Scientists have long used genetic switches to turn genes on and off, but they have struggled to control intermediate settings. Now researchers have engineered a DNA dimmer that allows them to adjust a gene’s activity level. By adding measured amounts of anhydrotetracycline (ATc) to a population of genetically modified yeast cells, scientists at the University of Texas M. D. Anderson Cancer Center were able to precisely control the production of green fluorescent protein. Doubling the concentration of ATc, for instance, made the cells glow twice as brightly. Even small changes in gene activity can change cell behavior dramatically, so this fine-tuning may open up new avenues for studying gene function.
Just as engineers rearrange capacitors and resistors to create different electric circuits, researchers can arrange gene promoters and repressors—stretches of DNA that control gene activity—to create gene circuits with different properties. Such circuits have already been used to build a genetic clock and to synthesize cellular machinery that can follow basic logic commands such as AND, OR, and NOR ("not OR").
Biological physicist Gábor Balázsi says his team’s discovery of the genetic dimmer circuit was serendipitous. “We were originally testing for something else,” he says, “so when we found the relationship between ATc and fluorescence, we couldn’t believe it.” Their next step is to investigate whether the circuit works in mammalian cells. If so, it could help researchers understand the effects of genes operating at different intensities and may eventually have applications in therapies for genetic disorders.