Objetivo 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. Ámbito científico engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensorsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesclassical mechanicsfluid mechanicsfluid staticsmedical and health sciencesclinical medicineembryologynatural sciencesphysical sciencesopticslaser physics Programa(s) 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) Tema(s) ERC-AG-LS3 - ERC Advanced Grant - Cellular and Developmental Biology Convocatoria de propuestas ERC-2011-ADG_20110310 Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Aportación de la UE € 1 237 637,08 Dirección RUE MICHEL ANGE 3 75794 Paris Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Julie Zittel (Ms.) Investigador principal Michel Labouesse (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Francia Aportación de la UE € 1 237 637,08 Dirección RUE MICHEL ANGE 3 75794 Paris Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Julie Zittel (Ms.) Investigador principal Michel Labouesse (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE La participación finalizó Francia Aportación de la UE € 1 257 866,92 Dirección Rue Laurent Fries 1 67404 Illkirch Graffenstaden Ver en el mapa Región Grand Est Alsace Bas-Rhin Tipo de actividad Research Organisations Contacto administrativo Steve Brooks (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
