Objective
"Integrin-mediated cell adhesion is essential for the development and homeostasis of multicellular organisms. Integrins are ubiquitously expressed heterodimeric adhesion receptors consisting of α and β subunits. They exhibit two striking properties; they can regulate their affinity for ligands and assemble large signalling hubs called adhesomes. Both properties depend on the α and β cytoplasmic tails; when integrins switch from inactive to active conformations their weakly associated tails separate and recruit adhesion proteins leading to adhesome assembly. How active integrins revert to the inactive state, and how the weak α/β tail association is maintained is largely unknown. The mechanistic contribution of individual integrin classes to the recruitment of proteins to the adhesome and how adhesome signalling is induced is also unclear. In this proposal we will address these fundamental questions in 4 specific aims. In the first aim we will identify proteins that keep integrin tails associated and define the roles of their tail binding with respect to integrin inactivation and turn over. In the second aim we will utilize high-resolution quantitative mass spectrometry to define how different integrins assemble adhesomes with common and specific components that signal in highly regulated manners. Our third aim will determine how integrin tails nucleate an adhesion complex that expedites further interactions with multiple binding partners by performing crosslinking proteomics of adhesion proteins bound to different β integrin tails in vitro. In the fourth aim we will use genetically engineered mice to determine how ubiquitously expressed proteins of the adhesome perform organ- and cell type-specific functions. Completion of these aims will help define the fundamental mechanisms whereby integrins control their complex signalling networks. This has implications for our understanding of development and disease as integrins play key roles for almost all cellular functions."
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 proteomics
- natural sciences biological sciences cell biology
- natural sciences chemical sciences analytical chemistry mass spectrometry
- medical and health sciences basic medicine physiology homeostasis
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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.
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-2012-ADG_20120314
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
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.