FUNCTIONAL CHARACTERIZATION OF MRB8180-CONTAINING COMPLEXES IN TRYPANOSOME RNA EDITING

Ph.D. Trypanosoma brucei is the causative agent of Human African Trypanosomiasis and nagana in cattle. Additionally, two close cousins to this parasite, T. cruzi and species of Leishmania, also cause disease in humans. Collectively, these organisms are found on every continent except for Antarctica...

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Bibliographic Details
Main Authors: Simpson, Rachel, orcid:0000-0003-2330-3410
Other Authors: Read, Laurie, Microbiology and Immunology
Format: Doctoral or Postdoctoral Thesis
Language:English
Published: State University of New York at Buffalo 2019
Subjects:
Online Access:http://hdl.handle.net/10477/79857
Description
Summary:Ph.D. Trypanosoma brucei is the causative agent of Human African Trypanosomiasis and nagana in cattle. Additionally, two close cousins to this parasite, T. cruzi and species of Leishmania, also cause disease in humans. Collectively, these organisms are found on every continent except for Antarctica and considered Neglected Tropical Diseases. Studying the basic biology of these parasites provides valuable information for drug design efforts as parasite-specifc biology has the potential be an effective drug target with minimal effects on the host. Uridine insertion/deletion RNA editing is an essential, parasite-specifc process that is found in all kinetoplastids. Through this process, mitochondrial mRNAs are modifed by specifc insertion and deletion of uridines. Editing generates functional open reading frames that encode mitochondrial respiratory proteins. Both enzymatic and non-enzymatic factors are required for RNA editing and much is still unknown about how this process proceeds and how it is regulated. The roles of numerous non-enzymatic factors have remained opaque in part due to the limitations of conventional methods to interrogate the order and mechanism by which editing progresses and thus the roles individual proteins play in mediating this progression. To overcome this limitation, I developed a novel bioinformatic platform, the Trypanosome RNA Editing Alignment Tool (TREAT), which allows us to examine whole populations of partially edited sequences using high throughput sequencing.