Objectif 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 receptor (TCR) 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 organizstion which affects signalling efficiency. However, the biophysical mechanism(s) that control protein distributions and hence the rate of molecular interactions remains poorly understood. Uniquely, I have recently developed two key technologies to unravel how protein clustering and the biophysical properties of the lipid bilayer regulate specific interactions at the molecular level. These are single-molecule, super-resolution localisation microscopy with novel statistical cluster analysis and quantification of membrane biophysical properties beyond the limit of conventional microscopy using new environmentally sensitive fluorescent probes and picosecond time-resolved excitation/detection. The research will therefore 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 including pathogenic disease, cancer and autoimmune disease. Champ scientifique natural sciencesbiological sciencescell biologycell signalingnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicineimmunologyautoimmune diseases Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2012-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2012-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur KING'S COLLEGE LONDON Contribution de l’UE € 100 000,00 Adresse STRAND WC2R 2LS London Royaume-Uni Voir sur la carte Région London Inner London — West Westminster Type d’activité Higher or Secondary Education Establishments Contact administratif Paul Labbett (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
