Project description
A dial rather than a switch for cellular 'stickiness' may lead to more precise control
A cell's ability to stick to molecules in its local environment plays an important role in processes from normal embryonic development and wound healing to inflammation and cancer metastasis. Integrins are a large family of adhesion receptor molecules that span the cell membranes and mediate dynamic remodelling of the cytoskeleton during adhesion and migration. The first step is integrin activation via a complicated and still unclear process. The EU-funded PoInt project is shedding light on integrin activation by combining studies of single molecules, molecular complexes, multi-cellular constructs and organised 3D tissue cultures. The ultimate goal is more effective therapies with fewer side effects for numerous conditions characterised by cell adhesion gone rogue.
Objective
Integrin-mediated adhesion to the extracellular matrix is a prerequisite for the development and homeostasis of multicellular organisms. A hallmark of integrins is that ligand binding requires an “integrin activation” step affecting the shape of the entire molecule is induced by the integrin tail- and actomyosin-binding adaptor proteins talin and kindlin. In a second step, integrins cluster and assemble a gigantic signaling hub, where they integrate biochemical and biophysical signals to achieve their functional output. Due to the lack of combined expertise and suitable technologies, the key steps of integrin activation are still largely unknown and the underlying physical principles still need to be identified. We propose a multifaceted approach combining quantitative single molecule measurements, reconstitution of minimal and cellular adhesion complexes as well as development of multicellular structures and organoids. We propose four aims. In our first aim we will unravel how forces are propagated through the talin-integrin tail bonds and how force-induced integrin shape changes affect signaling. In the second aim we will use novel force spectrometers to determine energy landscapes and the high-resolution structure of fibronectin-integrin complexes. In our third aim we will use in vitro model membranes to test how integrin tail-binding adaptors, cortical F-actin and specific domains of integrins induce integrin clustering. With our fourth aim we will unravel how integrins integrate chemical and biophysical signals during organ development. Using the proposed synergistic approach, we will decipher fundamental principles of cell adhesion biology. Furthermore, our research will result in a better understanding of the fundamental mechanisms regulating adhesion signaling that will allow us to develop strategies to curb adhesion functions without completely blocking integrins, thus limiting the enormous side effects of current interventions.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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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-SyG - Synergy 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-SyG
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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.
80539 MUNCHEN
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.