Ruslan Afasizhev
Boston University, MA·Biochemistry
Trypanosoma brucei is a single-celled parasite that causes African sleeping sickness and related animal diseases in sub-Saharan Africa. Its mitochondrion handles genetic information in unusual ways.
- Fields
Biochemistry
Microbiology & Immunology
Biophysics
- Topics
Trypanosoma brucei
African trypanosomiasis
sleeping sickness
- Grants
- 3 known grants, through Jul 2030
What they work on
- Define how complexes built around KRET1, an enzyme that adds U-tails to RNA, couple tailing with RNA degradation in the T. brucei mitochondrion, using proteomics, imaging, and cryo-EM.
- Determine the natural RNA targets and cryo-EM structures of the TUTases KRET2 and MEAT1 to reveal how editing sites are selected and how uridines are inserted into mRNA.
- Characterize the mitochondrial RNA polymerase complex and its transcription factors in bloodstream and insect forms of T. brucei, and map maxicircle and minicircle promoters.
- Rebuild an active mitochondrial transcription complex in the test tube to test how sense and antisense transcription start sites define mRNA ends.
- Solve cryo-EM structures of RNA editing substrate binding complexes (RESCs) at distinct stages, and test whether the helicase KREH2 drives editing by remodeling RESCs and releasing guide RNA.
More about the research
Many messenger RNAs, the copies of genes used to make proteins, must be heavily edited before they work. In this editing, uridine (U) building blocks are inserted or removed at sites chosen by short guide RNAs (gRNAs). These processes are essential for the parasite's survival, so they could be targets for drugs. The lab studies three steps in the life of mitochondrial RNA: how it is made (transcription), how its ends are tailed, processed, and degraded, and how it is edited. A recurring tool is cryo-electron microscopy (cryo-EM), which reveals the structure of molecular machines in near-atomic detail.
Why it matters
African trypanosomiasis affects some of the most marginalized populations and economies of sub-Saharan Africa, and current drugs only partly control it. The mitochondrial RNA processes studied here are essential for parasite survival. Understanding them could reveal new drug targets against T. brucei and related parasites. RNA editing research in trypanosomes has also informed genome-altering technologies in the past.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Christian Tschudi
Yale University, CT·Microbiology & Immunology
Determine how T. brucei parasites receive the signal to begin making the metacyclic VSG (mVSG) coat that lets them infect mammals, using parasites induced to develop by switching on the RNA-binding protein RBP6.
Arthur Gunzl
University of Connecticut, CT·Microbiology & Immunology
Determine how the cyclin-dependent kinase CRK9 controls spliced leader trans splicing in Trypanosoma brucei, including whether it phosphorylates the splicing factor TSR1, using parasites with chemically inhibitable analog-sensitive CRK9.
Scott Bailey
Johns Hopkins University, MD·Biochemistry
Determine how CRISPR-associated proteins use small guide RNAs to locate and destroy foreign DNA or RNA in prokaryotes, using cryo-EM structures together with biochemical, biophysical and cell-based assays.
The school
Boston University: 26 labs on PI Pages, $784M a year on research, 630 research doctorates a year.
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