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Modeling stochastic gene expression in growing cells.

David Gomez1, Rahul Marathe2, Veronika Bierbaum3

  • 1Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14424 Potsdam, Germany; Department of Physics, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany.

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Gene expression noise, influenced by low molecule counts and cell volume, impacts gene circuit bistability. Computational methods reveal how noise and volume changes affect gene regulation dynamics.

Keywords:
AutoregulationBistabilityCell divisionGenetic circuitsNoiseStochastic gene expressionVolume growth

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Area of Science:

  • Systems Biology
  • Computational Biology
  • Molecular Biology

Background:

  • Gene expression is a stochastic process with fluctuations at transcription, translation, and mRNA degradation.
  • These fluctuations are significant when cellular molecule numbers (mRNA, proteins) are low.
  • Regulated gene expression introduces complexity due to time-dependent protein synthesis rates influenced by transcription factors and cell volume growth.

Purpose of the Study:

  • To computationally model the effects of cell volume growth on gene expression noise.
  • To investigate how noise and cell volume impact the bistability of a gene circuit with positive autoregulation.

Main Methods:

  • Incorporating cell volume growth into simulations by stochastically adding volume elements.
  • Analyzing a gene circuit model with positive autoregulation exhibiting bistability.
  • Simulating the effects of varying noise strength (via reduced regulatory protein copy number) and cell volume.

Main Results:

  • Cell volume growth affects protein synthesis rates, making them time-dependent.
  • The region of bistability in the studied gene circuit is diminished by increased noise (lower regulatory protein copy number).
  • Cell volume plays a critical role in determining the region of bistability across different noise strengths.

Conclusions:

  • The developed computational method effectively models cell volume growth effects on gene expression noise.
  • Noise and cell volume are key determinants of gene circuit bistability, particularly in systems with low molecule counts.
  • This generalizable method can be applied to analyze other complex gene regulation scenarios where analytical solutions are challenging.