EastBio: How do ubiquitin writers control malaria transmission?

Protein ubiquitination is a key regulatory process that controls many aspects of eukaryotic life. Both free living and pathogenic organisms employ ubiquitination mediated protein networks to adapt to their environment. Plasmodium, which is the causative agent of malaria has a complex life cycle involving differentiation between asexual stages causing disease and the sexual stages necessary for spread of the disease. Transmission competent stages or gametocytes in the human malaria parasite, P. falciparum follow a complex development process which can take up to 17 days. During this time the parasite is a master shape-shifter and has affinities for different tissue niches. Using small molecule inhibitors, we recently discovered that the ubiquitin machinery is essential for parasite stage transitions. In this project you will exploit the power of activity based probes (ABPs) to discover enzymes which write the ubiquitin code and underpin accurate development of Plasmodium falciparum gametocytes. The discovery and characterisation of these enzymes could identify new transmission blocking strategies to prevent the spread of malaria.

The project will train you in advanced proteomic and genetic methodologies. If keen you will also have the opportunity to explore cutting-edge microscopy methods including super-resolution methods.