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Content archived on 2024-05-27

Inflammatory bowel disease: analysis of environmental, immunological and genetic influences using model systems

Objective

Chronic inflammatory diseases of the intestine impose significant healthcare, social and economic problems throughout Europe. A multifactorial aetiology with environmental, immulogical and genetic components is suggested. The proposal will use three mouse models of intestinal inflammation to examine the interactions between the intestinal bacterial micro flora and the mucosal immune system. The effects of individual bacterial species and their defined antigens on induction and regulation of pathogenesis will be investigated in selectively re- colonised germfree systems. The role of the intestinal epithelium and associated extra cellular matrix components will be explored. New model systems to analyse the involvement of specific gene transcription factors in the initiation and control of mucosal inflammation will be produced.
1 Produce germfree IL-10 and Galphai2 KO mice, 100% for Galphai2 KO, IL-10 KO not pursued;
2 Produce germfree b-LACK beta-TCR mice, strategy changed;
3 Isolate and culture commensal and pathogenic gut bacteria, 100%;
4 Produce transcription factor-modified cells and chimeric mice, 50%;
5 Colonise germfree mice, 100%;
6 Define effect of bacterial colonisation on colitis pathogenesis, 100%;
7 Production of bacteria-reactive T cell lines and clones, 100%;
8 Generate b-LACK-reactive T cell lines and clones, 100%;
9 Determine effect of microflora bacteria on induction of regulatory T cells, 90%;
10 Fully characterise effect of bacteria on colitis immunopathology, 100%;
11 Analyse contribution of epithelium to induction and regulation of colitis, 100%;
12 Produce genetic induction models of colitis, 80%.

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Topic(s)

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Funding Scheme

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Coordinator

UNIVERSITY OF BRISTOL
EU contribution
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Address
Senate House, Tyndall Avenue
BS8 1TH BRISTOL, CLIFTON
United Kingdom

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Total cost

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Participants (7)

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