*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***

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*_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 ?-thymosin **(**?T) **and WH2 domains in actin self-assembly dynamics.**These smallubiquitous 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 ?T/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**, epi**fluorescence 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 <http://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.*

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Louis RENAULT
Laboratoire d'Enzymologie et Biochimie Structurales (LEBS)
Bat. 34, CNRS,
1, avenue de la Terrasse
91 198 Gif-sur-Yvette cedex, FRANCE

Phone: (+)33-1 69 82 34 89 (inside France: 01 69 82 34 89)
Fax: (+)33-1 69 82 31 29
email: louis.rena...@lebs.cnrs-gif.fr
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