The Language of the Brain: A Profile of Ulrich Müller

By Madeline McCurry-Schmidt

Every sound hits the ear the same way—through vibrating air molecules. That’s when the brain takes over, interpreting the difference between the sound of a human voice and the honk of a car horn, the difference between Bach and Beyoncé.

At The Scripps Research Institute (TSRI) and its Dorris Neuroscience Center, Professor Ulrich Müller investigates exactly how the nervous system processes sound and what happens when the brain doesn’t respond to external stimuli properly. As director of the Dorris Neuroscience Center and chair of the Department of Molecular and Cellular Neuroscience at TSRI, Müller studies the genetic causes of hearing impairment and conditions, such as autism and schizophrenia, linked to a brain region called the neocortex.

“All of it is related to understanding diseases that affect the nervous system,” said Müller.

By probing the nervous system, Müller has found new ways to diagnose disease and develop potential treatments.

A Home for Neuroscience

For Müller, science is about exploration. Growing up in Cologne, Germany, Müller was fascinated by nature documentaries showing the lives of animals on the African savannah and the oceans deep. In school, this translated into a love of biology, chemistry and physics.

Müller trained as a biochemist at Albertus Magnus University in Cologne. After spending some time researching DNA tumor viruses, Müller decided to shift his research focus to neuroscience.

“I do think it is the ultimate frontier,” said Müller. “If we can understand how the brain works, I think we’ll understand a lot about how we work, what the world is about and how we perceive it.”

Müller returned to Europe after completing postdoctoral work at the University of California, San Francisco. While working as a researcher in Switzerland, however, Müller realized that he missed the collaboration and independent research that he’d experienced in American labs. In 2003, he returned to the United States to join the TSRI faculty.

“For me, coming to Scripps was like a homecoming,” said Müller. “You have all the freedom to just follow your ideas and do your work. You are not burdened by bureaucracy or external things that can distract you from your key mission to really pursue scientific ideas.”

Unscrambling the Signals

Müller’s work at TSRI has led him to new insights into disease. To him, the key is to figure out how the brain translates the external world into an internal world.

“You have mechanical signals, those are sound waves, and we have to translate them somehow into electrical signals, which are the language of the brain,” Müller said.

Sometimes the signaling process goes haywire. In humans, the most common type of sensory impairment is deafness. According to the National Institute on Deafness and Other Communication Disorders, nearly half of people over 75 experience age-related hearing loss. Though the condition falls under one umbrella term, presbycusis, it can have many causes, from changes in the inner ear to disturbances along the nerve pathways to the brain.

Some of the causes of age-related hearing loss are genetic, so Müller uses cloning techniques to identify relevant genes. By understanding the mutations involved in hearing loss, researchers hope to develop ways to reverse the process.

In 2004, Müller and his colleagues identified a genetic mutation linked to deafness in some people with age-related hearing loss and children with Usher syndrome, a leading cause of deaf-blindness. The mutation affected the production of a complex protein, called cadherin 23, which is on hair cells in the inner ear and is critical to the hearing process.

Müller’s lab also identified harmonin and protocadherin 15, two proteins that work with cadherin 23 to sense sound vibrations and send electrical signals to the brain. And in 2012, the lab identified a protein called TMHS, which had been found in people with common forms of inherited deafness.

“We have discovered some of the genes related to disease, and those are used today to diagnose people who have, for example, hearing impairment,” said Müller.

The Big Questions

For Müller, each experiment is personal. “I think a fantastic aspect of being a scientist is that you can really follow your own ideas,” Müller said.

For example, he wonders about the piano-like structure of the ear, with regions that sense high notes and regions that sense low notes. Why is the ear built that way?

Müller encourages his lab members to pursue answers to these kinds of big questions, to try new experiments on the edge of science. “You have to follow your own instincts,” he said.

Outside the lab, Müller and his two daughters explore nature with the same passion that he had when he was a boy watching nature documentaries. Some days, they go out to the lagoons and beaches of San Diego to spot shells and little creatures in the sand.

Are they budding biologists? Who knows, said Müller, but they certainly enjoy learning about the mysteries of the world. “I can see the same joy in them that I experienced,” Müller said.

Send comments to: press[at]scripps.edu