Objective
The project seeks to understand the molecular events involved in the recognition by thrombin of various cell membrane and plasma proteins. The project is focused on thrombin functions that are highly susceptible to contribute to thrombosis and associated disorders : (i) receptor-mediated cell activation, (ii) feed-back amplification of thrombin production by activation of factor V and factor VIII, (iii) thrombin inactivation by its physiological inhibitor, antithrombin.
The final enzyme of the coagulation cascade, thrombin, plays a key role in the development of arterial thrombosis, associated inflammation and atherosclerosis. Thrombin is a multifunctional enzyme which induces both the conversion of fibrinogen to fibrin and cell activation, and also regulates its own production, by interacting with a number of cell membrane and plasma proteins. The X-ray crystallographic structure of the human enzyme in complex with various specific inhibitors has been elucidated, revealing that thrombin's structure can be divided in several functional regions that recognize different chemical moieties of other molecules. The remarkable specificity of thrombin for its various natural substrates, ligands and inhibitors may be ascribed to multiple interactions with the different functional regions (active site and exosites) of the enzyme, but the detailed mechanisms of these interactions remain to be resolved.
The aim of the collaborative study is to identify the particular residues of thrombin that are important for its interaction with the receptor, factor V, factor VIII and antithrombin. Five teams of researchers will contribute with their extensive previous experience in the field of thrombin research and will combine their efforts by providing a wide variety of unique methodology, from site-directed mutagenesis, through rapid-kinetics, to X-ray crystallography and nuclear magnetic resonance spectroscopy. It is hoped that the information provided by the project will be most helpful in devising new strategies for inhibition of specified thrombin functions and improvement of the prevention of arterial thrombosis.
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.
- medical and health sciences clinical medicine angiology vascular diseases
- natural sciences earth and related environmental sciences geology mineralogy crystallography
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences physical sciences optics spectroscopy
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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Funding Scheme
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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.
Coordinator
75870 PARIS
France
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.