Regulation of the Development of Trypanosoma brucei

University Of California, San Francisco, San Francisco CA

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Abstract

Enter the text here that is the new abstract information for your application. This section must be no is the new abstract information for your application. This section must be no longer than 30 lines of text. 6. ti' IL' I.) PROJECT SUMMARY/ABSTRACT <[unreadable]c[unreadable] .-U. The parasitic protozoa, Trypanosoma brucei spp., are the causative pathogens of spp., African sleeping sickness in humans and nagana in cattle. They are a family of sickness in humans and nagana in cattle. deeply branched eukaryotes that exhibit many unique features during their cell cycle progression. Due to the presence of a single mitochondrion in each cell, the nuclear progression. Due to the presence mitochondrion each cell, the nuclear T. brucei cycle and mitochondrial cycle in T. bruce! have to be coordinated for a fruitful cell to be fruitful cell division, suggesting also that cytokinesis could be controlled by either of the two cycles. Our studies indicated that cytokinesis is primarily regulated by the regulated cycles. Our studies indicated the mitochondrion in the insect (procyclic) form but by the nucleus in the bloodstream form form of T. brucci. We also observed that a block of mitosis achieves genuine mitotic T. brucei. fonm arrest in the procylic form but not in the bloodstream form, which continues with reform, The bloodstream entries into a new G1 phase and nonstop nuclear DNA synthesis. The bloodstream 01 phase and nonstop fonm form is thus apparently lacking the spindle assembly checkpoint, which is present unusual command, and functioning in the procyclic form. These unusual changes in command, never functioning in the procyclic form. previously, observed among any other eukaryotes previously, prompted us to examine some of the protein kinases in T.brucci known to control both mitosis and cytokinesis in other protein kinases in I brucei known to control both mitosis and cytokinesis The Polo-like kinase (TbPLK) turns out regulating eukaryotes. The Polo-like kinase (TbPLK) turns out regulating only cytokinesis and and localizing to the flagellum attachment zone (FAZ) in T. brucei. The Aurora-like localizing to the flagellum zone (FAZ) in T. bruceL The Aurora-like (TbAUK1) resides in a novel chromosomal passenger kinase (TbALJK1) resides in a novel chromosomal passenger complex (CPC) that trans-localizes from the central spindle midzone in late anaphase across the nuclear envelope to the FAZ and then transcends down from the anterior to the posterior end along the FAZ to separate the cell into two. This is a most unusual mode of separate the cell into two. This cytokinesis. We plan to pursue it further by tracing the CPC trans-localization with cytokinesis. We plan to pursue it further by tracing the CPC trans-localization with time-lapse imaging and dissecting the specific roles of TbPLK and TbAUK1 and their TbAUK1 potential interactions during this fascinating process with the eventual goal of potential interactions during this fascinating process with the eventual goal establishing the cell regulation in T. brucei a useful model system for advanced basic T. anti-trypanosomiasis chemotherapy. research as well as a potential target for anti-trypanosomiasis chemotherapy. well O.0 x<3y[unreadable] ... L[unreadable]2 3.3 CND TAD 7'' D[unreadable][unreadable]a 7[unreadable]C y[unreadable]@ f0/1 E ... 575 >'0 .,,, T-0 00Z5 m-~ c[unreadable]) ..N Of" off 30[unreadable] .L.