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Content archived on 2024-06-18

Genetic and environmental factors that control inflammation-driven colon cancer

Objective

"The human gastrointestinal tract is colonized by an abundant and diverse bacterial microbiota that exist in a mutualistic relationship with the host that promotes intestinal health. Maladaptation in this host microbial dialogue leads to a deranged inflammatory response and inflammatory bowel disease (IBD) that can progress to colon cancer. The complex interplay between genetic and environmental factors and their impact on intestinal inflammation are starting to be deciphered in IBD, however little is known about how they influence the transition from colitis to cancer. We recently established a relevant model of bacteria-driven invasive colon cancer and have mapped both genetic and immune pathways that perpetuate disease. Genetic susceptibility maps to a 1.7mb region on chromosome 3 containing the candidate gene Alpk1, an alpha-kinase. This locus mediates its effects through the IL-23 driven innate lymphoid cell response and we have identified the cytokine IL-22 as a key player in driving the tumour cell response. We will use a multi-disciplinary approach to probe the interaction between genetics, microbial drivers and inflammatory pathways that promote colon cancer. BAC transgenics and cell-type specific knock-out mice will be used to establish the function of Alpk1 in bacteria driven colon cancer. In vivo models will be complemented by novel 3D colonic organoid and crypt cultures generated from epithelial stem cells from normal or tumor tissue allowing analysis of microbial and cytokine signals that influence intestinal epithelial cell and stem cell function. Deep sequencing combined with bacterial cell culture will identify changes in the intestinal microbiota that drive tumourigenesis. Results from mouse models will be translated to analysis of human colorectal cancer. These studies will uncover new pathways involved in bacterial interaction, intestinal inflammation and tumour formation that may offer new therapeutic targets in IBD and colon cancer."

Fields of science (EuroSciVoc)

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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.

Call for proposal

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ERC-2013-ADG
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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.

ERC-AG - ERC Advanced Grant

Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
EU contribution
€ 2 484 620,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)

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