My laboratory is mainly interested in understanding the molecular mechanism of mitosis and cytokinesis. We use Trypanosoma brucei, a unicellular eukaryote and the causative agent of human sleeping sickness, as a model organism to address the fundamental questions of how mitosis and cytokinesis are regulated and coordinated during cell division. The current focus is on the cell cycle regulatory pathways 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. 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 the HslVU protease on mitochondrial DNA replication.
We use a combination of genetics, biochemistry, cell biology, molecular biology, chemical genetics, and proteomics to elucidate the molecular and cellular basis of cell cycle control in trypanosomes. We hope to provide a few drug targets for anti-trypanosome chemotherapy.