Objective Epithelial polarity is one of the most fundamental types of cellular organization, and correct cellular polarization is vital for all epithelial tissue. Failure to establish polarity leads to severe phenotypes, from catastrophic developmental deficiencies to life-threatening diseases such as cancer. Despite knowing much about the signalling and trafficking machinery vital for polarity, we lack quantitative knowledge about the intracellular mechanical processes which organize and stabilize epithelial polarity. This presents a critical knowledge gap, as any elaborated understanding of intracellular organization needs to include the forces and viscoelastic mechanical properties that position organelles and proteins. As such, the main aim of POLARIZEME is to determine the intracellular mechanical processes relevant for epithelial polarization, thus providing a mechanical understanding of polarity. We will combine advanced optical tweezers technology with cutting-edge molecular biology tools to rigorously test new intracellular transport concepts such as the active, diffusion-like forces that can position organelles or the recently introduced cortical actin flows that can drag polarity-defining proteins around the cell. Thus we propose (i) to quantify active forces and intracellular mechanics and their relation to organelle positioning, (ii) to quantify polarized cortical and cytoplasmic flows, and (iii) to measure the forces and mechanical obstacles relevant for direct vesicle trafficking. These quantitative biophysics experiments will be supported by mathematical modelling and the development of two new instruments which (a) allow for automated intracellular mechanics measurements over extended time periods and (b) combine multi-view light-sheet microscopy with optical tweezers and UV ablation. Overall, we will provide a new access to understand and describe polarity by merging the physical and biological aspects of its initiation, maintenance and stability. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesbiophysicsnatural sciencesmathematicsapplied mathematicsmathematical modelnatural sciencesbiological sciencesmolecular biology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-COG - ERC Consolidator Grant Call for proposal ERC-2017-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS Net EU contribution € 1 255 415,14 Address Wilhelmsplatz 1 37073 Gottingen Germany See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00 Beneficiaries (2) Sort alphabetically Sort by Net EU contribution Expand all Collapse all GEORG-AUGUST-UNIVERSITAT GOTTINGEN STIFTUNG OFFENTLICHEN RECHTS Germany Net EU contribution € 1 255 415,14 Address Wilhelmsplatz 1 37073 Gottingen See on map Region Niedersachsen Braunschweig Göttingen Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00 WESTFAELISCHE WILHELMS-UNIVERSITAET MUENSTER Participation ended Germany Net EU contribution € 740 148,86 Address Schlossplatz 2 48149 Muenster See on map Region Nordrhein-Westfalen Münster Münster, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00
