Dataset Information

Gardner2000 - genetic toggle switch in E.coli

ABSTRACT: Gardner2000 - genetic toggle switch in E.coli The behaviour of the genetic toggle switch and the conditions for bistability has been studies using a synthetic, bistable gene circuit. This model is described in the article: Construction of a genetic toggle switch in Escherichia coli. Gardner TS, Cantor CR, Collins JJ Nature. 2000 Jan 20;403(6767):339-42. Abstract: It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy. This model is hosted on BioModels Database and identified by: BIOMD0000000507 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

SUBMITTER: Nicolas Le Novère

PROVIDER: BIOMD0000000507 | BioModels | 2014-01-19

REPOSITORIES: BioModels

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Publications

Construction of a genetic toggle switch in Escherichia coli.

Gardner T S TS Cantor C R CR Collins J J JJ

Nature 20000101 6767

It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic t ...[more]

PMID: 10659857

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Project description:Mandlik2012 - Synthetic circuit of IPC synthase in Leishmania A genetic circuit for the targeted enzyme inositol phosphorylceramide (IPC) synthase belonging to the protozoan parasite Leishmania is constructed by Mandlik et al. (2013). This model is described in the article: Synthetic circuit of inositol phosphorylceramide synthase in Leishmania: a chemical biology approach Mandlik V., Limbachiya D., Shinde S., Mol M, S., Singh, S. J Chem Biol. January 2013 Abstract: Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targeted enzyme inositol phosphorylceramide synthase belonging to the protozoan parasite Leishmania. To explore the dynamic nature of the circuit designed, simulation was done followed by circuit validation by qualitative and quantitative approaches. The genetic circuit designed for inositol phosphorylceramide synthase (Biomodels Database—MODEL1208030000) shows responsiveness, oscillatory and bistable behavior, together with intrinsic robustness. This model is hosted on BioModels Database and identified by: MODEL1208030000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . 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.

Project description: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.

Project description: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 beha viors 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, bacteri ophage T7 RNA polymerase and Escherichia coli ribonuclease H, to produce and degrade RNA signals. In t his 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 si gnals, showed up to five complete cycles. To demonstrate modularity and to explore the design space fu rther, 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 p rocess, identified experimental conditions likely to yield oscillations, and explained the system's ro bust response to interference by short degradation products. Synthetic transcriptional oscillators cou ld prove valuable for systematic exploration of biochemical circuit design principles and for controll ing nanoscale devices and orchestrating processes within artificial cells. Note: The paper describes 7 models (MODEL1012090000-6) and all these are submitted by the authors. This model (MODEL1012090000) corresponds to the Simple model for both mode I and II (Design I and II). The model reproduces timecourse figure plotted in the supplementary material (page 10 of Supplementary material) of the reference publication. 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.

Project description:This is the model of the minmal 2 feedback switch described in the article: Synthetic conversion of a graded receptor signal into a tunable, reversible switch. Santhosh Palani and Casim A. Sarkar, 2011, Molecular Systems Biology 7:480; doi: 10.1038/msb.2011.13 The ability to engineer an all-or-none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network switches have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (nH420), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady-state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal-transduction pathways. This model is parametrised for a transcription factor and receptor feedback strength of 3, TFs = 3 and Rs = 3. To reproduce figure 1 E, the parameters TFs and Rs have to be varied accordingly. Nomenclature for the model: L : Ligand R : Receptor C : Ligand-Receptor Complex I : Inactive Transcription Factor X : C bound to I A : Active Transcription Factor 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.

Dataset Information

Gardner2000 - genetic toggle switch in E.coli

Publications

Construction of a genetic toggle switch in Escherichia coli.

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