Development of genetic circuitry exhibiting toggle switch or oscillatory behavior in Escherichia coli

Cell. 2003 May 30;113(5):597-607. doi: 10.1016/s0092-8674(03)00346-5.


Analysis of the system design principles of signaling systems requires model systems where all components and regulatory interactions are known. Components of the Lac and Ntr systems were used to construct genetic circuits that display toggle switch or oscillatory behavior. Both devices contain an "activator module" consisting of a modified glnA promoter with lac operators, driving the expression of the activator, NRI. Since NRI activates the glnA promoter, this creates an autoactivated circuit repressible by LacI. The oscillator contains a "repressor module" consisting of the NRI-activated glnK promoter driving LacI expression. This circuitry produced synchronous damped oscillations in turbidostat cultures, with periods much longer than the cell cycle. For the toggle switch, LacI was provided constitutively; the level of active repressor was controlled by using a lacY mutant and varying the concentration of IPTG. This circuitry provided nearly discontinuous expression of activator.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacterial Proteins*
  • Biological Clocks / genetics*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins*
  • Gene Expression Regulation, Bacterial / genetics*
  • Gene Expression Regulation, Enzymologic / genetics*
  • Genes, Bacterial*
  • Glutamate-Ammonia Ligase / biosynthesis
  • Glutamate-Ammonia Ligase / genetics
  • Lac Operon / genetics*
  • Membrane Transport Proteins / biosynthesis
  • Membrane Transport Proteins / genetics
  • Monosaccharide Transport Proteins*
  • Mutation / genetics
  • Nitrogen Fixation / genetics
  • Promoter Regions, Genetic / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reproducibility of Results
  • Symporters*


  • Bacterial Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • GlnK protein, Azorhizobium caulinodans
  • LacY protein, E coli
  • Membrane Transport Proteins
  • Monosaccharide Transport Proteins
  • Repressor Proteins
  • Symporters
  • lactose permease
  • glutamine synthetase I
  • Glutamate-Ammonia Ligase