Trypanosoma brucei is the causative agent for human African trypanosomiasis (sleeping sickness) that threatens tens of millions of people in 36 sub-Saharan countries. The parasite has a very unique and complex lifecycle in both the tsetse fly and its mammalian hosts. Within the tsetse fly, trypanosomes undergo three main phases of development, which are the procyclic, epimastigote, and metacyclic stages. The procyclic and epimastigote parasites are both proliferative, but do not cause disease in mammals, whereas the metacyclic ones are quiescent but highly infectious to humans. The process by which the procyclic parasites acquire infectivity and develop into metacyclic parasites is called metacyclogenesis.
Several proteins triggering metacyclogenesis in cultured trypanosomes have been identified by Dr. Christian Tschudi’s group at the Yale School of Medicine. We are now collaborating with the Tschudi lab to elucidate how these proteins mechanistically promote the developmental progression of T. brucei to infectivity. By now we have managed to clone all these genes, and the target proteins could be successfully overexpressed and purified from bacteria. We are now seeking a motivated master’s student to carry out further biochemical and structural studies on these proteins to unveil the molecular mechanism underlying their function in the parasite. This work, once completed, is expecting to provide guidance for developing novel therapeutic strategies by blocking the metacyclogenesis of trypanosomes.
Requirements: Studies of Molecular Biology, Microbiology, Biochemistry, Chemistry or related fields. Interested students please send your CV and cover letter to email@example.com.
Thesis duration: 12 months; salary: 440EUR per month.
Kolev, N.G., Ramey-Butler, K., Cross, G.A., Ullu, E., and Tschudi, C. Developmental progression to infectivity in Trypanosoma brucei triggered by an RNA-binding protein. Science (2012), 338(6112): 1352-1353.
Shi H, Butler K, and Tschudi, C. A single-point mutation in the RNA-binding protein 6 generates Trypanosoma brucei metacyclics that are able to progress to bloodstream forms in vitro. Mol. Biochem. Parasitol. (2018), 224: 50-56.
Center for Medical Biochemistry
Max Perutz Labs
Medical University of Vienna
Dr. Bohrgasse 9/3, 1030 Vienna, Austria