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MechanoFate SIGNED

From mechanical stress to vascular fate

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 MechanoFate project word cloud

Explore the words cloud of the MechanoFate project. It provides you a very rough idea of what is the project "MechanoFate" about.

stresses    occurring    aberrant    post    rsc    cyclic    nuclear    nucleus    translationally    regulation    differentiated    mechanical    activate    regenerative    poorly    undifferentiated    differentially    regulate    insensitive    signals    molecular    interdisciplinary    proteins    questions    therapeutic    alteration    life    trigger    expression    stretch    stabilizes    despite    physiological    protect    force    cardiovascular    bearing    assays    virtually    specify    designed    signaling    cells    identification    answer    remodelling    turn    genetic    biology    constant    expressed    medicine    transmission    cell    science    contribution    stem    stress    biophysical    whereas    yield    vessel    mechanotransduction    phenotypic    gene    combining    modified    vascular    hypothesis    insights    differentiation    blood    environment    phenotype    besides    structural    fate    cues    defines    proteomic    normal    inflammation    resident    transmitted    rscs    mechanisms    biochemical   

Project "MechanoFate" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙498˙412 €
 EC max contribution 1˙498˙412 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙498˙412.00

Map

 Project objective

In the vascular system, cell phenotype and fate are driven by the mechanical environment. Whereas physiological mechanical stress defines and stabilizes normal cell phenotype, aberrant mechanical signals trigger phenotypic alteration, leading to inflammation and vascular remodelling. Despite recent advances, how mechanical cues impact gene expression to specify cell phenotype remains poorly understood. Our hypothesis is that mechanical stresses are transmitted to the nucleus where they activate signaling pathways, which in turn regulate gene expression, but what are these mechanotransduction mechanisms occurring within the nucleus? Besides, while most vascular cells respond to mechanical force, Resident Stem Cells (RSCs) are virtually insensitive and remain undifferentiated despite constant cyclic stretch. What are the molecular mechanisms which protect RSCs from stretch-induced differentiation? To answer these questions, we designed an interdisciplinary proposal which gathers biophysical, biochemical and genetic assays, with the following objectives: I) To determine how nuclear mechanotransduction pathways regulate vascular cell phenotype in response to mechanical cues. By combining proteomic and biophysical assays, we will identify nuclear proteins that are post-translationally modified in response to mechanical stress, then we will determine their contribution to gene expression regulation and vascular cell differentiation. II) To identify the molecular mechanisms which protect RSCs from stretch-induced differentiation. We will identify differentially expressed force-bearing structural elements in RSCs compared to more differentiated vascular cells and we will evaluate their impact on gene expression, stress transmission, RSC differentiation and blood vessel formation. The proposed project will yield new insights in different areas of life science from cell biology to potential identification of new therapeutic targets in cardiovascular and regenerative medicine.

 Publications

year authors and title journal last update
List of publications.
2017 Julien Aureille, Néjma Belaadi, Christophe Guilluy
Mechanotransduction via the nuclear envelope: a distant reflection of the cell surface
published pages: 59-67, ISSN: 0955-0674, DOI: 10.1016/j.ceb.2016.10.003
Current Opinion in Cell Biology 44 2019-05-29
2017 Angélique Millon-Frémillon, Julien Aureille, Christophe Guilluy
Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
published pages: , ISSN: 1940-087X, DOI: 10.3791/55330
Journal of Visualized Experiments 121 2019-05-29
2016 Néjma Belaadi, Julien Aureille, Christophe Guilluy
Under Pressure: Mechanical Stress Management in the Nucleus
published pages: 27, ISSN: 2073-4409, DOI: 10.3390/cells5020027
Cells 5/2 2019-05-29

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