October 04, 2021

Scripps Research neuroscientist Ardem Patapoutian receives 2021 Nobel Prize in Physiology

October 04, 2021

Scripps Research Professor Ardem Patapoutian, PhD, has been awarded the Nobel Prize in Physiology or Medicine for groundbreaking research that solved a long-standing mystery of how the body senses touch and other mechanical stimuli.

Patapoutian, a professor in the Dorris Neuroscience Center at Scripps Research in La Jolla, CA, and a Howard Hughes Medical Institute investigator, shares the prize with David Julius, PhD, at the University of California San Francisco for their discoveries of receptors for temperature and touch.

The Nobel Prize committee cited the discoveries by Patapoutian and his colleagues of two ion channels, PIEZO1 and PIEZO2, that are necessary for the cells to respond to mechanical stimuli.

The breakthrough by Patapoutian led to a series of papers from his and other groups, demonstrating that the Piezo2 ion channel is essential for the sense of touch, the Nobel committee wrote. Moreover, Piezo2 was shown to play a key role in the critically important sensing of body position and motion, known as proprioception.

The committee added that in further work, Piezo1 and Piezo2 channels have been shown to regulate additional important physiological processes including blood pressure, respiration and urinary bladder control.

Dr. Patapoutian, together with Dr. Julius, unlocked one of the mysteries of life, how do we sense temperature and pressure, says Peter Schultz, President and CEO of Scripps Research. The Nobel Prize is wonderful recognition of these discoveries. I have followed Ardem's career closely since he first came to Scripps Research and can say that he is an extraordinary scientist, mentor, and colleague and a wonderful person.

Starting with a basic question

Patapoutian says he had originally set out to investigate a fundamental question, how pressure and touch are perceived. But simple questions led to very complex discoveries, which continue today.

It turns out those mechanical pressure sensors control a wide array of biological needs, going far beyond the pain of a pinch or the pleasure of a caress, and extending to how one cell communicates with another, how we sense our body in time and space, how our organs move, and more.

Mechanosensation is how cells talk to each other by force, Patapoutian says. We didn't know the importance of pressure sensors to the body until we first found them. Blood pressure hypertension is affected, as well as bladder fullness. We talk about a key that unlocks a door that opens to a room. These receptors are the key to the door of understanding biology and disease.

The research has produced much that was unexpected. For example, Piezo1 is expressed in red blood cells and immune cells and may be involved in protection from malaria as well as affecting the amount of iron in blood, he says.

The exploration of PIEZOs continues. They may be involved in tracking how much the stomach stretches during a meal, and how much food passes through the intestines during digestion. They appear to be involved in neuropathic pain, too.

Painstaking labor

Ion channels act as gates in a nerve cell's outer membrane, letting electrically charged ions in or out, in the process, changing the neuron's electrical state.

They're small and difficult to study; the neurons they populate are also rare. So, it took considerable effort to find an effective way to study them reliably in the lab, he says. First, they needed cells that grew easily in a test tube and showed a measurable response when probed with a pipette.

Next, they worked through a process of elimination, knocking out one ion channel at a time until they discovered ones that, if eliminated, prevented the cells from reacting to the poke. Patapoutian recalls the moment in 2009 that his low-key postdoctoral researcher Bertrand Coste, PhD, brought him the news in his office: I think I've got it.

He was so calm, at first Patapoutian wasn't excited. They walked back to the lab together, so Coste could demonstrate.

We realized he had found what we had been looking for years, he recalls.

Subsequent structural studies revealed nature's artistic genius. The PIEZO1 molecule, viewed through a specialized electron microscope, is an all-in-one protein that does its job without having to connect to other proteins. It features curved blades that encircle a central pore. The blades physically move, like a circular valve.

It's a beautiful structure, he says. Ion channels are a port, and they do two things, they are closed or open. When they are open, they have 10 million ions per second flow through.

Patapoutian's group has found other ion channels involved in the perception of physical and chemical stimuli, as well, including TRPA1, which plays an essential role in pain and inflammation, and SWELL1, which maintains cell volume at an equilibrium with the fluids around it. His team has also identified GPR68, a cell mechanoreceptor that detects blood flow.

We're just now beginning to identify how these neurons gather information from our organs, to decipher the neural circuits that process that information before it goes to the brain, and to figure out what the brain does with that information, he said in a recent interview.

Gratitude to colleagues

In addition to being an HHMI investigator, Patapoutian is the Scripps Research Endowed Chair in Neurobiology at the institute's Dorris Neuroscience Center.

Patapoutian studied chemistry at the American University of Beirut in Lebanon, then went on to earn a BS, Magna Cum Laude, in molecular, cellular and developmental biology from the University of California, Los Angeles. He earned his PhD at the California Institute of Technology working with Barbara Wold, PhD, and pe

LINK:	https://www.scripps.edu/news-and-events/press-room/2021/20211004-ardem...
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