Construction of a genetic toggle switch in Escherichia coli

  title={Construction of a genetic toggle switch in Escherichia coli},
  author={Timothy S. Gardner and Charles R. Cantor and James J. Collins},
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 λ 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… 

Synthetic networks: oscillators and toggle switches for Escherichia coli.

Studying these two kinds of synthetic networks helps advance the understanding of natural bistable systems and oscillators, such as the circadian oscillators controlling gene expression in many types of cells, and the genetic systems controlling the cell cycle and differentiation in metazoans.

Genetic toggle switch

  • Engineering, Biology
  • 2018
The design of a genetic toggle switch is analyzed, and its switching between two stable states is observed in living bacteria.

Progress toward the construction of a tri-stable genetic toggle switch in E. coli

The tristable toggle switch, constructed and characterized as an iGEM 2006 project at Brown University, is composed entirely of Biobricks from the Registry of Standard Biological Parts, providing support for the iG EM hypothesis and has implications for biotechnology and gene therapy.

A genetic bistable switch utilizing nonlinear protein degradation

This work demonstrates the first use of dynamic expression of an orthogonal and heterologous protease to tune a nonlinear protein degradation circuit, and is potentially a more robust and tunable topology for use in prokaryotic systems.

Construction of an in vitro bistable circuit from synthetic transcriptional switches

Construction of larger synthetic circuits provides a unique opportunity for evaluating model inference, prediction, and design of complex biochemical systems and could be used to control nanoscale devices and artificial cells.

Regulatory circuit design and evolution using phage λ

The results strongly support the idea that complex circuits can arise during the course of evolution by a combination of simpler regulatory modules and underscore the advantages of modifying a natural circuit as an approach to understanding circuit design, systems behavior, and circuit evolution.

Control of the dynamical behavior of the Repressilator by Quorum Sensing

Synthetic gene oscillators are simpler in their organization and have potential to increase the knowledge of natural gene networks with oscillatory behavior and have been proposed theoretically to use quorum sensing mechanism to introduce a coupling between oscillators.

A synthetic phage λ regulatory circuit

The circuitry of phage λ, which grows lytically, forms stable lysogens, and can switch from this regulatory state to lytic growth is applied, using a combinatorial approach to isolated phage variants with behavior similar to that of WT λ.

Progress toward construction and modelling of a tri-stable toggle switch in E. coli

The tri-stable switch, designed, modelled, and partially constructed as an iGEM 2006 project at Brown University, is to be composed entirely of Biobricked parts from the Registry of Standard Biological Parts.



A genetic switch : phage λ and higher organisms

Eukaryotic Gene Regulation - Experiments and Examples: Designing an Efficient DNA-binding ProteinStrong and Weak InteractionsControl of Transcription in Eukaryotes and Prokaryotes - a common mechanism.

Independent and tight regulation of transcriptional units in Escherichia coli via the LacR/O, the TetR/O and AraC/I1-I2 regulatory elements.

Controlling the expression of the genes encoding luciferase, the low abundance E.coli protein DnaJ and restriction endonuclease Cfr9I not only demonstrates that high levels of expression can be achieved but also suggests that under conditions of optimal repression only around one mRNA every 3rd generation is produced.

Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells.

The fraction of infected cells selecting the lysogenic pathway at different phage:cell ratios, predicted using a molecular-level stochastic kinetic model of the genetic regulatory circuit, is consistent with experimental observations.

Stochastic mechanisms in gene expression.

  • H. McAdamsA. Arkin
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
This work has analyzed the chemical reactions controlling transcript initiation and translation termination in a single such "genetically coupled" link as a precursor to modeling networks constructed from many such links.

Expression of a gene cluster kaiABC as a circadian feedback process in cyanobacteria.

A negative feedback control of kaiC expression by KaiC generates a circadian oscillation in cyanobacteria, and KaiA sustains the oscillation by enhancing kaiA expression.

Computational functions in biochemical reaction networks.