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DEciphering Species-specific dImorphism in inteGriN-ExtraCellular matrix Mechanobiology

Objectif

The extracellular matrix (ECM) consists of complex, heterogeneous, and fibrous networks. ECM varies in different species and sexes. The dynamic adjustment of cellular behaviours to such species-specific dimorphic ECM properties is processed by transmembrane receptors named integrins in cells and essential for nearly every physiological process. Yet, a majority of in vitro biomaterial-cell studies strikingly neglect species and sex of ECMs and cells as biological variables. This causes a severe gap in the accurate understanding of species- and sex-specific cell-biomaterial dynamics and in turn discrepancy between in vitro studies and clinical trials. This project thereby aims to systemically elucidate species-specific dimorphism in spatiotemporally integrin-mediated cell-ECM mechanobiology in understanding original human cell biology and designing ideal ECM niches to develop genuine in vitro human tissue models. This will be realized by first verifying the existing species-specific dimorphism in ECMs and cells including structural/biophysiochemical analysis in purified ECM proteins and cell-deposited ECMs (Aim 1). We will bottom-up engineer 2D and 3D ECM platforms to recapitulate species-specific dimorphic microenvironments and determine how the species and sex of the engineered ECMs modulate spatiotemporal responses of cells with different species and sex (Aim 2). The integrin-mediated underlying signalling pathways with regards to cell-ECM species and sex will be then investigated to provide a thorough mechanobiological understanding (Aim 3). Finally, we will apply the species-specific dimorphic mechanobiology obtained from the above aims to better design ECM niches to precisely orchestrate stem cell fate decisions and develop in vitro tissue models such as organoids (Aim 4). DESIGN-ECM has the potential to better design in vitro cell studies/tissue models and interpret such in vitro data accordingly by reckoning with species and sex of biomaterials and cells.

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Programme(s)

Thème(s)

Régime de financement

HORIZON-ERC - HORIZON ERC Grants

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Appel à propositions

(s’ouvre dans une nouvelle fenêtre) ERC-2026-STG

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Institution d’accueil

UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN
Contribution nette de l'UE
€ 1 500 000,00
Coût total
€ 1 500 000,00

Bénéficiaires (1)