Objective Cells sense, affect and respond to their environment through the fundamental function of adhesion. Several types of adhesion sites, which are mediated via dynamically maintained multi-protein structures, anchor extracellular-matrix proteins to the cytoskeleton. Despite considerable efforts, the long-standing questions of how adhesion sites are formed, structured and regulated remain unanswered. In this research plan we will investigate desmosomes and adherens junctions by cryo-electron tomography of cells and tissue. The principal objectives are: (a) to visualize the molecular architecture and reveal the structural differences of the adhesion sites under various conditions and influences, i.e. mutations, wounds, etc. (b) to reveal their molecular association to the cytoskeleton (intermediate and actin filaments respectively), and to chart the network of interactions underlying cellular adhesion, and (c) to develop novel pattern recognition and classification techniques in order to structurally characterize the adhesion sites in toto by cryo-electron tomography of vitreous sections. We will use pattern recognition techniques and locally averaged cryo-electron sub-tomograms to quantify the macromolecular complexes in terms of stoichiometry and protein interactions in situ at high resolution (~3 nm). In particular, we aim to reveal how a pool of constituent proteins is organized in the two adhesion sites. Significant amounts of information coming from immunogold electron microscopy, fragments from X-ray structures, force measurements with atomic force microscopy, and structural bioinformatics will be integrated into our cryo-electron tomograms. This research will pioneer structural comparisons of protein networks at nanometer resolution in situ and in toto. The experimental and theoretical methods that will be developed would be indispensable for studying any spatially constrained protein network whose state depends on local properties. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesgeneticsmutationnatural sciencescomputer and information sciencesartificial intelligencepattern recognition 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) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2009-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN EU contribution € 1 724 400,00 Address THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main Germany See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Achilleas Frangakis (Prof.) Administrative Contact Kristina Wege (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN Germany EU contribution € 1 724 400,00 Address THEODOR W ADORNO PLATZ 1 60323 Frankfurt Am Main See on map Region Hessen Darmstadt Frankfurt am Main, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Principal investigator Achilleas Frangakis (Prof.) Administrative Contact Kristina Wege (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
