Abstract
Synthetic genetic circuits allow us to modify the behavior of living cells. However, changes in environmental conditions and unforeseen interactions between a circuit and the host cell can cause deviations from a desired function, resulting in the need for time-consuming physical re-assembly to fix these issues. Here, we use a regulatory motif controlling transcription and translation to create genetic devices whose response functions can be dynamically tuned. This approach allows us, after assembly, to shift the on and off states of a sensor by 4.5- and 28-fold, respectively, and modify a genetic NOT gate to allow its transition from an on to off state to be varied over a 7-fold range. In both cases, “tuning” leads to trade-offs in the fold-change and separation between the distributions of cells in on and off states. By using mathematical modelling, we derive design principles that are used to further optimize these devices. This work lays the foundation for adaptive genetic circuits that can be tuned after their physical assembly to maintain functionality across diverse environments and design contexts.