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Listening to Cells: Ardem Patapoutian at Work

By Madeline McCurry-Schmidt

When biologist Ardem Patapoutian needs to think, he jumps in the Pacific Ocean. He has found that his best ideas come when he’s outside—swimming, running or biking. As he paddles above the kelp forests, he contemplates one of the world’s most complicated networks: the human nervous system.

Patapoutian, professor and member of the Dorris Neuroscience Center at The Scripps Research Institute (TSRI) and investigator with the Howard Hughes Medical Institute, studies how cells “talk” to each other and send signals through the body.

“Our research has relevance to pain, but also to many other biological processes, such as controlling blood pressure, atherosclerosis and glaucoma,” said Patapoutian. “Our hope is that our research will translate into helping to alleviate human suffering.”

A Sense of Adventure

Patapoutian never planned on becoming a biologist. He was aiming to get into medical school, so he thought he’d work in a lab to get a good letter of recommendation.

“It just so happened that I absolutely fell in love with doing research and biology,” said Patapoutian. He realized that he could discover fundamental aspects of life, like how cells function, and apply them to improve human health.

After earning a Ph.D. in biology at the California Institute of Technology, Patapoutian began a postdoctoral fellowship at the University of California, San Francisco. There he worked in the lab of physiologist Louis Reichardt, a mentor with an inspiring sense of adventure.

“He was the first American to climb K2 [the second-highest mountain on Earth] and also went up Everest from a side that was never taken before,” said Patapoutian. “One thing I learned from him was not to go to him and say ‘this is not possible.’”

In Reichardt’s lab, Patapoutian studied several receptors involved in cell signaling. When Patapoutian arrived at TSRI in 2000, he focused his research on sensations related to touch, specifically, how cells react to changes in temperature and pressure.

“For example, how do you sense light wind on your arm or when a hammer hits your finger? All of these are mechanical forces that get translated into signaling,” he said.

So how do cells talk? Understanding this requires a look at cells at the molecular level.

New Treatments for Pain

Swing a hammer toward a nail and miss, hitting your finger instead. A network of cells, proteins and chemical signals spring into action as pain shoots up from your stubbed digit. This reaction is a kind of mechanosensation, the process that transforms external stimuli (a hammer hitting a finger) into neural impulses (the sensation of pain).

The human body depends on mechanosensitive cells. As we go about our days, blood vessels use pressure sensing to control movement of blood, and eye tissues use pressure sensing to control the buildup of fluids.

Cell by cell, protein by protein, Patapoutian is getting closer to understanding the mechanisms behind devastating diseases, including chronic pain. In 2010, he and his team published a landmark paper in the journal Science, identifying a class of proteins that detect touch.

Scientists had long known that sensory nerves in skin detect pain, heat, cold and other stimuli using specialized “ion channel” proteins in their outer membranes. Patapoutian took this research further by identifying a family of sensory nerve proteins known as piezo proteins (piezi is the ancient Greek word for pressure).

In 2012, Patapoutian and his team published a follow-up study in the journal Nature showing that piezo proteins are ion channel proteins essential to the sensation of painful touch.

His work has also revealed the functions of important cells in the body. In a paper published in the journal Nature last spring, Patapoutian’s team showed the role of Merkel cells, special skin cells that react to “soft touch.”

Last spring, Patapoutian and his colleagues also published a paper in the journal Cell about the SWELL1 protein, which helps cells regulate their volume to keep from swelling excessively.

“Understanding more about this protein’s role in diseases, such as immune deficiency, stroke, and diabetes will be the next step,” wrote National Institutes of Health Director Francis Collins in a blog post about the SWELL1 study.

A “Golden Age” in Biomedical Science

From his La Jolla, California lab, where his wetsuit hangs behind his office door, Patapoutian has helped TSRI researchers forge new connections with biomedical research groups.

“It’s a close-knit community—very collaborative in nature,” said Patapoutian.

In 2013, Patapoutian was named an investigator at the Howard Hughes Medical Institute and last March, Patapoutian was part of an agreement with the Genomic Institute of the Novartis Research Foundation (GNF) that makes it easier for scientists at TSRI to collaborate with GNF scientists and share resources from the pharmaceutical world.

Patapoutian’s interest in working with GNF has helped his lab speed up mechanosensation research. In a recent experiment, a postdoctoral researcher in his lab used a robotic system at GNF to shift from processing 72 assays (tests) per year to processing 384 assays per minute.

At TSRI, close to cutting-edge technology and enthusiastic collaborators, Patapoutian believes biomedical research is in a “Golden Age.”

“I’ve been very lucky because this is an absolutely fascinating field of research,” he said.

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“Our research has relevance to pain, but also to many other biological processes, such as controlling blood pressure, atherosclerosis and glaucoma,” says TSRI Professor and HHMI Investigator Ardem Patapoutian. Click for video. (Photo by Sandy Huffaker/AP Images for HHMI.)