- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 05 May 2020
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
58FORWARDS. (The 1958 Birth Cohort: Fostering new Opportunities for Research via Wider Access to Reliable Data and Samples). 11 Jun 2015
The 1958 Birth Cohort (1958BC) recruited 17,416 British newborns 3-9 March 1958. A Biomedical Resource (58BMR) was later created by the biomedical survey (Strachan, Power, Bynner [2002/3]) to include extensive questionnaire data, physical measures and biosamples on 1958BC participants. The biosamples, stored in ALSPAC laboratories at the University of Bristol, include blood, urine and saliva (9,000+ participants), DNA (8000+), lymphoblastic cell lines (7,500+). Most participants providing DNA h ave been genome-wide-genotyped (data held at European-Genome-Phenome-Archive). Other data are held at UK-Data-Archive, managed by Centre for Longitudinal Studies. The 58BMR is used widely by biomedical, social and population scientists nationally and worldwide. 58FORWARDS will maintain and develop the infrastructure for managing, linking and releasing biosamples/data from 58BMR, facilitating scientific exploitation by making biosamples/data readily available for sharing. 58FORWARDS has three aim s: (1) Fund and support pre-existing procedures and systems that have underpinned the 58BMR for >10 years; (2) Ensure targeted development of key systems and procedures to meet rapid, and understandable, changes in the strategy of national funders regarding infrastructural support for major UK cohorts; (3) Ensure that access to data and biosamples from the 58BMR remains streamlined and secure through all maintenance and development work.
The key goal of my proposed research is to examine whether T cells are able to regulate epithelial behaviour of the gut and skin via provision of signals through epithelial TNFR and subsequent activation of the alternative NF-kappaB signalling pathway and resulting transcription network. Strong evidence from other epithelial tissues indicates that T cells signal through these receptors to regulate epithelial behaviour, including in thymic epithelium where these T cell mediated signals are requi red to drive normal epithelial development(1). In other instances these signals may be mis-appropriated, with pathological consequences (for example Treg RankL driven mammary breast cancer metastasis) (2). My key goals are 1. To examine TNFR expression by gut and skin epithelium in normal homeostasis and during inflammation and subsequent repair. The expression of TNF ligands on T cell subsets within gut and skin will be examined in parallel. 2. To determine the roles of these receptors in models of gut and skin inflammation and subsequent epithelial recovery, by deletion of receptors in epithelial subsets using conditional mouse knockout models. 3. To determine the role that alternative NF-kappaB signalling plays in skin and gut epithelium inflammation, healing and homeostasis, by constitutively switching on this pathway in epithelial subsets.
It has recently been recognised that there are effects of heavy metals on babies and children at levels previously thought to have been of no concern. The fetus is particularly vulnerable because of the high rate of cell division and differentiation. Thus, relatively low levels of exposure that do not harm the mother may have a profound effect on the development of the fetus and its growth and development during childhood. This project will make use of data from a prospective birth cohort study: the Avon Longitudinal Study of Parents and Children. This provides a unique and powerful opportunity to evaluate the long-term outcomes of in utero exposure to Pb, Cd and Hg on children and to enable identification of associations between maternal levels and cognitive and behavioural outcomes in the child. The aims of the study are: (1) to identify the predictors of Pb, Cd and Hg levels in pregnancy with a view to identifying interventions that will minimise exposure; (2) to identify the predic tive value of maternal levels on a variety of childhood educational and developmental outcomes up to age 18 years; (3) to identify the role of maternal genetics and epigenetics in modifying these relationships.
Engaging the brain's reward system: A neuroscience-informed games-based approach to teaching and learning 01 Oct 2014
Playing a key role in developing a biomedical research strategy for the University of Bristol. Identifying and enabling the necessary interactions and providing funding to support interdisciplinary workshops and pilot projects. Identifying and nurturing the next generation of talented clinical and non-clinical health researchers from inside and outside Bristol and supporting our research community with prestigious Elizabeth Blackwell Fellowships. Ensuring our research is continually grounded by real clinical, social and public health needs, working with Bristol Health Partners, industry and other partners to deliver adoptable solutions. Establishing an open and lively dialogue with patients and the public, and involving them in the future of our health research. Providing expertise in developing partnerships, as well as access to information, potential collaborators, and research resources.
Unlocking the structure, mechanism and cellular assembly of key multiprotein complexes in human gene transcription. 03 Dec 2014
Human DNA contains ~20,000 genes, giving rise to ~100,000 proteins including isoforms andvariants. This enormous complexity is exploited by the cell to intricately assemble transient andstable multiprotein complexes, critical for cell homeostasis and development, in both health anddisease.Understanding structure is vital to explaining protein function and fundamental to drugdiscovery. Knowledge has improved dramatically over the past decades due to an enormousincrease in the number of structural analyses of individual proteins. Much less is known aboutmultiprotein complexes, often due to technical challenges in their provision and analysis, whichhave yet to be fully resolved.An essential first step in biogenesis is gene transcription. In humans, this process isregulated by complexes comprising often ten or more subunits, which arrange insuperstructures that cooperate at the interface of chromatin, fine-tuned by activating andrepressing modalities.How does the cell manage such complexity? How does it decide when to express whichgenes, and what are the functional architectures involved? How are proteins assembled intomultiprotein complexes, and what are the factors that assist in this process? The same proteinsmay exist in distinct complexes; are there specific mechanisms controlling their commitment?How do errors occur and how can we correct them?These questions are central to biology, which I plan to address in this proposal. We willstudy the archetypical general transcription factor complex TFIID, a multiprotein co-activator,SAGA (Spt-Ada-GCN5-acetyl-transferase) and a multiprotein co-repressor, NuRD (NucleosomeRemodeling and Deacetylation complex) in a comprehensive, integrated approach. As we havedone in the past, we expect to develop innovative tools in the process.My vision is to understand the cellular mechanisms of these protein machines, theirassembly process from gene to functional complex, their interdependence in gene regulationand the factors that control them. I aim to provide and roll-out tools and technologies requiredfor addressing questions of such complexity on a (more) routine basis. Understanding thesemechanisms will clarify how malfunctions can lead to pathologies. This in turn will help developstrategies for the design of new therapeutic interventions.
The focus of my research is head and neck cancer (HNC). HNC describes cancers arising from the mouth (oral cavity), voice box (larynx), throat/upper gullet (pharynx), salivary glands, nose and sinuses, primary bone tumours of the jaw and middle ear. Approximately 8000 new cases of HNC are diagnosed in England and Wales each year. Although progresses have been made in terms of diagnosing and treating these cancers, survival remains poor. For instance, five year relative survival for larynx cancer is around 66% and oral cavity 58%. During my PhD, I will be looking to identify biological and lifestyle predictors of outcomes in people with head and neck cancer. I will be using data collected from the Head and neck 5000 study, a UK-wide clinical cohort study in people with HNC, which is run by researchers from Bristol University.
Angiogenesis is the term given to the branching of new blood vessels from existing vasculature; this activity extends, matures and maintains the primaryvascular network formed during early embryogenesis. The resulting circulatory system plays an essential role in physiology and consequentially disruption toits formation and conservation is a contributing factor to a vast number of diseases. As a pre-requisite to the development of treatments for vascular diseases, a large part of scientific research focuses on understanding the mechanisms governing the angiogenic process. Although many questions still remain the importance of the cytoskeleton in blood vessel outgrowth is clear. For this project I will take three cytoskeletal-associated proteins previouslyhighlighted as candidate angiogenic regulators. I will be investigating the role of the GEF Dbs, the fomin Daam2, and the GAP srGAP2 in endothelial cells.Using a mixture of in vitro and in vivo techniques I wish to determine whetherthey contribute to angiogenesis, and if so what signals do they respond to andwhat are the consequences of their deregulation. It is through these answers that I hope to further characterise the complex network of regulatory signals governing the angiogenic process.