Objective
Focal adhesions (FAs) are receptor complexes that couple the extracellular matrix (ECM) to the actin cytoskeleton, allowing inside-out and outside-in signaling between cells and their environment. FA formation is triggered by activation of integrin receptors, which interact with cytoplasmic ligands to connect with the actin cytoskeleton and regulate numerous signaling pathways. FA maturation requires force transduction between the actin cytoskeleton and ECM, which results in protein recruitment, likely through conformational changes and force-dependent protein deformation. The molecular mechanisms regulating this process are largely unknown, though many of the key components have been identified and are well characterized in vivo. I will carry out a hierarchal reconstruction of the core FA components, namely talin, vinculin, and integrin, both alone and in the presence of actin filaments or a force-generating actomyosin network. This will allow direct observation of (1) how core components of FAs assemble and regulate each other, (2) how actin impacts the formation and structure of this core complex, and (3) the effect of force on the assembly, overall complex structure, and conformational states of individual proteins. Interactions between key proteins will be analyzed both biochemically and structurally using cryo-EM in a step-wise manner to obtain a comprehensive image of FA assembly. Recent technical advances have made cryo-EM an ideal tool for solving high-resolution reconstructions of macromolecular complexes like FAs. Structural approaches will be augmented by light microscopy experiments, to provide a dynamic view of complex assembly and regulation. By using multidisciplinary, innovative approaches, this project will address both functional and structural questions about FA assembly, yielding insight into key interactions and therapeutic targets that will directly benefit biomedical research in this field.
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
- natural sciences physical sciences optics microscopy
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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-EF-ST - Standard EF
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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-2017
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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.