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Emergent genetic oscillations in a synthetic microbial consortium

Science  28 Aug 2015:
Vol. 349, Issue 6251, pp. 986-989
DOI: 10.1126/science.aaa3794

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Engineering cell population behavior

Attaining the full promise of synthetic biology will require designing population-level behaviors of multiple interacting cell types. As a start, Chen et al. engineered two strains of the bacterium Escherichia coli to produce signaling molecules that regulate transcription in the complementary strain (see the Perspective by Teague and Weiss). The signaling circuit was successfully designed to produce feedback loops that produce synchronous oscillations in transcription between the two strains. A mathematical model helped determine how to modulate the oscillations and control their robustness to perturbations.

Science, this issue p. 986; see also p. 924

Abstract

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types—an “activator” strain and a “repressor” strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.

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