Description du sujet de thèse

This thesis will study the spontaneous phase separation of an assembly of amoeba cells in hypoxia, i.e. when lacking oxygen. At high density, a dividing population of Dictyostelium discoideum cells, referred to as Dicty, spontaneously separates into multicellular aggregates with a well-defined size and a collection of single cells. We have already demonstrated that this phenomenon stems from the competition between cell-cell adhesion and aerotaxis, the tendency of Dicty cells to follow oxygen gradients.
The proposed interdisciplinary project will investigate other aspects of this microphase separation: 1- the mechanism responsible for aggregate motion which remains unknown, 2- the highly dynamic nature of the aggregates, in stark contrast with phase separation in inert systems and 3- the 3d structure of the aggregates and the role of oxygen gradients in that structure.
To do so, the hired student will develop both experimental and numerical strategies. Experimentally, the objectives will be to run new, better controlled experiments to better quantify the dynamics of the process through image analysis, aggregate tracking and data analysis. Then, to address the mechanism of locomotion of the aggregates, especially asking whether this comes from cellular exchanges between them and the gas of single cells, we will use single cell tracking in both phases by fluorescence live microscopy in 3D (xy + time) or 4D (xyz + time). Finally, cell biology approaches combined with 3d microscopy (spinning disk, light sheet) will be used to resolve the 3d structure of the aggregates.
Numerically, the hired student will run cellular Potts models reproducing the main characteristics of Dicty cells: persistent motion, cell adhesion and aerotaxis. The first aim will be to reproduce, in 2d, the complex dynamics observed and quantified experimentally. The second will be to develop three dimensional simulations to test the hypothesis that vertical oxygen gradients are responsible for the 3d structure of the aggregates.

Contexte de travail

The PhD will be carried out in the Biophysics team at the Institut Lumière Matière in Lyon. It will be part of an ANR-funded project involving biologists, biophysicists, theoretical physicists and mathematicians. The hired student will thus have a profile combining experimental and theoretical skills with a demonstrated willingness to work at the interface between physics and biology and strong skill in scientific programming of active matter systems. Experience in cell biology, 3Dmicroscopy and/or cellular Potts model would be a plus.