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.
Zhang Y, Huang Y, Srivathsan A, Lim TK, Lin QS and He CY (2018). The unusual flagellar targeting mechanism and functions of the trypanosome orthologue of the ciliary GTPase Arl13b. J Cell Science http://jcs.biologists.org/content/early/2018/08/09/jcs.219071
Sun SY, Kaelber JT, Chen M, Dong X, Nematbakhsh Y, Shi J, Dougherty M, Lim CT, Schmid MF, Chiu W, and He CY (2018). Flagellum couples cell shape to motility in Trypanosoma brucei. PNAS https://doi.org/10.1073/pnas.1722618115
Xia J, Kong L, Zhou L-J, Wu S-Z, Yao L-J, He C, He CY and Peng H-J (2018). Genome-wide biomolecular fluorescence complementation-based proteomic analysis of Toxoplasma gondii ROP18’s human interactome shows its key role in regulation of cell immunity and apoptosis. Frontiers in Immunology 9:61
Lim LZ, Ee S, Fu J, Tan Y, He CY and Song J (2017). Kinetoplastid membrane protein-11 adopts a four-helix bundle fold in DPC micelle.FEBS Lett. 591(22):3793-3804
Chen M, Dai W, Sun SY, Jonasch D, He CY, Schmid MF, Chiu W and Ludtke SJ (2017). Convolutional neural networks for automated annotation of cellular cryo-electron tomograms. Nature Methods 14:983-985.