NSF Award
0614882
The trypanosomatids are a group of protozoan parasites that have been intensively studied because of their adverse impact on a number of biological systems. Representative is Trypanosoma brucei which is the causative agent of nagana, a wasting disease of domestic cattle and horses in southern and central Africa. Trypanosomatids are also somewhat unusual in the eukaryotic world in that their genetic regulatory mechanisms are principally under the control of post-transcriptional mechanisms. Our understanding of the genetic mechanisms underlying transcription initiation of RNA polymerase I and II in these parasites is only recently emerging. The characterization of the RNA polymerase III promoters of the trypanosomatids, and the transcription factors that bind to and activate them remains meager. The objective of this project is to identify novel transcription factors (TFs) from the parasitic protozoan T. brucei, specifically of RNA polymerase III genes. This is of fundamental biological importance as RNA polymerase III is responsible for the production of components essential to protein production including the 5S ribosomal RNA and transfer RNA. This project will utilize a double-pronged biochemical approach towards the identification of TFIII proteins. First we will employ two putative pol III promoter sequences as the target for TFIII-specific interactions. Second we will elucidate the protein interaction networks in TFIII transcriptional complexes. <br/><br/>The elucidation of TFIII-class proteins will initiate studies directed towards understanding the fundamental processes leading to rRNA and tRNA production in these parasites, and whether they act in an analogous fashion to that of higher eukaryotes, or with significantly different mechanisms. In addition, extensive studies in trypanosomatids have shown that the transcriptional apparatus in these organisms display many unique features. Therefore it is hypothesized that novel transcription factors and transcriptional mechanisms will be discovered in these pathogenic organisms, and will shed light on diverse evolutionary pathways undertaken by these microbial eukaryotes.<br/><br/>This project will be important in the establishment of a combined biochemistry and genetics project in the Principal Investigator's laboratory at the University of Maryland Eastern Shore (UMES), a historically black university. The training possibilities will be greatly enhanced in that undergraduate students will have increased research opportunities in the Principal Investigator's laboratory in a molecular biology based project. In addition, one high school teacher from the Maryland Wicomico County school system (35 % minority enrollment in biology) will be recruited per year to develop skills for enhanced teaching capability. Finally, UMES is a partner in the University of Maryland Marine, Environmental, and Estuaries Science (MEES) graduate program. Therefore minority students studying for MS and PhD degrees will be afforded training in the biotechnology component of the program.
