Project description
Control of intestinal stem cells activity and tissue homeostasis
Tissues with high turnover rates, such as the intestine, depend on stem cells as a source to provide differentiated cells to maintain homeostasis (i.e. a stable equilibrium) in tissue. In the gut, self-renewal relies on the proliferative activity of the intestinal stem cells (ISC), coupled with cell loss to maintain intestinal homeostasis. The fruit fly gut represents a prime model for studying ISC function in adult tissue homeostasis. The EU-funded FlyGutHomeostasis project exploits the genetic amenability of the fruit fly to understand the ISC activity control by niche-derived and systemic signals. The goal is to identify intra- and inter-organ circuitries enabling communication between the intestine and other organs, as well as environmental inputs, to promote homeostasis.
Objective
Due to its remarkable self-renewing capacity, the fly gut has recently become a prime paradigm for studying stem-cell function during adult tissue homeostasis. This capacity for self-renewal relays on the proliferative activity of the intestinal stem cells (ISC), which is tightly coupled with cell loss to maintain intestinal homeostasis. ISC proliferation is controlled by multiple local and systemic signals released from the ISC niche (enterocytes (ECs), enteroendocrine (EE) cells, enteroblasts (EBs), and visceral muscles (VMs)) and non-gastrointestinal (non-GI) organs. Despite the physiological divergence between insects and mammals, studies have shown that flies represent a model that is well suited for studying stem cell physiology during ageing, stress, and infection. As a saturating approach to identify local and systemic signals controlling intestinal homeostasis in steady-state and challenged conditions, RNAis will be used to known down all genes encoding secreted peptides specifically in ECs, EEs, or VMs and all genes encoding transmembrane and membrane-associated proteins in the VMs. The proposed screens should identify novel intra- and inter-organ circuitries allowing communication between the gut and other organs to provide organismal health. In addition, the systematic knockdown of secreted peptides from the ISC niche could identify gut-derived signals that couple changes in environmental inputs, such as nutrient availability, with systemic changes in feeding behavior, energy balance, and metabolism. Since large-scale approaches are not feasible in vertebrate models, the signals identified in the above screens could potentially reveal novel couplings contributing to mammalian GI homeostasis and disease. The final part of the proposed project aims a deciphering the molecular signals coupling epithelial fitness with ligand-independent TNFR activation to control ISC division and epithelial turnover in steady-state, challenged and pathological conditions.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences zoology entomology
- natural sciences biological sciences zoology mammalogy
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
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.
ERC-STG - Starting Grant
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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.
(opens in new window) ERC-2018-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1165 KOBENHAVN
Denmark
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