Objective The overall aim of this project is to identify key biophysical mechanisms that control the spatial arrangement of signalling proteins and membrane lipids in the regulation of T cell activation. During an immune response, T cells are activated in response to antigenic peptides in a process that requires the formation of multi-molecular signalling complexes. It is known that many T cell signalling proteins (such as the kinase Lck and the scaffold protein LAT) are not randomly distributed within the plasma membrane thus giving rise to lateral organization which affects signalling efficiency. However, the biophysical mechanism(s) that control protein distributions and hence the rate of molecular interactions remains poorly understood. Two of the principal mechanisms are compartmentalisation of the membrane by lipid microdomains (the ‘lipid raft’ hypothesis) and by the cortical actin meshwork (the ‘picket-fence’ model). The two key technologies needed to unravel how protein clustering and the biophysical properties of the lipid bilayer regulate specific interactions at the molecular level have now been developed. These are single-molecule, super-resolution localisation microscopy and quantification of membrane biophysical properties using new-generation environmentally sensitive fluorescent probes. Using these methods, the proposed project will generate unique insights into the biophysical mechanisms that govern the formation of the protein clusters and complexes during early T cell signalling events. This knowledge is critical to our understanding of the molecular basis of T cell activation during the immune response and has potential applications in the development of therapeutic treatments for a range of conditions. Fields of science natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopymedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesbiochemistrybiomoleculeslipids 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-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution KING'S COLLEGE LONDON EU contribution € 1 402 513,00 Address STRAND WC2R 2LS London United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Principal investigator Dylan Myers Owen (Dr.) Administrative Contact Paul Labbett (Mr.) 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 KING'S COLLEGE LONDON United Kingdom EU contribution € 1 402 513,00 Address STRAND WC2R 2LS London See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Principal investigator Dylan Myers Owen (Dr.) Administrative Contact Paul Labbett (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
