Obiettivo The nuclear pore complex (NPC) is one of the most intricate components of eukaryotic cells and is assembled from ~30 Nucleoporins (Nups) in an unknown manner. Here I present an experimental result driven hypothesis, namely that the composition of the NPC varies across human cell types. As a consequence, the nucleocytoplasmic transport system might be fine-tuned to fulfill specific tasks in various cell types and to adjust the composition of the nuclear compartment. In the research proposed here, cell-type specific structural changes of NPCs will be monitored using systems approaches. The strength of single molecule methods such as cryo electron tomography (cryoET) will be synergistically combined with the strength of mass spectrometry (MS) to measure protein dynamics across cellular states. The outcome will be an atlas of the human NPC containing cell-type and functional state specific structural properties, namely nucleoporin copies per NPC, spatial restraints of protein interfaces, subunit positioning, and shape information. This research will facilitate the generation of a common structural modeling framework by providing the critical information of composition and spatial arrangement. It will furthermore elucidate how NPC composition and structure is adjusted as a function of the biological state of the cell. The long term goal is to integrate the different types of structural data using fitting, docking, and topological modeling approaches in order to project functionally specific compositional data onto structural models of the human NPC. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural scienceschemical sciencesanalytical chemistrymass spectrometry Programma(i) 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) Argomento(i) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Invito a presentare proposte ERC-2012-StG_20111109 Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante EUROPEAN MOLECULAR BIOLOGY LABORATORY Contributo UE € 1 415 860,00 Indirizzo Meyerhofstrasse 1 69117 Heidelberg Germania Mostra sulla mappa Regione Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo di attività Research Organisations Ricercatore principale Martin Beck (Dr.) Contatto amministrativo Jillian Rowe (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto EUROPEAN MOLECULAR BIOLOGY LABORATORY Germania Contributo UE € 1 415 860,00 Indirizzo Meyerhofstrasse 1 69117 Heidelberg Mostra sulla mappa Regione Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Tipo di attività Research Organisations Ricercatore principale Martin Beck (Dr.) Contatto amministrativo Jillian Rowe (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
