Description du sujet de thèse

Epithelia are polarised tissues with permeability and mechanical barrier functions. Throughout life, the integrity of epithelia is constantly challenged by cell division, cell intercalation, extrusion of apoptotic cells or collective delamination of pre-tumour cells. Remarkably, these events occur without the tissue tearing. The team's project aims to decipher the underlying mechanisms using an invertebrate model, Drosophila, and a vertebrate model, Xenopus. Adhesive junctions (AJs) and focal adhesions (FAs) are the two main adhesive structures that ensure the formation of robust mechanical contacts, enabling the transmission of cytoskeletal force to support changes in the shape of cells and tissues. The host team has demonstrated that integrin-based contacts are assembled at the AJ disassembly site. This is particularly the case at tri-cellular junctions (TCJs), the points of contact between three epithelial cells, integrating the biochemical and mechanical signals required during cell extrusion, planar and radial intercalation, and the collective delamination of pre-tumour cells. At the heart of this PhD project is the hypothesis that AJs-FAs adhesion switching maintains the mechanical integrity of the tissue.
Using a combination of genetic approaches, quantitative and non-invasive super-resolution confocal imaging, and biophysics, we propose to study the assembly of FAs, their link to force generation by the actomyosin cytoskeleton, and then their function(s) during extrusion and collective delamination of pre-tumour cells. Our working hypothesis is that the narrowing of the length of intercellular junctions causes a shear stress that triggers the local dismantling of AJs and, concomitantly, the assembly of FAs apically, in the plane of the AJs. The research project will study whether FAs constitute an alternative adhesion system to support the remodelling of AJs and TCJs and thus ensure mechanical homeostasis in proliferative tissues. The objectives of the proposal are to answer the following questions:
- What are the dynamics, site of assembly and function of FAs during collective extrusion and delamination?
- What are the mechanical links between FAs and actomyosin in TCJs during cellular rearrangement?
- What are the mechanistic links between FAs and TCJ components?

Contexte de travail

The IGDR is a joint research unit of the CNRS and the University of Rennes, located on the Rennes Villejean Campus. The IGDR is made up of sixteen teams of researchers and a staff of 200, including researchers/teaching researchers, clinicians, post-docs, PhD students, engineers and technicians of various nationalities (United Kingdom, Poland, Denmark, Spain, Australia, India, Chile, Argentina and Brazil). In the field of fundamental research, the Epithelia Dynamics and Mechanics team describes and studies the molecular mechanisms by which the integrity of epithelia is preserved during cell division, cell intercalation, extrusion of apoptotic cells and delamination of pre-tumour cells. Our research themes, using invertebrate and vertebrate models, combine approaches from genetics, cell biology and soft matter physics. The host team is made up of 10 people, including 4 researchers, 2 post-docs, 2 PhD students and 2 engineers.

Contraintes et risques

38h30 weekly no time constraints (no shifts) travel for national and international conferences travel for collaborative projects.

Informations complémentaires

N.A.