Objective
The cross talk between the host and the microbiota is believed to be the major determinant of health and disease in the gastrointestinal tract. Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the intestine with unclear aetiology. Deregulation of the cross talk between the intestinal microbiota and the host immune system is considered a main factor contributing to IBD. Genomic studies revealed associations of NOD2 and of genes regulating autophagy and ER stress with an increased risk for IBD. Mutations in these pathways compromise Paneth cell dependent epithelial antibacterial defences causing alterations in the intestinal microbiota, termed dysbiosis. However, mutations in NOD2 or autophagy genes are not sufficient to cause intestinal inflammation in humans or in mice, suggesting that dysbiosis by itself cannot cause inflammation but additional, as yet unidentified, factors are required to precipitate the pathogenesis of IBD in genetically susceptible individuals. Mouse model studies revealed that epithelial specific mutations sensitizing intestinal epithelial cells to apoptosis or necroptosis triggered spontaneous intestinal pathologies with many features of human IBD, including loss of Paneth cells, impaired epithelial antimicrobial defences and chronic intestinal inflammation. We hypothesize that pathways controlling programmed cell death critically contribute to the pathogenesis of IBD by acting on Paneth cells to regulate epithelial antibacterial defences and simultaneously regulating intestinal epithelial cell survival and the integrity of the epithelial barrier. The aims of this research proposal are: a) to dissect the pathways regulating Paneth cell death and the development of dysbiosis in the gut, and b) to elucidate the additional genetic or environmental factors regulating intestinal epithelial barrier integrity that are likely to synergise with Paneth cell dysfunction and dysbiosis to trigger chronic intestinal inflammation.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences basic medicine immunology
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-ADG_20120314
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
50931 KOLN
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.