Fatty Acids and Parasitism: Towards a Better Understanding of Lipid Metabolism in Trypanosoma Brucei
Date of Award
8-2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Biochemistry and Molecular Biology
Committee Chair/Advisor
Kimberly Paul
Committee Member
James Morris
Committee Member
Lukasz Kozubowski
Committee Member
Nishanth Tharayil
Abstract
Trypanosoma brucei is an extracellular eukaryotic parasite that causes sleeping sickness in humans and cattle. As an extracellular parasite, T. brucei relies on the host’s nutrients to satisfy its growth requirements. The parasite is unusual because it does not uptake most of the host’s lipid species. Instead, T. brucei prefers to perform de novo synthesis of most lipid species. One of the lipid species that T. brucei can both uptake and synthesize is fatty acids. In my thesis work, I investigated the dynamics of fatty acid uptake, metabolism, and utilization of T. brucei. My work starts by determining the nature of the fatty acid uptake of T. brucei using a biochemical approach. I discovered that the uptake of C12:0 fatty acid was not saturable. I then investigated the possibility of lipid remodeling under the knockdown of acetyl-CoA carboxylase (ACC), the key enzyme in T. brucei’s fatty acid de novo synthesis. I found that even though there was no significant change in the lipid group, the fatty acids utilized by the lipid group changed when we performed ACC knockdown. Finally, I investigated the possibility of exogenous fatty acids as a regulation mechanism for the abundance and activity of ACC. I found that although ACC abundance did not significantly change with exogenous fatty acid addition, T. brucei’s growth was affected by these fatty acids. This work helps to better understand the role of the T. brucei ACC in de novo synthesis of fatty acids and the uptake mechanisms of these important biomolecules.
Recommended Citation
Saliutama, Joshua, "Fatty Acids and Parasitism: Towards a Better Understanding of Lipid Metabolism in Trypanosoma Brucei" (2023). All Dissertations. 3365.
https://tigerprints.clemson.edu/all_dissertations/3365