Rachel Jackson

PhD thesis: Investigating population heterogeneity in Orientia tsutsugamushi

I am interested in how pathogens interact with human cells to cause disease. Orientia tsutsugamushi is an obligate intracellular bacterium which causes scrub typhus, a mite-borne infection that is a leading cause of non-malarial febrile illness in South and South East Asia. There are limited options for clinically practical diagnostic tests for scrub typhus, which is predominantly endemic in rural areas. In addition to this, natural immunity is not long lasting and very limited across different strains as there is a high degree of antigenic variability. In one infection, a person may be infected with multiple strains, further limiting the effectiveness of homologous immunity.
The life-cycle of Orientia tsutsugamushi involves differentiation of the bacterium from the intracellular state localised in a perinuclear localised microcolony, to the extracellular state which buds from the surface of cells in a virus-like manner. Previous data from the Salje lab indicates that these states have differences in protein expression. However, a global approach has not yet been taken to characterise these distinct states. Utilising spatial transcriptomics and proteomic approaches, the aim of this project is to (1) define the distinct subpopulations of Orientia tsutsugamishi within an infected cells, and (2) characterise the key factors which drive this differentiation. Understanding the life cycle of Orientia tsutsugamushi may also be important for developing diagnostics and vaccines for scrub typhus.

Who or what inspired you to pursue your research interests?
During my undergraduate degree in Mathematics and Biology, I realised how much I enjoyed working on molecular mechanisms. My goal is to harness my training in mathematics, computational approaches, and molecular biology to participate in cross-disciplinary research. I want to provide insights into the underlying molecular biology in how our cells fight disease, with the potential to lead to novel therapies.