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

Membrane proteins—the molecular gateways embedded in cell surfaces—often stop working properly when scientists remove them from their natural fatty surroundings to study them. This matters because many crucial drug targets, including G-protein coupled receptors, solute carriers, and sigma receptors, are dynamic proteins that lose their structure and function when extracted into detergent micelles. Researchers cannot reliably test how potential drugs interact with these proteins if the proteins themselves are already damaged by the isolation process. The team will develop mass spectrometry methods to examine these drug targets while they remain in their native membrane environments, challenging them with agonists, antagonists, inhibitors, and lipids without removing them first. If successful, this approach could transform how scientists screen drugs for conditions ranging from cancer—where solute carriers increase expression during tumour progression—to mitochondrial and lysosomal disorders. The methods will also be applied to less-studied receptors involved in COVID-19 infection, particularly those linked to endocytosis and viral recognition pathways. This is primarily fundamental science aimed at solving a technical bottleneck, but better drug-target validation could eventually accelerate development of more effective therapeutics across multiple disease areas.