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Biomechanics and signaling in models of congenital heart valve defects

Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understan... ver más

31/05/2024

IMPERIAL COLLEGE O...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND ME... 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 H2020 notifico la concesión del proyecto el día 2024-05-31

ERC-CoG-2015: ERC Consolidator Grant Scope:Objectives

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3 Participantes

IMPERIAL COLLEGE OF SCIENCE...

798.87K€ | Lider

NOEL ALIMENTARIA

175.92K€ | Participante

CERBM-GIE

1.20M€ | Participante

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Duración del proyecto: 90 meses Fecha Inicio: 2016-11-25
Fecha Fin: 2024-05-31

Líder del proyecto

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND ME... 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 Mechanical forces are fundamental to cardiovascular development and physiology. The interactions between mechanical forces and endothelial cells are mediated by mechanotransduction feedback loops. My lab is interested in understanding how hemodynamic forces modulate cardiovascular function and morphogenesis. Overall, our recent work is unraveling the biological links between mechanical forces, mechanotransduction and endothelial cell responses. The heart beats 2.6 billion times in a human lifetime and heart valves are amongst the most mechanically challenged structures of the body. The cardiac valves are made of endocardial cells (EdCs) and extracellular matrix components. Most valve diseases have their origins in embryogenesis, either as signs of abnormal developmental processes or the aberrant re-expression of fetal gene programs normally quiescent in adulthood. This project is directed towards the elucidation of the biomechanical mechanism of mechanotransduction at the subcellular and molecular level and in addressing how EdCs integrate this information to form and maintain a functional cardiac valve. We will identify the mechanosensors at work in EdCs and their roles during cardiac valve development and repair. To do so, we will implement unique optical methodologies the lab has pioneered to characterize endocardial mechanotransduction: 1) Optical tweezing combined with mechanical stress reporters to test the mechanosensitivity of EdCs; 2) High resolution live microscopy and mathematical modeling to quantify mechanical forces; 3) 3D cell lineage studies to understand how cells respond and organize during pathological valve development. We will also use high-throughput mRNA- and ChIP-sequencing to characterize the transcriptional network activated by forces. When completed this proposal will shed light on a critical, but little explored, aspect of congenital valve defects and will be useful for identifying new targets for therapeutic interventions.

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