Project description
Mechano-chemical adhesion regulation during cell division
Focal adhesions are large multiprotein complexes that anchor cells to the extracellular matrix and convert mechanical forces into biochemical signals, regulating key cellular processes. When a cell divides, these anchors must temporarily disassemble – a precisely timed process that, if mishandled, can cause errors in chromosome separation. The molecular mechanisms coordinating cell cycle progression and adhesion dynamics are unknown. With the support of the Marie Skłodowska-Curie Actions programme, the TENSION project aims to investigate a potential mechano-chemical adhesion regulation using groundbreaking single-molecule tools to monitor biochemical reactions on proteins under physiological mechanical forces. The findings could fundamentally reshape our understanding of how physical and chemical signals cooperate to control core life processes.
Objective
Mechanical forces are increasingly recognized as key regulators of cell behavior, acting alongside traditional chemical and electrical cues. These forces are detected at focal adhesions (FAs), large multiprotein complexes thar convert physical stimuli into biochemical signals that control key cellular processes. During mitotic entry, however, FAs must disassemble to ensure correct chromosome segregation, suggesting a tightly regulated interplay between adhesion dynamics and cell cycle progression. Yet, the molecular mechanisms underpinning this crosstalk remain unknown. Talin is the core mechanosensitive protein in FAs, directly linking integrins to actin and recruiting binding partners in a force-dependent manner. Preliminary data and recent literature indicate that CDK1, the master cell-cycle kinase, interacts with talin domains to potentially phosphorylate them, hinting at a previously unrecognized mechanochemical pathway for adhesion regulation. However, how mechanical forces regulate chemical reactivity to govern mechanotransduction processes remains poorly understood. This owes mainly to experimental limitations in the study of the biochemistry of mechanically stretched proteins. Leveraging on novel single-molecule technology developed by the host lab, I aim to characterize how CDK1 interacts and phosphorylates talin domains under physiological forces to regulate its function in FAs. This novel enabling methodology will allow me to directly monitor binding and enzymatic reactions and characterize their mechanical regulation. By integrating these single-molecule data with novel protein biochemistry methods and cellular models, I will establish a cross-scale understanding of how CDK1-mediated talin phosphorylation regulates FA remodeling across the cell cycle. The results of the project will provide a new mechanochemical framework for adhesion regulation and establish a broadly applicable toolkit for studying the chemical regulation of mechanosensitive proteins.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences biophysics
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences molecular biology structural biology
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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2025-PF
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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.
WC2R 2LS London
United Kingdom
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