Post-doctoral position for structural studies on multifunctional intrinsically disordered actin-binding domains, CNRS, in Paris suburbs, France

A 2-year post-doctoral position for structural studies on modular proteins containing multifunctional intrinsically disordered actin-binding domains is available at the Laboratory of Structural Enzymology and Biochemistry (LEBS), CNRS, in Paris suburbs, France. Starting date: October/november 2011. European funding - monthly gross salary: ~ 2 500 euros.

Project:

Structural basis governing the functional versatility of intrinsically disordered WH2 domains in actin assembly dynamics

Job description:

            The actin cytoskeleton relies on the ability of actin ATPase to self-assemble into polarized filaments which provide in all cells mechanical force for cell shape maintenance, traffic or membrane deformation. It forms a dynamic structural network constantly remodeled in non-muscle cells by many actin-binding proteins.

The postdoctoral research project study the structural basis governing the functional versatility of β-thymosin (βT) and WH2 domains in actin self-assembly dynamics. These small ubiquitous actin-binding domains are intrinsically disordered but functional with highly variable sequences. Found as single or repeated modules in numerous signalling modular proteins they appear to regulate very versatile functions in actin assembly dynamics [recent reviews: Husson et al. (2010) Annals of the New York Academy of Sciences 1194, 44-52; Carlier et al., (2011) Int Rev Cell Mol Biol. 2011;290:55-85].

We try to establish the structure-function relationship of βT/WH2 domains and the structural basis of their multifunctionality through a multidisciplinary approach integrating biochemical studies (rapid kinetics mechanisms of protein-protein interaction and self-assembly of actin), biophysical (hydrodynamic characterizations, epifluorescence microscopy in reconstituted motility medium) and structural (small-angle X-ray scattering in solution and X-ray crystallography). These techniques are used (1) to identify in vitro all existing activities in actin assembly found in different modular model WH2-containing proteins regulating massive actin assembly in cell migration, developmental processes or bacterial pathogen invasion, and (2) to understand how these functions are regulated by small sequence variations, their intrinsic flexibility, some arrangements in repeats or associations with other regulatory adjacent domains [Bosch et al. (2007) Molecular Cell 28, 555-68; Husson et al. (2011) Molecular Cell 43, 464-77].

            The laboratory LEBS at CNRS provides state-of-the-art equipment for protein expression, purification and characterisations by biochemical and biophysical methods. Crystallization robotics are available in-house and we have regular access to synchrotron sources.

Skills required:

 The successful candidate should have a PhD in biochemistry/structural biology/biophysics/biology with less than 3-4 years postdoctoral experience and strong practical skills in molecular biology and protein crystallography, with strong interests for multidisciplinary approaches on protein-protein interactions (www.lebs.cnrs-gif.fr/carlier/carliereng.html).

Location:
            The laboratory is located in a very pleasant green setting within the large CNRS campus of Gif-sur-Yvette which is 45 mn away from Paris via local railway (RER B). We benefit from a dynamic scientific surrounding, in close vicinity to Paris labs, Orsay University, the Atomic Energy Commissariat (CEA) center of Saclay and the SOLEIL synchrotron (5 min away by car).

Contact:

            Please send a CV, a short summary of your research experience and letters of recommendation of two referees to Louis Renault (renault_at_lebs.cnrs-gif.fr). I will be happy to provide further information to interested candidates.