Regulation of bacterial gene expression in response to environmental and metabolic stress

EDUCATION:

1968   B.A., Microbiology, University of California, Riverside
1976   Ph.D., Microbiology, University of California, Davis

POSITIONS HELD:

Postdoctoral Associate, Department of Biology, Georgia State University, Atlanta, 1976-78
Postdoctoral Fellow, Department of Microbiology, UC Berkeley, Berkeley, California, 1978-81
Postdoctoral Fellow, Department of Biochemistry, UC Davis, Davis, California, 1981-84
Professor and Food Microbiologist, Department of Food Science and Technology, UC Davis, Davis, California, 1984 - present

RESEARCH OBJECTIVES - LAY TERMS

My research addresses two areas of broad importance to Food Science: (i) the mechanisms regulating bacterial gene expression in response to environmental stress, and (ii) basic mechanisms of transcriptional control. We study the interface between signal transduction systems and the RNA polymerase enzyme of the Gram positive, spore-forming bacterium Bacillus subtilis. In bacteria, alterations of gene expression in response to environmental change are often controlled by the association of alternative sigma factors with the catalytic core of RNA polymerase, thus re-programming the promoter recognition specificity of the enzyme to turn on new sets of genes. We have found that sigma-B from Bacillus subtilis mediates a general stress response in both the logarithmic and stationary growth phases. Stationary phase metabolism is an important but poorly understood aspect of bacterial physiology; Bacilli produce the bulk of the world food supply of food-grade enzymes, and these enzymes are all products of stationary phase metabolism. Furthermore, stationary phase gene regulation in Bacillus subtilis has much in common with regulation in other bacteria that are important for human health and welfare, including Gram positive food pathogens such as Clostridia, Staphylococci and other Bacilli.

RESEARCH OBJECTIVES - FOR PEERS

Our experimental focus is the role of RNA polymerase in controlling stationary phase gene expression in the Gram positive, spore-forming bacterium Bacillus subtilis. This analysis will contribute to understanding the functions, interactions, and regulation of the transcriptional machinery of a model developmental system, including the RNA polymerase catalytic core, the sigma factors that determine promoter recognition, and interacting accessory factors. Bacillus subtilis cells manifest diverse responses in stationary phase, including expression of genes important for transition to the non-growing state, initiation of the sporulation process, development of genetic competence , and production of extracellular enzymes and antibiotics. Alternative sigma factors have a central role in coordinating these events. Thus it is important to understand the molecular mechanisms that regulate sigma factor activity and interaction with the RNA polymerase core enzyme. Our primary goal is to investigate the physiological role and regulation of sigma-B, an alternative sigma factor implicated in stress response. A combined biochemical and genetic approach addresses the following questions: (1) What genes are controlled by sigma-B; (2) What are the molecular mechanisms controlling sigma-B activity in response to stress signals; (3) How do sigma-B and other dispensable sigma factors interact with the RNA polymerase core? Specific aspects of this research will be directly relevant to understanding stationary phase and stress-induced regulation in a broad range of bacteria, including antibiotic biosynthesis by Streptomyces species and the production of virulence factors by bacterial pathogens.

RECENT SIGNIFICANT FINDINGS/ACCOMPLISHMENTS

• a) Discovery of a key regulatory factor in Bacillus subtilis that activates a new set of genes in response to environmental stress
• b) Biochemical and genetic characterization of a signal transduction pathway that senses and integrates multiple environmental and metabolic signals
• c) Isolation and characterization of genes for the alpha, beta, and betaÕ core subunits of Bacillus subtilis RNA polymerase

SELECTED PUBLICATIONS:

• Transcription factor sB of Bacillus subtilis controls a large stationary phase regulon. S.A. Boylan, A.R. Redfield and C.W. Price. 1993. Journal of Bacteriology 175:3957-3963.
• Stress-induced activation of the sB transcription factor of Bacillus subtilis. S.A. Boylan, A.R. Redfield, M.S. Brody and C.W. Price. 1993. Journal Bacteriology 175:7931-7937.
• Four additional genes in the sigB operon of Bacillus subtilis that control activity of the general stress factor sB in response to environmental signals. A.A. Wise and C.W. Price. 1995. Journal of Bacteriology 177:123-133.
• Genetic and transcriptional organization of the region encoding the b subunit of Bacillus subtilis RNA polymerase. K.J. Boor, M.L. Duncan and C.W. Price. 1995. Journal of Biological Chemistry 270:20329-20336.
• Streptolydigin resistance can be conferred by alterations to either the b or bÕ subunits of Bacillus subtilis RNA polymerase. X. Yang and C.W. Price. 1995. Journal of Biological Chemistry 270:23930-23933.
• Genetic and transcriptional organization of the Bacillus subtilis spc-a region. J.-W. Suh, S.A. Boylan., S.-H. Oh and C.W. Price. 1996. Gene 169:17-23.
• Bacillus subtilis operon under the dual control of the general stress transcription factor sB and the sporulation transcription factor sH. D. Var—n, M.S. Brody and C.W. Price. 1996. Molecular Microbiology 20:339-350.
• Homologous pairs of regulatory proteins control activity of Bacillus subtilis transcription factor sB in response to environmental stress. C.M. Kang, M.S. Brody, S. Akbar, X. Yang and C.W. Price. 1996. Journal of Bacteriology 178:3846-3853.
• Opposing pairs of serine protein kinases and phosphatases transmit signals of environmental stress to activate a bacterial transcription factor. X. Yang, C.M. Kang, M.S. Brody and C.W. Price. 1996. Genes and Development 10:2265-2275.
• Modulator protein RsbR regulates environmental signaling in the general stress pathway of Bacillus subtilis. S. Akbar, C.M. Kang, T.A. Gaidenko and C.W. Price. 1997. Molecular Microbiology 24:567-578.
• Bacillus licheniformis sigB operon encoding the general stress transcription factor sB. M.S. Brody and C.W. Price. 1998. Gene 212:111-118.
• Serine kinase activity of a Bacillus subtilis switch protein is required to transduce environmental stress signals but not to activate its target PP2C phosphatase. C.M. Kang, K. Vijay and C.W. Price. 1998. Molecular Microbiology 30:189-196.
• Threonine phosphorylation of modulator protein RsbR governs its ability to regulate a serine kinase in the environmental stress signaling pathway of Bacillus subtilis. T.A. Gaidenko, X. Yang, Y.M. Lee and C.W. Price. 1999. Journal of Molecular Biology 288:29-39.
• Two genes from Bacillus subtilis under the sole control of the general stress transcription factor sB. S. Akbar, S.Y. Lee, S.A. Boylan and C.W. Price. 1999. Microbiology 145:1069-1078. A PP2C phosphatase containing a PAS domain is required to convey signals of energy stress to the sB transcription factor of Bacillus subtilis. K. Vijay, M.S. Brody, E. Fredlund and C.W. Price. 2000. Molecular Microbiology 35:180-188.
• Protective function and regulation of the general stress response in Bacillus subtilis and related Gram positive bacteria. C.W. Price. 2000. IN: G. Storz and R. Hengge-Aronis (eds). Bacterial Stress Responses, American Society for Microbiology, Washington, D.C., pp.179-198.