Research Interests: We have long studied bacterial plasmid-encoded resistance to inorganic and organic mercury compounds (the mer locus) as a model for (a) gene regulation by toxic metals, (b) microbial detoxification of environmental hazards, and (c) the influence of toxic metals on the commensal microbiota of vertebrates. Our present work on mer focuses on structure-function and dynamic studies of the two major types of MerR protein and on the unique interactions of the classical Tn21 MerR regulator with RNA polymerase during repression and activation and with MerD during shut-down of mer operon expression. In this work we collaborate with the groups of Jeremy Smith and Liyuan Liang at the Oak Ridge National Laboratory. We also have a growing interest in the molecular basis of mercury intoxication. With collaborators Sue Miller at UCSF and Mary Lipton at the Pacific Northwest National Laboratory we have devised a computational filter based on the seven stable isotopes of Hg to identify, at the individual peptide scale using LC-MS/MS proteomics, those proteins most vulnerable to forming adducts with organo-mercurials. We are now beginning a new project to similarly define the inorganic mercury "exposome" and to use this approach in collaboration with Judy Wall at Missouri for high-throughput discovery of proteins involved in mercury methylation by sulfate reducing bacteria. We have also worked in the area of lateral gene transfer in prokaryotes with special emphasis on the dissemination by plasmids and transposons of genes for resistance to toxic metals and antibiotics. We are now wrapping up two major sequencing projects on large, mobile plasmids of meticillin-resistant Staphylococcus aureus (MRSA) and of several genera of marine bacteria, agricultural pathogens, and bacteria important in biofuel fermentation.
