MORPHORCE

The input of mechanical forces to morphogenesis and wound healing: a systematic dissection

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	France [FR]
Totale costo	2˙495˙504 €
EC contributo	2˙495˙504 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-ADG_20110310
Funding Scheme	ERC-AG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-05-01   -   2017-04-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE  Organization address address: Rue Laurent Fries 1 city: ILLKIRCH GRAFFENSTADEN postcode: 67404 contact info Titolo: Dr. Nome: Steve Cognome: Brooks Email: send email Telefono: +33 3 88 65 33 94 Fax: +33 3 88 65 32 03	FR (ILLKIRCH GRAFFENSTADEN)	beneficiary	1˙395˙778.28
2	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Ms. Nome: Julie Cognome: Zittel Email: send email Telefono: +33 1 42349416 Fax: +33 3 42348723	FR (PARIS)	hostInstitution	1˙099˙725.72
3	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Prof. Nome: Michel Cognome: Labouesse Email: send email Telefono: +33 3 88 65 33 93 Fax: +33 3 88 65 32 01	FR (PARIS)	hostInstitution	1˙099˙725.72

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 Obiettivo del progetto (Objective)

'The importance of mechanical forces in biology is well accepted, yet an integrated view of their mode of action in vivo is lacking. We intend to characterize in-depth the physical forces and cellular processes that coordinate the morphogenesis of different cell types contributing to an organ, taking the C. elegans embryo as a paradigm. We will achieve this by pursuing three axes: 1. Building on our discovery of a hemidesmosome-based mechanotransduction pathway that operates between contracting muscles and epidermal cells, we will combine genetic analysis with single-molecule biophysical methods to address three issues. i) What is the primary mechanosensor responding to tension within hemidesmosomes and how does it work? ii) How are all epidermal targets of muscle tension activated? iii) What is the biophysical mechanism stabilizing epidermal cells between muscle contractions? 2. We will test several features of a finite element model predicting a key role of microtubule-based epidermal stiffness and hydrostatic pressure in elongation. We will combine quantitative mechanical measures with force biosensors and laser ablation to define how these resistive forces contribute to embryo elongation along the anterior-posterior axis. 3. To extend our conclusions to the medical field, we will knockdown homologues of proteins identified in C. elegans, as well as proteins of the same families, in keratinocytes with partially damaged hemidesmosomes. Cells will be submitted to wound assays or grown on a stretchable substrate. Positive hits will be further characterized and tested in mouse models with partially defective hemidesmosomes. We foresee that this project will identify conserved proteins and processes relaying mechanical forces, and thus shed light on the mechanical basis of morphogenesis. We also expect our work to have strong impact in medicine, since the outcome of many pathologies, including wound healing and cancer, is thought to be strongly influenced by forces.'