Bungo Akiyoshi

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Bungo Akiyoshi is a Wellcome Senior Research Fellow at the Wellcome Centre for Cell Biology, University of Edinburgh. He is interested in understanding the mechanism of how cells accurately transmit their genetic material during cell division.

He obtained his PhD in 2010 from the University of Washington/Fred Hutchinson Cancer Research Center in Seattle where he purified the macromolecular kinetochore complex from budding yeast in the lab of Sue Biggins. He then moved to the Sir William Dunn School of Pathology, University of Oxford to join Keith Gull's lab, where he discovered an unconventional type of kinetochores in Trypanosoma brucei.

In 2013, Bungo started his group in the Department of Biochemistry, University of Oxford supported by Royal Society and Wellcome Trust Sir Henry Dale Fellowship, and was awarded a Wellcome Senior Research Fellow in 2018. He moved to the University of Edinburgh in March 2023 to continue studying how unconventional kinetochore proteins play conserved kinetochore functions in trypanosomes.

Akiyoshi lab website 

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 that causes African sleeping sickness. 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 approaches, including structural biology and biophysics techniques. By understanding the unique kinetoplastid kinetochores, we aim to reveal fundamental principles of chromosome segregation mechanism in eukaryotes. 

Key questions

• What determines where kinetoplastid kinetochores are assembled without CENP-A? 
• How are kinetoplastid kinetochores organized? 
• How do conserved mitotic regulators ensure accurate chromosome segregation in kinetoplastids?

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KKT2 and KKT3 are homologous protein kinases that form the base of kinetoplastid kinetochores. They have three domains that are highly conserved among kinetoplastids: an N-terminal protein kinase domain that regulates kinetochore functions, the central domain, and C-terminal divergent polo boxes that recruit other kinetochore proteins. The central domain is responsible for the centromere localization of KKT2 and KKT3. Crystal structures of the KKT2 central domain reveal that it consists of the centromere localization (CL) domain and a C2H2-type zinc finger.