New HHMI investigator says appointment liberates his science

Ronald R. Breaker, Ph.D., has never shied away from less-charted scientific waters, but he says the best thing about his selection in March as a Howard Hughes Medical Institute (HHMI) investigator is that the institute’s largely unrestricted support will “allow me to become much more aggressive in taking bigger risks.”

Breaker’s penchant for unconventional science has served him well. In his pathbreaking work on “riboswitches,” Breaker has shown that cells can regulate their function in ways that biologists would only recently have considered possible.

In the laboratory, RNA strands can fold into intricate three-dimensional structures known as aptamers, which precisely recognize targets, much like antibodies do. Breaker has engineered aptamers to detect minute quantities of potential bioterrorist agents. But most biologists thought of aptamers as just a handy tool, and few imagined that they played any role in living things.

However, because aptamers work so well in the lab, Breaker was convinced that they must exist in nature. Three years ago, he stunned the scientific world by showing that aptamers not only exist in bacteria, but they switch genes on and off, a function previously thought to be the sole province of proteins acting on DNA. These natural aptamers, which Breaker calls riboswitches, may be important new drug targets in humans, and Breaker has co-founded a company to search for aptamer-based gene therapies.

Breaker, the Henry Ford II Professor of Molecular, Cellular and Developmental Biology, is one of 43 newly appointed HHMI investigators, the first selected by the institute in five years. He joins 15 other Yale HHMI investigators among the 341 designees at biomedical research centers nationwide.

Being able to pursue “risky” experiments “is a great honor,” Breaker says. “I feel tremendously lucky to be in this situation.”