Targeting membrane proteins in their native environments - Mass spectrometry meets cell biology

The overarching goal of my research is to understand the relationship between membrane proteins and their lipid surroundings. This is important since many membrane proteins are unable to retain their structure and function when extracted from their native environment and reconstituted into a membrane mimetic. Dynamic proteins, for example G-protein coupled receptors, solute carriers and sigma receptors, are intimately connected to their membrane environments and prone to loss of function and activity in detergent micelles. To overcome this disconnect we will develop and apply our mass spectrometry approaches to examine dynamic drug targets within their membrane context. Our key goals will be to challenge these receptors and transporters with agonists, antagonists, inhibitors and lipids effectively in situ. Examples include solute carriers which during tumour progression respond to the need for an altered metabolism by increasing expression. Analogous methods will be used to uncover the targets of mitochondrial and lysosomal therapies. Many of our research themes converge on consequences of the COVID-19 pandemic. While this remains an area of intense scientific scrutiny we will focus on the less-studied receptors and 'infection enhancers', and contribute to understanding the roles of lipids in the endocytosis and viral recognition pathways.