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EFFECT OF ARGININE METHYLATION ON THE ENZYMATIC ACTIVITY AND FUNCTION OF TbLpn IN TRYPANOSOMA BRUCEI
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Pelletier, Michel
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2020-05
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Trypanosoma brucei is a protozoan parasite which causes Human African trypanosomiasis (HAT). Trypanosoma brucei is vector borne carrier by the tsetse fly of Sub-Saharan Africa. If left untreated, Human African trypanosomiasis is almost always fatal and represents a very serious health risk. Another version of the disease known as Animal African trypanosomiasis (AAT) also exist and threatens the livestock of farmers. There are two stage of the disease, the first blood steam phase and the second central nervous system phase. In the second phase, T.brucei is able to penetrate the blood brain barrier and cause very pronounced disturbances. This phase is where the disease gets its less formal name, "African Sleeping Sickness" due to the sleep disturbances and neurological symptoms prevalent in the second phase. Treatment options and outlooks are better in the first phase and get significantly worse in the second phase. Many of the treatments available are incredibly toxic, have very pronounced side effects, and often involve painful injections. As a result, a more effective means of treating HAT is necessary. The research in this paper seeks to determine the role of protein arginine methylation of specific arginine residues in TbLpn expression and subcellular localization. TbLpn is a lipin protein found in T.brucei that is homologous to human and yeast lipins. TbLpn is likely involved in membrane biosynthesis and is regulated post transcriptionally by protein arginine methylation. Utilizing site directed mutagenesis, specific arginine residues on a wild type plew TbLpn plasmid were mutated into lysine residues. These specifically changed arginine residues will then be used in T.brucei in order to observe the effects on protein interaction and sub cellular localization.