Grant: CIHR Fellowship

Yersinia pestis is the causative agent of the plague, and is responsible for the death of millions of people during massive pandemics. It is highly pathogenic as it can prevent the host's immune response and overwhelm it with massive growth. In combination with easy dissemination and potential weaponization of drug-resistant Y. pestis strains, there is a need to understand the mechanism of infection for medical countermeasures. Ail (adhesion invasion locus) is a membrane protein on the cell surface of Y. pestis and is a key virulence factor. Ail is thought to contribute to the pathogenesis through interaction with Vn (vitronectin), a serum protein that regulates various physiological processes including blood clotting and immune system. Their interaction can enhance bacterial attachment to human cells, suppress host immunity, and inhibit coagulation. Despite being important players of pathogenesis, the exact mechanism of Ail and Vn interaction is unknown. My work will, thus, focus on elucidating their interaction at the atomic level, where I will characterize the molecular structure of Vn then identify Ail-binding motifs on Vn and Vn-binding motifs on Ail through biophysical techniques. All of these interactions will be tested and validated using biochemical assays and cell-based assays. This transdisciplinary project will identify essential binding motifs to provide key targets for drug development and further advance our understanding of mechanisms behind Y. pestis pathogenesis.