Professor and Chair
Jacobs School of Medicine & Biomedical Sciences
Gene Expression; Metabolism; Microbial Pathogenesis; Molecular and Cellular Biology
The adaptive success of bacteria depends, in part, on the ability to sense and respond to their environment. Metals such as iron and manganese are important nutrients that can often be limiting, and therefore cellular metabolism must be modified to either scavenge the nutrients or use alternative processes that do not require the metal.
Bradyrhizobium japonicum belongs to a group of related organisms that form a close or intracellular relationship with eukaryotes in a pathogenic or symbiotic context. This bacterium serves as a model to study related pathogens that are refractive to genetic and biochemical study.
Our lab seeks to understand the mechanisms by which cells maintain iron homeostasis at the level of gene expression. We discovered the global transcriptional regulator Irr that controls iron-dependent processes. Irr is stable only under iron limitation, where it positively and negatively controls target genes. We are interested in understanding the mechanism of this conditional stability, how Irr regulates genes, and the functions of numerous genes under its control. Moreover, Irr integrates iron homeostasis with manganese metabolism, providing a link between the two nutrients.
Identifying the Irr regulon and iron stimulon has given us important clues into how bacteria traffic iron into and out of the cell. Recent work suggests that B. japonicum not only adapts at the level of gene expression, but can mutate rapidly to accommodate new nutritional sources in the environment.