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CHIM - Shigella sonnei in Vietnamese adults - Development funds
<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… more
Malaria Controlled Human Infection Model - application development
<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>
Implementation of ISARICC's 2018-2022 Strategic Plan
<p>Bridging funds for transition to ISARICC's 2018-2022 Strategic Plan</p>
<p>'Sacred Water' – an engagement project run by artist Lena Bui, was a creative space for researchers at OUCRU-Nepal and people living in the Kathmandu Valley to discuss health with a focus on water. However, the earthquake of 2015 caused many participants to reflect on a wider view of health. Lena became interested in what people turn to for a sense of wellbeing - cultural… more
Vacation Scholarships 2017 - University of Oxford
<p>Vacation Scholarships 2017-University of Oxford</p>
Open access award.
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
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.
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
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
Biomedical vacation scholarship
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
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
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
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
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
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.
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.
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
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