Spartalis Thales R, Foo Mathias, Tang Xun
Cain Department of Chemical Engineering, Louisiana State University, Baton Rouge, LA 70803, USA.
School of Engineering, University of Warwick, Coventry CV4 7AL, UK.
J R Soc Interface. 2025 Jan;22(222):20240467. doi: 10.1098/rsif.2024.0467. Epub 2025 Jan 22.
Integral controller is widely used in industry for its capability of endowing perfect adaptation to disturbances. To harness such capability for precise gene expression regulation, synthetic biologists have endeavoured in building biomolecular (quasi-)integral controllers, such as the antithetic integral controller. Despite demonstrated successes, challenges remain with designing the controller for improved transient dynamics and adaptation. Here, we explore and investigate the design principles of alternative RNA-based biological controllers, by modifying an antithetic integral controller with prevalently found natural feed-forward loops (FFL), to improve its transient dynamics and adaptation performance. With model-based analysis, we demonstrate that while the base antithetic controller shows excellent responsiveness and adaptation to system disturbances, incorporating the type-1 incoherent FFL into the base antithetic controller could attenuate the transient dynamics caused by changes in the stimuli, especially in mitigating the undesired overshoot in the output gene expression. Further analysis on the kinetic parameters reveals similar findings to previous studies that the degradation and transcription rates of the circuit RNA species would dominate in shaping the performance of the controllers.
积分控制器因其能够完美适应干扰而在工业中得到广泛应用。为了将这种能力用于精确的基因表达调控，合成生物学家致力于构建生物分子（准）积分控制器，例如对偶积分控制器。尽管已取得了显著成功，但在设计控制器以改善瞬态动力学和适应性方面仍存在挑战。在此，我们通过用普遍存在的天然前馈回路（FFL）修改对偶积分控制器，来探索和研究基于RNA的替代生物控制器的设计原则，以改善其瞬态动力学和适应性性能。通过基于模型的分析，我们证明，虽然基本对偶控制器对系统干扰表现出出色的响应能力和适应性，但将1型非相干FFL纳入基本对偶控制器可以减弱由刺激变化引起的瞬态动力学，特别是在减轻输出基因表达中不期望的过冲方面。对动力学参数的进一步分析揭示了与先前研究相似的结果，即电路RNA种类的降解和转录速率在塑造控制器性能方面起主导作用。
