CAREER: Biological and Molecular Studies of Trypanosomal Ribonucleases H

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9600920 Campbell The research portion of this CAREER proposal concerns RNases H, widely distributed enzymes found in systems ranging from retroviruses to humans. They specifically degrade the RNA strands of RNA:DNA duplex hybrids, an important function in DNA replication. The distribution of RNases H further suggests that they are centrally positioned to regulate key decisions in DNA replication and nucleic acid metabolism in all biological systems. Dr. Campbell will initiate studies to establish the roles played by RNases H in eukaryotic DNA replication and cell growth using the protozoan Trypanosoma brucei. Expression patterns of the major RNase H, TbbRNHI, of T. Brucei will be established; activity patterns of the expressed and purified recombinant enzyme will be defined; and mutations that result in catalytically altered enzyme will be identified. The educational plan consists of adding innovative changes to a new course recently introduced into the Brown undergraduate curriculum and implementing a program to mentor and ignite under-represented minority student learning and scientific interest. RNase H is an enzyme that specifically degrades the RNA strand of DNA:RNA hybrids (H for hybrid). The RNase family is widely distributed, found in systems ranging from retroviruses to humans. They are function in controlling the replication of DNA, and thus are critical to the life cycles of retroviruses as well as eukaryotic organisms. In this project, the role of RNase H in a complex organism, the protozoan Trypanosoma brucei, will be studied in an effort to learn more about their function in cells. The education component adds innovative changes to a new course on fundamental concepts in modern biology, as well as a program to stimulate under-represented students to pursue academic careers. ***