Objective
There has been tremendous progress in understanding the importance of the microenvironment and its chemical signals for homeostasis of stem cell niche in the intestine and for tumor invasion and metastasis formation in many different tissues. However, the way stromal cells such as myofibroblasts or cancer-associated fibroblasts (CAFs) use mechanical forces to shape the extracellular matrix and consequently dictate the response of epithelial cells remains unexplored at the single-cell level mainly due to limited imaging tools. Here we propose a multi-disciplinary approach, at the interface of cancer cell biology and physics, aimed to understand how myofibroblasts contractility influences epithelial cell functions in physiological (homeostasis) and pathological (cancer) conditions using the gut as a model.
Specific aims:
1. Characterize myofibroblasts in gut mucosa. Using omics analysis, mouse models and optogenetic tools we will obtain molecular signatures of myofibroblasts, characterize their migration, proliferation and contractile capacities.
2. Determine the role of myofibroblasts contractility in gut epithelial homeostasis. Using gut-on-chip and intravital imaging we will determine if supracellular contractility of myofibroblasts is necessary to maintain crypt shape upon mechanical stimuli.
3. Determine the role of CAF alignment in cancer progression. We will use 3D in vitro models to explore if CAFs alignment prevents or stimulates cancer cell invasion. Using mesentery metastasis mouse model, we will test if CAFs alignment can generate collagen bundles that cancer cells use to metastasize.
4. Explore if CAF alignment can induce therapy resistance and tumor relapse. Using human samples of rectal cancer before and after chemo-radiotherapy we will determine if CAFs alignment can protect cancer cells from therapy and stimulate metastasis formation.
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 oncology
- 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)
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.
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-COG - Consolidator 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-2017-COG
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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.
75654 PARIS
France
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.