Splicing and sexual development in Plasmodium
Supervisor: Dr Katarzyna Modrzynska, School of Infection & Immunity
The malaria-causing parasite, Plasmodium, has a complex life cycle with >10 highly adapted developmental stages generated based on a relatively small and highly compact genome. For example, inside the human red blood cell, it can develop in male, female or asexual form, all of which are characterised by different function and morphology. While the balance between these forms is key to successful parasite transmission, we know little about the molecular mechanism regulating the different developmental trajectories. Interestingly, the majority of parasite genes have introns, and recent in-depth analysis of the transcriptomes of different life stages revealed an extensive degree of differential splicing. Different variants of the key molecules involved in DNA replication, signalling and gene expression have been observed, suggesting that mRNA maturation is a factor in generating the observed cell diversity.
The aim of the proposed project is to investigate the role of different splicing variants in parasite sex determination, DNA replication and gene expression regulation. The selected student will gain experience in parasite molecular biology (including the generation of transgenic malaria parasites) and in a range of highly transferable next-generation techniques including single-cell transcriptomics and long-read sequencing.
During the initial rotation project the student will use bulk and single-cell transcriptomics to characterise the parasite lines forced to express one of the two sex-specific variants of a nuclear protein essential for male sex determination.