PerspectiveCell Signaling

Concentrating (on) Native Proteins to Control Cell Fate

Science  20 Sep 2013:
Vol. 341, Issue 6152, pp. 1349-1351
DOI: 10.1126/science.1243994

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Synthetic biology has ambitious goals—to engineer and repurpose cells for applications ranging from medicine to energy (1, 2). Such achievements require robust designs for programming cell behavior. Signaling pathways within cells integrate information from the environment to drive specific gene expression programs, so from an engineering perspective, these pathways represent prime interventional targets for harnessing control of cellular decision-making (3). The output of a signaling pathway ultimately depends on the dynamics of its constituents, which, in turn, are determined by their concentrations and interactions. Given that these properties are hard-wired into the genome of the organism, how might cell fate be artificially regulated without manipulating the host's DNA? On page 1358 of this issue, Galloway et al. (4) demonstrate that this can be accomplished by introducing synthetic genetic controllers into the host to modulate the activity of a native signaling pathway. Cell fate “rerouting” in yeast was accomplished by using these genetic controllers to conditionally increase the concentrations of key endogenous proteins in a mitogen-activated protein kinase (MAPK) pathway, thereby reshaping the signaling dynamics and cellular response without introducing new proteins into the network.