The role of nanoscale receptor clustering in regulating T cell activation
Prof D Owen
Prof M Canals
No more applications being accepted
Competition Funded PhD Project (UK Students Only)
T cells survey antigen presenting cells (APCs) for signs of infection by forming a cell-cell contact called the “immunological synapse” within which T cell receptors (TCRs) interact with potentially pathogenic foreign peptides displayed. Therefore, the threshold of stimulation needed for T cells to activate has important implications for health and disease. Since the 2000s, it has been known that the TCR is not randomly distributed at the cell surface but actually forms “T cell microclusters”. We hypothesise this clustering is partly responsible for setting the thresholds at which T cells activate. This project aims to understand how the nanoscale clustering characteristics of the TCR and its downstream interacting partners influences the threshold required for T cell activation. This will be done using the latest cutting edge advances in single-molecule localisation microscopy, a form of super-resolution fluorescence microscopy to map the distribution of TCRs at the synapse with nanometer precision. We will aim to understand now the nano-architecture is different in cells that show different activation threshold and seek to manipulate the nano-architecture to control downstream signalling using genetic manipulations and small molecule pharmacological agents.
Applicants should have a strong background in immunology or biophysics. They should have a commitment to research in immunology and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in immunology, cell biology or physics.
Please check the MRC website for full eligibility criteria View Website