Date of Award

8-2012

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Biological Sciences

Advisor

Paul, Kimberly

Committee Member

Temesvari , Lesly

Committee Member

Morris , James

Abstract

This master's thesis focuses on how disruption of fatty acid metabolism affects both host adaptation and immune evasion in the deadly eukaryotic parasite, Trypanosoma brucei. In Chapter 1, I review the current literature on African trypanosomiasis, fatty acid synthesis, immune evasion, and lipid metabolism. In Chapter 2, I investigate how disruption of the fatty acid synthesis pathway affects the parasite's ability to evade the host immune defenses. When T. brucei acetyl-CoA carboxylase (TbACC) is knocked down by RNA interference (RNAi), fluid phase and receptor mediated endocytosis pathways are greatly affected, suggesting that fatty acid synthesis is necessary for both endocytic pathways. Further, the parasite's ability to clear surface immune antigens was reduced under ACC-RNAi conditions. In Chapter 3, I begin to elucidate the connection between fatty acid synthesis, fatty acid uptake, and lipid storage. ACC-RNAi caused a significant reduction in the number of lipid droplets. This effect can be reversed by the addition of external fatty acids, suggesting that lipid droplets are possibly a sorting site for both internally synthesized fatty acids as well as fatty acids taken up from the environment. Therefore, fatty acids are believed to be internalized to the ER, transferred to the lipid droplet, and then incorporated into the fatty acid synthesis pathway, where they can be utilized within the cell or returned to the lipid droplet. These studies serve as a preliminary linkage between fatty acid metabolism and host-parasite interaction, which is needed to fully understand T. brucei and bring forth a new cure.

Included in

Cell Biology Commons

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