OHSU

Rebecca Seal, PhD, 1999

Rebecca Seal, PhD, was among the first students to enter the Neuroscience Graduate Program (NGP) at OHSU, in 1993. She began her research career by studying the structure and function of glutamate transporters in the lab of then-NGP faculty member Susan Amara. In her own lab at the University of Pittsburgh, Seal now studies a once “oddball” vesicular glutamate transporter that turned out to be a key player in hearing.
 
Although Seal now runs her own successful lab, a career path to Principal Investigator-ship was never a sure thing. After graduate school, Seal considered leaving academia for biotech. “That [idea] drew me to San Francisco.” Seal was offered a job at Genentech in 2001 but declined, because the company had just done away with their neuroscience program. Instead, she accepted an offer to postdoc in the lab of Robert Edwards at the University of California, San Francisco. Edwards was working on cloning the vesicular glutamate transporters (vGluTs), and Seal picked up a project working on vGluT3. “At the time, it was considered the oddball of the vGluT family.”

vGluT1 and 2 are expressed in most cells that release glutamate. But vGluT3 showed up in non-glutamatergic cells. “It was a challenge to study,” says Seal, “because people were saying, ‘It doesn’t function like the other vGluTs. It has a different role.’ Some even said, ‘It’s not supposed to exist anymore. It doesn’t do anything.’ That was tough.” But Seal persevered, making and characterizing knockout mice lacking the vGluT3 transporter. “One phenotype argued against the notion that vGluT3 wasn’t important: the mice were profoundly deaf.” Seal eventually found that vGluT3 packages glutamate for release from inner hair cells, the primary sensory cell for hearing in the cochlea. Experiments showed that although sound activated the hair cells, they couldn’t transmit the signal at the first synapse. “Our finding established [vGluT3] as a bona-fide vGluT,” says Seal.

Seal continues to explore the hidden roles of this unappreciated molecule beyond hearing, in somatosensory and pain physiology. This may seem a far cry from the molecular-level work Seal did starting out, but this too fulfills her career vision. After finishing her work in the NGP, she knew she “wanted to do something more at the level of behavior and circuits.” She certainly has done that, now tackling physiology questions with an ex vivo preparation she calls “a cool and powerful technology.” In the mouse prep, a neural circuit is left intact between the skin, the dorsal root ganglia—the nodules that house the skin’s sensory neurons—and the spinal cord, where they make their first synapse. By labeling vGluT3-expressing neurons, she can record from them in the dorsal root ganglia and see what kinds of stimuli—delivered at the skin—activates these neurons.
 
Seal found her training in the NGP provided a good mix of rigor and congeniality. “The caliber of the scientists is really high, and then it’s small enough that you can really get to know everybody,” she says. One of Seal’s fondest memories from graduate school is of a course taught by NGP faculty Craig Jahr and Gary Westbrook in which students read and discussed journal articles. The small class was very interactive with excellent instructors, she says, “so it was really high quality.” The fact that the course was held in Vollum Institute Director Dick Goodman’s “secret” library up in 4M made it even cooler.

Seal has some advice for graduate students just starting out. “First, figure out what the important questions are.” When faced with the opportunity to work in different labs, choose a lab where you can work on a project that’s both super interesting to you and could have real significance to the field. But perhaps just as important, Seal says, is ”keeping in touch with the senior people that really got to know you, like your advisors.” Seal embodies that advice, maintaining productive relationships with other researchers. Karl Kandler, a scientist she collaborated with in San Francisco, is also now at Pitt as head of the Auditory Research Group. “He’s like a mentor to me here now. His support makes it easier to work on projects in hearing.” And Susan Amara, Seal’s NGP mentor, is her chair in the Department of Neurobiology at Pitt. “When people you admire as scientists also admire you, it helps to nurture those relationships because these people will continue to give you good advice at all stages of your career. And it can be mutually beneficial by bringing out more good science for all”. And that’s ultimately the goal for any successful researcher.