Cel Many picornaviruses are human pathogens that cause diseases varying in symptoms from common cold to life-threatening encephalitis. Currently there are no anti-picornavirus drugs approved for human use. We propose to study molecular structures of picornaviruses and their life cycle intermediates in order to identify new targets for anti-viral inhibitors and to lay the foundations for structure-based development of drugs against previously structurally uncharacterized picornaviruses.We will use X-ray crystallography to determine virion structures of representative viruses from Parechovirus, Kobuvirus, Cardiovirus, and Cosavirus genera and Human Rhinovirus-C species. We will use cryo-electron microscopy to study picornavirus replication complexes in order to explain the mechanism of copy-choice recombination of picornavirus RNA genomes that leads to creation of new picornavirus species. We will determine whether picornavirus virions assemble from capsid protein protomers around the condensed genome or if the genome is packaged into a pre-formed empty capsid. Furthermore, we will investigate how picornaviruses initiate infection by analyzing genome release from virions and its translocation across lipid membrane.A major innovation in our approach will be the use of focused ion beam micromachining for sample preparation that will allow us to study macromolecular complexes within infected mammalian cells by cryo-electron tomography. Our analysis of virion structure, cell entry, genome replication, and particle assembly will identify molecular details and mechanism of function of critical picornavirus life-cycle intermediates. Dziedzina nauki medical and health scienceshealth sciencesinfectious diseasesRNA virusesnatural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesgeneticsgenomes Program(-y) 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) Temat(-y) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Zaproszenie do składania wniosków ERC-2013-StG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca Masarykova univerzita Wkład UE € 1 997 556,80 Adres Zerotinovo namesti 9 601 77 Brno Czechy Zobacz na mapie Region Česko Jihovýchod Jihomoravský kraj Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Veronika Mikitova (Dr.) Kierownik naukowy Pavel Plevka (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko Masarykova univerzita Czechy Wkład UE € 1 997 556,80 Adres Zerotinovo namesti 9 601 77 Brno Zobacz na mapie Region Česko Jihovýchod Jihomoravský kraj Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Veronika Mikitova (Dr.) Kierownik naukowy Pavel Plevka (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
