Descrizione del progetto
Gli attori molecolari nella topografia dell’epitelio intestinale
L’epitelio è un tessuto esteso che ricopre le superfici esterne e interne del nostro corpo, tra cui la cute e l’intestino. Oltre a svolgere un ruolo di barriera fisica, l’epitelio intestinale funge da regolatore dell’assorbimento di sostanze nutritive e interagisce con il microbiota. Ciononostante, si sa poco sui meccanismi che ne determinano l’architettura e la dinamica. Il progetto TOPOGRAPHYSENSING, finanziato dall’UE, sta esaminando il ruolo della molecola di adesione cellulare epiteliale (EpCAM, epithelial cell adhesion molecule), una glicoproteina transmembrana. I ricercatori valuteranno il modo in cui EpCAM rileva segnali di tipo meccanico dal microambiente per guidare l’organizzazione spaziale delle cellule epiteliali nell’intestino.
Obiettivo
Intestine epithelium consists of spatially segregated cells that organize into groups of various functions at different locations
of the 3D curved epithelial monolayer. How geometric cues contribute to the maintenance of the sophisticated epithelial architecture and dynamics in 3D remains unknown until now. Recently, the Ladoux's laboratory has found that EpCAM-modulated cell contractility associated with the epithelial monolayer polarity, cytoskeletal arrangement, and cell-cell adhesion in 3D context. In contrast to 2D context, the EpCAM-defective tissue shows a loss of collective cellular spatial organization and forms a disordered multi-layered epithelium when exposed to substrates of 3D topographies. In addition, Ankyrin-G and α/β-spectrin network which participates in cortical tension modulation was identified as the main interacting partner with EpCAM in epithelial cells. These observations lead us to hypothesize that EpCAM allows the tissue to sense and conform to complex 3D topographies in an orderly manner. However, the molecular mechanisms and other related functions of EpCAM-mediated mechanotransduction remain unknown. As large scale mechanosensing has been shown to occur primarily through the actin cytoskeleton which permeates the tissue to form a network, we aim to understand the interactions between the EpCAM-mediated pathway and actin modulation and/or E-cadherin adhesion sites that may allow 3D topographical sensing. Our working hypothesis is that EpCAM forms an integral part of the cellular responses to topographic cues that has a more general role in controlling epithelial architecture and dynamics through the regulation of actomyosin networks, or vice versa. Here, we propose to scrutinize EpCAM-mediated mechanotransduction by generating a platform with precise control of geometric factors and microenvironmental cues using a range of multidisciplinary approaches including microfabrication, biophysics, and advanced molecular biology techniques.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programma(i)
Argomento(i)
Invito a presentare proposte
(si apre in una nuova finestra) H2020-MSCA-IF-2018
Vedi altri progetti per questo bandoMeccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
75794 Paris
Francia