Clinical PhD Programme at the University of Oxford: 'The identification of autoimmune susceptibility genes using ENU mutagenesis.' (360G-Wellcome-094446_Z_10_Z)

The identification of autoimmune susceptibility genes using ENU mutagenesis The aim of this project is to advance the understanding of basic mechanisms in autoimmunity by studying ENU mouse strains that have a defective immune response to self-antigens. In order to increase the yield of autoimmune phenotypes in the inbred ENU pedigrees, a sensitized screen has recently been developed using the Y chromosome autoimmune accelerator (Yaa) introduced to the C57BL/6 (B6) mouse. The aim of this studentship will be: (i) to characterise Yaa strains that develop heritable systemic autoimmunity ? anticipated to be marked by antinuclear antibodies, immune complex formation and renal disease. (ii) To identify the causative mutations by mapping and sequencing using high throughput whole genome analysis and matching to reference genome. To develop a pipeline for sequencing that will reduce dependence on mapping. (iii) Combine the functional and genetic knowledge in order to understand new mechanisms of pathogenesis and normal regulation; this will involve in vitro and in vivo methods for studying gene function and expression. (iv) Relate the findings to human disease and models of self tolerance. The project will provide training in basic immunology and a wide range of laboratory techniques, as well as renal histopathology and sequencing work.