Research Interests / Cyp102 / Genotoxicity / Course Information
Research in my laboratory is divided between two major projects. The main goal of the first project is to obtain a detailed understanding of the mechanism by which substrate molecules interact with the cytochrome P450 102 enzyme (Cyp102) of the bacterium Bacillus megaterium. The overall aim of the second major project is to investigate the genotoxicity of benzene in mice. We are particularly interested in determining if benzene induced mutations play a significant role in the development cancers that result from exposure to benzene.
. Among the more than 481 known cytochrome P450 enzymes (P450s) (1), the Cyp102 fatty acid hydroxylase of B. megaterium ATCC 14581 has proved to be a fruitful model for investigating structure/function relationships in a P450. Features of Cyp102 that have established it as a premier model include the availability of a high resolution crystal structure (2.0 , R = 0.16) (2), high specific activity, ease of purification, high solubility of the protein in aqueous buffers (3,4), and an increasing number of research groups actively investigating its structure and function. In addition, activity assays are greatly simplified because unlike most other P450s, Cyp102 does not require a separate P450 reductase protein for monooxygenase activity (4). Our experimental approach for studying substrate binding and enzyme activity involves a combination of site-specific mutagenesis, protein biochemistry and computer-aided molecular modeling.
. Benzene is a highly toxic, ubiquitous environmental pollutant that causes cancer in humans and animals. One of the goals of this project is to extend our discovery that benzene is able to increase the mutation frequency in DNA of lung, and spleen tissues of mice (Mullin et al., Mutat. Res. 327:121-129, 1995) and causes a very specific pattern of mutations in lung tissues (Mullin et al., Carcinogenesis, in press 1998). These discoveries provide the first evidence that benzene can increase the frequency of gene mutations, and are important findings in regard to the mechanism by which benzene acts as a carcinogen because cancer is a genetic disease in which mutations are required to achieve a fully malignant state. Current studies underway involve identifying genes of mice that mediate benzene genotoxicity, and measuring sex specific differences in genotoxicity.
The two courses that I teach are Microbiology, CELL422, and Molecular Biology, CELL311. Students may access the course outlines for Microbiology and Molecular Biology.
In the Fall semester 2000, I started using Blackboard, an on-line teaching tool, for Microbiology and Molecular Biology. Students currently enrolled in my courses will be able to access lecture presentations, notes, a list of recommended links to outside sources of information, and submit homework online.