Department of Bioengineering, California Institute of Technology, Pasadena, CA, USA.
This a model from the article: Synthetic in vitro transcriptional oscillators. Kim J, Winfree E Mol. Syst. Biol. 2011 Feb 1;7:465. 21283141 , Abstract: 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. Notes: The paper describes 7 models (MODEL1012090000-6) and all these are submitted by the authors. This model (MODEL1012090001) corresponds to the Simple model of the three-switch ring oscillator (Design III). The model reproduces figure 6 (central figures) of the reference publication. The time is rescaled by s=v_d/K_I*t where K_I=0.333 and v_d=1 (for alpha = 1) and v_d=0.5 (for alpha = 0.5). i.e. For alpha = 1, s = 0.003 * t (roughly 10 unitless time = 1hr; the time-course should be run for 60 timeunits (6hrs) to get figure 6a). For alpha = 2, s= 0.0015 * t (roughly 5 unitless time = 1hr; the time-course shoue be run for 100 timesunits (20hrs) to get figure 6b). 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. For more information see the terms of use . 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.