Cookies disclaimer

I agree Our site saves small pieces of text information (cookies) on your device in order to deliver better content and for statistical purposes. You can disable the usage of cookies by changing the settings of your browser. By browsing our website without changing the browser settings you grant us permission to store that information on your device.

Current Filters

Recipients:
Broadfield Primary School
University of Oxford
Amounts:
£500 - £1,000
Award Year:
2017

Results

CHIM - Shigella sonnei in Vietnamese adults - Development funds 17 Nov 2017

<p>Diarrhoea remains a major cause of childhood morbidity and mortality globally. The vast majority of the 2 billion<br> annual diarrhoeal infections occur in low and middle-income countries (LMICs). Members of the genus <em>Shigella</em><br> are key agents of diarrhoea in LMICs, and <em>S. sonnei </em>is replacing <em>S. flexneri </em>as the predominant species globally.<br> There is a necessity to improve our knowledge of <em>S. sonnei</em> infections in LMICs, with a specific requirement to<br> better understand host-pathogen interactions and the natural history of disease in a setting where the organism<br> is well understood, well described, and associated with a significant disease burden. Therefore, we aim to<br> establish a Controlled Human Infection Model (CHIM) of <em>S. sonnei</em> diarrhoea in healthy Vietnamese adults.&nbsp;</p> <p>&nbsp;</p> <p>This is an innovative project will be the first CHIM study conducted at the Vietnam MOP.&nbsp; Therefore, it is imperative that the project is carefully designed in consultation with all relevant stakeholders. In order to ensure that the proposal is developed to the required standard in the timeframe available, I am requesting funds to employ an international postdoctoral assistant, with a background in microbiology and clinical research on a consultancy basis.&nbsp;</p>

Amount: £21,120
Funder: The Wellcome Trust
Recipient: University of Oxford

Malaria Controlled Human Infection Model - application development 17 Nov 2017

<p>We wish to apply for funds to develop the malaria CHIM application. These are for a Co-investigators/stakeholders meeting to be held in Bangkok, Thailand, on 30<sup>th</sup> and 31<sup>st</sup> January 2018 and to support a writing meeting of the PIs in February 2018 in Kilifi, Kenya.</p>

Amount: £22,186
Funder: The Wellcome Trust
Recipient: University of Oxford

Dengue Controlled Human Infection Model - Development Grant 17 Nov 2017

<p>Following a positive response to the&nbsp;preliminary submission for grant funding&nbsp;to&nbsp;establish a Dengue Controlled Human Infection Model (Dengue-CHIM )&nbsp;in Ho Chi Minh City, Vietnam, I am submitting this request&nbsp;for a small grant&nbsp;to assist in refining and&nbsp;developing the main proposal prior to&nbsp;final&nbsp;submission in March 2018.</p> <p>&nbsp;</p> <p>During this pre-submission phase I plan to employ an experienced&nbsp;post-doctoral immunologist to carry out a) a scoping review of the current landscape of dengue vaccines in development, and b) a review exploring the&nbsp;current understanding of the immune response to/protection from&nbsp;DENV infection and disease, particularly focusing on&nbsp;immune correlates of protection.&nbsp;</p> <p>&nbsp;</p> <p>This will be the first application of a Dengue-CHIM approach in any dengue&nbsp;endemic setting, and&nbsp;raises a number of important bioethical&nbsp;concerns. Therefore I also plan to employ a Vietnamese social science research assistant for a period of 4 months&nbsp;to engage with&nbsp;key Vietnamese stakeholders to discuss the important issues surrounding endemic setting&nbsp;CHIMs,&nbsp;conduct preliminary informal interviews with these individuals, and help to develop the agenda for&nbsp;a 2 day &nbsp;workshop&nbsp;focused on Bioethics and Stakeholder Engagement related to endemic setting CHIMs that will take place in early March.<br> &nbsp;&nbsp;</p> <p>&nbsp;</p> <p>&nbsp;</p>

Amount: £23,690
Funder: The Wellcome Trust
Recipient: University of Oxford

A realist review of community engagement with health research 07 Dec 2017

<p>The project will conduct a comprehensive review of community engagement using a realist review approach appropriate for tackling the conceptual complexity and practical diversity of the field. A review team with worldleading expertise in the theory and practice of CE will be supported by an advisory panel of internationally renowned realist review scholars. The review will begin with engagement with malaria research as a &lsquo;pathfinder&rsquo; topic &ndash; and draw on a network of content experts, implementers and funders to input into and validate the review, ensuring its findings are widely disseminated and embedded in international CE work.</p> <p>Wellcome, BMFG and leading global health funders and implementation partners will benefit from a consolidated evidence base to underpin development of CE strategies in global health research and interventions. Outputs will include articles in peer reviewed open-access journals, an accessible evidence base on MESH/HELP, including context-relevant guidance for developing and evaluating CE strategies, and a critical mass of academics, practitioners, implementers and funders with a mutual interest in strengthening the theory and practice of engagement. In this way the review will spearhead the beginnings of a &lsquo;science&rsquo; of community engagement and outline a clear value proposition for CE in global health research (14).</p>

Amount: £260,250
Funder: The Wellcome Trust
Recipient: University of Oxford

Overcoming contraceptive discontinuation by overcoming side-effects: paving the way for personalized contraception in Ethiopia 04 Dec 2017

<p>In the developing world, millions of women discontinue hormonal contraception due to the experience of debilitating physiological side-effects (e.g. excessive and irregular bleeding), yet the causes of these adverse effects is not known. This project will be the first to test the hypothesis that side-effects are caused by unnecessarily high dosage of exogenous hormones in hormonal contraceptives (e.g. injectables) compared with women&rsquo;s endogenous hormones, with the aims of accumulating primary evidence for optimizing contraception to communities and individuals. The research will focus on the use of injectables in Ethiopia, where unmet needs for contraception reach the highest levels in Africa. The PI will build on both an interdisciplinary team of researchers in anthropology, population health, epidemiology, microbiology and medicine and a long-term collaboration with the Institute of Development and Policy Research of Addis Ababa University to implement and run the project. The findings will act as a stepping stone to both engage pharmaceuticals and scale-up the research to produce a statistical model for delivering contraception, predicting, given a woman&rsquo;s context, the range of contraceptive doses minimizing side-effects whilst still suppressing ovulation. This predictive model will be taken to stakeholders worldwide to stimulate transformational innovations for designing and delivering variable-dose contraceptives.</p>

Amount: £97,126
Funder: The Wellcome Trust
Recipient: University of Oxford

Vacation Scholarships 2017 - University of Oxford 16 Jun 2017

<p>Vacation Scholarships 2017-University of Oxford</p>

Amount: £15,500
Funder: The Wellcome Trust
Recipient: University of Oxford

Improving health outcomes for looked after children and young people 25 May 2017

<p>Previous research suggests that looked after children are less likely to be treated in the way that the statutory guidance on promoting the health and well-being of looked after children recommends, and that they receive worse healthcare in comparison to their non-looked after peers. They also have worse experiences of the health service, and due to complex and time consuming policies and procedures, are treated inefficiently or inappropriately. My POSTnote will seek to summarise the current policy context on promoting the health of looked after children and young people, consider any related issues that may need to be addressed in future policy and explore the latest research and information on how best to promote their health. By promoting their long-term health outcomes, care leavers should be more able to go on to lead successful and happy lives, in which they are able to contribute to society. By undertaking this fellowship I hope to better understand:</p> <ul> <li>The process of creating a rigorous POSTnote for parliamentarians</li> <li>How parliamentarians use research to inform policy</li> <li>The process of policy development</li> <li>The role of Select Committees, and</li> <li>The role of All Party Parliamentary Groups</li> </ul>

Amount: £8,010
Funder: The Wellcome Trust
Recipient: University of Oxford

ISA-InterMine: accelerating and rewarding data sharing 06 Jul 2017

<p>There is a growing recognition that research should be carried out in an open fashion, making data available early and in a reusable form to maximise worldwide research output. However, fulfilling this promise requires front-line researchers to comply with current data management standards as required by the data policies of funders and journals. These are additional burdens to research that will give them little immediate return.</p> <p>&nbsp;</p> <p>Thus we propose to create a cloud-based, open-source, extensible data collection and presentation platform that will provide scientists with: (1) immediate reward for their annotation efforts through sharable data visualisation, integration outputs and exploration tools; (2) standardised web services to facilitate script-based data manipulation and analysis; (3) an easy-to-use pipeline for preparing their data for publication; (4) incentives to improve data quality, accessibility, and machine-actionability at the appropriate level of granularity; and (5) allow institutions and other parties to host the platform to ensure its availability and reliability.</p> <p>&nbsp;</p> <p>We will do this by building on the success and complementarity of the ISA tools suite (Oxford) and the InterMine platform (Cambridge) to make it quicker and easier to generate rich integrated dynamic web sites at single paper/lab scale up to consortium scale.</p>

Amount: £504,250
Funder: The Wellcome Trust
Recipient: University of Oxford

Data sharing platforms to improve treatment outcomes in neglected tropical diseases 06 Jul 2017

<p>We will develop data-sharing platforms to assimilate and collaboratively interrogate global data on i) schistosomiasis ii) soil transmitted helminths, iii) visceral leishmaniasis, iv) melioidosis and v) scrub typhus. This proposal will support the development of the technical platform and curation of data from tens of thousands of patients enrolled to treatment trials and programmatic data of these diseases for use in collaborative meta-analysis to answer key public health questions. The platform&rsquo;s technical infrastructure will include secure data upload, auditable mapping of multi-disciplinary datasets to a standardised data structure, searchable data inventory and systems to request and receive data. The governance framework will ensure terms of data access that follow principles of equitable and ethical data sharing under the guidance of Science Advisory Committees nominated by the relevant disease communities. Support for the coordination and production of scientific output from the platform will be provided to ensure impact. Platform construction will leverage the expertise and investment in our existing malaria data platform, the WorldWide Antimalarial Resistance Network (WWARN). Prior funding has supported the development of successful pilot platforms for visceral leishmaniasis and schistosomiasis/soil-transmitted helminths, and we will assess the feasibility and impact of establishing platforms for melioidosis and scrub typhus.&nbsp;</p>

Amount: £1,406,744
Funder: The Wellcome Trust
Recipient: University of Oxford

LipID: A Lipid Annotation Tool for Membrane Proteins 06 Jul 2017

<p>Interactions of membrane proteins with lipids are important in their stability, regulation, and targeting. These interactions are of biomedical importance given the roles of membrane proteins in disease and as drug targets; with drugs often acting via lipid binding sites. We will develop a computational pipeline and database for molecular simulations to predict the structure, specificity, and affinity of membrane protein/lipid interactions. This will provide a unique 'computational biochemistry' resource for functional annotation of membrane protein structures, identifying potentially druggable sites. Building upon our MemProtMD methodology (http://sbcb.bioch.ox.ac.uk/memprotmd/), we will provide a server enabling simulation-based predictions of lipid binding sites to membrane protein structures, defining the structural basis of lipid interactions for each protein alongside predictions of lipid specificity and affinities. We have successfully established proof-of-principle methodologies which allow us to predict and explore free energy landscapes of membrane protein-lipid interactions. This technology needs methodological development to improve the accuracy, applicability, and robustness of predictions of lipid-protein interactions. We will develop a high-throughput software pipeline for lipid annotation of membrane proteins (LipID) for both known and new structures of two major groupings of membrane protein: (i) receptors, channels, and transporters from humans; and (ii) membrane proteins from pathogenic bacteria.</p> <p>&nbsp;</p>

Amount: £719,367
Funder: The Wellcome Trust
Recipient: University of Oxford

Forecasting dengue cases: Vietnam as a case study 19 Jun 2017

<p>Vector-borne infectious diseases continue to be a burden to Vietnam&rsquo;s economy and population health. Understanding the spatiotemporal patterns of the disease transmission is thus vital for planning resources and targeting control measures. In this work, we propose a large-scale study on how different factors interact and contribute to the dynamics of dengue in Vietnam.</p> <p>We will employ multiple modelling techniques to analyse the dynamics of the disease and how to best predict future cases. We hypothesise that urbanisation has played a significant role in deriving the distribution of the Aedes mosquito and on dengue transmission, and will therefore incorporate factors about urbanisation gained from satellite images into predictive models. These models will use three main methods: statistical, mechanistic and machine learning.</p> <p>The key goal is to predict the number of new dengue cases as far as possible, and we will work in collaboration with those who use the forecasts to assess the most useful timeframe and accuracy. A particular aim will be the prediction of upcoming hotspots of dengue transmission so that hospitals can plan their resources. We will work to present the results clearly so they can best be used to help to reduce dengue burden in Vietnam.</p>

Amount: £82,952
Funder: The Wellcome Trust
Recipient: University of Oxford

The Ethics of Genome Editing in Livestock 17 Jul 2017

<p>Genome editing in livestock (GEL) could potentially be used to mitigate urgent global problems of infectious disease, antimicrobial resistance, global warming, and animal suffering while also increasing agricultural productivity. Despite its imminence and potentially transformative potential, there has been minimal ethical debate about GEL. This project will provide the first in-depth philosophical analysis of GEL, focussing on four questions on which such research is most urgently needed: (1) How far do ethical concerns raised in relation to conventional genetic engineering using previous techniques carry over to GEL? (2) Are the arguments in favour of GEL best understood in terms of cost-benefit analysis, an obligation to 'arm ourselves for the future' or an obligation to correct past complicity in unethical agricultural practices? (3) How should duties to animals be understood in the context of GEL, and what is the relative importance of welfare, respect, and avoidance of commodification? (4) Would application of GEL to improve human and animal welfare entail complicity in maintaining unethical agricultural practices and if so, how could this complicity be reduced or offset? I will then investigate how my findings bear on how GEL should be regulated, and on related areas of public policy.</p>

Amount: £227,968
Funder: The Wellcome Trust
Recipient: University of Oxford

The evaluation of effective healthcare delivery in China using electronic medical records for 10 years in 0.5M participants in the China Kadoorie Biobank 02 May 2017

<p>This&nbsp;DPhil project will&nbsp;assess the social determinants and&nbsp;equality&nbsp;in hospital care delivery and use, in 0.5 million participants who have been followed up for 10 years in the China Kadoorie Biobank. The first&nbsp;goal&nbsp;of this research is&nbsp;to&nbsp;evaluate differences in the annual rates of people hospitalised, the annual rates of hospital admissions per person, and the average length of stay (ALOS) overall and for 10 of the most frequent causes of hospitalisation (5 mostly unavoidable and 5 mostly avoidable causes)&nbsp;over the last 10 years and by&nbsp;region, hospital-tier, type of health insurance (HI) package and socioeconomic characteristics. Another goal&nbsp;is to study the variation&nbsp;in hospital care costs in China, considering&nbsp;LOS, and use of specialised procedures and&nbsp;major treatments, overall and for the 10 most frequent causes<strong> </strong>of hospitalisation over the last 10 years, by region, hospital-tier, HI package, and socioeconomic characteristics.&nbsp;Finally,&nbsp;the inequalities behind the variation in use&nbsp;and costs of hospital care will be investigated across&nbsp;regions, HI package and socioeconomic characteristics. This will provide the reliable quantitative evidence to evaluate operational defects and plan&nbsp;initiatives to improve&nbsp;healthcare delivery by individual hospitals, HI organisations and the wider community in China.</p>

Amount: £95,184
Funder: The Wellcome Trust
Recipient: University of Oxford

Healing Heathen Lands: Protestant Missions and Public Health in British India, 1855-1956 17 Jul 2017

<p>This project will explore the role of Protestant missions in the making of British Indian public health by tracing the interactions between evangelical, colonial and vernacular sources. It will argue that Protestant missionaries in South Asia did not merely play a complementary role to imperial biomedicine. It will examine the ways in which missions&nbsp;contributed towards shaping colonial health policies as well as knowledge of colonial disease and treatment. The project would also explore the extent to which Indians and their knowledge was involved in medical missions.&nbsp;This work will add on&nbsp;to&nbsp;histories of imperial medicine, international health, global history, colonial Christianity and postcolonial studies.</p> <p>&nbsp;</p> <p>The key goal of the project is to produce a monograph explaining the distinctiveness and significance of Protestant missionary medicine in South Asia. The project will be contributing to the emerging literature on British voluntary religious organisations in the making of imperial public health. It will also contribute to the broader literature on the relationship of modern science and&nbsp;medicine with Christianity.&nbsp;</p>

Amount: £174,774
Funder: The Wellcome Trust
Recipient: University of Oxford

Decision-making by lymphocytes 11 Jul 2017

<p>It was recognized sixty years ago that a &ldquo;trigger mechanism&rdquo; must initiate immune responses. Today, however, not even the broad features of the mechanism are fully agreed, despite its intrinsic scientific interest and the remarkable clinical utility of modulating lymphocyte behaviour. We do know, however, that it encompasses two separate events: receptor triggering <em>per se</em>, and the integration of multiple triggering outputs. Breakthrough developments in fluorescence imaging mean that we can now study molecular behaviour at cell-cell interfaces at single-molecule resolution, in real time. This means that we can directly test whether TCR triggering is explained by a theory relying on the local, physical exclusion of phosphatases from sites of receptor engagement and phosphorylation, called the kinetic-segregation model. We will explore how 'close-contact' formation affects the interplay of local signaling molecules, and test our theory using quantitative models of receptor signaling. We will also study the emergent properties of the types of modular networks known to mediate downstream signaling in T cells and, building on these findings, test a new, simple theory of signal integration. This programme of work will produce a fuller understanding of decision-making by lymphocytes, and a richer framework for thinking about immunotherapy.</p>

Amount: £2,400,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Control of T cell responses by accessory receptors revealed by phenotypic models 11 Jul 2017

<p>T cells orchestrate immune responses crucial for the elimination of infections and cancers. They do this by initiating a diverse set of effector responses when their T cell surface receptors (TCRs) recognise these threats. It is now appreciated that a large number of other, &ldquo;accessory&rdquo;, receptors shape these responses. Indeed, the remarkable clinical success of checkpoint inhibitors and chimeric antigen receptors is based on perturbing accessory receptor signalling. Despite extensive research into the underlying biochemistry, we have yet to formulate canonical models of signalling that can predict how accessory receptors shape T cell responses. Here, we propose to use a mathematical method known as adaptive inference to identify signalling models directly from T cell response data, without prior biochemical assumptions. The method produces what we term &quot;phenotypic models&quot; because it coarse-grains over molecular information. These models provide effective pathway architectures showing how accessory receptors integrate (or not) with TCR signalling to shape response phenotypes. This will move the field beyond the current stimulatory/inhibitory binary paradigm of accessory receptors. The work offers a different way to study receptor regulated signalling pathways and the predictive power of the phenotypic model will be exploited for T cell-based therapies.</p>

Amount: £1,783,754
Funder: The Wellcome Trust
Recipient: University of Oxford

Can a system intervention employing team-based case review help improve quality and safety of paediatric hospital care in Kenya? 11 Jul 2017

<p>In Kenya 6% of children admitted to hospital die, a figure many times higher than developed countries. Severe illness and co-morbidity underlie many deaths and require a coordinated response from health-worker teams to deliver multiple interventions safely across admission periods of several days. This can expose many team and system weaknesses that need to be addressed to improve outcomes. I will build on prior work in Kenya to:</p> <ol> <li>Comprehensively describe quality and safety concerns, avoidable mortality, their relationship with case severity and case complexity and the changing epidemiology of care in multiple Kenyan county hospitals</li> <li>Co-design the tools and procedures that enable multi-site, team-based case review (TCR) to diagnose and tackle inpatient quality and safety concerns locally and at scale</li> <li>Test if intervention can reduce the frequency of modifiable factors that undermine quality and safety of hospital care and reduce potentially avoidable mortality</li> <li>Undertake empirical work to refine a theory of change supporting a detailed process evaluation and critical exploration of mechanisms of intervention effect spanning individual providers, teams, organisations and institutions</li> </ol> <p>This work will be a major contribution to the field of quality and safety in Africa and help develop scalable improvement interventions.</p>

Amount: £2,553,243
Funder: The Wellcome Trust
Recipient: University of Oxford

Molecular characterisation of antibiotic tolerance in Mycobacterium tuberculosis 11 Jul 2017

Tuberculosis, caused by Mycobacterium tuberculosis still causes 1.8 million deaths per year and takes months to years to treat. Long treatment times are due to subpopulation(s) of bacteria that, although genetically susceptible, are not killed effectively by antibiotics – termed antibiotic tolerance. Understanding mechanisms of antibiotic tolerance is the key to shortening treatment times for tuberculosis. We have recently shown that mycobacteria use the essential amidotransferase GatCAB to regulate rates of specific errors in gene translation and that mistranslation is both necessary and sufficient for tolerance to rifampicin – the most important anti-tuberculous drug. However, the precise molecular mechanisms by which GatCAB and the mycobacterial translation machinery control fidelity are not understood. We have also recently identified further mechanisms which contribute to rifampicin tolerance. We now propose to determine the mechanism by which GatCAB modulates mistranslation rates. We also propose three complementary forward genetic screens to a) comprehensively identify the pathways that regulate mycobacterial translational fidelity; b) employ bacterial genome-wide association studies to identify mutations that influence rifampicin tolerance in clinical isolates, and c) use saturating transposon insertion mutagenesis and deep sequencing to identify mycobacterial genes that cause differential rifampicin susceptibility in a murine model of antibiotic treatment.

Amount: £236,883
Funder: The Wellcome Trust
Recipient: University of Oxford

Understanding mechanisms that drive pain perception in early human development 11 Jul 2017

<p>Pain in infancy has negative long-term consequences and its prevention is a clinical priority, but adequate treatment requires mechanistic understanding of the structural and functional development of human nociceptive circuitry. Recent scientific and technological advances provide insights into how noxious information is transmitted to the infant brain, providing a platform to ask how intrinsic brain network connectivity and the environment affect noxious-evoked brain activity, behaviour and ultimately pain perception in the developing infant nervous system.&nbsp;<strong>The fellowship goal is to understand the mechanisms that drive and modulate&nbsp;pain perception in early human development.</strong> I will ask whether inherent differences in how the brain behaves at rest influence&nbsp;variability in noxious-evoked activity, and will determine how this relationship is altered by environmental factors and pathology. I will establish how the development of structural and functional network connectivity alters noxious-evoked brain activity, and influences the dynamic relationship between brain activity and behaviour. I will translate this mechanistic understanding into clinical practice by conducting a clinical trial of an analgesic (fentanyl) during a minor surgical procedure, and will establish whether our newly-developed measures of noxious-evoked brain activity are suitable for use in infant analgesic dose-finding studies.</p>

Amount: £1,953,181
Funder: The Wellcome Trust
Recipient: University of Oxford

Understanding mechanisms that drive pain perception in early human development 11 Jul 2017

<p>Pain in infancy has negative long-term consequences and its prevention is a clinical priority, but adequate treatment requires mechanistic understanding of the structural and functional development of human nociceptive circuitry. Recent scientific and technological advances provide insights into how noxious information is transmitted to the infant brain, providing a platform to ask how intrinsic brain network connectivity and the environment affect noxious-evoked brain activity, behaviour and ultimately pain perception in the developing infant nervous system.&nbsp;<strong>The fellowship goal is to understand the mechanisms that drive and modulate&nbsp;pain perception in early human development.</strong> I will ask whether inherent differences in how the brain behaves at rest influence&nbsp;variability in noxious-evoked activity, and will determine how this relationship is altered by environmental factors and pathology. I will establish how the development of structural and functional network connectivity alters noxious-evoked brain activity, and influences the dynamic relationship between brain activity and behaviour. I will translate this mechanistic understanding into clinical practice by conducting a clinical trial of an analgesic (fentanyl) during a minor surgical procedure, and will establish whether our newly-developed measures of noxious-evoked brain activity are suitable for use in infant analgesic dose-finding studies.</p>

Amount: £60,000
Funder: The Wellcome Trust
Recipient: University of Oxford