Dynamically Reshaping Signaling Networks to Program Cell Fate via Genetic Controllers

Abstract

Toward Synthetic Biology The detection of an appropriate point to intervene in a cellular pathway and minimize off-target effects on other cellular processes present problems for the design of circuits that control cellular signaling pathways and thus direct cell function. Galloway et al. (p. 1358 , published online 15 August; see the Perspective by Sarkar ) report progress on these challenges in the yeast Saccharomyces cerevisiae . A molecular control system was developed to direct the yeast cells to one of three cell fates. To avoid disruption of other cellular controls, exogenous ribozyme-based controllers that interfaced with the endogenous control circuits were used, which avoided genetic alteration to the cells. After enhancing the control circuits with feedback loops to make their behavior more reliable, the circuits were used to modulate the abundance of particular components that acted as critical regulators of yeast cell-fate decisions. This allowed direction of cell fate in response to a chosen chemical stimulus. These strategies may be adaptable to allow similar direction of the physiological state of mammalian cells, for example, to allow therapeutic applications of synthetic biology.