POST-DOCTORAL POSITION in Paris Labortory of Mucosal Entry of HIV &Mucosal Immunity, Institut Cochin, Paris France Structure / function relationship of HIV envelope in a membrane context: Optimization of an HIV immunogen inducing an HIV protective immunity AIDS, as a sexually transmitted disease, is mainly transmitted via HIV-1at mucosal site and requires therefore development of a mucosal vaccine able to block the initial interaction of HIV with mucosal cells We have characterized a conserved region of HIV envelope glycoprotein gp41 that is able to induce, upon mucosal vaccination in the simian model HIV neutralizing antibodies. Furthermore, this region is also the target of mucosal antibodies present in secretion of HIV resistant individuals, highly exposed to the virus but remaining seronegative. Up to now nobody is able to induce such immunity in normal individual or animals using the gp41 protein or part of it as an immunogen. We thus suspect that some conformational particularities could explain such behavior and understanding these particularities may help to develop vaccine against AIDS. The HIV envelope gp41 region we have defined appears therefore very promising. However, the viral immunogen need to be optimized, by structure/function analyzes. The Research project will aim at understanding, using different biophysical and NMR means the interaction of one of conserved regions HIV envelope glycoprotein, gp41, with membranes (cellular and viral). The experiments will consist in: - Production & purification of different recombinant gp41 subdomains - Studies of gp41subdomain interactions with membranes the viral and the target one, which are very different and influence the gp41 structure by CD, SPR spectrofluorimetry and finally NMR. Positive results will be also evaluated using specific cell culture experiments to appreciate impact on HIV transport across mucosal cells. The optimized immunogen will finally be tested for its immunogenicity within the European Excellence Network on Induction of novel HIV neutralizing antibody to which the laboratory participate. The candidate should have experience in Molecular biology and NMR technology. Experience in cell biology and immunology are welcome. Financial funding for the project an fellow is already available. The host lab directed by Morgane BOMSEL in Paris, is specialized in HIV mucosal entry and mucosal Immunity. see web site at: http://institut.cochin.inserm.fr/rubric_recherche/I18NFolder.2004-0614.2029605042/biologie_cellulaire/copy_of_copy_of_I18NFolder.2004-0701.7394078607/index_html/en/view Contact M. Bomsel: mogane.bomsel@inserm.fr Unité 567 UMR 8104 Paris V