The difference between what an organism can do (genetic potential) and what it actually does (phenotype) is often regulated at the level of transcription. Our laboratory studies Bacillus subtilis, a Gram-positive soil bacterium and genetic model system. We are interested in the global patterns of transcriptional control and the mechanisms of the corresponding regulatory proteins and pathways.
Current projects include:
Antibiotic stress. Antibiotics that act on the cell envelope (including vancomycin and bacitracin) trigger global stress responses coordinated, in part, by alternative sigma subunits for RNA polymerase. Some of the genes induced by antibiotic stress play a direct role in antibiotic resistance, a growing problem among Gram positive pathogens.
Oxidative stress. Exposure of cells to reactive oxygen and nitrogen species (such as hydrogen peroxide, superoxide, and nitric oxide) induces the expression of multiple regulons coordinated by several different transcription factors. For example, we have described both PerR and OhrR as regulators that directly sense reactive oxygen species. Resistance to oxidative and nitrosative stress is important for many bacterial pathogens.
Metal ion homeostasis. To grow in the complex and varied environment of the soil, B. subtilis must be able to obtain all essential metal ions while at the same time excluding (or actively effluxing) toxic metal ions. We have described transcription factors that directly sense Fe(II), Mn(II), Zn(II), and Cu(I) and regulate the expression of the corresponding uptake and/or efflux systems.
Students in our laboratory can expect to gain experience in a wide range of techniques as applied to this model genetic system. Most research projects will include some or all of the following:
· genomics (e.g. DNA microarray analyses; computer-based approaches to defining regulons),
· classical genetics (e.g. Tn10 and random mutagenesis, transformation, transduction),
· molecular genetics (e.g. site-directed and PCR-based mutagenesis)
· biotechnology (e.g. development of new screens for antibiotics)
· biochemistry (e.g. protein purification, DNAse I footprinting, primer extension, in vitro transcription)
· structural biology (we are currently collaborating on the structure determination for several of our regulatory proteins).
John Helmann earned bachelor's degrees in Chemistry and Biology (University of California, Santa Cruz) in 1982. He then joined the Department of Biochemistry at the University of California at Berkeley where he studied bacterial RNA polymerase with Dr. Michael Chamberlin and earned a Ph.D. in 1987. From 1987 to 1990, Dr. Helmann worked as a post-doctoral fellow with Dr. Christopher T. Walsh at the Harvard Medical School. His post-doctoral research, on the regulation of bacterial mercuric ion resistance determinants, was supported by the Jane Coffin Childs Memorial Medical Research Foundation. Dr. Helmann joined the Section of Microbiology at Cornell as an Assistant Professor in 1990 and joined the graduate field of Biochemistry, Molecular, and Cell Biology in 1991. He was promoted to Associate Professor in 1996, Professor in 2002, and became Department Chair in 2010.