The candidate plans to pursue a research career focused on the chemistry, enzymology, and genetics of DNA damage and repair with both immediate and long-term emphasis on the application of molecular biology and genetic techniques to address fundamentally important problems in the area of radiation biology and carcinogenesis. An important component of these goals, and an immediate objective, is to expand my current research expertise by becoming more proficient in the techniques and applications of gene isolation, identification, and manipulation. Another immediate goal is to acquire expertise in the application of 2D NMR and computer modelling techniques for deducing DNA structures containing radiation-induced damages. In both cases this can be accomplished on the Emory campus through close contract and collaborations with two of my colleagues. A Research Career Development Award will free substantial time commitments (currently devoted to teaching and university service) to allow almost full- time (85% or greater) pursuit of my research goals which would include a sufficient amount of time to gain proficiency in the areas cited above. The research time generated by the RCDA will be particularly important for carrying out these studies during the academic year. The RCDA would also contribute substantially towards the realization of an important, long-term goal for this candidate; to provide an excellent research training environment for graduate students and postdoctoral fellows. Emory University is rapidly developing its basic science research program, a component of which will be the completion of a new biological sciences research building that my laboratory will occupy at the end of 1989. The goal of the candidate's research proposal is to gain an understanding of the role mediate by redoxyendonuclease (RE), a DNA repair enzyme that recognizes a variety of base damage products, in the eukaryotic cellular response to oxidative and radiation-induced damaged of DNA.
The specific aims are directed towards gaining an understanding of the enzymology, genetics, and regulation of these enzymes in yeast and human cells. The cloning and characterization of the yeast RE gene will permit study of the regulation of this enzyme in response to radiation-induced DNA damage in yeast cells. The gene probes and antibodies generated in the yeast RE studies may have utility for probing RE's from other species, including humans. A long-term goal of these studies will be to apply the methods and expertise acquired in these studies to characterize other eukaryotic enzymes involved in the repair of oxidative and radiation-induced DNA damage. By uniting biochemical, molecular biological, and genetic approaches, it is anticipated that a more complete understanding of how RE and subsequently, other DNA repair enzymes maintain the genetic stability of eukaryotic cells, including humans, will emerge.
