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Rock-paper-scissors: Engineered population dynamics increase genetic stability.

ABSTRACT: Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most applications is the presence of selective pressures that lead to high mutation rates for engineered bacteria. A common strategy is to develop cloning technologies aimed at increasing the fixation time for deleterious mutations in single cells. We adopt a complementary approach that is guided by ecological interactions, whereby cyclical population control is engineered to stabilize the functionality of intracellular gene circuits. Three strains of Escherichia coli were designed such that each strain could kill or be killed by one of the other two strains. The resulting "rock-paper-scissors" dynamic demonstrates rapid cycling of strains in microfluidic devices and leads to an increase in the stability of gene circuit functionality in cell culture.

SUBMITTER: Liao MJ

PROVIDER: S-EPMC6988775 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Rock-paper-scissors: Engineered population dynamics increase genetic stability.

Liao Michael J MJ Din M Omar MO Tsimring Lev L Hasty Jeff J

Science (New York, N.Y.) 20190901 6457

Advances in synthetic biology have led to an arsenal of proof-of-principle bacterial circuits that can be leveraged for applications ranging from therapeutics to bioproduction. A unifying challenge for most applications is the presence of selective pressures that lead to high mutation rates for engineered bacteria. A common strategy is to develop cloning technologies aimed at increasing the fixation time for deleterious mutations in single cells. We adopt a complementary approach that is guided ...[more]

PMID: 31488693

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