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:
University of Oxford

Results

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

Diarrhoea remains a major cause of childhood morbidity and mortality globally. The vast majority of the 2 billion annual diarrhoeal infections occur in low and middle-income countries (LMICs). Members of the genus Shigella are key agents of diarrhoea in LMICs, and S. sonnei is replacing S. flexneri as the predominant species globally. There is a necessity to improve our knowledge of S. sonnei infections in LMICs, with a specific requirement to better understand host-pathogen interactions and the natural history of disease in a setting where the organism is well understood, well described, and associated with a significant disease burden. Therefore, we aim to establish a Controlled Human Infection Model (CHIM) of S. sonnei diarrhoea in healthy Vietnamese adults. This is an innovative project will be the first CHIM study conducted at the Vietnam MOP. 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.

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

Institutional Translation Partnership Award (iTPA): Thailand Major Overseas Programme 30 Sep 2018

The team at MORU will focus on closing the gap between research and implementing interventions, building capacity and expertise to support early translation to improve the health of people in low-income countries.

Amount: £988,404
Funder: The Wellcome Trust
Recipient: University of Oxford

open access award 2017/18 30 Sep 2018

Not available

Amount: £100,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Flexible task representations for intelligent behavior 24 Apr 2018

A long research tradition in cognitive neuroscience has investigated the role of the prefrontal cortex (PFC) in flexible goal-directed behaviour. This work has yielded important insights, e.g., that the PFC’s coding properties flexibly adapt when task demands change to prioritise goal-relevant information. However, it relies primarily upon the use of familiar and explicitly instructed tasks that provide poor fit to human behaviour in naturalistic and open-ended environments, and likely miss essential aspects PFC function. I therefore propose to study the representations that form within PFC as humans learn to perform complex categorisation tasks with only minimal external instruction. I hypothesise that during learning the PFC will form abstract representations of the task’s latent structure, that support not only performance in the given task, but also provide provides a scaffold for learning in similar environments. Using representational similarity analyses, in combination with multiple brain recording techniques (fMRI, MEG, ECoG), I will measure how stimulus-evoked neural responses change adaptively during learning, and test if these changes generalise to novel task environments with similar structure. These findings will provide important new insights about the coding mechanisms by which PFC supports flexible behaviour in complex, naturalistic environments.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford
Amount: £11,000
Funder: The Wellcome Trust
Recipient: University of Oxford

Investigating the GWAS-identified target NCX3 in nociception 30 Sep 2018

Evolutionary, pain is a protective sensation. However, it can persist beyond its usefulness and become debilitating for patients. Chronic pain affects up to one half of the population in the UK (Fayaz et al, 2016). Currently, the treatment options are limited and discovering new drug targets is of great importance. In a recent genetic study (genome-wide association study), we identified a gene (SLC8A3 encoding the protein NCX3), which was associated with higher pain sensitivity to experimental pain stimuli in healthy participants. My thesis will therefore focus on studying the function of NCX3 on a molecular, cellular and systems level. NCX3 is an important part of the machinery that moves ions in and out of cells. Its role in pain is poorly understood, but previous reports show that it is involved in regulating Ca2+ levels in pain-sensing neurones. Inhibition of NCX3 can cause increased Ca2+ in these cells leading to higher activation of the central nervous system and increasing pain sensation. To investigate the function of NCX3, I will use genetically modified mice lacking the gene as well as isolated pain-sensing neurones. Our genetic data, combined with published results, makes NCX3 an attractive target for future research and drug discovery.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Signal transduction of the GPCR Smoothened: a key protein in Hedgehog-regulated morphogenesis and oncogenesis 30 Sep 2018

In complex multicellular organisms, cell-to-cell communication is often managed by morphogen gradients. The secreted Hedgehog ligands fall within this class, as they act in this manner during embryonic development. The Hedgehog signalling pathway (stimulated by these morphogens) tightly regulates crucial developmental processes including body patterning and symmetry. Serious developmental disorders result from inactivation of this pathway during embryogenesis, including holoprosencephaly and cyclopia. Hedgehog signalling is also active through stem cell programs throughout adult life, and aberrant Hedgehog activation, either ligand dependent or mutations in pathway components, can lead to cancer including medulloblastoma and basal cell carcinoma. The G-protein coupled receptor (GPCR) Smoothened is a key protein of this pathway, as it initiates the intracellular cascade, and is already targeted by anti-cancer drugs including Vismodegib and Sonidegib. However, the mechanism of signal transduction has only been poorly characterised. This project aims to explore this using both structural and biophysical approaches. We will study the mechanism and interplay of the two identified ligand-binding sites and the dynamics of agonist association with Smoothened. The ultimate goal is to determine the structure of active-state Smoothened and hence describe the mechanism by which its signal is transmitted across the plasma membrane.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Large-scale data integration to advance mechanistic inference and precision medicine in type 2 diabetes 17 Jul 2018

Advances in understanding the genetic and genomic basis of complex diseases have had limited impact on the delivery of translational goals, including those concerning personalised management. Recently, we have shown that, by integrating information on quantitative trait associations and tissue-specific regulatory annotation, genetic variants influencing type 2 diabetes (T2D) predisposition can be characterised in terms of the pathophysiological processes through which they operate. The central hypothesis of this proposal is that this allows a deconstruction of T2D pathophysiology that addresses phenotypic and clinical heterogeneity, promotes mechanistic insights, and reveals novel translational opportunities. The approach begins with generation of "process-based" genetic risk scores that better capture patterns of individual T2D-predisposition and phenotype. I will refine these risk scores, more precisely characterise the cellular, molecular and physiological events they reflect, and describe their relationships to clinical outcomes. For multifactorial diseases, there are limits to the clinical prediction achievable through genetics alone: I will combine genetic risk scores with measures of individual external and internal environment, and with clinical and biomarker data, to generate "integrated risk profiles".This approach aims to advance understanding of the pathophysiological basis of T2D and deliver precise, personalised information for key clinical outcomes including complication risk and therapeutic response.

Amount: £2,234,438
Funder: The Wellcome Trust
Recipient: University of Oxford

Plasmodium vivax Volunteer Infection Studies in Thailand 12 Mar 2018

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 Plasmodium vivax 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. 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. 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.

Amount: £996,222
Funder: The Wellcome Trust
Recipient: University of Oxford

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

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, "accessory", 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 phenotypic models 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.

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

All-optical interrogation of neural circuits during behaviour 26 Oct 2016

Neural circuits display complex spatiotemporal patterns of activity on the millisecond timescale. Understanding how these activity patterns drive behaviour is a fundamental problem in neuroscience. To address this challenge, I have recently introduced a novel approach that combines simultaneous two-photon calcium imaging and two-photon targeted optogenetic photostimulation with the use of a spatial light modulator (SLM) to provide 'all-optical' readout and manipulation of the same neurons in vivo. I propose to probe the neural code in mouse barrel cortex during sensory-guided behavioural tasks by using this approach to uncover the underlying mechanisms of decoding and encoding of information by ensembles of neurons. I will train mice to make perceptual decisions based on quantitative control of cortical activity, as well as perturb neural activity in somatosensory cortex while animals are performing discrimination tasks using their whiskers. I can perform decisive tests of theoretical models describing the neural code by assessing the spatiotemporal pattern of activation required in somatosensory cortex to drive a behavioral response. These experiments will shed light on how many neurons with which functional signature are minimally sufficient to subserve a percept.

Amount: £1,320,200
Funder: The Wellcome Trust
Recipient: University of Oxford

Utilising snake endogenous toxin inhibitors for the development of improved antivenom treatments 09 Nov 2016

Snake envenoming causes significant annual mortality, predominantly in the developing world. Currently the only effective treatment is antivenom, which is produced by hyperimmunising large animals with crude venom, and then extracting and purifying the antibodies raised against the snake proteins. This method requires keeping and maintaining large numbers of livestock, a key contributor to the high cost. Furthermore, the efficacy of antivenom is completely dependent on the venom sample(s) utilised for production, and the animal-derived antibodies can cause unwanted immunogenic effects in the patient, such as anaphylaxis. This project aims to make steps towards developing new antivenom treatments by utilising the endogenous toxin inhibitors used by snakes to protect themselves from their own venom. First, both the toxin and toxin inhibitor repertoire of 5 species of venomous snake will be elucidated using multi-'omic' technologies. Candidate inhibitors will be expressed in human cell lines, and subsequently tested experimentally to determine their efficacy in neutralising venom effects which cause the most life-threatening pathology. This method will revolutionise the antivenom field, and pave the way to developing treatments which are more cost effective, have fewer side effects, require no live animals, and have a greater and wider efficacy in treating snakebite.

Amount: £250,000
Funder: The Wellcome Trust
Recipient: University of Oxford

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

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. 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. 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.

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

Evidence for a pathogenic link between lung inflammation and autoimmune arthritis 27 Apr 2017

Our overall objective is to experimentally identify the early immunological events which trigger a spontaneous breach of tolerance in genetically susceptible mice, and, which can be linked to the development of arthritis. We will analyse the immunological reactivity of the lungs of susceptible mice to environmental stresses such as microbes. Our purpose is to identify early biomarkers of autoimmune initiation, which will be assessed for suitability as treatment targets with translational relevance. We will seek to determine the benefits of administration of anti-microbial agents for amelioration of lung inflammation with a view to prevention of autoimmune disease progression.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Oxford

Wellcome Centre for Integrative Neuroimaging 30 Oct 2016

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 WT Centre for Integrative Neuroimaging will enable novel insights into brain function that span levels of description, and therefore bridge the gap between laboratory neuroscience and human health. This will require fundamental discoveries concerning relationships between species and between scales, and major technological developments for mapping big-data discoveries onto neurobiological mechanisms. We will bring together diverse investigators who can tackle different themes within this grand challenge. Within each theme, neuroimaging will be used alongside complementary methodologies, ensuring that it takes inspiration from, and has impact on, areas beyond its typical reach.

Amount: £11,463,085
Funder: The Wellcome Trust
Recipient: University of Oxford

Wellcome Centre for Ethics and Humanities 30 Oct 2016

Building on the University of Oxford’s outstanding track record for research in ethics and the humanities, the Wellcome Centre for Ethics, Innovation, Globalisation and Medicine will conduct world-leading research on the ethical challenges presented by advances in medical science and technology. Much contemporary medical ethics, with its origins in 20th Century concerns, is no longer fit for purpose. New thinking is required. Through its research and engagement activities, the Centre will lead debate on the ethical requirements for 21st Century scientific research capable both of improving health and of commanding public trust and confidence. The Centre’s research will focus on four themes. The first will address challenges presented by the use of large-scale data-driven science. The second, will engage critically with ethical problems presented by developments in genomics. The third will investigate the ethical and social implications of neuroscience. The fourth will explore ethical questions arising out of greater global connectedness and interdependence. These activities will be complemented by a programme of cross-cutting research activities engaging with the issues presented by the convergence of these developments. The Centre will put in place a well-resourced, cutting-edge, and attractive programme of public engagement activities around the key issues addressed by its research.

Amount: £2,991,157
Funder: The Wellcome Trust
Recipient: University of Oxford

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

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: The process of creating a rigorous POSTnote for parliamentarians How parliamentarians use research to inform policy The process of policy development The role of Select Committees, and The role of All Party Parliamentary Groups

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

Core Support for the East African Major Overseas Programme 30 Jun 2016

Our application provides the platform for a uniquely inter-disciplinary scientific programme linking biomedical, social and health systems research to deliver scientific insights of global importance to human health. We will work based from Kenya (Kilifi and Nairobi) and Eastern Uganda (Mbale). The Kilifi Programme will tighten its focus on our integrated platform (i.e. linked hospital/demographic/molecular surveillance) and legacy of continuous epidemiological data and stored samples over 25 years. Work in Mbale will consolidate a leading centre of clinical investigation in an area of hyper-endemic malaria transmission, and the Nairobi Programme will increase its independence with a focus on international disease mapping and health systems. Our major scientific themes include vaccines (including pre and post-licensing studies with exploratory immunology and epidemiological components), genomics and infectious disease transmission, clinical research (focusing on multi-centre clinical trials and the pathophysiology of critical illness with a developing programme on neonatal and maternal health), public health (with an emphasis on spatio-temporal analyses) and health systems research. The Programme is delivered by 29 PIs (i.e. scientists with independent funding). Training is central to our vision, and additional awards support 18 post-doctoral scientists and a projected 50 PhD students during the next 5 years.

Amount: £26,595,243
Funder: The Wellcome Trust
Recipient: University of Oxford

Core award for the East African Major Overseas Programme - KES portion 30 Jun 2016

Our application provides the platform for a uniquely inter-disciplinary scientific programme linking biomedical, social and health systems research to deliver scientific insights of global importance to human health. We will work based from Kenya (Kilifi and Nairobi) and Eastern Uganda (Mbale). The Kilifi Programme will tighten its focus on our integrated platform (i.e. linked hospital/demographic/molecular surveillance) and legacy of continuous epidemiological data and stored samples over 25 years. Work in Mbale will consolidate a leading centre of clinical investigation in an area of hyper-endemic malaria transmission, and the Nairobi Programme will increase its independence with a focus on international disease mapping and health systems. Our major scientific themes include vaccines (including pre and post-licensing studies with exploratory immunology and epidemiological components), genomics and infectious disease transmission, clinical research (focusing on multi-centre clinical trials and the pathophysiology of critical illness with a developing programme on neonatal and maternal health), public health (with an emphasis on spatio-temporal analyses) and health systems research. The Programme is delivered by 29 PIs (i.e. scientists with independent funding). Training is central to our vision, and additional awards support 18 post-doctoral scientists and a projected 50 PhD students during the next 5 years.

Amount: £18,904,756
Funder: The Wellcome Trust
Recipient: University of Oxford

Capture NanoporeSeq: A novel technique for targeted full-length transcript sequencing and gene expression analysis 08 Apr 2016

The accurate characterization and quantification of expressed gene isoforms is essential to understanding how genetic variation affects gene expression and ultimately disease risk. However, the expressed isoforms identified by standard RNA sequencing methods are often incorrect due to the near ubiquitous presence of alternative gene isoforms in the human transcriptome. This project aims to address this problem by developing a novel technique (Capture NanoporeSeq) to perform full-length cDNA sequencing of target human genes and so unambiguously identify which isoforms are expressed. Capture NanoporeSeq will combine Oxford Nanopore long-read sequencing, which can sequence full-length cDNAs, with targeted RNA sequencing (CaptureSeq), which will provide high sensitivity for targeted gene isoforms. Once developed, Capture NanoporeSeq will be validated in post-mortem human brain tissue to identify and quantitate the expression of gene isoforms from genomic regions linked to neuropsychiatric disorders. Capture NanoporeSeq will significantly improve our ability to accurately characterize and quantify gene expression. This will be of immediate use in neuropsychiatric disease genetics where many risk genes have lowly expressed disease-linked isoforms and/or complex splicing patterns, helping to illuminate the impact that disease-associated genetic variation has on gene expression.

Amount: £86,822
Funder: The Wellcome Trust
Recipient: University of Oxford