Agostino Guarino

Agostino Guarino, Davide Fiore, Mario di Bernardo

The synthetic toggle switch, first proposed by Gardner & Collins [1] is a MIMO control system that can be controlled by varying the concentrations of two inducer molecules, aTc and IPTG, to achieve a desired level of expression of the two genes it comprises. It has been shown [2] that this can be accomplished through an open-loop external control strategy where the two inputs are selected as mutually exclusive periodic pulse waves of appropriate amplitude and duty-cycle. In this paper, we use a recently derived average model of the genetic toggle switch subject to these inputs to synthesize new feedback control approaches that adjust the inputs duty-cycle in real-time via two different possible strategies, a model based hybrid PI-PWM approach and a so-called Zero-Average dynamics (ZAD) controller. The controllers are validated in-silico via both deterministic and stochastic simulations (SSA) illustrating the advantages and limitations of each strategy

Davide Fiore, Agostino Guarino, Mario di Bernardo

In this letter, we analyze a genetic toggle switch recently studied in the literature where the expression of two repressor proteins can be tuned by controlling two different inputs, namely the concentration of two inducer molecules in the growth medium of the cells. Specifically, we investigate the dynamics of this system when subject to pulse-width modulated (PWM) input. We provide an analytical model that captures qualitatively the experimental observations reported in the literature and approximates its asymptotic behavior. We also discuss the effect that the system parameters have on the prediction accuracy of the model. Moreover, we propose a possible external control strategy to regulate the mean value of the fluorescence of the reporter proteins when the cells are subject to such periodic forcing.