Gene Regulation by DOT1 Methyltransferases in the African Trypanosome Parasite
EMSL Project ID
51818
Abstract
The protozoan parasite Trypanosoma brucei causes fatal sleeping sickness in humans with 60 million people at risk. As an early-branching eukaryote, trypanosomes exhibit significant deviations in chromatin structure and gene regulation from most eukaryotes, which can be exploited for therapeutic purposes. However, our limited knowledge of chromatin structure and function in trypanosomes is a major obstacle to these efforts. Hence, we propose structural studies of the DOT1A and DOT1B methyltransferases, which perform key functions in cell cycle regulation and antigenic variation, and their substrate – the nucleosome. Given the plethora of cryo-EM structures of nucleosome-protein complexes, cryo-EM is ideally suited to visualize the nucleosome with and without DOT1 enzymes and provide insights into their mechanism of action. Since DOT1-mediated processes are essential for the parasite, this research may have a large impact on global health by exploiting the unique attributes of protozoan DOT1 enzymes to inform novel therapies for sleeping sickness.
Project Details
Start Date
2021-02-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members