School of Mechanical, Aerospace and Automotive Engineering, Coventry University, Coventry, CV1 5FB, UK.
School of Engineering, University of Warwick, Coventry, CV4 7AL, UK.
NPJ Syst Biol Appl. 2022 Feb 15;8(1):7. doi: 10.1038/s41540-022-00216-x.
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.
生物钟系统是生物体内部的生物钟，负责协调生物过程以适应昼夜和季节变化。生物钟系统的干扰（例如，病原体攻击、环境突然变化）通常会导致病理生理反应（例如，人类的时差反应、植物生长迟缓等）。鉴于此，合成生物学家正在逐步采用利用合成反馈控制电路来减轻干扰对生物钟系统的影响的想法。为了便于设计这种控制器，需要合适的模型。在这里，我们扩展了我们最近开发的植物生物钟模型——扩展 S 系统模型——以对不同生命领域的生物钟系统进行建模。然后，我们使用这种建模策略，基于对偶积分反馈（AIF）控制器，开发了一种设计框架，当基因因外部干扰而失去功能时，该框架可以恢复其生物钟特征。使用 AIF 控制器的动机是其最近的成功实验实现。我们的研究结果为生物钟生物学家提供了一种系统和通用的建模和设计方法，用于实现生物钟系统的合成反馈控制。
