Prior to starting my PhD, I completed a BSc in Pharmacology at the University of Leeds. During my second year of study, I developed a particular interest in molecular pharmacology and structure-based drug design, so when given the opportunity to choose a final year research project, I focussed on determining the structure of a component of a bacterial adhesin protein by X-ray crystallography. This opportunity allowed me to develop my skills in protein expression and purification, and I was fortunate enough to obtain diffracting crystals. After graduating, I worked as a research assistant at Leeds University and St James’s Hospital, investigating cell-signalling pathways associated with an autoimmune disorder. These two projects informed my decision to pursue a PhD in structural and molecular biology.
G protein-coupled receptors (GPCRs) are a family of well-known membrane proteins involved in important physiological processes, such as vision, olfaction and taste. In recent years, more evidence suggests some GPCRs expressed in vascular endothelial cells are sensitive to shear stress, a frictional force exerted on the vessel wall by flowing blood. In this project, I will use cryo-electron microscopy (cryo-EM) and pulsed electron-electron double resonance spectroscopy (PELDOR) to characterise the structure and conformational dynamics of putative mechanosensitive GPCRs. This work will increase our understanding of the molecular mechanisms underlying mechanotransduction.