Investigating epigenetic regulation of immune cells responding to viral infection.

Immune protection provided by immune memory underpins successful vaccines and is mediated mainly by memory lymphocytes and long-lived antibody- secreting cells. In particular, B cell memory is key to providing a rapid and robust response upon secondary infection and continual serum antibody protection. We are working to elucidate the crucial epigenetic mechanisms that generate and maintain B cell memory, and how B cells may retain molecular and functional plasticity under chronic pathogenic pressure. In particular, chronic infectious diseases in which the pathogen is not effectively cleared from the body, such as HIV and hepatitis C, have posed longstanding challenges to global health. Thus, there is a critical need for new strategies to prevent and/or treat chronic viral infection.

We have taken a molecular approach to unlocking memory B cell potential. We will apply the cutting-edge techniques single cell RNA-sequencing and single cell ATAC-sequencing to understand the epigenetic regulation of B cell diversity. This Master of Data Science Project will analyse and integrate these single cell datasets using Seurat, then undertake sequence motif analysis and transcription factor footprinting. Pseudotime analysis will be undertaken to visualise the trajectory of the cells in acute and chronic infection, enabling us to determine what key changes occur that may lead to the reprogramming of the memory B cell population during chronic infection. We will investigate whether we can use this analysis to predict a divergence point where memory B cell changes in chronic infection become irreversible.