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Search results (Displaying 75 grants)

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Earliest award date
02 Feb 2009
Latest award date
07 Dec 2009
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Amount: £150,000
Development of a protein purification system for identifying human DNA repair proteins, and their functional study.
Fanconi Anemia (FA) is a genetic disease characterized by various developmental defects and predisposition to, cancer in patients. So far, mutations in 13 genes have been identified in patients (Wang, 2007). \he corresponding proteins are recognized as FA proteins and function together in DNA inter-strand cross-link (ICL) repair, also known as the FA pathway. Several major steps in ICL repair hav… more
Amount: £152,906
Study of genetic & epigenetic differences in monozygotic twins with extremely discordant phenotypes.
The aim of the project is to sequence and analyse the genomes, methylomes and transcriptomes of two monozygotic twins, discordant for a wide range of disease phenotypes and conditions, in order to find the candidate causative differences, which would be then further characterized functionally and studied in larger disease cohorts.
Amount: £152,906
Exploiting linkage disequilibrium and other auxiliary information to improve genotype calling.
We intend to develop methods to call genotypes that use both allele signal intensity from arrays and linkage disequilibrium information from public reference data such as the HapMap (Frazer, Ballinger et al. 2007) and 1 000 Genomes (Siva 2008) projects. This will involve a combination of the haplotype phasing component of imputation techniques (Marchini, Howie et al. 2007; Howie, Donnelly et al. … more
Amount: £152,906
Characterizing the role of AEBP2 at Polycomb-regulated genes
The Polycomb Repressive Complexes (PRCs) are multisubunit chromatin modifying complexes Originally characterized in Drosophila melanogaster as regulators at the homeotic (Hox) genes, these complexes are now known to act as repressors in embryonic stem cells (ES cells) at many genes involved in differentiation. Recently, AE1-binding protein (AEBP2) was discovered to be a stable component of PRG2 c… more
Amount: £152,906
Amount: £16,560
The role of the inflammasome in chronic infection.
Immune homeostasis in the gastrointestinal tract is tightly regulated in order to provide protective immunity from pathogens, whilst concurrently suppressing excessive reactivity directed towards the commensal micro-flora. In humans, perturbation of this balanced immune response presents as inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, which are characterize… more
Amount: £152,906
Identification of cellular immune correlates of clinical disease and immune evasion strategies of varicella-zoster virus.
We aim to determine why varicella-zoster virus elicits a poor circulating CD8+ cytotoxic T lymphocyte (CTL) response despite being an endogenous pathogen. First we will investigate whether such responses are adequately elicited at local sites of VZV replication in skin lesions compared to peripheral blood. We will then focus on understanding immune evasion mechanisms employed by the virus that po… more
Amount: £152,906
Innate immune responses induced by licensed and experimental T-cell inducing vaccines for TB and malaria.
1. To investigate the innate immune response to T-cell inducing vaccines using different viral vectors and different inserts, across individuals and populations, and to investigate how different antigens within the same viral vector affect this response. 2. To correlate these innate immune responses with adaptive immune responses as measured by IFN-? ELISpot and multi-parameter flow cytometry and… more
Amount: £152,906
The role of macrophages and T-cell apoptosis/necrosis in acute HIV-1 infection and associated gastrointestinal inflammation.
Gastrointestinal macrophages maintain an anti-inflammatory milieu that can be destabilized by the recruitment of pro-inflammatory monocytes. HIV infection of mucosal CD4+ T cells results in massive death of these cells by apoptosis and necrosis, and these cells will be taken up by both resident and recruited macrophages. Since uptake of apoptotic and necrotic debris can activate pro-inflammatory … more
Amount: £152,906
Analysis of T cell responses to HIV-1 infection in Kenyan infant cohorts.
General aim: to determine immunological correlates that contribute to lack of viral suppression during vertical transmission of HIV-1 in two Kenyan infant cohorts. Specific aims 1) To determine the varying capacity of infant cytotoxic T lymphocytes (CTL) to suppress HIV-1 replication 2) To investigate the mechanism by which CD4+ T cell and dendritic cell (DC) responses contribute to the lack of v… more
Amount: £152,906
Accelerated long-term forgetting and the role of sleep in memory
The main aims of this project are to investigate: (1) the role of sleep in memory consolidation, and (2) the contribution of a deficit in sleep-dependent consolidation to accelerated long-term forgetting (ALF) - a newly described memory impairment associated with temporal lobe epilepsy.
Amount: £151,662
The genetic architecture of obesity.
1) To construct a model for the effect of common variants on phenotype. Estimate the contribution of common variants to the heritability of obesity, and map this contribution. 2) Perform joint analysis of multiple obesity-related phenotypes, using the techniques described in 1) 3) Use expression data to investigate the causal relationships between effective loci and traits.
Amount: £152,906
The role of the pol II CTD in expression of human snRNA genes .
The mammalian genes for the U1 and U2 spliceosomal snRNAs provide ideal model systems to study fundamental mechanisms underlying expression of pol II-transcribed genes. These short genes are structurally distinct from protein coding genes and ubiquitously expressed at high levels. As in expression of protein coding genes, the heptapeptide repeats comprising the CTD of the large subunit of pol II … more
Amount: £396,633
Innate immune activation of macrophages during Colitis.
Ulcerative colitis arises from breakdown of the dynamic balance between intestinal microflora and the host immune response. The importance of pathogenic and regulatory subsets of T cells in colitis is well established. However, no systematic study has been carried out to investigate the direct involvement of macrophages in intestinal inflammation. Previously, I have defined a novel innate activat… more
Amount: £202,713
Replication for central obesity associations arising from WTCCC studies.
We propose a pilot study to test the association of 100,000 specific polymorphisms with a range of common diseases using a two stage case-control study design. The study will include diabetes, breast cancer, cardiovascular disease, bipolar disorder, and other diseases (2,000 samples each), as well as two common control groups (up to 3,000 samples total) for further evaluation. Positive associat… more
Amount: £30,000
Responsibility and Morality within Personality Disorder.
My research aims to integrate analytic philosophy with scientific research into, and clinical knowledge and treatment of, personality disorder, in order to understand what it is and the place of morality and responsibility within it. My principal theoretical aim is to draw on my philosophical expertise and my first-hand knowledge of clinical data and treatment to: (i) establish the extent to whic… more
Amount: £141,927
The role of the von Hippel-Lindau Hypoxia-inducible factor (VHL-HIF) pathway in cardiac and skeletal muscle energetics.
This project aims to investigate the metabolic phenotype in mice engineered to have the Chuvash Polycythemia mutation. This is interesting because the Chuvash mutation causes a modest elevation in the hypoxia inducible factor family of transcription factors, and this enables us to study the effects of hypoxia signalling on metabolism without the confounding influence of actual periods of low oxyg… more
Amount: £216,547
Does inhibition of PIM kinase represent a novel mechanism to regulate the activity of ABCG2?.
ABC efflux pumps such as ABCG2 play an important role in treatment success in several diseases including cancer, where they can confer resistance to chemotherapy. ABCG2 is also expressed in healthy tissues and therefore influences pharmacokinetic profiles of drugs in the body. Consequently, a great deal of effort has been directed towards generating drugs capable of inhibiting efflux pumps. Unfor… more
Amount: £168,220
Discovering the function, structure, and evolutionary impact of proteins created de novo (i.e. not by duplication), in particular in viruses and in bacteria.
Novel proteins are thought to be created mostly through gene duplication. However, recent studies showed that de novo protein creation occurs at an unexpectedly high rate. I have shown that a particular subset of de novo proteins, those encoded by viral overlapping genes, are abundant and relatively easy to identify. These proteins have unusual sequence and structure properties (being unstructure… more
Amount: £224,299