(27bg) Feedforward Loop-Based Antithetic Controller for Improved Adaptation Dynamics

Synthetic biologists thrive to design genetic circuits for robust regulation of target gene expression, such as oscillator, pulse generator, and the recently proposed antithetic controller for disturbance rejection and adaptation. Since its advent, antithetic controller has been pursued both theoretically and experimentally, and have demonstrated the capability of endowing adaptation to environmental disturbance. However, limitations with the antithetic controller such as the oscillatory transient dynamics have also started to attract efforts for improvement. Here we present a new antithetic controller which leverages feedforward loops to mitigate adaptation error and to improve transient dynamics. We demonstrate in simulation with biologically relevant kinetic parameters that incorporating either an incoherent or coherent feedforward loop can reduce oscillatory behavior with improved adaptation accuracy, as compared to the base antithetic controller. We anticipate findings from our work to guide future design of synthetic biological controllers, particularly in making use of native biological motifs for improved performance.