Bacterial cells are pretty small. In fact, a typical bacterium is ~5,000 times smaller than an aspirin. Despite this smallness, bacteria are genetically wired to carry out dynamic, sophisticated programs that regulate cellular processes in both time and space. Although bacteria lack the extensive subcellular membrane compartmentalization of their eukaryotic counterparts, they serve as excellent simplified models to address fundamental questions in cell biology such as: how is positional information "encoded" across the landscape of a cell? What drives the cell cycle? What determines cell size? What signals lead to cellular differentiation? How do cell's integrate changing nutrient status/environment with the the rest of physiology to maintain homeostasis?

 

To address these questions (and others), we use the model organism Bacillus subtilis, a bacterium with superb molecular, genetic, and cell biological tools that conveniently differentiates into multiple cell types.

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You can read more about B. subtilis here and here.

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Below are topics we have published on.

We seek to understand how cells integrate and manipulate environmental/nutrient signals to elicit the metabolic changes we think drive cell cycle and development. 

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Guo, T., A.M. Sperber, I.V. Krieger, Y. Duan, V.R. Chemelewski, J.C. Sacchettini, and J.K. Herman (2023) Bacillus subtilis YisK possesses oxaloacetate decarboxylase activity and exhibits Mbl-dependent localization. PMID: 38047707 ("Editor's pick")

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Guo, T. and J.K. Herman (2023) 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.

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 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 rearranged.

 

Many of our studies have focused on the synthesis, organization, and interplay between the two largest “structures” in bacteria:  the cell envelope and the nucleoid. 

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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.

Like eukaryotes, bacteria can form multiple cell types. For example, B. subtilis can differentiate from chained cells into swimming cells or form a quiescent spore. We want to understand the signals and molecular changes driving cell fates. 

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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 and is regulated by increased expression & activity of an alternative sigma factor, SigD. We discovered that SigD levels & activity are modulated 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) that accumulates 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, but is distinct from Phr peptides and ComX. This finding is significant because it suggests that both sufficient Spo0A-P & at least one other condition 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.

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 spawned several exciting projects that lead us to begin investigating the role of metabolism in shaping (yes pun) the organization & architecture of the cell, and in driving cell fate.

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Guo, T., A.M. Sperber, I.V. Krieger, Y. Duan, V.R. Chemelewski, J.C. Sacchettini, and J.K. Herman (2023) Bacillus subtilis YisK possesses oxaloacetate decarboxylase activity and exhibits Mbl-dependent localization. PMID: 38047707 ("Editor's pick")

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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.