Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesbasic medicineimmunologyautoimmune diseases
Convocatoria de propuestas
FP7-PEOPLE-2012-CIG
Consulte otros proyectos de esta convocatoria
Régimen de financiación
MC-CIG - Support for training and career development of researcher (CIG)Coordinador
WC2R 2LS London
Reino Unido