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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.

£1,890,493

10 Apr 2018

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
Planned Dates: End Date 2023-10-15T00:00:00+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
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