Understanding the mechanism of chromosome segregation in the kinetoplastid parasite Trypanosoma brucei

Nearly a billion people are at risk of infectious diseases caused by kinetoplastid parasites. Kinetoplastids are a group of eukaryotes that are evolutionarily highly divergent from commonly studied eukaryotes. Our overall objective is to reveal how unconventional machinery and regulatory networks drive proliferation of kinetoplastid parasites using Trypanosoma brucei as a model. Centromeres and their associated intricate kinetochore machinery (~60 proteins) are essential for mediating accurate chromosome segregation in all eukaryotes. Since the identification of the first kinetochore proteins ~40 years ago, it appeared that kinetochore structure and their regulation would be broadly similar across all eukaryotes. It was therefore surprising when we discovered that kinetochores in Trypanosoma brucei are composed of unique proteins, KKT1-to-KKT25. These highly divergent kinetochores provide an attractive drug target for combating kinetoplastid diseases. Our goal is to understand how the unique components and underlying centromeres are organized to carry out conserved kinetochore functions. We will also dissect the nature of noncanonical cell cycle control executed by conserved mitotic regulators. Identification of novel mechanisms will not only provide opportunities for drug development against kinetoplastid parasites but also deepen our understanding of intricate chromosome segregation machinery in all eukaryotes.