Editors' ChoiceBioengineering

Toward Synthetic Biology

Sci. Signal.  24 Sep 2013:
Vol. 6, Issue 294, pp. ec228
DOI: 10.1126/scisignal.2004745

The detection of an appropriate point to intervene in a cellular pathway and minimize off-target effects on other cellular processes presents problems for the design of circuits that control cellular signaling pathways and thus direct cell function. Galloway et al. (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 the control circuits were enhanced 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.

K. E. Galloway, E. Franco, C. D. Smolke, Dynamically reshaping signaling networks to program cell fate via genetic controllers. Science 341, 1235005 (2013).[Abstract][Full Text]

C. A. Sarkar, Concentrating (on) native proteins to control cell fate. Science 341, 1349–1351 (2013).[Abstract][Full Text]