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BIOMD0000000507 - Gardner2000 - genetic toggle switch in E.coli

 

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Reference Publication
Publication ID: 10659857
Gardner TS, Cantor CR, Collins JJ.
Construction of a genetic toggle switch in Escherichia coli.
Nature 2000 Jan; 403(6767): 339-342
Department of Biomedical Engineering, Center for BioDynamics, Boston University, Massachusetts 02215, USA.  [more]
Model
Original Model: BIOMD0000000507.xml.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL1401190000
Submission Date: 19 Jan 2014 18:39:39 UTC
Last Modification Date: 04 Mar 2014 12:20:24 UTC
Creation Date: 19 Jan 2014 19:51:18 UTC
Encoders:  Vijayalakshmi Chelliah
   Nicolas Le Novère
set #1
bqbiol:hasTaxon Taxonomy Escherichia coli
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
bqbiol:isVersionOf Gene Ontology regulation of gene expression
Notes
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:

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.

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.

Model
Publication ID: 10659857 Submission Date: 19 Jan 2014 18:39:39 UTC Last Modification Date: 04 Mar 2014 12:20:24 UTC Creation Date: 19 Jan 2014 19:51:18 UTC
Mathematical expressions
Reactions
production of U degradation of U production of V degration of V
Rules
Assignment Rule (variable: Umodif)      
Physical entities
Compartments Species
compartment U V IPTG
Global parameters
alpha1 alpha2 beta gamma
K nu Umodif Initial for K
Initial for nu      
Reactions (4)
 
 production of U  → [U];   {V} , {V}
 
 degradation of U [U] → ;   {U}
 
 production of V  → [V];  
 
 degration of V [V] → ;   {V}
 
Rules (1)
 
 Assignment Rule (name: parameter_7) Umodif = species_1/(1+species_3/ModelValue_4)^ModelValue_5
 
Functions (2)
 
 toggle repressor production lambda(alpha, X, n, alpha/(1+X^n))
 
 toggle repressor production with induction lambda(alpha, X, n, alpha/(1+X^n))
 
 compartment Spatial dimensions: 3.0  Compartment size: 1.0  (Units: litre)
 
 U
Compartment: compartment
Initial concentration: 0.0  (Units: mole)
 
 V
Compartment: compartment
Initial concentration: 0.0  (Units: mole)
 
 IPTG
Compartment: compartment
Initial concentration: 0.0  (Units: mole)
 
Global Parameters (9)
 
 alpha1
Value: 156.25
Constant
 
 alpha2
Value: 15.6
Constant
 
 beta
Value: 2.5
Constant
 
 gamma
Value: 1.0
Constant
 
   K
Value: 2.9618E-5
Constant
 
   nu
Value: 2.0015
Constant
 
  Umodif  
 
 Initial for K
Value: 2.9618E-5
Constant
 
 Initial for nu
Value: 2.0015
Constant
 
degradation of U (1)
 
 k1
Value: 1.0
Constant
 
degration of V (1)
 
 k1
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000507

Curator's comment: (updated: 19 Jan 2014 19:51:02 GMT)

The curve that represent the experimental result (red dots) in figure 5a of the reference paper is reproduced here. The simulation was done using Copasi v4.11 (Build 65).

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