Objective
Integrin aIIb,B3 is the major platelet fibrinogen receptor and plays an important role in haemostasis by mediating platelet aggregation and thrombus formation. B3 integrins are also involved in a variety of pathological processes including thrombosis, tumor invasion and metastasis, and have become major targets for drug development. Inherited molecular defects in the aIIb or ,B3 subunits have been identified in Glanzmann's thrombasthenia patients, and shown to be responsible for defective platelet aIIb,B3 receptor function. The aim of this project is to stably express autofluorescent, GFP-tagged wild type and mutant aIIbB3 receptors in mammalian cells, in order to investigate their biosynthetic pathway and intracellular trafficking by 3 colour confocal microscopy as well as biochemical analysis of the posttranslational processing. We hope that these studies will contribute to a better knowledge of the structural requirements necessary for integrin aB dimerization, posttranslational processing, intracellular trafficking, recycling and signal transduction, and provide some clues for the understanding of the reduced surface expression of aIIbB3 in GT type II patients. Identification of structural domains necessary for receptor transport and surface expression could lead to the development of a new generation of therapeutics aimed to specifically inhibit ,B3 integrin intracellular processing pathways in a way similar to those characterized for mutant B3 integrins in GT patients. Training content (objective, benefit and expected impact)
As integrins mediate a large variety of pathological processes, the identification of structural domains involved in integrin subunit-subunit interactions, intracellular transport and integrin affinity modulation is extremely important for the design of a new generation of therapeutics that could act intracellularly in a cell type specific manner by inhibiting integrin processing pathways. This project could also help to validate the concept thatinhibition of the integrin endocytosis pathway could prevent integrin-dependent viral, bacterial or parasite internalicontribute to the development of drugs designed to block 3 integrin mediated viral, bacterial or parasite internalization into host cells. Links with industry / industrial relevance (22)
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 basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine angiology vascular diseases
- engineering and technology materials engineering colors
- natural sciences physical sciences optics microscopy confocal 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.
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.
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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.
Coordinator
1511 Luxembourg
Luxembourg
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.