Post-genomic approaches to inflammatory bowel disease - cell biology, pathophysiology, and therapeutics
Lead Research Organisation:
University of Oxford
Department Name: Nuffield Dept of Clinical Medicine
Abstract
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Technical Summary
Inflammatory bowel disease (IBD) is a major health problem worldwide, for which exciting new genetic and pathophysiological research promises to yield advances that will increase our diagnostic and therapeutic capability.
We propose to form a co-operative group that is uniquely placed both nationally and internationally to exploit these advances to further our understanding of IBD, and improve clinical practice. The co-operative includes Professor Jewell, who leads population-based IBD genetic research in the UK, Professor Segal, who contributes state-of-the art proteomics facilities, and leading experts in specialised cells that are involved in IBD pathogenesis: Dr Keshav (Paneth cells), Dr MacPherson (intestinal dendritic cells), Dr Powrie (regulatory T lymphocytes), Professor Gordon (macrophages), and Professor Segal (neutrophils). We are based in two Universities with outstanding biomedical research facilities, constituting an environment that will support our work. Our groups comprise basic science and clinical researchers who have worked together in the past, and continue to do so.
By increasing interaction and collaboration between our groups, and holding regular scientific meetings, we will create a critical mass of investigators focussed on IBD, and a scientific community that will synergistically expand the scope and impact of our individual research, allowing us to initiate ambitious new projects. In particular, we will rapidly exploit the discovery of new genes by Professor Jewell?s group, by performing experimental studies using animal models and human tissue. Secondly, we will use our expert knowledge of specialised cells to identify new candidate genes, and to interrogate the existing DNA database more efficiently. Thirdly, we will collaborate to define critically important cell-cell interactions in intestinal inflammation, some of which we are already investigating. Finally, we will use proteomics to study the function of newly identified IBD susceptibility genes, and generically to study the secreted and regulated protein repertoire of specialised cells involved in IBD.
We propose to form a co-operative group that is uniquely placed both nationally and internationally to exploit these advances to further our understanding of IBD, and improve clinical practice. The co-operative includes Professor Jewell, who leads population-based IBD genetic research in the UK, Professor Segal, who contributes state-of-the art proteomics facilities, and leading experts in specialised cells that are involved in IBD pathogenesis: Dr Keshav (Paneth cells), Dr MacPherson (intestinal dendritic cells), Dr Powrie (regulatory T lymphocytes), Professor Gordon (macrophages), and Professor Segal (neutrophils). We are based in two Universities with outstanding biomedical research facilities, constituting an environment that will support our work. Our groups comprise basic science and clinical researchers who have worked together in the past, and continue to do so.
By increasing interaction and collaboration between our groups, and holding regular scientific meetings, we will create a critical mass of investigators focussed on IBD, and a scientific community that will synergistically expand the scope and impact of our individual research, allowing us to initiate ambitious new projects. In particular, we will rapidly exploit the discovery of new genes by Professor Jewell?s group, by performing experimental studies using animal models and human tissue. Secondly, we will use our expert knowledge of specialised cells to identify new candidate genes, and to interrogate the existing DNA database more efficiently. Thirdly, we will collaborate to define critically important cell-cell interactions in intestinal inflammation, some of which we are already investigating. Finally, we will use proteomics to study the function of newly identified IBD susceptibility genes, and generically to study the secreted and regulated protein repertoire of specialised cells involved in IBD.
