1. Department of Biomedical Engineering,
2. Center for BioDynamics and
3. Center for Advanced Biotechnology, Boston University, 44 Cummington Street, Boston, Massachusetts 02215, USA

Correspondence to: James J. Collins^1,2 Correspondence and requests for materials should be addressed to J.J.C. (e-mail: Email: jcollins@bu.edu). Plasmid sequences are available at http://cbd.bu.edu/abl/toggle.

Abstract

It has been proposed¹ 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 switch² and the Cyanobacteria circadian oscillator³. 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.