Grant: Doctoral Research Award: Canada Graduate Scholarships

Every cell is surrounded by a membrane that separates its contents from the environment and allows them to exist as stand-alone units. Embedded in this membrane are proteins that play crucial roles in the uptake of nutrients, cell communication and generally allow the cell to interact with its environment. Their importance in vital cellular processes, and easy accessibility on the outside of cells, make membrane proteins (MPs) the target of over half of all therapeutic drugs. Despite their fundamental and therapeutic importance, the study of MPs lags behind the study of proteins inside of the cell. The main barrier to MP study is their hydrophobic (water-hating) nature. Practically all methods biochemists have developed to investigate proteins require the protein to be first dissolved in water-based solutions. This proves difficult for MPs, as they tend to unfold and crash-out of these water solutions. Through my research I strive to overcome this incompatibility of MPs with water-based solutions to discover new research and therapeutic tools. Specifically, I will use the peptidisc technology - a new method for stabilizing MPs in water - to discover nanobodies (Nbs) against pathogenic bacterial outer membrane proteins (OMPs). Nbs are a type of antibody - molecules used by our own immune system to recognize and eliminate pathogens. Conventional antibodies have shown promise for their ability to tightly bind MPs, however due to their bulky size, they are not able to access the buried essential portions of pathogenic OMPs. Nbs are much smaller than Abs and can bind deep, hidden portions of bacterial OMPs, potentially upsetting their function. I hypothesize that Nbs will be able to access these hidden essential OMP portions and therefore kill bacterial pathogens. With the rise of antimicrobial resistance, these Nbs have the potential to offer new tools in the fight against pathogenic infections.