In our lab, we seek to understand how bacteria potentiate environmental fluxes into the requisite changes in physiology required for adaptation & survival. We primarily utilize the model organism Bacillus subtilis, a bacterium with superb genetic tools that can differentiate into multiple cell types.
Subcellular organization in bacteria
The study of bacterial cell biology has intensified in the last decade, driven by technological advances in live-cell imaging & the urgent need to identify new drugs to combat emerging antibiotic-resistant bacteria. As a result, we now appreciate that bacteria localize macromolecules to specific cellular locations, often in dynamic & temporally regulated ways essential to life. We investigate the functional consequences of spatially organizing cellular processes with the ultimate goal of discovering the primary determinants leading to the establishment & maintenance of the subcellular organization. Our current studies focus on the synthesis, organization, and interplay between the two largest structures in the cell: the cell envelope and the nucleoid.
Brown, E.E., A.K. Miller, I.V. Krieger, R.M. Otto, J.C. Sacchettini, and J.K. Herman. A DNA-binding protein tunes septum placement during Bacillus subtilis sporulation. J. Bacteriol. 201(16) (2019).
A. K. Miller, E. E. Brown, B. T. Mercado, J.K. Herman. A DNA-binding protein defines the precise region of chromosome capture during bacillus sporulation. Mol. Microbiol. 99 (2016).
Y. Duan, J. D. Huey, J. K. Herman. The DnaA inhibitor SirA acts in the same pathway as Soj (ParA) to facilitate oriC segregation during Bacillus subtilis sporulation. Mol. Microbiol. 102(3) (2016).
Small molecule signals
Intracellular Signaling. To survive, bacteria must continuously monitor changes in nutrient status & adjust their physiology. During rapid growth, our lab strain grows predominantly as non-motile, chained cells. The decision to switch to a single-cell, motile mode occurs during the transition between rapid growth & stationary phase, which is regulated by increased expression & activity of an alternative sigma factor, SigD. We discovered that SigD levels & activity are controlled by cellular levels of the small intracellular molecules GTP & p(ppGpp). This work is significant because it provides evidence that graded levels of key intracellular signaling molecules regulate developmental decisions (and transcriptional programs). We hypothesize that intracellular levels of one or more small molecules is also responsible for coordinating DNA replication rates, protein synthesis, transcription, & cell growth/division with cellular nutrient status.
Q. A. Ababneh and J. K. Herman. CodY regulates SigD levels and activity by binding to three sites in the fla/che operon. J. Bacteriol. 197(18) (2015).
Q. A. Ababneh and J. K. Herman. RelA inhibits Bacillus subtilis motility and chaining. J. Bacteriol. 197(18) (2015).
Extracellular Signaling. In a separate project related to signaling and development, we discovered a protein-based extracellular signaling molecule (FacX) accumulating in the post-exponential phase that promotes efficient entry of B. subtilis into the developmental program of sporulation. FacX is a novel quorum-sensing molecule (distinct from Phr peptides and ComX) that coordinates environmental quality status with the developmental decision to sporulate. Our findings are significant because they suggest that both sufficient Spo0A-P & at least one other extracellular signal are required for efficient initiation of sporulation.
Q. A. Ababneh and J. K. Herman. A secreted factor coordinates environmental quality with Bacillus development. PLoS One. 12 (2015).
Gene function discovery
To advance our mechanistic understanding of how bacterial cells encode positional information, we developed and implemented a novel pipeline to systematically identify & characterize important missing factors in cellular organization. We have identified more than 20 gene products that affect cell shape, perturb nucleoid structure or dynamics, or lead to the generation of shorter or longer cells. This branch of the lab has spawned several exciting projects & lead us to investigate the role of metabolism in “shaping” the organization & architecture of the cell.
To Academic Professional Track Faculty