Objectif Bacterial pathogens secrete effector proteins to manipulate host cells during infection. In Gram-negative bacteria the conserved type 3 secretion system (T3SS) delivers effector proteins to the host cell in a spatiotemporal manner. Although major T3SS constituting components were identified the function of this macromolecular complex remains elusive which is why the transport mechanism is not understood yet.Here, I present my research proposal of the functional and structural analysis of the T3SS with respect to the effector transport dynamics. The proposal is divided in three sections addressing the T3SS architecture, the cytosolic mechanism preceding effector molecule release and the molecular mechanisms of secretion regulation.Research focus of the first section is on the 3-dimensional structural analysis of isolated T3SS. The proposed studies should help detecting structural features related to the effector transport. A combination of electron microscopy (EM) and mass spectrometry is proposed to analyze the structure and surface properties of the transport channel together with bound effector molecule. I am also planning localization of bound lipids as well as to detect lipid induced structural changes in the T3SS by EM. Characterization of cytosolic processes, preceding the translocation is the focus of the second section. Effector molecule targeting, insertion into the T3SS channel and the chaperone function will be studied using a combination of biochemical and biophysical techniques.Finally I propose experiments to analyze the T3SS regulation. Here, the research focus is on host signal reception and downstream posttranslational modifications inside bacteria as well as on conformational dynamics of the T3SS needle tip complex.The overall goal of the proposed work is to understand the molecular mechanisms of the T3SS. I believe these studies will impact both the understanding of bacterial pathogenesis as well as the transmembrane transport of proteins. Champ scientifique natural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural scienceschemical sciencesanalytical chemistrymass spectrometry Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Appel à propositions ERC-2012-StG_20111109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Contribution de l’UE € 269 382,91 Adresse INHOFFENSTRASSE 7 38124 Braunschweig Allemagne Voir sur la carte Région Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Michael Straetz (Dr.) Chercheur principal Michael Kolbe (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH Allemagne Contribution de l’UE € 269 382,91 Adresse INHOFFENSTRASSE 7 38124 Braunschweig Voir sur la carte Région Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Michael Straetz (Dr.) Chercheur principal Michael Kolbe (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Participation terminée Allemagne Contribution de l’UE € 1 218 857,09 Adresse HOFGARTENSTRASSE 8 80539 Munchen Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Contact administratif Ulrike Schell (Mrs.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
