Bacterial cells are pretty small.  In fact, a typical bacterium is about 10,000X smaller than an aspirin.  Despite this "smallness" bacteria are genetically wired to make dynamic, sophisticated developmental decisions that regulate cellular processes in both time and space. 

 

Like eukaryotes, prokaryotes can form different cell types.  For example, Bacillus subtilis can differentiate from chained cells to swimming cells, form a quiescent spore, or enter a competent state. We are interested in understanding the molecular basis leading to these different cell fates. In particular, we want to understand how bacteria integrate and manipulate environmental/nutrient signals to elicit the metabolic changes we think drive cell cycle and development. 

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To grow, divide, and differentiate, cells must localize macromolecules to specific cellular locations, often in dynamic & temporally regulated ways. We investigate the functional consequences of this spatial organization with the ultimate goal of discovering the primary determinants driving it. In bacteria, many molecules appear to localize through diffusion-capture mechanisms and exhibit patterns of localization (especially polar and punctate-helical) that suggest cells have an underlying architecture. We would like to understand how this architecture is established, maintained, and/or rearranged.  Many of our studies focus on the synthesis, organization, and interplay between the two largest “structures” in bacteria:  the cell envelope and the nucleoid.

     

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 (yes pun) the organization & architecture of the cell.

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Duan, Y., A.M. Sperber, and J.K. Herman (2016) YodL and YisK possess shape-modifying activities that are suppressed by mutations in Bacillus subtilis mreB and mbl. PMID: 27215790.

 

Wagner-Herman, J.K., R. Bernard, R. Dunne, A.W. Bisson-Filho, K. Kumar, T. Nyguen, L. Mulcahy, J. Koullias, F.J. Gueiros-Filho, and D.Z. Rudner. (2012) RefZ facilitates the switch from medial to polar division during spore formation in Bacillus subtilis. PMID: 22730127.

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Wagner, J.K. , K. A. Marquis, and D. Z. Rudner (2009). SirA enforces diploidy by inhibiting the replication initiator DnaA during spore formation in Bacillus subtilis. PMID: 19682252.

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 these key intracellular molecules influence developmental outcomes.

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Ababneh, Q.A. and J.K. Herman. (2015) CodY regulates SigD levels and activity by binding to three sites in the fla/che operon. PMID: 26170408.

Ababneh, Q.A. and J.K. Herman. (2015) RelA Inhibits Bacillus subtilis motility and chaining. PMID: 25331430.

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Extracellular Signaling.

In a separate project related to signaling and development, we discovered a peptide-like extracellular signaling molecule (FacX) accumulating in the post-exponential phase that promotes efficient entry of B. subtilis into the developmental program of sporulation. FacX acts like a quorum-sensing molecule, distinct from Phr peptides and ComX, that coordinates environmental quality status with the developmental decision to sporulate. This finding is significant because it suggests that both sufficient Spo0A-P & at least one other extracellular signal are required for efficient initiation of sporulation.

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Ababneh, Q.A. and J.K. Herman. (2015) A secreted factor coordinates environmental quality with Bacillus development.  PMID: 26657919.

Miller, A.K. and J.K. Herman (2022) RefZ and Noc act synthetically to prevent aberrant divisions during Bacillus subtilis sporulation. PMID: 35506695.

 

Brown, E.E., A.K. Miller, I.V. Krieger, R.M. Otto, J.C. Sacchettini, and J.K. Herman (2019) A DNA-binding protein tunes septum placement during Bacillus subtilis sporulation. PMID: 27489185.

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Miller, A.K., E.E. Brown, B.T. Mercado, and J.K. Herman. (2016) A DNA-binding protein defines the precise region of chromosome capture during Bacillus sporulation. PMID: 26360512.

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Duan, Y., J.D. Huey, and J.K. Herman (2016) The DnaA inhibitor SirA acts in the same pathway as Soj (ParA) to facilitate oriC segregation during Bacillus subtilis sporulation. PMID: 27489185.

Guo, T. and J.K. Herman (2022) Magnesium modulates Bacillus subtilis cell division frequency. PMID: 36515540.

Discussed on ASM's "This Week in Microbiology" (beginning 5:00)

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Sperber, A.M. and J.K. Herman (2017) Metabolism shapes the cell. PMID: 28320879.