Studies of GPCR signalling using single molecule protein-protein interaction quantum biosensors

G protein coupled receptor coordinate functions of our body by transmitting extracellular hormonal to the inside of the cell. Upon hormone binding, they activate G proteins. Subsequently, they are phosphorylated and recruit another class of signalling molecules, arrestins. Ultimately, signalling events in cell are protein-protein interactions modulated by post-translational modifications.
Because GPCRs exist in multiple conformations in the absence of the ligands, and there are multiple G proteins, receptor kinases and arrestins, the signalling process is very heterogeneous. Biologically and pharmacologically relevant events may represent only a small fraction of all observed protein-protein interactions, making it sometimes difficult to observe the important events as they are "masked" by other, more prevalent but less important, binding interactions. Single molecule techniques can advance our understanding of signalling events, leading to better understanding the signalling cascades and ultimately contributing to drug discovery.

The goal of this project is to develop quantum biosensors to study GPCR signalling.

The student will engineer GPCRs to incorporate paramagnetic tags that will translate protein-protein interactions into observable changes in atomic scale defects in diamond, Nitrogen Vacancies (NV). These changes can be optically detected. Nanosized diamonds rich in NVs will be attached to the proteins and act as quantum biosensors. This part of the project will be done in the Veprintsev lab. The quantum sensing experiments will be performed using a bespoke microscope developed within the Mather group and augmented with metalenses (Kenney) for enhanced sensitivity.

The project combines multiple technical developments of both GPCR expression and protein engineering and chemical biology, as well as progress in quantum biosensing, with the unique combination of expertise provided supervisors.