MechanoFate
Financiado
From mechanical stress to vascular fate
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 alterat...
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.
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Duración del proyecto: 73 meses
Fecha Inicio: 2015-05-28
Fecha Fin: 2021-06-30
Fecha Fin: 2021-06-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-06-30
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2014:
ERC Starting Grant
Cerrada
hace 10 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
582.63K€ |
Participante