Grant: Doctoral Research Award: Canada Graduate Scholarships

Syphilis is caused by the bacterium Treponema pallidum (Tp), which is transmitted sexually, and vertically between mother and fetus. Tp infections are chronic and characterized by several distinct stages of disease interspersed with periods of symptomatic latency. Global initiatives to eradicate syphilis have focused on screen-and-treat methodologies, however, rising syphilis rates paired with healthcare inaccessibility stress the complementary need for a syphilis vaccine. Tp spreads through the vasculature system to establish systemic infection. The endothelium lines host vasculature and is comprised of endothelial cells. Endothelial cells function as a barrier and recruit immune cells to clear invading pathogens. Our laboratory has demonstrated that Tp can adhere to, and cross, the endothelium to access organs and tissues. However, the host and bacterial mechanisms that underly this process are incompletely understood. To design a vaccine for syphilis it is critical that we understand these interactions in detail. Previous investigations conducted in our lab have identified protein and transcript expression changes in endothelial cells exposed to Tp. These studies identified several high-relevance host cellular pathways that Tp modulates to cross the endothelial barrier. This current research project will investigate these mechanisms in greater detail by describing the host cellular signaling events that initiate changes in host cellular function (and cellular architecture) that allow Tp endothelial traversal. This work will identify host receptors and signalling proteins that are differentially activated during Tp contact and will allow us to investigate the Tp proteins that induce their activation. Further, using live-cell microscopy, we will track the activation of these pathways in real-time. Understanding the host cellular responses to Tp will allow design of a vaccine that prevents Tp endothelial traversal and induces a protective immune response.