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Fishing for Hearing

May 25, 2009 8:00 AM

Evolution is the progressive change of heritable traits. But change isn’t always good.

Take the ability to hear, for example. Lower vertebrates, including frogs, fish, and some birds, can regenerate hair cells in the inner ear that enable hearing. After mammals branched off the evolutionary tree, however, this enviable trait was lost. Couple this inability to regenerate with the fact that common causes of hair cell death in humans—exposure to loud noises, treatment with certain antibiotics, and the aging process—can be unavoidable, and the result is that hearing loss is one of the most prevalent disabilities in people.

“Comparing the regeneration process between fish and mammals will hopefully teach us at which step it is disrupted in mammals,” explained Tatjana Piotrowski, Ph.D., assistant professor in the Department of Neurobiology and Anatomy at the School of Medicine. “Specifically, we want to understand how hair cell regeneration occurs in zebrafish. This could provide an entry point for therapeutic treatment in humans.”

Piotrowski was awarded a grant last spring from the Inner Ear Hair Cell Regeneration Research Initiative at the National Organization of Hearing Research (NOHR). She and co-investigator Alejandro Sánchez Alvarado, Ph.D., U professor of neurobiology and anatomy, and a Howard Hughes Medical Institute investigator, will receive $200,000—the largest award NOHR gives annually to one research team—over the next two years.

“Everyone who works on hair cell regeneration wants this grant,” said Thomas N. Parks, Ph.D., U of U vice president for research and professor of neurobiology and anatomy. “Zebrafish are the best genetic animal model for studying hair cell regeneration, and I think Tatjana’s approach is very promising.”

Receiving a coveted award was not merely a stroke of luck for Piotrowski. She has progressively changed the trajectory of her life personally as well as  professionally.

As a teen, she longed to see what lay beyond Herrenberg, Germany, the small town where she grew up. She worked as an au pair in San Francisco and audited university classes. The experience opened her eyes to the academic independence enjoyed in the United States. “Young assistant professors here have much more freedom in what they can study,” she said. “If you don’t succeed, you don’t succeed. But at least they give you the opportunity to try.”

In the United States, Piotrowski imagined, she could research a subject she loved: “I always liked fish and had aquaria as a kid.” She delighted in watching fish and performing even the mundane aspects of their everyday care. Though she entered the master’s program at the University of Tübingen, Germany, she arranged to conduct her thesis under R. Glenn Northcutt, Ph.D., a respected professor of comparative neurobiology at the University of California, San Diego.

She studied in primitive fishes the anatomy of the lateral line, a sensory organ that detects water movement necessary for schooling, catching prey, and avoiding predators. The organ is comprised of neuromasts, which are clumps of cells—including hair cells like those in the human inner ear—that line the fish on both sides. Piotrowski became fascinated with this unique organ.

Although tempted to remain in the United States, she couldn’t pass up an opportunity to obtain her doctorate under Nobel laureate Christiane Nüsslein-Volhard, Ph.D. At the University of Tübingen, Nüsslein-Volhard had just initiated the first large-scale mutagenesis screen of a vertebrate in which fish were treated with chemicals that randomly mutate genes and their offspring examined for inherited anatomical defects. For example, if mutant fish had no eyes and a disruption in gene X, then that gene likely regulates eye development. Zebrafish were used because of their rapid generation time and large brood sizes.

“We made a lot of progress understanding how many vertebrate genes work,” said Piotrowski. “The experience convinced me that research was what I wanted to do in life.”

After earning her Ph.D., Piotrowski moved to Baltimore. She had two reasons: she was awarded a postdoctoral fellowship under zebrafish embryologist Igor Dawid, Ph.D., at the National Institutes of Health, and she wanted to live closer to Sánchez Alvarado, then a staff associate at the Carnegie Institute of Washington. The couple had met two years prior. They were married in 1999 and have two children.

When it came time to search for faculty positions, Piotrowski and Sánchez Alvarado eschewed universities located in big cities. “The U had a large, strong developmental biology community,” said Piotrowski. “They were also supportive of faculty who have families.”

After six years in Utah, Piotrowski knows her decision was the right one. With the NOHR grant, she is modifying a genetic screen to discover genes that regulate hair cell regeneration. Her screening strategy is to kill hair cells in mutagenized fish by soaking them in neomycin, an antibiotic that also kills human inner ear hair cells. By identifying fish whose hair cells cannot regenerate, she will pinpoint genes that are necessary for this process. Already she has found three potential regeneration mutants.

Sometimes, as Piotrowski has discovered in her own life, change can be good.

Read the complete article in Health Sciences Report.

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