How do membrane microenvironment and receptor mobility influence signalling cross-talk during stimulation by an antigenic ligand?

Dynamic complexity is an emerging paradigm for cell surface receptors and one that explains why the membrane microenvironment influences their function.

We have shown for the chemokine receptor CCR5 that ligand stimulation triggers plasma membrane re-organisation and internalisation as does stimulation of surface Toll-like receptor 2 by an antigenic component of the Staphylococcus aureus cell-wall. How these recently discovered events are dynamically orchestrated remains unknown.

The proposed PhD project aims to unravel how membrane diffusion and molecular interactions affect these receptors. It will use novel chemical biology labelling strategies combined with a cutting-edge biophysical approach to assess receptor dynamics in the membrane of living cells and, for the first time, in real-time. You will use ensemble and single-molecule fluorescence microscopy approaches developed in our research groups to probe membrane receptor movements.

Experiments will be carried out on well-characterised cell-lines expressing surface receptors that can be fluorescently-labelled using epitope-programmed bond-forming reactions. This project should rapidly generate valuable findings leading to a better understanding of the complex behaviour of receptors in the cellular membrane.