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PhysCoMeT

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Physical basis of Collective Mechano-Transduction: Bridging cell decision-making...

Physical basis of Collective Mechano-Transduction: Bridging cell decision-making to multicellular self-organisation There is growing evidence that mechanical forces emanating from the tissue microenvironment can activate biochemical signalling to control gene expression, in a process known as mechanotransduction, for tissue regeneration and org... ver más

30/06/2027

UCPH

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-02-15

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2021-STG: ERC STARTING GRANTS

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1 Participantes

UCPH

1.50M€ | Lider

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Últimas noticias

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

29-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 37 concesiones

Duración del proyecto: 64 meses Fecha Inicio: 2022-02-15
Fecha Fin: 2027-06-30

Líder del proyecto

KOBENHAVNS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto There is growing evidence that mechanical forces emanating from the tissue microenvironment can activate biochemical signalling to control gene expression, in a process known as mechanotransduction, for tissue regeneration and organ development. Importantly disruption of this effect by changes in the microenvironment leads to pathological responses including tissue fibrosis and cancer. The advent of new force measurement techniques and high-resolution microscopy have made it possible to isolate impacts of mechanics from genetic and chemical factors, giving unprecedented access to investigate fundamental questions on how mechanical cues at the tissue scale affect signalling at a single cell level. The proposed research aims to reveal the physics of mechanotransduction in the context of multicellular aggregates, focusing on the impact of mechanical forces from multicellular motion and the mechanical feedback from the activation of biochemical signalling. My central hypotheses are: (i) localisation of mechanical stresses by the cell environment instructs transcriptional activation to direct multicellular behaviour and (ii) the gradients of mechanical forces in a growing multicellular aggregate can act as guidance cues for the morphology of growing tissue. I combine experiments on breast cancer cells of varying degrees of aggressiveness, with multiscale modelling - discrete and continuum simulations - to explain the interconnection of transcriptional activation and multicellular motion. This will fill the gap between biochemistry at the cell level and mechanics at the tissue level and is essential to the understanding of physical mechanisms that lead to healthy behaviour or malfunctioning of tissue, as well as to finding proper therapies for diseases that emerge at tissue scales. Moreover, in a field dominated by genetic and chemical understandings, the outcomes of this project will provide a fresh view based on the biophysics of force transmission across the tissue.

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