First Genetic Toggle Switch Engineered At Boston University

(Boston, Mass.) - The first-ever "genetic toggle switch," designed to control the activity of genes, was recently engineered by scientists at Boston University's Center for BioDynamics (CBD) and Department of Biomedical Engineering. Working with the bacteria Escherichia coli, the researchers were able to successfully switch the expression of genes between stable on and off states by applying a brief chemical or temperature stimulus. The work is reported in the January 20 issue of Nature.

"Regulatory circuits that are stable in both the on and off positions exist naturally in some very specialized genetic systems," says James J. Collins, director of CBD and co-author, "but this is the first time anyone has been able to create a synthetic bistable on/off switch to control the expression of a gene - a switch that can be generalized to a variety of genes in many different organisms, including human cells."

The toggle also represents the core technology for additional genetic control devices. "Minor modifications to the toggle can be made to produce a genetic sensor with an adjustable threshold - a system in which genes are activated or repressed when a specific threshold is reached," notes Timothy S. Gardner, a Ph.D. candidate in biomedical engineering and lead author of the study. "This type of sensor would be useful in controlling diabetes, for example, by automatically activating the synthesis of insulin when blood glucose reaches a particular level." Such a system also has potential applications in the detection of biological warfare agents - turning the body's own cells into sensors that alert the individual to the presence of dangerous substances, and even triggering the production of an antidote.

Moreover, the toggle switch itself can function as an artificial cellular memory unit, the basis of cell-based computing. "Since Richard Feynman's visionary suggestion, in 1959, of engineering submicroscopic devices, the concept of nanoscale robotics has sparked researchers' imaginations," says Gardner. "In recent years, this possibility has frequently been identified with microelectromechanical devices. We suggest that nanoscale robotics may take on a 'wetter' form, namely, a living cell. Ultimately, we envision the combination of genetic toggles, genetic sensors, sequential expression networks, and other devices into a 'Genetic Applet' - a self-contained and fully programmable genetic network for the control of cell function."