An Extended Design Framework of Antithetic Integral Feedback Controller for Restoring Disrupted Circadian Gene Profiles

Since its conceptual inception, the antithetic integral feedback (AIF) controller has attracted the attentions of synthetic biologists to implement it as part of their biomolecular synthetic circuitries design. The successful implementation of the AIF controller in the laboratory is the culmination of realising an integral control in synthetic biology. To facilitate the optimal design of the AIF controller, models describing the biological system of interest is often required. With copious model structures available describing the same biological system, this raises the question on whether the design of AIF controller is model structure dependent. Using the circadian system as our case study, we extend our previous design criteria of AIF controller for linear and S-System model structures to accommodate Michaelis-Menten/Hill function model structure. Our findings show that the design framework of the AIF controller is applicable to Michaelis-Menten/Hill function model structure with some modifications, thereby allowing control designers to work with any model structure of interest in optimising the design of the AIF controller parameters.