Objective There is mounting evidence that the spatial and temporal organization of ligands at cell-cell interfaces modulates signaling. In particular, for Eph receptors and their ligands (ephrins) this phenomenon is widely recognized but poorly understood due to difficulties in controlling and analyzing membrane protein microenvironments at the nanoscale. A combination of different techniques ranging from DNA nanotechnology to high resolution microscopies via standard biochemical techniques and computational tools will be used to provide a molecular understanding of the roles of the spatial and temporal organization of ligands in receptor signaling. Substrates that recreate the intramembrane signalling geometry at cell-cell contacts are designed and produced by employing ligand decorated DNA nanostructures anchored on artificial supported lipid bilayers. This allows an unparalleled control of spatial distribution of the ligands and their dynamics. TIRF/STORM super-resolution microscopy is used to measure size and dynamics of clustering and biochemical assays will quantify the receptor spatial distribution and activation levels. Together with computational simulation and modeling of clustering dynamics, these efforts will lead to a molecular mechanism of spatial organization of ligands and receptors during clustering and how this affects signaling. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesphysical sciencesopticsmicroscopysuper resolution microscopynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesmathematicspure mathematicsgeometry Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator KAROLINSKA INSTITUTET Net EU contribution € 185 857,20 Address Nobels Vag 5 17177 Stockholm Sweden See on map Region Östra Sverige Stockholm Stockholms län 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 Total cost € 185 857,20