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SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC4597888 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

Chen Ye Y Kim Jae Kyoung JK Hirning Andrew J AJ Josić Krešimir K Bennett Matthew R MR

Science (New York, N.Y.) 20150801 6251

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 spa ...[more]

PMID: 26315440

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Project description:The metabolic capabilities of microbes are the basis for many major biotechnological advances, exploiting microbial diversity by selection or engineering of single strains. However, there are limits to the advances that can be achieved with single strains, and attention has turned toward the metabolic potential of consortia and the field of synthetic ecology. The main challenge for the synthetic ecology is that consortia are frequently unstable, largely because evolution by constituent members affects their interactions, which are the basis of collective metabolic functionality. Current practices in modeling consortia largely consider interactions as fixed circuits of chemical reactions, which greatly increases their tractability. This simplification comes at the cost of essential biological realism, stripping out the ecological context in which the metabolic actions occur and the potential for evolutionary change. In other words, evolutionary stability is not engineered into the system. This realization highlights the necessity to better identify the key components that influence the stable coexistence of microorganisms. Inclusion of ecological and evolutionary principles, in addition to biophysical variables and stoichiometric modeling of metabolism, is critical for microbial consortia design. This review aims to bring ecological and evolutionary concepts to the discussion on the stability of microbial consortia. In particular, we focus on the combined effect of spatial structure (connectivity of molecules and cells within the system) and ecological interactions (reciprocal and non-reciprocal) on the persistence of microbial consortia. We discuss exemplary cases to illustrate these ideas from published studies in evolutionary biology and biotechnology. We conclude by making clear the relevance of incorporating evolutionary and ecological principles to the design of microbial consortia, as a way of achieving evolutionarily stable and sustainable systems.

Dataset Information

SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

Publications

SYNTHETIC BIOLOGY. Emergent genetic oscillations in a synthetic microbial consortium.

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