Programmable cells: Interfacing natural and engineered gene networks

TLDR

Novel cellular behaviors can be obtained by coupling engineered gene networks to a cell’s natural regulatory circuitry through appropriately designed input and output interfaces. The study demonstrates how an engineered genetic circuit can construct cells that respond to biological signals in a predetermined and programmable fashion. The authors use a modular design to interface a genetic toggle switch with the SOS DNA‑damage pathway and a Vibrio fischeri quorum‑sensing pathway in *E. coli*, enabling engineered cells to form biofilms upon DNA damage and to activate protein synthesis at high cell density.

Abstract

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: ( i ) the SOS signaling pathway responding to DNA damage, and ( ii ) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of “plug-and-play” genetic circuitry that can be used to create cells with programmable behaviors.