Trypanosoma brucei (锥形虫) is a flagellated protozoan parasite undergoing complex life cycle alternation between tse-tse fly vector (procyclic form) and mammalian hosts (bloodstream form). While replicating in the bloodstream of the mammalian host, it causes African Sleeping Sickness in humans and Nagana in cattle. With no immediate prospect of vaccines, and no satisfactory drug treatments, development of new therapies is urgent.
In addition to the medical importance, the parasite’s simple cellular organization and molecular accessibility provide an excellent opportunity to study the regulation of organelle duplication and cell division in protozoan organisms. T. brucei, among the earliest divergent eukaryotes studied in a laboratory, is a unicellular organism that contains a single copy of each major organelles including a nucleus, a mitochondrion, a flagellum and a Golgi apparatus, each occupying a characteristic cellular location and duplicating at a specific time during the cell cycle.
Trypanosoma brucei as a model organism
T. brucei causes African Sleeping Sickness in humans and Nagana in cattle, bringing huge economic burdens to many developing countries that can least afford it.
As a model system, the single-celled T. brucei is one of the earliest divergent eukaryotic organisms studied in laboratories (Hedges 2002). Genomic databases of T. brucei and related species are complete. Development in advanced molecular genetics methods such as inducible expression and RNAi allows rapid characterization of protein functions.
Furthermore, T. brucei has a simple cellular anatomy with a single copy of nucleus, mitochondrion, flagellum, and Golgi, suitable for fluorescence microscopic and electron microscopic studies. Duplication and segregation of these organelles take place in a strict temporal and spatial order, allowing rapid and reliable identification of cell cycle stages in an unsynchronized population.
Using T. brucei as a model organism, we study the organization of cellular structures and the regulation of their co-ordinated duplication/segregation during cell cycle.
A reconstruction of the parasite using EM images.
Shima Bayat, Brasseur A, Chua XL, Zhang Y, Zhou Q, Low Boon Chuan, and He CY, LRRP1 is a RanGTPase activating protein essential for flagellum functions in Trypanosoma brucei. Journal of Cell Science, accepted.
Li FJ* and He CY* (2014) Acidocalcisome acidification is required for autophagy in Trypanosoma brucei. Autophagy (in press)
Sherrif O, Lim Li-Fern and He CY (2014) Tracking the biogenesis and inheritance of subpellicular microtubule inTrypanosoma brucei with inducible YFP-tubulin. BioMed Research Internationl 2014: 893272. doi: 10.1155/2014/893272.
Sun Y, Wang C, Yuan YA, He CY (2013). An intra-cellular membrane junction mediated by flagellum adhesion glycoproteins links flagellum biogenesis to cell morphogenesis in Trypanosoma brucei. Journal of cell science 126(Pt 2): 520-31
Gheiratmand L, Brasseur A, Zhou Q, He CY (2013). Biochemical Characterization of the Bilobe Reveals a Continuous Structural Network Linking the Bi-lobe to Other Single-copied Organelles in Trypanosoma brucei. The Journal of biological chemistry. 288:3489-3499.
Li FJ*, Shen Q, Wang C, Sun Y, Yuan AY and He CY* (2012) A role of autophagy in Trypanosoma brucei cell death. Cell. Microbiol. 14(8): 1242-56.
Wang M, Gheiratmand L, He CY (2012) An interplay between Centrin2 and Centrin4 on the bi-lobed structure in Trypanosoma brucei. Mol Microbiol. 83(6): 1153-61.
Yang PY, Wang M, Liu K, Ngai MH, Sheriff O, Lear MJ, Sze SK, He CY*, Yao, SQ*(2012) Parasite-Based Screening and Proteomic Profiling Reveal Orlistat™, an FDA-Approved Drug, as a Potential Anti-Trypanosoma brucei Agent. Chem. Eur. J. 18, 8403-8413.
Yang PY, Wang M, Li L, Wu H, He CY*, Yao SQ* (2012) Design, Synthesis and Biological Evaluation of Potent Azadipeptide Nitrile Inhibitors and Activity-Based Probes as Promising Anti-Trypanosoma brucei Agents. Chemistry. 18(21): 6528-41
Zhou Q, Liu BH, Sun Y, He CY (2011) A coiled-coil and C2 domain-containing protein is required for FAZ assembly and cell morphogenesis. J Cell Sci. 124 (Pt22): 3848-58.
Koyfman AY, Schmid MF, Gheiratmand L, Fu CJ, Khant HA, Huang D, He CY, Chiu W (2011) Structure of Trypanosoma brucei flagellum accounts for its bihelical motion. Proc Natl Acad Sci U S A. 108 (27): 11105-11108.
Zhou Q, Gheiratmand L, Chen Y, Lim TK, Zhang J, Li S, Xia N, Liu B, Lin Q, He CY (2010). A comparative proteomic analysis reveals a new bi-lobe protein required for bi-lobe duplication and cell division in Trypanosoma brucei. PLoS One. 5(3): e9660.