Ziyin Li Lab:Notebook/Cell Cycle Regulation in Trypanosomes

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Project Description/Abstract
We are interested in understanding the molecular mechanisms of mitosis and cytokinesis. We use Trypanosoma brucei, a unicellular microbial eukaryote and the causative agent of human sleeping sickness, as a model system to address the fundamental questions of how mitosis and cytokinesis are regulated and coordinated during cell division. The advantage of using T. brucei as a model is that this organism is evolutionarily ancient, and thus it provides a unique distant reference point for dissecting crucial biological processes. The current focus is on the cell cycle regulatory circuits consisting of protein kinases such as Aurora B kinase, Polo-like kinase and Tousled-like kinase, spindle-associated motor proteins, and ubiquitin ligases.

We are also interested in the role of ubiquitin-dependent and -independent proteolysis in various cell biological processes. ATP-dependent protease complexes are present in all three kingdoms of life where they ride the cell of mis-folded or damaged proteins and control the level of certain regulatory proteins. These proteases include the 26S proteasome in eukaryotes, Archaea, and Actinomycetales and the HslVU protease in eubacteria. Currently we are investigating the function and regulation of various ubiquitin-dependent pathways and the ubiquitin-independent HslVU-mediated proteolysis pathway in T. brucei. The current focus is on three proteolytic pathways: the Cullin-RING ubiquitin ligase (CRL) and the anaphase-promoting complex/cyclosome (APC/C) on cell cycle control and HslVU protease on mitochondrial DNA replication licensing.