title: Synchronous long-term oscillations in a synthetic gene circuit.
abstract: Synthetically engineered genetic circuits can perform a wide variety of tasks but are generally less accurate than natural systems. Here we revisit the first synthetic genetic oscillator, the repressilator, and modify it using principles from stochastic chemistry in single cells. Specifically, we sought to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. We show that this modification created highly regular and robust oscillations. Furthermore, some streamlined circuits kept 14 generation periods over a range of growth conditions and kept phase for hundreds of generations in single cells, allowing cells in flasks and colonies to oscillate synchronously without any coupling between them. Our results suggest that even the simplest synthetic genetic networks can achieve a precision that rivals natural systems, and emphasize the importance of noise analyses for circuit design in synthetic biology.
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.|Biophysics Program, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Laurent
authors.initials: L
authors.lastname: Potvin-Trottier
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.|Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Lord
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, UK.
authors.forename: Glenn
authors.initials: G
authors.lastname: Vinnicombe
authors.affiliation: Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Johan
authors.initials: J
authors.lastname: Paulsson
mesh_terms: D001683:Biological Clocks / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000235:genetics*; D005813:Genes, Synthetic / Q000235:genetics*; D005818:Genetic Engineering; D008957:Models, Genetic; D012107:Research Design; D058615:Synthetic Biology / Q000379:methods*