Research Interests

The goal of the research in my laboratory is to understand the integration of metabolic pathways that results in the robust physiology associated with microbes.  In this effort we emphasize a biochemical genetic approach that utilizes in vivo analyses to inform the design of in vitro experiments. Currently the work in the lab is in two general areas.

1) Understanding the Rid system of endogenous metabolite stress.  My laboratory recently identified a new stress system that is conserved across all domains.  We showed that enamine metabolites, which are necessary intermediates in some PLP-dependent reactions, are able to damage cellular components. The RidA protein family (previously YjgF/YER057c/UK114) is responsible for deaminating the enamines to generate stable keto acid products.  These findings have opened an exciting new field of study in the lab. Immediate questions include; which enzymes generate enamine stressors? Which enzymes are targets of the damage? What is the specificity of RidA homologs? What are the biochemical consequences of lacking RidA in various organisms.  This project has not only defined a new stress and cellular response to it, but has implications for our understanding of the composition and characteristics of the cellular milieu.

2) Exploring metabolic integration and redundancy. By virtue of the selective pressure exerted through millions of years of evolution, a living cell is likely to be the most well tuned and complex system in existence. The research in the laboratory takes advantage of the emerging technologies to better understand molecular details of metabolic processes and identify the mechanisms used to integrate these processes into a productive physiology.  In our study of metabolic integration, we use a well-characterized biosynthetic pathway as a “nucleation point” from which to build and expand a model system.  Our strategy has been to utilize genetic techniques to identify metabolic connections to this central pathway and thus build a defined network that we can then dissect on the molecular level. A solid understanding of metabolic integration is critical for the advancement of many fields including; metabolic diseases, drug discovery, synthetic biology, successful manipulation of microbes for societal uses, etc.

Students from my laboratory have strong training in classical and molecular genetics particularly as applied to metabolic questions.  In addition they are exposed to, and utilize, standard biochemical and molecular biological approaches.  The students are encouraged to think logically about big biological questions and how to tease them apart. I strive to train students to think beyond linear pathways and transcriptional regulation to appreciate the integrated nature of metabolism and the inherent chemistry.

Biotechnology, biofuels, biocatalysts, fermentation, food microbiology

Interactions of microorganisms with the environment, and their roles in natural communities

Roles of microbes in disease, beneficial symbiosis, pathogenesis, parasitology, and immunology

Elucidating biological phenomena by analyzing nucleic acid and protein sequences from microbes and microbial communities

Diversity of metabolic and energy-generating pathways.

Research Interests:

Our research examines the physiology, systematics and ecology of environmentally important microorganisms, but especially the methane-producing archaea and the marine alpha proteobacteria. Of special interest is to understand the complete organism, from the biochemical mechanisms it uses to accomplish its day-to-day tasks of living to its interactions with other organisms and its environment in general. Every organism has its own story.

The methanogens are strictly anaerobic autotrophs which obtain energy from the synthesis of methane gas. They catalyze the terminal step in the anaerobic decomposition of organic matter, and about 1.6 % of the CO2 fixed worldwide is released to the atmosphere by the activity of these bacteria. As autotrophs they are also unusual because they are commonly found closely associated with heterotrophic bacteria and protists. Our studies of the methanogens have focused on Methanococcus, which is common in estuarine environments. Currently, we are using genetic methods to elucidate novel biosynthetic pathways and mechanisms of H2 metabolism.

The roseobacters play important roles in the transformation of carbon and sulfur compounds in the ocean and estuarine environments. Currently, we are studying the metabolism of dimethylsulfonium propionate (DMSP), a common osmolyte and major source of atmospheric sulfur, by Siliicibacter pomeroyii. Studies of this model organism provide insights into the mechanisms of DMSP degradation in the natural environments.

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.