BBSRC DTP PhD Studentship: Understanding the hierarchy of cell division in trypanosome parasites

Closes: 16 January 2024

Location: University of Nottingham

Project Supervisor: Bill Wickstead

About the project:

Correct cell division is essential to life. However, the way in which division is achieved differs greatly between organisms. This is particularly the case for many important parasites, the division of which is often very different from the cells of their host. Understanding this cell division machinery is important to understanding the fundamental biology of the parasite, but also because differences between parasite and host present opportunities for the development of new treatments. African trypanosomes are single-celled parasites of the blood. They cause a deadly disease in humans in sub-Saharan Africa and a wasting disease of cattle that kills ~3 million cattle per year and creates an estimated loss of ~$4 billion from African economies. African trypanosomes have an unusual genome structure that is linked to their pathology and encompasses ~120 chromosomes all of which are moved by a cell division machinery that is very different from most other eukaryotes. How this system works is an important outstanding question in parasitology and will tell us how the system evolved as well as which parts are potential targets. The lab has developed a genetic method that allows us to quickly decode the fitness costs of removing specific components of the cell division machinery. This means we now know the essential components of cell division in 3 important trypanosome species. In this project, a student will use these essential components to decode the dependency relationships between the components (e.g. which parts recruit which) and also study how they affect spindle assembly and cytokinesis in the different disease-relevant trypanosome species. A small number of these components are being developed as targets for small molecule inhibitors and the student will also use their lines to understand how specific drugs perturb the process of cell division. The student will work closely with post-doctoral researchers in the lab who have helped developed the genetic technology and are screening libraries of 100,000s of mutants to identify genes involved in specific aspects of the process. By combining these genome-wide approaches with specific mutants, we are seeking to decode the hierarchy behind the essential parts of the chromosome segregation machinery and look for ways to inhibit the parasite-specific parts of the process.

Funding Notes

This fully funded, 4-year PhD project is part of a competition and is funded by the University of Nottingham BBSRC Doctoral Training Partnership and is open to students worldwide. Funding will cover tuition fees and stipend at the UKRI rate, plus an annual research grant toward bench consumables.