BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.pdfhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.pnghttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.xpphttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL1012090003?filename=MODEL1012090003.mprimaryOK200jongmin kimNon-curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/MODEL101209000321283141falseBioModelsSBMLModelsKim2011 Oscillator DetailedII2011MODEL1012090003Jongmin Kim, Erik WinfreeJongmin Kim21283141, The construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells.. null, 7. Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.jongmin@dna.caltech.educalifornia institute of technologyThe construction of synthetic biochemical circuits from simple components illuminates how complex behaviors can arise in chemistry and builds a foundation for future biological technologies. A simplified analog of genetic regulatory networks, in vitro transcriptional circuits, provides a modular platform for the systematic construction of arbitrary circuits and requires only two essential enzymes, bacteriophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In this study, we design and experimentally demonstrate three transcriptional oscillators in vitro. First, a negative feedback oscillator comprising two switches, regulated by excitatory and inhibitory RNA signals, showed up to five complete cycles. To demonstrate modularity and to explore the design space further, a positive-feedback loop was added that modulates and extends the oscillatory regime. Finally, a three-switch ring oscillator was constructed and analyzed. Mathematical modeling guided the design process, identified experimental conditions likely to yield oscillations, and explained the system's robust response to interference by short degradation products. Synthetic transcriptional oscillators could prove valuable for systematic exploration of biochemical circuit design principles and for controlling nanoscale devices and orchestrating processes within artificial cells.Synthetic in vitro transcriptional oscillators.Kim Jongmin J, Winfree Erik EOscillator Device, Oscillator.biochemical pathways, HERV-K(III) Pol protein, HERV-K10 Pol protein, Ribonucleic, Synthetic Organelle, artificial sequence, chemical properties, Ribonuclease H, experimental, Processes, Biocatalysts, bacterium E3, Organelle, Foundation, cellular catabolism, Integrase, protrusion, HERV-K115 Pol protein, IN, Escherchia coli, Gene Products, cellular degradation, HERV-K18 Pol protein, Enteroinvasive Escherichia coli, Enterococcus coli, synthetic genetic interaction (sensu inequality), HERV-K_19p13.11 provirus ancestral Pol protein, Non Polyadenylated, RNA Gene Products, RT, study, Synthetic, methods, anatomical systems, Escherichia/Shigella coli, enzymes, reference sample, HERV-K(C1a) Pol protein, HERV-K_1q23.3 provirus ancestral Pol protein, breakdown of chemical, catabolism, experimental section, stubby, synthetic genetic interaction defined by inequality, E coli, E. coli, genetic, Non-Polyadenylated RNA, Eschericia coli, Enteroaggregative Escherichia coli, Enzyme, HERV-K_11q22.1 provirus ancestral Pol protein, bacteriophage T7 induced RNA polymerase, HERV-K_7p22.1 provirus ancestral Pol protein, T7 RNA polymerase, biotransformation, Synthetic Cell, Behaviors, SIMPLE, constitutitional genetic, chemical structure, RNase H, chemical composition, Controlled, TP53I7, Alkalescens-Dispar Group, cellular breakdown, RNA, Controlling, Bacterium coli, lumen, anatomical protrusion, chemical characterization, HERV-K_5q33.3 provirus ancestral Pol protein, Process, degradation, ribose nucleic acid, space, familial, ribonucleic acids, Protocell, artificial gene, enzyme activity, RNS, EAggEC, synthetic DNA, Enteroaggregative E. coli, Cell, Acceptance Processes, HERV-K102 Pol protein, shortened, HERV-K107 Pol protein, Acceptance Process, Artificial., HERV-K108 Pol protein, Diffusely Adherent E. coli, Bacillus coli, Artificial Organelles, Artificial Organelle, PIG7, yeast nucleic acid, HERV-K_19q11 provirus ancestral Pol protein, Ribonukleinsaeure, Organelles, synthetic, pentosenucleic acids, secretion, Ribonucleic acids, 3.1.26.4, anatomical spaces, Calf Thymus, Artificial Cell, breakdown of molecule, Artificial, Acceptance, ribonucleic acid, Acid, Diffusely Adherent Escherichia coli, lumen space, RNAase H, Enteroinvasive E. coli, biodegradation, HERV-K_3q27.2 provirus ancestral Pol protein, Non Polyadenylated RNA, HERV-K110 Pol protein, Non-Polyadenylated, Endoribonuclease H, HERV-K(C7) Pol protein, Ribonucleic Acid, chemical content, HERV-K113 Pol protein, synthetic constructs, experimental procedures, Reverse transcriptase, SYNTHETIC CONSTRUCT sequences, breakdown of substance, Protocells, Bacterium coli commune, HERV-K(C19) Pol protein, spine, Synthetic Organelles, Cells, Biocatalyst, Synthetic Cells, artificial, inherited genetic, HERV-K_8p23.1 provirus ancestral Pol protein, Feedbacks, HERV-K(HML-2.HOM) Pol protein, short, hereditary, 2.7.7.49, HERV-K_1q22 provirus ancestral Pol proteinextent, AW488255, Sectors, Public Sectors, Tb11, YB, NetrinA, AUTSX5, number, D430049E23Rik, Copyrights, NOVH, CCN3, QM, FBXW4, netrin, Yb, Hek6, Cek6, Public Enterprise, Enterprises, CG2706, fs(1)M104, ENSMUSG00000074119, ERP, APUDoma, Erp, Elkh, Ebi, EBI, Public Domains, Tyrosine-protein kinase receptor EPH-2, EK6, SAP-2, Sap-2, IGFBP9, Public Enterprises, DmelCG4063, IBP-9, neuroendocrine tumour, Kiaa4053, 2.7.10.1, Solute carrier family 6 member 2, L10, Etrp, CT27014, NET1, SLC6A5, Tbl1, TBL1, NAT1, netA, NOVh, Enterprise, NET, Net, Elk, ELK, C130099E04Rik, completeness, Neuronally-expressed EPH-related tyrosine kinase, DmelCG2706, EPH tyrosine kinase 2, DXS648, SAP2, SMAP55, 9330129L11, neuroendocrine tumor, net, neuroendocrine neoplasm, presence., count in organism, Norepinephrine transporter, IGFBP-9, Public, Public Domain, Domains, EPH-like kinase 6, NOV, PlexA1, Domain, Data Base, Plxn1, CG4063, nov, hEK6, CG18657, E-2f, mKIAA4053, E-2g, fs(1)Y[b], l(2)k16213, DmelCG18657, Sector, EPHT2, C130088N23Rik, EG:95B7.8, 2600013D04Rik, PLXN1, DXS648E, netrin Asynthetic, artificial, synthetic genetic interaction defined by inequality, SYNTHETIC CONSTRUCT sequences, artificial gene, synthetic genetic interaction (sensu inequality), artificial sequence, synthetic DNA, synthetic constructs.falseKim2011_Oscillator_DetailedII This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92. 2011-02-172005-01-012010-12-09MODEL101209000321283141MODEL1012090003GO:0010468562