The circadian system—an organism’s built-in biological clock—is responsible for orchestrating biological processes to adapt to diurnal and seasonal variations. Perturbations to the circadian system (e.g., pathogen attack, sudden environmental change) often result in pathophysiological responses (e.g., jetlag in humans, stunted growth in plants, etc.) In view of this, synthetic biologists are progressively adapting the idea of employing synthetic feedback control circuits to alleviate the effects of perturbations on circadian systems. To facilitate the design of such controllers, suitable models are required. Here, we extend our recently developed model for the plant circadian clock—termed the extended S-System model—to model circadian systems across different kingdoms of life. We then use this modeling strategy to develop a design framework, based on an antithetic integral feedback (AIF) controller, to restore a gene’s circadian profile when it is subject to loss-of-function due to external perturbations. The use of the AIF controller is motivated by its recent successful experimental implementation. Our findings provide circadian biologists with a systematic and general modeling and design approach for implementing synthetic feedback control of circadian systems.
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FunderM.F. gratefully acknowledges the financial support of The Royal Society via research grant RGS/R2/180195. D.G.B. gratefully acknowledges the financial support of the EPSRC and BBSRC via research grants BB/M017982/1 to WISB and from the School of Engineering of the University of Warwick. O.E.A. wishes to acknowledge the financial support of the EPSRC (research grant EP/N017846/1). The authors would also like to thank Dr. Hafiz Ahmed from Nuclear Futures Institute, Bangor University for useful discussions on dynamical modeling.
- control theory
- Synthetic biology
ASJC Scopus subject areas
- Modelling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Drug Discovery
- Computer Science Applications
- Applied Mathematics