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MORPHORCE

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

The input of mechanical forces to morphogenesis and wound healing a systematic dissection 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... ver más

30/04/2018

CNRS

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2018-04-30 No tenemos la información de la convocatoria

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2 Participantes

CNRS

0.00€ | Lider

CERBM-GIE

N.D. | Participante

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Líder del proyecto

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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