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Architecture and inherent robustness of a bacterial cell-cycle control system.

Publication ,  Journal Article
Shen, X; Collier, J; Dill, D; Shapiro, L; Horowitz, M; McAdams, HH
Published in: Proc Natl Acad Sci U S A
August 12, 2008

A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 12, 2008

Volume

105

Issue

32

Start / End Page

11340 / 11345

Location

United States

Related Subject Headings

  • RNA, Messenger
  • RNA, Bacterial
  • Promoter Regions, Genetic
  • Models, Biological
  • DNA, Bacterial
  • DNA Replication
  • DNA Methylation
  • Chromosomes, Bacterial
  • Cell Cycle
  • Caulobacter crescentus
 

Citation

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Shen, X., Collier, J., Dill, D., Shapiro, L., Horowitz, M., & McAdams, H. H. (2008). Architecture and inherent robustness of a bacterial cell-cycle control system. Proc Natl Acad Sci U S A, 105(32), 11340–11345. https://doi.org/10.1073/pnas.0805258105
Shen, Xiling, Justine Collier, David Dill, Lucy Shapiro, Mark Horowitz, and Harley H. McAdams. “Architecture and inherent robustness of a bacterial cell-cycle control system.Proc Natl Acad Sci U S A 105, no. 32 (August 12, 2008): 11340–45. https://doi.org/10.1073/pnas.0805258105.
Shen X, Collier J, Dill D, Shapiro L, Horowitz M, McAdams HH. Architecture and inherent robustness of a bacterial cell-cycle control system. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11340–5.
Shen, Xiling, et al. “Architecture and inherent robustness of a bacterial cell-cycle control system.Proc Natl Acad Sci U S A, vol. 105, no. 32, Aug. 2008, pp. 11340–45. Pubmed, doi:10.1073/pnas.0805258105.
Shen X, Collier J, Dill D, Shapiro L, Horowitz M, McAdams HH. Architecture and inherent robustness of a bacterial cell-cycle control system. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11340–11345.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

August 12, 2008

Volume

105

Issue

32

Start / End Page

11340 / 11345

Location

United States

Related Subject Headings

  • RNA, Messenger
  • RNA, Bacterial
  • Promoter Regions, Genetic
  • Models, Biological
  • DNA, Bacterial
  • DNA Replication
  • DNA Methylation
  • Chromosomes, Bacterial
  • Cell Cycle
  • Caulobacter crescentus