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Circuit-Host Coupling Induces Multifaceted Behavioral Modulations of a Gene Switch
Andrew E Blanchard1, Chen Liao2, Ting Lu3
1Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois; Carl Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Biophysical Journal
|February 8, 2018
Summary
Circuit-host coupling significantly impacts synthetic gene switch behavior. This interaction affects single-cell dynamics and population-level cell growth, necessitating integrated modeling for synthetic biology.
Area of Science:
- Synthetic biology
- Quantitative systems biology
- Biophysics
Background:
- Quantitative modeling is crucial for rational design in synthetic biology.
- Traditional models treat gene circuits in isolation, neglecting host interactions.
- Emerging evidence highlights the significant impact of circuit-host coupling on gene circuit function.
Purpose of the Study:
- To systematically investigate the influence of circuit-host coupling on gene circuit dynamics.
- To analyze how host interactions modulate the behavior of a self-activating gene switch.
- To establish the necessity of integrated circuit-host system modeling.
Main Methods:
- Deterministic modeling
- Stochastic simulations
- Fokker-Planck equation formalism
- Analysis of a self-activating gene switch model
Main Results:
- Circuit-host coupling alters switch dynamics at both single-cell and population levels.
- At the single-cell level, coupling slows dynamics and increases steady-state value differences.
- At the population level, differential growth amplification favors cells with lower protein production.
Conclusions:
- Circuit-host coupling introduces complex quantitative and qualitative modulations to gene switch behavior.
- The extent of these modulations depends on the circuit's architectural parameters.
- A new paradigm integrating circuit-host system modeling is essential for understanding engineered gene networks.
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