PhD student in neuroscience "Deciphering the molecular links between actomyosin force, integrin regu

Updated: about 1 month ago
Location: Tremblay en France, LE DE FRANCE
Deadline: 31 Jul 2019

Established in January 2011, the Interdisciplinary Institute for Neuroscience (IINS) parent institutions are the CNRS (French National Center for Scientific Research) and the University of Bordeaux.
With 150 people and 12 research teams, IINS deploys multidisciplinary expertise to study molecular and cellular mechanisms involved in brain activity. The Institute develops innovative methods in imaging, chemistry, physiology and computer science. IINS is a major player in Aquitaine's neuroscience community and a leading component of Bordeaux Neurocampus and BRAIN, a cluster of excellence in Neuroscience.
The PhD student will work in Grégory Giannone's team under the supervision of Olivier Rossier.

The aim of this thesis project is: (1) to reconstitute, from purified proteins, minimal biomimetic adhesion complexes consisting of a supported lipid membrane containing integrins that will connect actomyosin on one side, and a microstructured extracellular matrix on the other side. These reconstituted systems will allow the study of the dynamics of nanoscale components by monitoring individual molecules, a technique well in place in the laboratory (Rossier et al, Nature Cell Biology 2012, Paszek et al, Nature 2014); (2) to identify the molecular mechanisms of integrin regulation that directly depend on the actomyosin contractile force and to understand how the physical properties of the ECM modify them. Finally we will seek to (3) validate the physiological relevance of our discoveries in living cell adhesion sites.
The PhD student will have to use a wide range of experimental approaches at the interface between Cell Biology, Biochemistry and Physico-Chemistry:
1 / Photonic imaging of super-resolution and tracking of individual proteins.
2 / Protein purification and reconstitution techniques with model lipid membranes (unilamellar vesicles and supported lipid membranes)
3 / Surface chemistry techniques for nano-patterning innovative substrates, compatible with super-resolution imaging and tracking of individual proteins, with which we can mimic the different physical parameters of the ECM (density and mobility of bio-adhesive molecules, rigidity, presence of glycocalyx)
4 / Cell line cultures in which we will control the expression of specific integrins and their associated regulators by the genomic editing technique by the CRISPR / Cas9 strategy. We will notably express the wild proteins but also mutated versions.
The PhD student will have to set up the corresponding methods of analysis and also conduct bibliographic analyzes, writing articles and projects, as well as presenting his results to an international audience

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