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- 04 Dec 2017
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Development of compounds that inhibit RAS-effector protein-protein interactions in cancer using a single antibody domain drug surrogate emulator approach
Prof Rabbitts and colleagues from the Weatherall Institute of Molecular Biology have been awarded Seeding Drug Discovery funding to develop small molecules specifically targeting the RAS-effector protein-protein interactions. The RAS family of oncogenes is among the most frequently mutated in human cancers. Using minimal antibody fragments, the group has characterized an anti-RAS VH segment whos… more
Cellular Structural Biology
OXION - Membrane Transport in Health and Disease
Chromosome and Developmental Biology.
Genomic medicine and statistics
The Use of the Internet to Train Clinicians to Implement Psychological Treatments.
Empirically-supported psychological treatments have been developed for a range of psychiatric disorders. If patients are to benefit from these treatments there is a need to develop effective and efficient means of training clinicians to deliver them. A programme of education research is proposed. The primary aim of this research is to evaluate the use of the internet to help clinicians acquire… more
An investigation into the e biology and function of the Themis B cell homologue Icb-1.
An investigation into the biology and function of the Themis B cell homologue lcb-1 The generation of an effective adaptive immune response to pathogens depends upon the appropriate selection and regulation of antigen-specific lymphocytes. T and B cell development and selection are both driven at different stages by the encounter between antigen receptors (TCRs and BCRs respectively) and target a… more
The research conducted by the Thailand-based clinical research programme has changed the treatment of both severe and uncomplicated malaria, and melioidosis. The central aim of this proposal is to develop and evaluate effective and practical means of diagnosing, treating, and, if possible, preventing the main tropical diseases responsible for significant morbidity and mortality in rural areas of … more
Elevated plasma levels of fibrinogen have been shown to be an independent risk factor for ischaemic heart disease and have also been associated with other thrombotic disorders such as stroke, peripheral arterial disease and venous thrombosis. This risk may be mediated in part via altered fibrin structure as we have demonstrated in myocardial infection (MI) patients and their first-degree relative… more
Melanopsin signalling: phototransduction, behavioural regulation and clinical relevance.
The first phase of funding of our WTPG contributed greatly to the discovery and initial characterisation of Opn4-based photosensitive retinal ganglion cells (pRGCs). However, there is much still to understand about this novel signalling pathway. Three key questions are addressed in our renewal: (i) How do melanopsin pRGCs signal light and what is the basis for their varied responses? The central … more
How does the Pericentriolar Matrix function in Centrosome Biology?
<p>Centrosomes are the major microtubule organising centres in many animal cells. They form when centrioles assemble an electron dense matrix of pericentriolar material (PCM) around themselves. Several hundred proteins are concentrated in the PCM, including many cell-cycle regulators and cell signalling molecules, and centrosomes function as important coordination centres within the cell. The und… more
Data sharing platforms to improve treatment outcomes in neglected tropical diseases
<p>We will develop data-sharing platforms to assimilate and collaboratively interrogate global data on i) schistosomiasis ii) soil transmitted helminths, iii) visceral leishmaniasis, iv) melioidosis and v) scrub typhus. This proposal will support the development of the technical platform and curation of data from tens of thousands of patients enrolled to treatment trials and programmatic data of … more
Bone Morphogenetic Protein signalling and stromal-epithelial interaction in intestinal inflammation and carcinogenesis.
<p>The intestinal mucosa is a complex ecosystem and the epithelium has a dynamic relationship with underlying stroma. Key aspects of intestinal homeostasis and disease states, including inflammatory bowel disease and cancer are characterized by the interdependence of the epithelial and stromal compartments.</p> <p>Inter-compartmental cell-signalling pathways regulate intestinal epithelial cell f… more
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
Statistical models of gene-environment interactions
<p>This PhD focuses on developing statistical methods to discover gene – 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
Overcoming contraceptive discontinuation by overcoming side-effects: paving the way for personalized contraception in Ethiopia
<p>In the developing world, millions of women discontinue hormonal contraception due to the experience of debilitating physiological side-effects (e.g. excessive and irregular bleeding), yet the causes of these adverse effects is not known. This project will be the first to test the hypothesis that side-effects are caused by unnecessarily high dosage of exogenous hormones in hormonal contraceptiv… more
Decoding the molecular identity of neurons
<p>Regulated gene expression underlies the specification of cell fate and the maintenance of cell-specific function. Cellular diversity is of particular importance in the brain where neural circuits are assembled from cells with unique properties. Many neurological and psychiatric conditions arise from dysfunction in the brain, and although molecules are the targets of therapeutic drugs, we know … more