Methyltransferase, Glucose Adaptation, and Import Complex in Trypanosoma Brucei

Author

Emily KnightFollow

Date of Award

5-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Genetics and Biochemistry

Committee Chair/Advisor

Dr. Meredith Morris

Committee Member

Dr. Jennifer Mason

Committee Member

Dr. Michael Sehorn

Committee Member

Dr. Lesly Temesvari

Abstract

Trypanosoma brucei is a kinetoplastid parasite responsible for human African trypanosomiasis (HAT) and nagana, a livestock wasting disease, which both endemic to sub-Saharan Africa. Unique to kinetoplastids are the specialized peroxisomes, named glycosomes, which compartmentalize the first several steps of glycolysis and gluconeogenesis, nucleotide sugar biosynthesis, and many other metabolic processes. Kinetoplastids are unique in that they have a single mitochondrion. In this work, I present the first study into SET domain proteins in any kinetoplastid parasites. We have characterized a predicted SET domain protein, TbSETD3, that localizes to the mitochondrion and a depletion of the protein results in growth defects and increased sensitivity to environmental stress and cell death. TbSETD3 appears to interact with several mitochondrial proteins, including transporters and membrane proteins. In Chapter 2, I characterize how cell growth, metabolism, and organelle morphology are affected by extracellular glucose levels in two strains of T. brucei. I use transcriptomics and proteomics to identify the pathways that mediate these distinct responses. This work indicates glucose induced changes in organelle morphology and function changes are accompanied by relatively small changes in transcript and protein levels highlighting the limitations of the ‘omics approaches in predicting cellular responses of these parasites. Finally, I have development a yeast complementation system in our laboratory and initial results indicate that two trypanosome-specific peroxins, TbPex13.1 and TbPex13.2, complement strains of yeast deficient for Pex13, though at different levels.

Recommended Citation

Knight, Emily, "Methyltransferase, Glucose Adaptation, and Import Complex in Trypanosoma Brucei" (2023). All Dissertations. 3293.
https://open.clemson.edu/all_dissertations/3293