Research

Understanding the mechanism of chromosome segregation.

We are interested in understanding the mechanism of how eukaryotic cells inherit their genetic material accurately at each round of cell division. We focus on the kinetochore, the macromolecular protein complex that drives chromosome segregation. Although it was widely believed that the structural core of kinetochores would be composed of proteins that are conserved in all eukaryotes (e.g. CENP-A, Ndc80), we discovered an unconventional class of kinetochore proteins (KKT1–25) in Trypanosoma brucei, an evolutionarily-divergent kinetoplastid parasite. Our current goal is to understand how they carry out conserved kinetochore functions such as binding to DNA or microtubules, as well as establishment of proper bi-oriented attachments. We also reconstitute kinetochore complexes and characterize them using various approach, including structural biology and biophysics. By understanding the unique kinetoplastid kinetochores, we aim to reveal fundamental principles of chromosome segregation mechanism in eukaryotes. If you are interested in joining us, please contact us!

• How is kinetochore position specified without CENP-A?
• How is kinetochore assembled without CENP-A?
• Which proteins bind microtubules? 
• How do kinetoplastid kinetochores achieve bi-orientation?
• How is the metaphase-to-anaphase transition regulated without a canonical spindle checkpoint?
• What is the structure of kinetoplastid kinetochores in cells?
• Can we isolate native kinetoplastid kinetochores?
• Can we reconstitute aspects of chromosome segregation using kinetoplastid kinetochore proteins in vitro?
• Can we target KKT proteins to prevent the growth of kinetoplastid parasites?

Our research is supported by

Wellcome Trust

Berrow Foundation