Two years funded post-doctoral position at Institut Pasteur (Paris) – In vitro reconstitution of intermediate filament dynamics

Two years funded post-doctoral position at Institut Pasteur (Paris) – In vitro reconstitution of intermediate filament dynamics

Context

Cell shape, mechanics and motility are determined to a large extent by the cytoskeleton composed of actin microfilaments, microtubules and intermediate filaments (IF). While the contribution of microtubule and actin filaments has been extensively investigated, the IF involvement has long been neglected. However there is a growing body of evidence that the three cytoskeleton types are acting in cooperation to achieve their functions, especially during cell migration and invasion (1-2). In this context, we propose to use the latest advanced microscopy tools coupled to biophysical, biochemical methods and theoretical modeling in order to gain more insight into the IF biophysical properties (3) and to elucidate how they are integrated inside the cell to fulfill their functional roles.

Objectives

The aim of the project is to recapitulate the functional modes of IF dynamics starting from a limited number of purified components placed in a simple and well controlled environment. First the post-doc fellow will set up an experimental system which allows the observation of single filaments assembly in situ using fluorescence microscopy (4) coupled to microfluidics. Then, this set up will be used to quantify the impact of the main regulators of IF dynamics, focusing on the crosstalk with the other types of cytoskeletal filaments.

Qualification

The project is funded by an ANR JCJC (2016) and is supervised by Cécile Leduc, in the “Cell polarity, migration and cancer” unit directed by Sandrine Etienne-Manneville. Starting date is flexible but should be prior to December 2018. Review of applications starts immediately with a dead line in April 2018. Applications from candidates with a PhD in biophysics and 0-3 years of relevant postdoctoral experience will be considered. We are looking for a talented scientist with expertise in biochemistry and microscopy, as well as a good theoretical background in biophysics. Previous experience in quantitative imaging and/or the cytoskeleton would be a plus. A high personal motivation to develop a challenging project is required.

To apply please submit a cover letter summarizing research interests and expertise, a CV, a list of publications, and names and contact information of two references, to Cécile Leduc cleduc@pasteur.fr.

Bibliographie:

1. (1)  Leduc C, Etienne-Manneville S. (2015) Intermediate filaments in cell migration and invasion: the unusual suspects. Curr Opin Cell Biol. 32:102-12.

2. (2)  Leduc C, Etienne-Manneville S. (2017) Regulation of microtubule-associated motors drives intermediate filament network polarization., J Cell Biol. 216:1689-1703

3. (3)  Block J, Schroeder V, Pawelzyk P, Willenbacher N, Köster S. (2015) Physical properties of cytoplasmic intermediate filaments. Biochim Biophys Acta. 1853:3053-64.

4. (4)  Winheim S et al (2011) Deconstructing the late phase of vimentin assembly by total internal reflection fluorescence microscopy (TIRFM). Plos one 6:e19202