Date of Award

5-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

John Siekierka

Committee Member

James Dyer

Committee Member

Carlos Molina

Abstract

Lymphatic filariasis and leishmaniasis are neglected tropical diseases that are caused by nematode and protozoal parasites. These diseases cause disfiguration, leaving their host socially marked, and in some cases cause more severe disease that can lead to death. These infections, which tend to persist for long periods of time, also lead to bacterial and fungal co-infections, which further exacerbate the disease. Currently there are insufficient treatment options. Current therapies are often too expensive, have toxicity associated with them and are subjected to growing resistance amongst parasite populations. In this thesis I investigated two potential drug targets. The first, is the parasitic nematode Brugia malayi (B. malayi), the causative agent of lymphatic filariasis, and the second, is the protozoal parasite Leishmania mexicana (L. mexicana), one of the causative agents of leishmaniasis. These targets are protein kinases which play critical roles in protecting these parasites from host immune responses and other forms of stress. They are termed, B. malayi, Bm-JNK and L. mexicana, Lmx-MPK1. I have expressed and purified recombinant Bm-JNK and Lmx-MPK1, characterized both kinases and established assays for both suitable for high-throughput drug screening. In addition, I have identified a novel pathway responsible for activation of Lmx-MPK1.

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