Project description
The role of focal adhesion kinase in progressive fibrosis
Mechanotransduction is a precisely regulated process in which disruption results in pathologies including tumorigenesis, chronic inflammation and fibrotic conditions. Recent studies have shown a relationship between abnormal fibrosis and altered patterns of focal adhesion kinase (FAK) activity and cell adhesion. However, the mechanistic link between FAK activity at individual focal adhesions and fibrosis remains elusive. The EU-funded MECHANO FIBROSIS project aims to identify the molecular events that regulate FAK activity during force transmission and sensing of mechanical force at individual focal adhesions. The research combines innovative molecular devices, light-activated cell-specific adhesive ligands and microscopy tools, enabling controlled force application at the individual focal adhesions and measuring cell responses in vitro and in vivo.
Objective
Mechanical forces drive fundamental physiological functions in living organisms, yet it remains unclear how forces are transduced into intracellular biochemical signals. Mechanotransduction is a tightly regulated process, and its disruption often results in pathologies including tumorigenesis, chronic inflammation and fibrotic conditions. Crucially, recent studies have shown an important relationship between abnormal fibrosis and altered patterns of focal adhesion kinase (FAK) activity and cell adhesion.
Prof. del Campo laboratory has pioneered the use of photo-triggerable ligands to spatiotemporally control cell adhesion and recently, Prof. García has demonstrated in vivo that spatiotemporal control of cell adhesion modulates fibrosis. In addition, Prof. García has demonstrated a strong relationship between cells adhesive force generation and FAK activation at individual focal adhesion (IFA). Despite the importance of FAK signalling in cancer and other pathologies, the mechanistic link between the FAK activity at individual focal adhesions and fibrosis remains elusive. To close this gap in our knowledge, there is a need to develop technologies capable of recapitulating dynamic force transmission at individual focal adhesions.
This project aims to elucidate the molecular events that regulate FAK activity during force transmission and sensing of mechanical force at individual focal adhesions. I will combine novel molecular devices, light-activated cell-specific adhesive ligands and microscopy tools to in situ apply controlled forces at individual FA and measure cell responses in 2D, 3D and in vivo contexts. Importantly, FAK loss- and gain-of-function experiments will provide the functional importance of FAK during mechanotransduction.
The fundamental investigation of mechanotransduction events will greatly advance our understanding of cell biology and inform future targets for fibrosis therapy, as mechanical forces is a driving factor in fibrosis progression.
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 cell biology
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
66123 Saarbruecken
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.