Infectious diseases remain a leading cause of livestock morbidity and death worldwide, making the development of new vaccines an important priority of biomedical research. Theileria parva is an intercellular tick-borne parasite that causes East Coast Fever (ECF), a lethal disease that kills about 1 million cattle annually in sub-Saharan Africa. Current ECF control strategies are either ineffective or unsustainable in the long-term1. T cells are not only the replication site for the parasite but also the determinants of effective host response to the parasite. However, a vaccine capable of generating robust T cell memory is still beyond our reach, partly due to an incomplete understanding of the molecular mechanisms for T cell speciation and/or features of antigen-delivery vehicles that can effectively deliver parasite antigens to T cells.
Previous studies have shown that T. parva-infected autologous CD4+ T-cells cultured in vitro more than 6 weeks result in self-limiting infection followed by the induction of protective immunity2. This project will exploit this feature of autologous T. parva-infected cells, by using single cell sequencing3 and immunology approaches, to understand the molecular determinants that regulate the development of a protective T cell response and the molecular fingerprints of an effective T. parva antigen delivery vehicle; information that can be integrated into future vaccine development studies.
The study objectives are to:
1. Identify the transcriptional hallmarks of pathogenic and attenuated T. parva-infected cells
2. Identify the parasite genes that are associated with the pathogenic or attenuated T. parva-infected cells.
3. Determine the T cell receptor sequences that are associated with T cells that induce immune memory.
Through this project the student should acquire a solid understanding of molecular biology, immunology, and computational biology. He/she will become proficient in a wide variety of cell and molecular biology techniques including derivation, culture and differentiation of T cells, western blotting, single cell sequencing, and genome editing. The project brings together the complementary expertise of the co-supervisors Dr. Tim Connelley (Veterinary immunology), Dr. Musa Hassan (functional genomics and computational biology) in a new collaboration where the student will have access to state-of-the-art facilities.