Reference : PhD Anne-Cecile Reymann
Cell architectures equilibrate and remodel perpetually. The cellular cortex is an active material that allows cells to maintain their shape, produce or sense forces. It is a submicron network under the cell membrane consisting mostly of actin filaments and myosin molecular motors. This actin cortex is key in maintaining such dynamical equilibrium by constant assembly-disassembly processes using a wide palette of molecular building blocks. Actin networks are in fact essential in many domains such as for cell divisions, cell identity acquisition or cell migration; defects of actin dynamics lead to severe phenotypes and is related to many illnesses.
My team studies the biophysical properties of the actomyosin cortex in early C. elegans development. We aim to reveal how these properties are regulated and change over time to control early morphogenesis processes during the first few divisions of the C. elegans embryo. My team is interdisciplinary at the interface of biochemistry, cell biology and physics. The idea is to back up hypothesis rising from direct in vitro observation using high resolution confocal spining disk with in vitro reconstitution with purified proteins and in silico numerical simulations whenever possible. This will allow us to cross scales from molecules to large-scale coherent material and open up new insights into the understanding of the architectural orchestration and regulation of actin cytoskeletal structures.
The specific aim of this PhD will be to fully understand the process of cortical actin assembly and answer the how/when/where questions related to it. We will start by characterizing the molecular orchestration of actin and actin binding molecules during the cortical assembly process in the C. elegans early embryo. Focus will specifically be given to the known main actor of actin nucleation at this stage, namely the formin CYK-1. Single particle tracking of endogenously labelled CRISPR proteins will be automated using MOSAIC toolbox. This study will be conducted and compared in different spatio-temporal context (oocyte to zygotic transition, polarization, first division or cortical homeostasis) and especially compared in between sisters cells of the developing embryo.
During C. elegans development, nearly every division produces daughter cells with different developmental trajectories through a remarquable invariant cell lineage. C. elegans has thus become an excellent model system for studying cellular symmetry breaking in a developmental context. In the early embryos, the initial series of asymmetric early divisions are crucial for generating diversity in cell sizes, cell contents and cell fates, thus producing the 6 founder cells and establishing the three main body axes of the embryo between the 1 to 6 cells stage. In some cases, these differences are imposed on daughters before or after division through inductive signals, but many of these divisions are intrinsically asymmetric, an initial symmetry-breaking step creates polarized distributions or activities of factors that control developmental potential. The proposed project will tackle this aspect focusing on the cellular cortical layer that both undergoes some asymmetric segregations of its constituents but is also a main driving force during these processes.
Actin dynamics in the C. elegans one-cell embryo during the initial cortical assembly process post fertilization. Scale bar 10 μm.
3 year PhD at the interface of cell biology/live imaging /quantitative biology/biophysics.
Date limite de candidature : 1 novembre 2018