Date of Award

8-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Biochemistry and Molecular Biology

Committee Chair/Advisor

Paul, Kimberly S

Committee Member

Morris , James C

Committee Member

Smith , Kerry

Committee Member

Sehorn , Michael

Abstract

My doctoral studies focused on studying FA metabolism in the deadly protozoan parasite T. brucei. In my dissertation, I will be addressing various aspects of the regulation of TbACC, which catalyzes the first committed step in FA synthesis. In the second chapter, I hypothesized that TbACC is regulated in response to environmental lipids. I examined changes in TbACC RNA, protein, and activity in response to different levels of environmental lipids in both BF and PF cells. I also delineated the mechanisms by which TbACC expression and activity is regulated by phosphorylation in response to altered lipid environments. In the third chapter, which has been published, we tested the effects of a compound in green tea extract known as epigallocatechin gallate (EGCG), a known inducer of AMPK, which phosphorylates ACC in other organisms. We tested the effect of EGCG on BF and PF growth. We also examined the effect of EGCG on TbACC activity and phosphorylation. In the fourth chapter, I demonstrated that TbACC in PF is also regulated by various allosteric regulators. I also showed that TbACC might form oligomers. Together these studies have given an insight on the ability of T. brucei to regulate its FA synthesis and the role this pathway may play in the survival of this deadly parasite in its hosts. This knowledge may be exploited in the future to find a better cure for Trypanosomiasis.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.