BCATENIN_MECHANICS

Mechanical activation of beta-catenin signalling

Coordinatore	more  Organization address address: 26, rue d'Ulm city: PARIS postcode: 75248 contact info Titolo: Ms. Nome: Corinne Cognome: Cumin Email: send email Telefono: +33 1 56 24 66 20 Fax: +33 1 56 24 66 27
Nazionalità Coordinatore	Non specificata
Totale costo	194˙046 €
EC contributo	194˙046 €
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-2012-IEF
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-03-01   -   2015-02-28

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT CURIE  Organization address address: 26, rue d'Ulm city: PARIS postcode: 75248 contact info Titolo: Ms. Nome: Corinne Cognome: Cumin Email: send email Telefono: +33 1 56 24 66 20 Fax: +33 1 56 24 66 27	FR (PARIS)	coordinator	194˙046.60

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 Obiettivo del progetto (Objective)

'During embryonic morphogenesis, cells do not only generate forces necessary for shape changes and tissue movement but also sense and respond to the forces exerted on them by neighbouring cells and tissues. Recent studies demonstrate, that these forces can act as mechanical cues during development regulating cytoskeletal remodelling, cell proliferation and gene expression. However, in most cases the molecular mechanism by which cells sense and transduce a mechanical signal into a biochemical signal remains to be discovered. Therefore, my proposed project aims at identifying the primary mechanosensitive element during Drosophila gastrulation that initiates the activation of the beta-catenin pathway in stomodeal cells in response to mechanical strain that leads to the release of beta-catenin from adherens junctions (AJ) and its translocation to the nucleus, where it activates the transcription of a key regulator gene. In order to identify the molecular mechanism that translates a mechanical strain signal into a biochemical signal I will analyse the AJ complex in vivo for molecular changes in its dynamic interaction and conformation upon mechanical deformation during gastrulation. For this, I will make use of advanced fluorescent microscopy techniques in conjunction with classical biochemical assays. In addition, I will perform in vitro two cell assays to determine the strength and type of deformation needed to induce a conformational change. Ultimately, the information gained about the mechanosensitive element will be used to design a fluorescent probe to directly monitor the mechano-activation in response to the morphogenetic movements during Drosophila gastrulation. To my knowledge, this would be the first time in vivo to visualise directly the activation of a primary mechanosensor.'