Understanding unconventional kinetoplastid kinetochores in Trypanosoma brucei (360G-Wellcome-210622_Z_18_Z)
I am interested in understanding the mechanism of how eukaryotic cells inherit their genetic material at each round of cell division. I have been studying 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, I discovered an unconventional class of kinetochore proteins (KKT1–20) in Trypanosoma brucei, an evolutionarily-divergent kinetoplastid parasite. My current goal is to understand how they carry out conserved kinetochore functions such as binding to DNA and microtubules. Based on preliminary data, I propose that two homologous protein kinases KKT2 and KKT3 lie at the base of the kinetoplastid kinetochore. I will aim to understand how these proteins localize specifically at the centromeric DNA using a variety of approaches. I will also characterize the KKT4 protein to reveal the mechanism of microtubule interaction. To understand the design principle of kinetoplastid kinetochores, I will reconstitute and characterize kinetochore subcomplexes. Finally, I will examine how the evolutionarily-conserved Aurora B kinase regulates the function of unconventional kinetoplastid kinetochores.
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Grant Details
Amount Awarded | 1890493 |
Applicant Surname | Akiyoshi |
Approval Committee | Science Interview Panel |
Award Date | 2018-04-10T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Senior Research Fellowship Basic |
Internal ID | 210622/Z/18/Z |
Lead Applicant | Dr Bungo Akiyoshi |
Partnership Value | 1890493 |
Planned Dates: End Date | 2023-02-28T00:00:00+00:00 |
Planned Dates: Start Date | 2018-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | South East |
Sponsor(s) | Prof Mark Sansom |