Signal transduction pathways in the trypanosome flagellum
Supervisor: Dr Michael Ginger
Human African Trypanosomiasis (HAT), more commonly known as sleeping sickness, is endemic in 36 countries in sub-Saharan Africa, and is invariably fatal if not successfully treated. Trypanosoma brucei, which causes HAT, is a flagellate protozoan parasite transmitted via the bite of an infected tsetse fly. The trypanosome flagellum is a whip-like organelle which plays a critical role in determining parasite motility. Moreover, a functioning flagellum is essential for the division and survival of pathogenic bloodstream trypanosomes, raising the possibility that interfering with flagellar function represents a novel way to kill trypanosomes [see Broadhead et al. Nature 409:224-7; Ginger et al. Nature Reviews Microbiology 6:838-50].
This project aims to investigate the signaling cascades necessary in the assembly and motility of the trypanosome flagellum; a potential outcome is the identification of novel drug targets against the trypanosome parasite. Candidate enzymes postulated to be involved in flagellar function, including two protein kinases already under study in the laboratory, will be investigated using a combination of molecular biology, cell biology and biochemical approaches (e.g. trypanosome cell culture and genetic manipulation, recombinant protein expression, live cell imaging and immunohistochemistry, proteomics via 2D electrophoresis and mass spectrometry).The project will be co-supervised by Dr Michael Ginger, Dr Karen Grant and Dr Paul McKean - informal enquiries are welcome to any of these supervisors.