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Content archived on 2024-06-18

Dynamic, stem cell-mediated self-renewal in the Drosophila intestine

Objective

Cells in intestinal epithelia turn over rapidly due to aging, damage, and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to renew the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with the loss of spent gut epithelial cells. This proposal addresses the mechanisms of dynamic self-renewal in the intestine of Drosophila. Our recent work has outlined a paradigm explaining intestinal homeostasis in Drosophila that could apply also to humans. A new lab is being established in Heidelberg where we wish to extend these studies. Our objectives are to understand: 1) How intestinal stem cell pool sizes are regulated; 2) How the cytokines and growth factors that mediate gut homeostasis are controlled; and 3) How these signals regulate the ISC cell cycle. Established genetic and cell biological methods will be applied, supported by molecular assays (microarrays, qPCR, ChIP/Seq) of gene control. New pathways of ISC control will be discovered via comprehensive genetic screens using transgenic RNAi and gene over-expression. In vitro culture of ISCs will be developed and used for live imaging and molecular analysis of the mechanisms controlling ISC proliferation and differentiation. These studies should elaborate a paradigm explaining intestinal homeostasis in flies that can guide studies in mammals, eventually contributing to the diagnosis and treatment for diseases in which gut homeostasis is disrupted, such as colorectal cancer and inflammatory bowel disease. Because stem cell biology is so highly relevant to wound healing, regeneration, cancer, aging and degenerative disease, this research could impact human health at many levels.

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

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2010-AdG_20100317
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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

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
EU contribution
€ 2 682 080,00
Address
SEMINARSTRASSE 2
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

No data

Beneficiaries (1)

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