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.