• Primary Faculty Profiles
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• Crane, John, M.D., Ph.D., Assistant Professor
• Genco, Robert, Ph.D., Distinguished Professor
• Gill, Steven, Ph.D.
• Knight, Paul, M.D. and Ph.D., Professor
• Lesse, Alan, Ph.D., Professor
• Murphy, Timothy, Ph.D., Professor
• O'Brian, Mark, Ph.D., Professor
• Rittenhouse-Olson, Kate, Ph.D., Associate Professor
• Russo, Thomas, Ph.D., Assistant Professor
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Faculty and Research

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Research Interests:

Regulation of heme metabolism, iron homeostasis and oxidative stress

The adaptive success of bacteria depends, in part, on the ability to sense and respond to external cues at the level of gene expression. Bradyrhizobium japonicum resides as a free-living soil bacterium or as the endosymbiont of soybean with root nodules. In addition to its agricultural significance, B. japonicum also serves as a model to study bacteria-eukaryote interactions more generally, including related pathogens that are refractive to genetic and biochemical study.

We are interested in the regulation of heme metabolism and its integration with iron homeostasis in B. japonicum. Hemes are needed for many cellular processes, and we have shown that heme plays important regulatory roles in cells. We are interested in the molecular basis of this novel regulatory mechanism. We identified the iron response regulator (Irr) protein as a regulator that couples heme biosynthesis with global iron metabolism. Irr responds to the iron through the status of heme to positively and negatively control the expression of genes within the Irr regulon.

Control of metal homeostasis is integrated with oxidative stress responses in cells. We have initiated a new project to characterize how manganese contributes to the oxidative stress response in B. japonicum, and the roles of Irr and other metalloregulatory proteins in this process.

Relevant references:

Yang, J., I. Sangwan, A. Lindemann, F. Hauser, H. Hennecke, H.-M. Fischer, and M.R. O’Brian. 2006. Bradyrhizobium japonicum senses iron through the status of heme to regulate iron homeostasis and metabolism.  Mol. Microbiol. 60: 427-437.

Puri, S. and M.R. O’Brian. 2006. The hmuQ and hmuD genes from Bradyrhizobium  japonicum encode heme-degrading enzymes. J. Bacteriol. 188: 6476-6482.

Yang, J., I. Sangwan, and M.R. O’Brian. 2006. The Bradyrhizobium japonicum Fur protein is an iron-responsive regulator in vivo. Mol. Gen. Genomics  276: 555-564.

 Gao, T. and M.R. O’Brian. 2007. Control of DegP-dependent degradation of c-type cytochromes by heme and the cytochrome c maturation system in Escherichia coli. J. Bacteriol.  189: 6253-6259.

Sangwan, I., S.K. Small and M.R. O’Brian. 2008. The Bradyrhizobium japonicum Irr protein is a transcriptional repressor with high affinity DNA binding activity. J. Bacteriol. 190: 5172-5177.

Small, S.K., S. Puri, I. Sangwan and M.R. O’Brian. 2009. Positive control of ferric siderophore receptor gene expression by the Irr protein in Bradyrhizobium japonicum. J. Bacteriol. 191: 1361-1368.

Hohle, T.H. and M.R. O’Brian. 2009. The mntH gene encodes the major Mn2+ transporter in Bradyrhizobium japonicum and is regulated by manganese via the Fur protein. Mol. Microbiol. In press.