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Search results (Displaying 26 grants)

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Earliest award date
31 Jan 2017
Latest award date
30 Sep 2018
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Using genetic diversity to map fine-scale epidemiology in malaria
<p>The recent evolution of artemisin-resistant strains of P.falciparum in Southeast Asia have highlighted the need for a deeper understanding of the genetic epidemiology of malaria and for more strategic implementation of malaria control resources. Assessment of the efficacy of these control efforts requires accurate and standardised estimates of epidemological parameters, such as transmission in… more
Amount: £0
Statistical models of gene-environment interactions
<p>This PhD focuses on developing statistical methods to discover gene &ndash; environment (G-E) interactions. To date there has been some interest in testing for G-E interactions in animal models, but limited success in uncovering examples of G-E interactions in humans. This is in part due to the problem of exposure assessment, or rather, because representative data on the environment of a numbe… more
Amount: £0
Planning meeting for Lancet Commission on Diagnosis
<p>The Lancet Commission on Diagnosis</p> <p>Phase 1 - Planning Meeting</p> <p>Following the publication of The&nbsp;Lancet Series on Pathology in Low and Middle Income &nbsp;countries in March, the Lancet asked me&nbsp;to lead a Lancet Commisison on Diagnosis (Pathology and Laboratory Medicine and Imaging). &nbsp;</p> <p>There will be two phases. &nbsp;The first will be a 1.5 day face-to-face… more
Amount: £8,000
Improving health outcomes for looked after children and young people
<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 proc… more
Amount: £8,010
Exploiting whole genome tagging of trypanosomes to identify new ciliopathy candidate genes in humans
<p>Ciliopathies are a range of human genetic diseases in which the normal functions of cilia/flagella are disrupted or prevented entirely. Ranging from mild to embryonically lethal, these diseases are often difficult to investigate as many do not appear to have clear links with particular genes or molecular mechanisms. This project aims to identify potential ciliopathy protein candidates and thei… more
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Mechanical testing of tendons and ligaments
<p>The mechanism for collagenous connective&nbsp;tissue damage is&nbsp;little understood. The micromechanics of collagenous tissues is&nbsp;important&nbsp;to understand as it may&nbsp;contribute&nbsp;to injury prevention and be useful in designing treatments for pre existing tissue damage. Bontempi et al in 2009&nbsp;theorised a relationship between the the probability density function of the str… more
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Evidence for a pathogenic link between lung inflammation and autoimmune arthritis
<p>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 autoi… more
Amount: £0
Myeloid effector cells in inflammation
<p>Dysregulation of inflammation underlies a range of chronic inflammatory disease. By increasing our understanding of inflammatory mechanisms we may be able to identify specific therapeutic targets to treat disease. &nbsp;Using a murine model of acute, resolving inflammation, with zymosan as stimulus, we create a physiological inflammatory system where we can observe the spatiotemporal relations… more
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How do CHRND mutations disrupt AChR cluster formation?
<p>The project aims to utilise mutations identified in congenital myasthenic syndromes to study the interactions of the muscle acetylcholine receptor (AChR) and its anchoring protein, Rapsyn.Widely quoted publications suggest that Rapsyn interacts with the M3-M4 intracellular loop of the AChR alpha, beta and epsilon subunits, however we have identified several kinships in which mutations in the M… more
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Design and development of a breathing powered prosthetic prototype
<p>The input required to control a prosthetic device greatly defines the subsequent precision that can be achieved. Robust mechanisms that are low-cost often use musculoskeletal motion for control. However, this often limits the level of control and applicability issues can arise when the system that is augmented also generates the power and drives the control. A device that is powered and contro… more
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Assessing the effect of the Xrn1 exoribonuclease on global and specific rates of protein synthesis
<p>Gene expression is a complex process requiring the coordination of transcription, transcript turnover, translation and proteostasis. When coordinated, these processes can be adapted to allow cells to respond to changes in growth rate and during differentiation. How these processes are coordinated remains a long-standing question. The exoribonuclease Xrn1 is proposed to coordinate transcription… more
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Investigating the role of cyclin-dependent kinases in the regulation of DNA repair by non-homologous end-joining
<p>DNA double-strand breaks (DSBs) are highly toxic lesions that can drive genome instability and cancer. In human cells, most DSBs are repaired by the non-homologous end joining (NHEJ) pathway, except when they occur during DNA replication or mitosis when NHEJ is toxic and can generate chromosomal translocations. NHEJ must therefore be tightly regulated to maintain genome stability. However, lit… more
Amount: £0
Structural studies of bacterial nucleic acid transport proteins
<p>Horizontal gene transfer contributes to genetic plasticity in bacteria and is of great clinical relevance as it contributes to the spread of antibiotic resistance genes. One mechanism of horizontal gene transfer in bacteria is transformation. While the phenomenon of transformation has been known for many decades, little is known about the mechanistic steps of exogenous DNA uptake into bacteria… more
Amount: £0
Structure of the Type Three Secretion System Export Gate
<p>I will study the mechanism of protein export in the injectisome by elucidating the structure of one of its central components, the export gate. The injectisome is a large, molecular nanomachine which injects effector proteins into cells of the hosts of many bacterial pathogens. The export gate is the protein channel at the heart of this syringe-like type three secretion system (T3SS), and the … more
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Organisation, packaging and transcription of dsRNA viral genomes
<p>First, the structure of the first genome layer of ?6 will be revisited with the goal of better separating the different conformations and obtaining a better resolution for each of them. Next, the pathing of the dsRNA and its interactions with the capsid will be studied to understand its organisation and connection to the inner layers at the molecular level. The calculated orientations will the… more
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Time Resolved Structural Analysis of Macromolecules and Assemblies
<p>The icosahedral, positive-sense RNA Foot and Mouth Disease (FMDV) remains a foe to the agricultural industry; causing vesicular disease of cloven-hoofed animals.<sup><br /></sup></p> <p>Converse to other picornaviruses, FMDV has a significantly greater pH and temperature sensitivity. In the quest for thermostable vaccine development, many wild type and mutant structures of the seven Foot and M… more
Amount: £0
KDEL Receptor Stuctural Determination & Biochemical Characterisation
<p>This project aims to characterise the KDEL receptor (KDELR) structurally, biochemically and biophysically. The KDELR is a membrane protein resident in the cis-golgi, where it binds the K-D-E-L amino-acid motif present on resident ER proteins, which have been transported to the Golgi via bulk flow. Once KDELR binds cargo, it initiates transport back to the ER via COPI mediated vesicles, where i… more
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Delineating meiotic gene expression of male mice
<p>The mechanisms of meiosis have important consequences for the evolution, fertility, and speciation of sexually reproducing organisms. However, the full gene expression programme of meiosis is not currently known, partly due to heterogeneity of the cell population which is averaged by bulk tissue RNA sequencing or micro-array analysis. It has recently become possible to transcriptionally profil… more
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Understanding the role of islet development in type 2 diabetes susceptibility.
<p>Genome-wide association studies (GWAS) have found over 100 loci associated with type 2 diabetes (T2D), but the causal mechanisms of the disease remain unclear. Pancreatic islets play a role in the development of T2D, and although the contribution of developmental processes to disease susceptibility has not yet been established, several of the GWAS loci localise near known genes for islet devel… more
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Dynamics of canonical and variant PRC1 interaction with chromatin at single-molecule resolution
<p>Polycomb Repressive Complexes (PRC) 1 and 2 are protein complexes with histone modifying activity that are key to regulation of gene expression in eukaryotic development. PRC1 ubiquitylates H2A at lysine 119 (H2AK119Ub1), while PRC2 methylates H3 at lysine 27 (H3K27), that function together on chromatin, recognising the modification deposited by the other, suggesting a feedback loop. PRC1 comp… more
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