Description du projet
Une étoile est née: les étoiles d’actine et leur rôle dans l’homéostasie de l’épithélium intestinal
La prolifération et la différenciation des cellules souches sont des processus essentiels au cours du développement et tout au long de la vie. Ces dernières assurent l’homéostasie tissulaire et le renouvellement, la réparation et la régénération continus des tissus et des organes. Les mécanismes qui sous-tendent l’homéostasie tissulaire ne sont pas bien compris. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet ActinStar étudiera le rôle potentiel d’un assemblage d’actine multicellulaire en forme d’étoile récemment découvert, appelé étoile d’actine, dans la différenciation des cellules souches et l’homéostasie des tissus dans la santé et la maladie. Le projet se concentrera sur l’homéostasie intestinale et l’épithélium, un tissu qui recouvre toutes les surfaces internes et externes du corps et qui se régénère en permanence.
Objectif
Faithful epithelial morphogenesis is crucial during development and tissue homeostasis. The dynamic intestinal epithelium is an appropriate model to study this field of research. Constant regeneration of epithelium is one of the main characteristics of intestinal homeostasis mediated by finely controlled balance between intestinal stem cell proliferation and differentiation. Therefore, it is instrumental to study mechanisms controlling intestinal organization to understand tissue homeostasis and function.
Actin cytoskeleton plays an important role in regulating epithelial morphogenesis. Recently, by using 2D and 3D intestinal organoids, the host lab has discovered a new unique multicellular star-shaped actin assembly, termed “actin stars” (AcSs) located in the basal domain of differentiated epithelium. This network is characterized by 6-branched star-shaped actin clusters covering the entire basal surface, with AcS node at the centroid of the cell and each branch of the star orthoradially connects the plasma membrane, and directly mirrors a corresponding branch from a neighbouring cell. They confirmed such actin structures in vivo in mouse small intestine. The AcSs may represent a large-scale inter-connecting meshwork in the differentiated epithelial domain.
Considering the novelty of these results, we would like to investigate the interplay between large-scale AcS networks and tissue morphogenesis. Here we aim to dissect the organization of AcS network, determine the processes leading to their formation, and understand the importance of AcSs for individual cells as well as epithelial assemblies. For that we will carry out a multi-disciplinary approach, combining the use of high-resolution imaging, optogenetics, genomics coupled to physical modelling.
We anticipate that our results will have a significant impact in understanding the role of AcSs in epithelial differentiation, tissue homeostasis in physiological and pathological conditions.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
75794 Paris
France