Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise

PLoS One. 2013 Apr 26;8(4):e62380. doi: 10.1371/journal.pone.0062380. Print 2013.

Abstract

Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / genetics*
  • Chromosomes, Bacterial / genetics
  • Computer Simulation*
  • Escherichia coli / cytology
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development*
  • Feedback, Physiological
  • Gene Dosage
  • Gene Expression Regulation, Bacterial*
  • Genes, Bacterial / genetics
  • Software
  • Time Factors

Grants and funding

This work was supported by the European Research Council (ERC); the National Natural Science Foundation of China (31171275 and 31171257); and Ministry of Science and Technology of China Grants (2009CB825607 and 2011CB910202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.