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A Practicable Method of Tuning the Noise Intensity at Protein Level.

Shih-Chiang Lo1, Chao-Xuan You1, Che-Chi Shu1

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Summary

Gene expression noise can be tuned using transcriptional delay in incoherent feedforward loops (FFLs). This method modulates noise intensity without altering steady-state behaviors, offering applications in synthetic biology.

Keywords:
attenuate stochastic fluctuationscontrol random gene regulationmanipulate stochasticitynoise buffering

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Area of Science:

  • Systems Biology
  • Synthetic Biology
  • Biophysics

Background:

  • Gene expression is inherently noisy, impacting cellular functions.
  • Controlling intracellular noise is crucial for many biological processes and synthetic systems.
  • Transcriptional delay is a key parameter in gene regulatory networks.

Purpose of the Study:

  • To investigate the role of transcriptional delay in modulating intracellular noise within an incoherent feedforward loop (FFL).
  • To demonstrate a method for tuning noise intensity without affecting deterministic steady-state behaviors.

Main Methods:

  • Utilized an incoherent feedforward loop (FFL) model.
  • Analyzed the coefficient of variation (COV) of target protein expression.
  • Incorporated experimentally observed distributions of transcriptional delay into simulations.
  • Employed the delay stochastic simulation algorithm.

Main Results:

  • Transcriptional delay in FFLs effectively modulates target protein noise intensity.
  • COV showed a near-linear relationship with transcriptional delay over a specific range.
  • Incoherent FFL reduced COV from 0.455 to 0.236, tunable up to 0.779 with delay.
  • Distributed delay slightly enhanced noise-tuning capabilities.

Conclusions:

  • A novel method for tuning intracellular noise intensity via transcriptional delay in FFLs was demonstrated.
  • This noise-tuning approach preserves deterministic steady-state behaviors.
  • The method is applicable to diverse synthetic biology systems.