RHOMECHANOVASC

Regulation of Rho proteins by mechanical forces in the vascular system

Coordinatore	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)    more  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Dr. Nome: Laure Cognome: Benhamou Email: send email Telefono: 33228080080 Fax: 33228080130
Nazionalità Coordinatore	France [FR]
Totale costo	213˙108 €
EC contributo	213˙108 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2009-IOF
Funding Scheme	MC-IOF
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-08-01   -   2013-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Dr. Nome: Laure Cognome: Benhamou Email: send email Telefono: 33228080080 Fax: 33228080130	FR (PARIS)	coordinator	213˙108.30

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 Obiettivo del progetto (Objective)

'As molecular links between mechanosensors and the regulation of cellular processes Rho proteins have a critical position in mechanotransduction. Interestingly during cardiovascular disease (CVD) involving aberrant hemodynamic forces Rho proteins are activated. How do mechanical forces regulate Rho proteins? How do they contribute to the mechanical adaptation of the cell? And How is this mechanism altered during CVD? To answer these questions we have designed a proposal in two phases with interdisciplinary approaches including biochemical assays, three dimensional force microscopy (3DFM) and in vivo analysis. 1.Outgoing phase: To determine how mechanical forces activate Rho proteins and to evaluate the involvement of Rho proteins during the mechanical adaptation to force. We will identify the mechanism of Rho proteins activation using an innovative biochemical assay developed in the host lab and we will evaluate their involvement in mechanical adaptation of the cell using 3DFM. 2.Return phase: To evaluate the pathophysiological relevance of the mechanisms identified during the first phase. We will determine the cellular functions downstream of the regulators identified during phase 1 and we will investigate their activities in two animal models of altered hemodynamic forces by using the small animal physiology core facility available in the return host. The proposed project will yield new insights in different areas of life science from fundamental cell biology to potential identification of new therapeutic targets. First the anticipated results will contribute to better understand how the cells modify their mechanical properties in response to force. This crucial mechanism is central in many aspects of biology. We will also evaluate the modulation of Rho regulators in animal models of CVD; this will permit identification of new pharmacological targets for this public health problem.'