnographic study </strong>of pressure ulcer (PU) prevention and management in a large hospital and community will examine whether the current focus on PUs as sites for clinical surveillance and accountability serves to capture the more holistic ‘culture of care’ (Francis 2013) that it is said to indicate. Drawing on contemporary debates about care within anthropology, sociology and Science and Technology Studies it will investigate how a focus on the role of time is essential to the study of care in the context of the NHS and an ageing population. And, through examining practice, it will seek practical and realistic ways to promote and maintain good care even when resources become limited.<br>
</p>
<p><strong>How can practices of PU prevention and management be strengthened in the face </strong><strong>of increasing resource shortages in UK healthcare provision?</strong></p>
<p><br>
To answer this question the study will focus on: what the key pressures are, how these alter over time; how they are addressed, by whom; how care is currently shared; and how the focus on time and care may inform PU prevention in the future. The study will take place in a London hospital and local community, to which access has been established with a clinical collaborator.</p>
|
| 05/05/2019 |
£141,231 |
|
UNIVERSITY OF OXFORD |
<p>The research proposed is a multi-sited ethnographic investigation into the relationship between industrial pollution as a health threat and the ongoing social, political, and moral struggle of two communities living in close proximity to polluting sites. Through a comparative study of the people of Taranto, Italy, and Tainan, Taiwan, this project seeks to explore the political dimensions of environmental health degradation and exposure by conceiving pollution as a complex symbolic configuration assembled at the crossroads of historical, scientific, legal, and interpersonal trajectories. Understanding how these communities make sense of their polluted worlds is fundamental in order to grasp their political aspirations and their self-collocation within local and global narratives of environmentalism.</p>
<p>This project expands and builds on Anna Lora-Wainwright's (2017) notion of <em>resigned activism </em>and seeks to scale up its theoretical framework to non-Chinese contexts of environmental degradation. Environmental justice research currently focuses on the local dimension of suffering, and calls for theoretical tools empowering marginalised communities to connect globally and participate in policy making at the international level. This research responds to this call and moves the field toward a global narrative of environmental health injustice, generating tools for the incorporation of ethnographic evidence into policy making and implementation.</p>
|
| 05/05/2019 |
£102,483 |
|
UNIVERSITY OF STRATHCLYDE |
<p style="margin-left: 0cm; margin-right: 0cm">Allergy is one of the chief causes of chronic disease in the developed world, with experts estimating that, by 2025, half of all Europeans will be affected by allergic disease. Rates of allergy are also increasing, with hospital admission for anaphylaxis increasing six-fold since the 1990s in the UK. The explanation for these surges in allergic disease, however, remain unclear. This project will inform ongoing historical and clinical research into the epidemiology of allergy by using a novel frame of reference: animals.</p>
<p style="margin-left: 0cm; margin-right: 0cm">The project begins by investigating how animals models were used to shape our first understandings of allergy during the early twentieth century. Unlike the histories of allergies that have been conducted thus far, this project will rely heavily on untapped French-language archival sources in Paris and Monaco. These include the papers of Nobel Prize-winning physiologist Charles Richet, which have only recently been made publicly available. It then uncovers the stories of those who have suffered from pet allergies, as well as clinicians and breeders who have tried to help such patients. Finally, the project turns to explore pets <em>with</em> allergies, and what this phenomenon says about the link between allergic pets and the environments we devise for them.</p>
|
| 05/05/2019 |
£154,512 |
|
LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE |
<p style="margin-left: 0in; margin-right: 0in">The research question is ‘<strong>how does participation in social autopsy influence citizen action to prevent maternal deaths?’ </strong>This qualitative study will use ethnographic observations and in-depth interviews to explore the nature and outcomes of participation during social autopsies for maternal deaths.</p>
<p style="margin-left: 0in; margin-right: 0in"> Citizen participation and social accountability theories recognize the importance of health co-production i.e citizens and health providers collaborating (Rifkin, 2014). Studies on social accountability focusing on citizens holding duty bearers to account have been conducted, (Ciccone <em>et al.</em>, 2014), but there has been little focus on holding citizens to account as health co-producers. A pilot study on social accountability in Kenya found that citizen participation was weak with limited feedback to health providers (World Bank 2015). The insights developed through this study will contribute to developing theory on participation and social accountability in a broader context.</p>
<p style="margin-left: 0in; margin-right: 0in">The 3-delay model is a framework that has identified delays that contribute to maternal mortality and can thus be applied in its prevention (Thaddeus <em>et.al </em>, 1994). The study explores participation during social autopsies and the extent to which citizens reflect and act on the delays for health co-production and mutual social accountability. </p>
<p style="margin-left: 0in; margin-right: 0in"><em>Key words: Social accountability, Citizen participation, Health co-production, Social autopsy</em></p>
|
| 05/05/2019 |
£81,189 |
|
UNIVERSITY OF GLASGOW |
<p style="margin-left: 0cm; margin-right: 0cm">Modern medicine has changed the long-term outcomes of heart disease, challenging stereotypical representations of the heart and its (mal)functions. Complex modern-day treatments, and the specialised knowledge required to communicate these, make it difficult for meaningful biomedical communication to accommodate the long-standing emotional/socio-cultural significance of the heart as a symbol of love, emotion and personal identity.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Popular literature, meanwhile, has tended to remain focussed on romanticised stories of tragic demise or the dramatic intensity of heart transplant. While offering ample opportunity to address the heart’s personal significance, these narratives are not representative of contemporary patient experience.</p>
<p style="margin-left: 0cm; margin-right: 0cm">Cardiovascular disease is the leading cause of death worldwide (WHO, 2016) and accounts for a greater percentage of Europe’s healthcare budget than either HIV or cancer (Remme, 2005). However, a search by subject of published pathographies revealed 122 results for cancer, 31 for AIDS and only 9 for heart disease, chronic or otherwise (Hawkins, 1999).</p>
<p style="margin-left: 0cm; margin-right: 0cm">By close analysis of post-1980 writing and engaging with cardiology service users to co-create new narratives, my research will investigate representational challenges posed by chronic heart disease, consider the potential impact of narrative text that reflects patient experience, and enable contemporary narratives of chronic heart disease to be shared.</p>
|
| 05/05/2019 |
£104,803 |
|
UNIVERSITY OF OXFORD |
<p>For this project, I aim to investigate the thesis that administering neurointerventions to sexual and violent psychopathic offenders is rendered ethically permissible on the grounds of improving offender welfare; and that this, in turn, imposes a duty on states and criminal justice systems to <em>develop, offer and perhaps even impose</em> safe and effective neurointerventions as a condition of parole on some such individuals.</p>
<p>My approach to this research is three-pronged. Firstly, I shall investigate whether neurointerventions geared towards <strong>1) </strong>reducing libido in the case of sex-offenders and <strong>2)</strong> increasing empathy in the case of psychopathic offenders, could plausibly be seen to improve the welfare of the individual upon whom the intervention is enacted. Secondly, I shall explore whether the promise of improvements to individual welfare afford a reason to judge the practice of employing neurointerventions ethically permissible. Thirdly, I shall examine whether this would impose an obligation on States to provide such neurointerventions.</p>
<p><strong>Key Goals</strong></p>
<ul>
<li>To explore an alternative justificatory framework for the use of neurocorrectives than that which is usually put forward;</li>
<li>To draw upon my biomedical, philosophical and psychological training to resolve the ethical questions raised by this sort of justification;</li>
<li>To deliver practical ethical guidance to policymakers.</li>
</ul>
<p> </p>
|
| 05/05/2019 |
£139,141 |
|
UNIVERSITY OF OXFORD |
<p><strong>Infectious content: Online misinformation & vaccine confidence in UK parents</strong></p>
<p><em>This research will investigate the nature of anti-vaccination messaging disseminated on social media and its effect on vaccine confidence among UK parents..</em></p>
<p>Vaccination is among the greatest achievements in human health. Yet successes in consolidating coverage are fragile even in the UK where childhood vaccine uptake continues to decline year-on-year. Anti-vaccination messaging on social media is widely decried as a causal factor fuelling parental concerns. Academic research is running to catch up with the scale and complexity of the challenge, which warrants nuanced and context-specific understanding. Simultaneously social media users are migrating towards closed messaging platforms and visual social networks, with relatively closed APIs, which make it harder for academics to access vaccine misinformation. Research is lacking and new approaches are required.</p>
<p>The proposed research will use a mixed-methods approach to map anti-vaccine claims and ideologies on visual platforms while recruiting focus groups of UK parents-turned-citizen-scientists to collect anonymised related content received on private messaging platforms. Research will examine ethical considerations including the right to parental choice, attitudes to mandatory vaccination, consent around the infiltration of private online spaces, and data privacy in line with GDPR.</p>
|
| 05/05/2019 |
£131,839 |
|
NEWCASTLE UNIVERSITY |
<p>In many ethnic-minority regions of China, multiple forms of medical practice and knowledge play a role in healthcare. As most of the major hospitals mainly serve cities, many people in rural areas can only access the health services provided by village practitioners who have studied one-year courses in medical institutions. Some people in ethnic minority communities also turn to religious forms of treatment, such as enchantment and rituals, which have often been the traditional means of healthcare. This means that multiple forms of healthcare coexist, but there is a lack of extensive, historically-grounded research on what this means in practice. My project will explore how this situation can be traced back to the early and mid-twentieth century by studying medical plurality in Guangxi, a peripheral, multi-ethnic province in Southwestern China. I will consider how medical practices and knowledge in different communities – Western missionaries, Western-trained doctors, Han Chinese and ethnic minorities – interacted with each other. A historical analysis of these relationships will allow us to understand the tensions that exist between different forms of healthcare today, and suggest pathways toward more cooperative forms of engagement among different medical communities. <br>
</p>
|
| 05/05/2019 |
£141,717 |
|
UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0cm; margin-right: 0cm">Throughout Chinese history, talismans have been central to healing for the vast majority of the population. From the Sui to the Qing dynasties (581-1644), talismans formed an imperially-sponsored medical discipline, after which they were permanently forsaken by the court. However, despite subsequent condemnation by the state, talismans remained pervasive throughout Chinese society until the first half of the twentieth century. This can be attested by the publication of an unprecedented wave of cheap almanacs and manuals of talismanic healing, as well as a dynamic economy revolving around these practices between the 1850s and 1940s. Paradoxically, this was precisely the period when the Chinese state began to marginalize talismans and other healing rituals from China’s public sphere, condemning them as at odds with a "modern" Chinese medicine. Combining historical and ethnographic analysis, I will examine the marginalization and survival of talismanic culture in Republican China (1912–1949). Print culture will provide copious textual evidence of the circulation of talismanic knowledge in Shanghai and the place of talismanic healers in its healthcare market, while fieldwork with a talismanic healer will offer a case study that ties together the historical and anthropological strands in an analysis of contemporary transmission and practice of talismanic healing.</p>
|
| 02/05/2019 |
£30,142 |
|
SCHOOL OF ADVANCED STUDY, UNIVERSITY OF LONDON |
<p>Meditation has become integral to modern life. NHS doctors prescribe mindfulness to reduce stress and manage pain and illness, while medical and neuroscientific research tests meditation’s effects. We believe that history and social science can also help improve meditation’s health outcomes.</p>
<p>This grant will gather experts to compare contemporary medical meditation—in its strengths and weaknesses—with other contemplative traditions. We will draw from Buddhist, Christian, and Islamic contemplative traditions and from the history of Western science, which in key respects emerged out of ascetic traditions. We will compare specific cases to the present, focusing on the community structures, cosmologies, and ideals of health associated with specific mind-body techniques. This holistic, comparative perspective may suggest ways to reposition and re-orient current practice.</p>
<p>Key goals:</p>
<p>-Develop a research network connecting diverse fields interested in contemplative practice and its effects (religious studies, anthropology, philosophy, history of science).</p>
<p>-Host workshops and discussions at the Warburg Institute, to sharpen questions, identify and explore case studies, establish an advisory board and collaborators, and prepare a larger collaborative grant.</p>
<p>-Develop strategies to engage wider audience and publics, including scholars, practitioners, and health professionals, to realize more meaningful, effective, and medically beneficial understandings and uses of meditation.</p>
|
| 02/05/2019 |
£29,904 |
|
PUBLIC HEALTH FOUNDATION OF INDIA |
<p style="margin-left: 0cm; margin-right: 0cm">India is diverse country which faces wide and varied public health challenges of both infectious and chronic diseases accompanied with extreme heat and air-pollution. Whereas lots of scientific research is being done, ethics has not entered the academic discourse in public health policy, practice, implementation, societal drivers and solutions. Sectors outside health which have a profound influence on health but don’t look at health considerations, need an ethical lens too. We aim to establish a robust network of global and Indian of experts in public health ethics and conduct a series of seminars which will enable a debate on various issues in public health and also train the MPH and other masters students on public health ethics. The seminars will be video recorded and uploaded for wider outreach and availability. Newer and emerging issues will be identified, ideas for future grant proposals will be explored and also the possibility of future collaborative grant proposals. We will explore the demand and need for an internship program in Public health ethics at PHFI for students of law and humanities. Ethics need to enter the core of health and preventive and promotive health and this is the beginning of the road.</p>
|
| 02/05/2019 |
£30,196 |
|
UNIVERSITY OF BRISTOL |
<p>This project seeks to explore opportunities for research and funding in the sensory history of healthcare environments. It has two main aims, with associated activities to achieve these running over a two-year period (one workshop, one large conference, and three project 'retreats'). Firstly, it will develop methodologies for an ambitious, collaborative, interdisciplinary monograph on senses in the modern British hospital for the 75<sup>th</sup> anniversary of the NHS. Secondly, it will expand a small existing group of UK-based scholars working on (or near) the subject of health/care senses to become (i) more international; and (ii) more collaborative with healthcare practitioners, designers and architects. Ultimately, the project will initiate and deepen interdisciplinary and international networks, with the ultimate goal of collaborative funding applications and publications. The project will work towards improving healthcare environments for all those who use them, as well as developing new approaches for scholars of medical humanities and sensory history.</p>
<p style="margin-right: 18.0pt"> </p>
|
| 02/05/2019 |
£29,401 |
|
UNIVERSITY COLLEGE LONDON |
<p>This project establishes the first cross-disciplinary international network of social scientists, geneticists and epidemiologists focused on longitudinal birth cohort studies in the Global North and South. Birth cohorts are increasingly recognised as important for understanding how biological, social, and environmental processes interact over time. This makes them central to an emerging terrain of what has been described as ‘biosocial’ research. Despite this, however, relatively few social scientists have engaged with or investigated longitudinal birth cohorts. There is an urgent need to co-ordinate and consolidate emerging efforts in this area to ensure that biological and social science research benefits from productive cross-disciplinary engagement. The proposed network ‘Biosocial Birth Cohort Research’ (BBCR) will enable a community of international researchers to examine the social, ethical and methodological challenges and opportunities of developing innovative cross-disciplinary research with birth cohort studies. It will be the first network dedicated to critically examining <em>and </em>intervening on the co-production of birth cohorts and biosocial science.</p>
|
| 02/05/2019 |
£26,706 |
|
UNIVERSITY OF SURREY |
<p style="margin-left: 0cm; margin-right: 0cm">FUTURESEX at the University of Surrey is developing a robust and sustainable network of scholars in sexuality studies, engaging with cutting-edge creative practices to do research relevant to minority groups.</p>
<p style="margin-left: 0cm; margin-right: 0cm"><strong>FUTURESEX: Academia and Activism</strong> will engage activists and community members with individuals from different stages of their academic career. Specifically, an activist-run workshop and a public lecture will help scholars in sexualities studies reflect on the history and future of the field. <strong>FUTURESEX: The Remix</strong> will explore how innovative methodologies and creative and artistic practices can inform research. A 2-day collaborative process with dancers will produce a performance and encourage thinking about research challenges in innovative ways. <strong>FUTURESEX 2020 </strong>will complete the programme with a 3-day international conference, asking <em>What can art, activism and academia tell us about the futures of sex, gender and sexuality?</em></p>
<p style="margin-left: 0cm; margin-right: 0cm">This grant will bring together PhD, ECRs and academics for regular shared social and intellectual exchange, developing new visions for research and publication guided by community concerns and creative practices. Funding is needed to make the events accessible to PhDs, ECRs, activists and artists.</p>
|
| 02/05/2019 |
£29,972 |
|
KING'S COLLEGE LONDON |
<p>We propose an international research network that focuses on the ways that race and biomedicine are mobilized beyond the lab in the 21st century. We seek to foreground how non-scientists are at the forefront of novel, plural, generative deployments of biomedical ideas of race that either entrench or resist historical ideas about race and its relation to biology across domains of environments, markets, and human rights. To do this we will 1) organize an international conference that will chart the global dimensions of 21st century uses of biomedical ideas of race in wide-ranging social arenas 2) hold an international workshop to deepen and develop the engagement among the key members of the network, 3) produce a series of scholarly and public-facing publications that detail contemporary initiatives that deploy biomedical ideas of race and 4) lay the groundwork for more ambitious collaborative research among network members. On the basis of these components, we will establish a multi-pronged, evolving, and long term plan to develop a robust programme of future research collaboration, including sourcing additional funding to guarantee the continued growth of the network and its work.</p>
|
| 02/05/2019 |
£29,461 |
|
NEWCASTLE UNIVERSITY |
<p>Our key goal is to establish a network and programme of activities that explore the intersection between medical and environmental humanities. Our ambition is to lead research in this field from an historically-informed humanities standpoint and to develop future research collaborations to consider the rich nature of human and non-human interrelationships and their impact on health and wellbeing. A series of thematic workshops will focus on the key challenges of Climate, Animals and Healthy Cities, and a biennial conference will be established to further research on the complex relationships between health and environment from a humanities perspective. We aim to develop new collaborative research proposals as well as build capacity. Therefore the network will use the programme of activities to support and encourage postgraduate students and postdoctoral researchers who work in these fields.<br>
</p>
|
| 02/05/2019 |
£21,007 |
|
UNIVERSITY OF DURHAM |
<p>It is a widely-shared assumption that we ought not to treat rational adults paternalistically. In particular, we should respect agents’ decisions about their own medical treatment. Yet in certain public health contexts it seems more appropriate to focus on promoting citizens’ well-being, rather than on respecting choices.</p>
<p>Indeed, in some contexts it is not obvious what respecting autonomous decisions would require. For example, when dealing with diverse groups with conflicting preferences, or when implementing public health policies for populations whose autonomous capacities might be called into question, such as children and disabled individuals. Do we still have a responsibility to avoid paternalism in these cases? Is paternalistic treatment even <em>possible</em> here, if we cannot identify the autonomous will of these individuals or groups?</p>
<p>The philosophical literature has produced sophisticated models of paternalism, but typically focuses on small-scale interactions between individuals. Thus, it fails to adequately engage with these more complex, but practically important, cases. Over four inter-disciplinary workshops, the proposed project aims to rectify this. We will stimulate new collaborative research to ground the philosophical discussion in the problems that are animating public and professional debate, as well as developing theoretical frameworks that can inform and structure potential policy responses.</p>
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| 02/05/2019 |
£39,000 |
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UNIVERSITY OF STRATHCLYDE |
<p> </p>
<p>Markets for intoxicating and psychoactive substances in both Africa and Asia seem to be rapidly changing (UNODC 2018). Yet this is not the first time that these continents have experienced such developments. Tobacco entered markets in both during the century after 1600, opium-smoking became popular in Asia in the 1700s, while cannabis and alcohol were identified as problem substances in Africa in the nineteenth century. This project will explore links between previous episodes and the contemporary situation, to better inform understandings of both.</p>
<p> </p>
<p>This project will:</p>
<p><br>
1. Connect historians around the world with those working in Asia and Africa, through the Alcohol and Drugs History Society (ADHS), in order to disseminate existing knowledge and to generate new research related to the history of psychoactive and intoxicating substances.<br>
2. Use two high profile ADHS conferences, one in Asia and one in Africa, to highlight the importance of historical research into these substances to both academic and non-academic user groups on these continents.<br>
3. Establish working relationships to grow a framework for the preparation of future post-graduates in the field.<br>
4. Scope out funding sources for future activities that will include further meetings, new research, postgraduate opportunities and impact-programmes.</p>
<p> </p>
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| 02/05/2019 |
£23,567 |
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UNIVERSITY OF STIRLING |
<p style="margin-left: 0in; margin-right: 0in">Image and performance enhancing drug (IPED) use is growing globally. Polydrug use is commonly reported by IPED users and includes both recreational drugs and drugs for controlling side effects of IPEDs. People who use IPEDs face the same risks as other groups who use or inject recreational drugs—including for blood borne viruses among injectors—but have far fewer targeted health services or information available for reducing or managing those risks. IPED use sits in the divide between sports doping research and that focused on more traditional (i.e. recreational) substance use. However, IPEDs and IPED use has been largely understudied by both groups of researchers, leaving a gap in our understanding of this population of users especially as it relates to polydrug use. I propose two sets of meetings/workshops that will 1) map the IPED/polydrug landscape in Scotland, and 2) provide a forum for knowledge exchange and network building among an international group of academics working on issues of IPEDs and polydrug use. The overarching objective of these two events is to build a robust research network for researchers and health practitioners working on issues related to polydrug use and IPEDs by bringing experts together for two knowledge exchange workshops.</p>
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| 02/05/2019 |
£31,827 |
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UNIVERSITY OF CAMBRIDGE |
<p>This application is to enable the Cambridge Department of History and Philosophy of Science, a major centre of research in history of medicine and health, and the leading international centre for history of reproduction, to continue the annual Cambridge Wellcome Lecture in the History of Medicine and to maintain and enhance our seminar series now that Wellcome core-funding awards have ended. The public lecture is the highlight of our year, an opportunity to showcase work, draw together a large community and invite advisors from Wellcome to speak to prospective and existing grantholders. The seminars, which alternate between ‘early medicine’, ‘modern medicine and biology’ and ‘generation to reproduction’, are an important forum for training, exchange and networking and the main intellectual focus for the department’s expanding group of historians of medicine and health. We will increase the value of the seminars by more routinely inviting colleagues from continental Europe, and by increasing access through covering the full cost of dinners. The reproduction theme develops our leadership role in that field; the other strands ensure intellectual breadth and provide space for new areas of special strength to emerge.</p>
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| 02/05/2019 |
£28,235 |
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UNIVERSITY COLLEGE LONDON |
<p style="margin-left: 0in; margin-right: 0in">This proposal focuses on an urgent humanitarian case: the case of Gaza. The projects will go beyond the tendency to approach health from a medical perspective, suggesting to examine how power, violence and health are entangled. This interdisciplinary research aims to understand how the organization of space affects the right to health of communities, suggesting that the linkages between health, death, life and space should be understood within a wider context, where freedom of movement, access to public services and infrastructure, as well as freedom from environmental hazards, are obvious and fundamental rights linked to space<strong>.</strong> Our objective is threefold: to document and critically analyse the effect of infrastructure demolition on health in Gaza especially in relation to: access to health services, access to nutrition, access to water; to nuance humanitarian interventions and their effects on health in Gaza; to examine emerging alternative forms of resilience in relation to health among Gaza inhabitants. The sensitivities of this proposal demand an in-depth conversation, consultation and advice from experts, beyond those already designated above, in the fields of health, sanitation and resources in violent conflict. Hence, a workshop will be organized with an advisory board of international experts who will support us.</p>
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| 02/05/2019 |
£30,300 |
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INSTITUTE OF MEDICAL ETHICS |
<p>This proposal seeks funding to develop and sustain a network of postgraduate students by bringing them together through a programme of activities over the duration of the grant. The key goals are to enable students to exchange ideas, develop skills and learn in a supportive space. The Postgraduate Bioethics Conference (PGBC) was first held in 2006 and its continuing success is in large part due to it being student directed. Last year, in recognition of the lack of a sustained network, we initiated a programme of events that proved to be very popular. Building on momentum is vital at this early stage of network development. With this in mind, we aim to hold two workshops between the two annual conferences. Reflecting on last year, we have asked for a 16 month grant period in order to allow sufficient time to plan and deliver events of the highest quality, whilst also producing a newsletter and commencing the alumni network. Events will be at a number of different universities and bursaries will ensure funding is not a barrier to access. All of the activities are aimed at increasing UK-wide engagement with bioethics research and ensuring the sustainability and inclusivity of the network. </p>
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