Objectif The proposed work seeks to determine the tertiary structure of the scrappy form of the prion protein. Prion diseases are marked by the conformational transition of the prion protein (PrP) from its cellular, dominantly alfa-helical form (PrPC) to a beta-she et-containing, protease-resistant form (PrPSc). Since PrPSc is insoluble and forms aggregates, most structure-determination methods are unfeasible. A new approach is proposed here for mapping the secondary structure of PrPSc, using mutant analogues of PrP, in which amino acids are systematically replaced by alfa-aminoisobutyric acid (Aib), an unnatural amino acid that cannot adopt backbone dihedral angles in the beta-sheet region of the Ramachandran map.These analogues can only be converted to the protease-resistant scrapie conformation when the residue replaced by Aib is in an alfa-helix (and not in a beta-strand) in the scrappy form. The tertiary structure of PrPSc than will be determined by computer modelling based on the experimentally determined secondary structure. This model will be validated experimentally by covalent cross-linking the appropriate segments of PrPSc. This structural information will facilitate the development of sensitive diagnostic procedure for early detection and effective treatment of the prion disease.I have conducted research for 6 years at Cornell University (US) and obtained expertise in protein folding and semi-synthesis as well as on the prion field. I would like now to return to Europe and capitalize my expertise in pursuing a carrier on conformational diseases as a principal investigator in a world-class European research institute. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingnatural scienceschemical sciencesorganic chemistryamines Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Appel à propositions FP6-2002-MOBILITY-5 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur BIOLOGICAL RESEARCH CENTER, HUNGARIAN ACADEMY OF SCIENCES Contribution de l’UE Aucune donnée Adresse Temesvari krt. 62 SZEGED Hongrie Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée
