Objective Protein complexes are central to many cellular functions but our knowledge of how cells assemble protein complexes remains very sparse. Biophysical and structural data of assembly intermediates are extremely rare. Particularly in higher eukaryotes, it has become clear that complex assembly by random collision of subunits cannot cope with the spatial and temporal complexity of the intricate architecture of many cellular machines. Here I propose to combine systems biology approaches with in situ structural biology methods to visualize protein complex assembly. I want to investigate experimentally in which order the interfaces of protein complexes are formed and to which extent structures of assembly intermediates resemble those observed in fully assembled complexes. I want develop methods to systematically screen for additional factors involved in assembly pathways. I furthermore want to test the hypothesis that mechanisms must exist in eukaryotes that coordinate local mRNA translation with the ordered formation of protein complex interfaces. I believe that in order to understand assembly pathways, these processes, that so far are often studied autonomously, need to be considered jointly and in a protein complex centric manner. The research proposed here will bridge across these different scientific disciplines. In the long term, a better mechanistic understanding of protein complex assembly and the structural characterization of critical intermediates will be of high relevance for scenarios under which a cell’s protein quality control system has to cope with stress, such as aging and neurodegenerative diseases. It might also facilitate the more efficient industrial production of therapeutically relevant proteins. Fields of science engineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringcontrol systemsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesmolecular biologystructural biology Keywords protein complex assembly local translation cryo electron tomography quantitative mass spectrometry nuclear pore complex Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-COG - ERC Consolidator Grant Call for proposal ERC-2016-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Net EU contribution € 717 179,09 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 717 179,09 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany Net EU contribution € 717 179,09 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 717 179,09 EUROPEAN MOLECULAR BIOLOGY LABORATORY Participation ended Germany Net EU contribution € 1 240 537,91 Address Meyerhofstrasse 1 69117 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 240 537,91
