COLLEGE STATION -- A cure for human deafness just might be swimming alongside the thousands of zebrafish in muggy rooms across the hall from Texas A&M University biologist Bruce Riley's office, and a recent renewal of a federal grant totaling $1.5 million over five years will move him closer to that goal.
Riley studies the inner-ear development of the striped tropical minnows because the genes of all vertebrates -- the taxonomic category to which both humans and fish belong -- are remarkably similar.
"Our research is founded on the simple idea that the genes that control the development of the inner ear are the same in fish and humans," Riley said. "We're trying to figure out what genes control regeneration of zebrafish hair cells, which control hearing. The hope is that if we can understand them, maybe we can figure out a way to coax a similar response out of the equivalent cells in a human. I absolutely believe that's going to happen in our lifetime. And in principle, it could literally be a cure for deafness."
Riley's research program, which broadly uses zebrafish as a model by which to investigate how genes control development, received the grant renewal from the National Institutes of Health to build on the momentum of a program he began with its support in 1998. The funding was provided by the NIH's National Institute on Deafness and Other Communication Disorders (NIDCD).
Riley's research often puzzles people. He often gets asked if fish can even hear. Although they don't have external ears, their hearing sense -- more like a protective instinct to help avoid predators -- is impressive, he said. Because zebrafish are part of a group of fish considered to be hearing specialists, he said they make the perfect laboratory specimen for which to study inner-ear development.
For generations, mice and fruit flies have been biologists' best laboratory friends. But in recent decades, researchers also have embraced the ubiquitous zebrafish, which also has many lab-friendly qualities. For instance, they're hardy, being native to the sewage-infested Ganges River in India. They also are known as a beginner's fish, because they're cheap, don't die easily, weather extreme heat and tolerate low-oxygen tension.
Riley says zebrafish reproduction makes them even more attractive to researchers. A zebrafish embryo matures from fleshy substance to developed fish in about 24 hours, a fraction of the three weeks or so it takes for mouse gestation or nine months for humans. This means rapid turnaround time between experiments. Zebrafish also produce transparent embryos, enabling researchers using microscopes to directly observe the effects of altering specific gene functions and to sidestep the messy process of studying mice embryos: scooping them out of the dead mother.
In his lab, Riley investigates how zebrafish regenerate hearing, a quality that most vertebrates have but that humans and all mammals seem to have lost somewhere along the evolutionary process. Researchers can zap a mature zebrafish hair cell with a laser, and a rapid regeneration response kicks in that restores the cell within 12-to-24 hours by reactivating early developmental genetic programs. It doesn't work that way in humans: Once a hair cell dies, it's lost forever. But figuring out the cells that control hair cell regeneration in zebrafish and how they work potentially could give insight into how to replicate that process in humans.
Riley's lab already has made key contributions to the field. In 2010, he published a paper which showed that the disruption in zebrafish of a gene he was studying called SOX2 prevents the regeneration of a destroyed hair cell. The human ear also has that gene, but soon after birth, the amount of expression of the gene is dramatically reduced, leading Riley to conclude that the reason humans have lost their capacity to regenerate lost hair cells likely is because they don‘t have enough SOX2.
"We want to know how SOX2 works in zebrafish so it could potentially tell us if this is a good candidate for a gene therapy approach in humans," Riley said.
Riley, who joined the Texas A&M Department of Biology faculty in 1995, was interested in zebrafish before inner-ear development. While searching for mutant phenotypes during a postdoctoral fellowship at the University of Utah, he saw a birth defect that had a subtle effect on inner-ear development. When he went to the library to study the topic further, he discovered that little was known genetically about the inner-ear development of vertebrates.
"I decided right then and there that I'd study inner-ear development," he said. "That's what I've been doing since."
To learn more about Riley and his research, visit https://www.bio.tamu.edu/FACMENU/FACULTY/RileyB.php.
