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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
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Restoring circadian gene profiles in clock networks using synthetic feedback control
Mathias Foo1,2, Ozgur E Akman3, Declan G Bates4
1School of Mechanical, Aerospace and Automotive Engineering, Coventry University, Coventry, CV1 5FB, UK.
NPJ Systems Biology and Applications
|February 16, 2022
Summary
Synthetic biologists can now restore disrupted biological clocks using a new modeling approach. This method employs synthetic feedback control circuits to fix gene function loss caused by external disturbances.
Area of Science:
- Systems Biology
- Synthetic Biology
- Chronobiology
Background:
- The circadian system, or biological clock, regulates daily biological processes and adapts organisms to environmental changes.
- Perturbations to the circadian system can cause various pathophysiological responses across different species.
- Synthetic biology offers potential solutions for mitigating circadian system disruptions using feedback control circuits.
Purpose of the Study:
- To develop a generalized modeling framework for circadian systems across diverse life forms.
- To design a synthetic feedback control strategy for restoring gene circadian profiles affected by perturbations.
- To provide a systematic approach for synthetic control of circadian systems.
Main Methods:
- Extended the existing plant circadian clock model (extended S-System model) to encompass broader biological kingdoms.
- Developed a design framework utilizing an antithetic integral feedback (AIF) controller.
- Applied the AIF controller to restore gene circadian profiles under simulated loss-of-function perturbations.
Main Results:
- Successfully modeled circadian systems beyond plants using the extended S-System approach.
- Demonstrated the efficacy of the AIF controller in restoring perturbed gene circadian profiles.
- Validated a systematic and generalizable method for synthetic control of biological clocks.
Conclusions:
- The extended S-System model provides a versatile platform for studying circadian dynamics across kingdoms.
- Antithetic integral feedback controllers offer a viable strategy for robust synthetic control of circadian rhythms.
- This research presents a significant advancement in engineering synthetic biology solutions for circadian system regulation.
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