Biomolecular Control Circuit With Inherent Bi-Stability Is Applicable for Automatic Detection of Gut Infection

Previously a variety of engineered biological circuits to control cell population have been developed. One possible implementation uses paradoxical feedback, where population control is achieved by using the same quorum sensing signal, produced and sensed by the cell population, to provide both positive (cell proliferation) and negative (cell death) feedback. Here, we extend the paradoxical feedback population control circuit with the addition of a detector to manipulate the activation of the circuit via modulation of an external signal. The detector design utilizes the inherent bi-stability within paradoxical feedback control to switch the cell population dynamics between two equilibrium states via an external signal. Through simulation, we first demonstrate that the bi-stability of the paradoxical feedback controller remains unaffected after the introduction of the detector. Also, the modified detector-population controller can automatically detect and respond to the external signal. We then show how the modified circuit can trigger the total elimination of the cell population using an additional external signal. Finally, we propose a solution for disturbance rejection by adjusting the concentration of a certain gene. Although the detector-population controller is used in the context of gut infection detection, it follows generalizable principles that can be used in various contexts.