Post-doctoral and PhD position : Structure-function of chemokine receptors
Corinne Vivès, Eva Pebay-Peyroula and Franck Fieschi, Institut de Biologie Structurale, UMR5075 CEA-CNRS-Univ. J.Fourier, 41, rue Jules Horowitz, F38027 Grenoble cedex 1, FRANCE In collaboration with Jean-Luc Popot, C.N.R.S./Université Paris-7 UMR 7099, Institut de Biologie Physico-Chimique, 13, rue Pierre-et-Marie-Curie, F-75005 Paris, FRANCE CXCR4 and CCR5 are chemokine receptors and belong to the 7 transmembrane G-Protein coupled receptor (GPCR) family. Besides their physiological functions, they have attracted the scientific community by their role in HIV internalization. So far the identification of HIV inhibitory molecules has been mainly empirical, as their rational design would request the structural characterization of the HIV co-receptors. Structural studies of membrane proteins are highly limited by the bottleneck of their production in quantities compatible with structural studies. In this context we have been involved in a collaboration to develop a method for the high level production of GPCRs in E.coli, taking CXCR4 and CCR5 as a working model. E.coli has proved to be an amazing machinery for protein recombinant expression but is not compatible with the functional expression of eukaryotic membrane proteins. To overcome the problem we address our proteins to inclusion bodies and are now able to produce mg quantities of purified receptors under denaturing conditions. Preliminary tests have already proven the feasibility of the protein refolding. We do provide two positions (one post-doctoral and one PhD) to work jointly on the refolding procedure optimisation using either classical detergent solutions or non-natural surfactants. A biochemical characterisation of the refolded proteins will be required (ligand binding capacity, stability....) with the final goal to achieve structural investigations. We have also developed in parallel a functional expression system that does not allow expression yield compatible with structural research but that will enable structure/function studies. The PhD position proposed requires a european student (except French) with a strong biochemistry and/or structural biology knowledge. The 3 year European funding could start before the end of 2008. For the post-doctoral project, we are looking for a graduate student with strong biochemical background, specific skills related to membrane protein biochemistry would be appreciated. A grant from the French National Research Agency will allow an 18 months funding and could start as soon as possible. The research will take place in one of the groups of the Membrane Protein Laboratory headed by Eva Pebay-Peyroula in the IBS (Structural Biology Institute) located within Grenoble scientific polygone ranked in the top european research centers. If you are interested, feel free to contact us to discuss the project to the following address. Do not hesitate to refer to our web sites. [EMAIL PROTECTED] http://www.ibs.fr/content/ibs_eng/home/ http://www.ibs.fr/content/ibs_eng/presentation/lab/lpm/
