Objective
After a decade of new insights into single molecule mechanics, my key interests are now directed towards asking how (a) mechanical forces can alter the structure-function relationship of proteins and (b) whether such force-regulated structural alterations are of physiological significance. Since forces are applied by cells via the transmembrane integrin junctions to the extracellular matrix, my goal is to decipher how the extracellular matrix protein fibronectin, integrins, and cytoplasmic scaffolding proteins that link integrins to the cytoskeleton are functionally regulated by force. Using high performance computational approaches, we will derive with Angstrom precision how their structures are changed when stretched using Molecular (MD) and Steered Molecular Dynamics (SMD). Knowledge how tensile forces alter the structure of proteins is central to develop experimentally testable mechanisms how force might regulate various functions. Experimentally, we will first address how the many different functions of fibronectin are regulated by force. This will involve quantitative studies how the interaction of fibronectin fibers with various serum proteins and growth factors is altered when mechanically strained. Preliminary studies show already that the strain-dependent binding can vary greatly among different serum proteins. We will then investigate whether the stretching and unfolding of extracellular matrix proteins co-regulates cell phenotypes. Finally, understanding the principles of mechanotransduction is not only crucial to gain far deeper insight into how cells work, but new technologies might be derived from these novel insights. Our longer-range goals are thus to develop new technologies that exploit proteins as mechanically regulated switches, from the design and screening of drugs that target mechanically strain proteins, to deriving new design principles how to better engineer tissue scaffolds that exploit mechano-regulated cell-matrix interactions.
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.
- engineering and technology materials engineering fibers
- natural sciences biological sciences biochemistry biomolecules proteins
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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.
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.
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.
ERC-2008-AdG
See other projects for this call
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.
Host institution
8092 Zuerich
Switzerland
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.