Reference : UMR7592-BENLAD-008
Workplace : PARIS 13
Date of publication : Friday, May 13, 2022
Scientific Responsible name : Benoit Ladoux
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2022
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly
Description of the thesis topic
The study of the effects of out-of-plane surface curvature on cell behavior is recent but gaining importance. It is of particular interest in the context of epithelia for which cells undergo negative and positive out-of-plane stereotypic curvatures such as intestinal epithelia. Although little is known about cell fate on curved substrates in vitro, surface curvature such as convexity and concavity has been shown to induce unexpected behaviors in epithelia such as cell spreading, migration, and architecture. We have developed methods to fabricate structures with curved surfaces at length scales of tens of microns (domes and wells). We will study how curved surfaces can induce particular modes of collective organization of cells, how this affects their dynamics and cell extrusion. We will use cell lines and intestinal organoids. We anticipate that cell extrusion in a collective could be spatially controlled by topography. We will study the role of curvature on the formation and dynamics of topological defects within curved epithelial tissues.
Our project relies on the specific combination of original and complementary approaches allowing mechanically controlled cell cultures on bioengineered and biomimetic substrates, high resolution live imaging techniques and the establishment of physical models to elucidate the dynamic and mechanical aspects of living tissues.
Our group is part of the Institut Jacques Monod (https://www.ijm.fr), which is housed in a brand new building on the new Paris campus. The Institut Jacques Monod is one of the leading public centers for basic research in biology in Paris and offers a state-of-the-art research environment. It offers a rich, multidisciplinary environment, as well as access to different experimental approaches in our laboratory and technological platforms to ensure adequate development of the research. The thesis will be supervised by Benoit Ladoux, team leader at IJM and co-supervised by RM. Mège.
Constraints and risks
The project is in line with our studies on collective cell migration. We study the collective behavior of cells in the context of tissue homeostasis but also in cell polarity and migration. To answer these questions, we are developing micro- and nanofabricated tools and micromanipulation to control the mechanical environment of cells. These tools are combined with molecular approaches and advanced techniques in light microscopy to study the influence of physical properties of the environment on collective cell migration and the organization of epithelial layers. We are characterizing how physical constraints can lead to emergent dynamical and mechanical properties of various epithelial tissues. Along this line, we develop mechanobiological models to better understand the cellular responses to their mechanical environment.
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