"Control of two antagonistic cellular phenotypes with a single molecule (2022-05-COPPEY)" project details

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General information

Application closed

2022-05-COPPEY

Optogenetics; Cell migration; Polariy; RhoA; Modeling

Control of two antagonistic cellular phenotypes with a single molecule

Director(s) and team

Mathieu Coppey

Light-based Observation and Control of Cellular Organization

Abstract

The LOCCO (Light-based Observation and Control of Cellular Organization) Team is composed of physicists and biologists tackling biological questions. We use quantitative live cell imaging together with precise spatiotemporal optogenetic perturbations to understand how protein dynamics - such as transport and reaction - ensure cellular order and functions. We are covering multiple scales, from transient molecular assemblies to cell migration and polarity, and even up to multicellular systems.   In the context of the EuReCa 2022 call, we propose a PhD subject on ‘paradoxical signaling’ in cell migration. The ability of cells to migrate is a fundamental biological process, implied in numerous situation such as cancer. Cells move thank to a balance between contraction and extension of their body which is finely orchestrated by a set of small proteins, the RhoGTPases. Among these, RhoA has a mysterious role: it has been shown that this protein is active both in contracting regions of the cell and in extending ones. How can the same protein be involved in two opposite processes? To answer this question, we propose to use optogenetics to activate RhoA with a spatial and temporal control in single cells. We know from preliminary experiments that we can indeed induce the two phenotypes with the same protein, but we are looking for the quantitative rules that dictate the choice.   Understanding how such signals can encode two distinct decisions would be transformative to explain how cells compute and answer to spatiotemporal signals, how they coordinate their molecular activities to migrate and how we can prevent cancer cells migration when RhoA is deregulated.

Requirements to apply for the PhD thesis project

Applicants should have a background in physics or math and be highly motivated to work in biology. We expect a solid knowledge of a computing language such as Matlab or Python for image analysis, modeling, and microscope control. The applicant should know some basics about fluorescence microscopy, molecular and cell biology, cell signaling, or be strongly motivated to learn them. Given the diversity of tasks (cell culture, transfection, microscopy, computer routines, mathematical modeling), we are looking for a resourceful applicant willing to learn.