Two scientists have won the 2021 Nobel Prize in Physiology or Medicineexternal link, opens in a new tab for their discoveries of receptors for temperature and touch.

David Julius, a professor at the University of California, San Francisco (UCSF), and a Howard Hughes Medical Institute (HHMI) Trustee, and Ardem Patapoutian, an HHMI Investigator at Scripps Research, have received the award for their work identifying receptors on sensory neurons that give us the ability to monitor temperature, pain, touch, and the location and movement of our body.

The Nobel Assembly at the Karolinska Institute announced the news at a press conference earlier today near Stockholm, Sweden. “The work by David Julius and Ardem Patapoutian has unlocked one of the secrets of nature by explaining the molecular basis for sensing temperature and mechanical force,” said Patrik Ernfors, an adjunct member of the Nobel Committee.

David Julius was elected an HHMI Trustee in 2020 (HHMI does not fund his work), and Ardem Patapoutian has been an HHMI Investigator since 2014. “This year’s prize recognizes how basic scientific discoveries can transform our understanding of the world,” said HHMI President Erin O’Shea. “We congratulate both David and Ardem – and also the many scientists who contributed to this groundbreaking work and continue to build on it.”

Thomas Perlmann, secretary-general of the Nobel Assembly and the Nobel Committee, spoke with both scientists by phone in the early morning hours on Monday. “They were incredibly happy, and, as far as I could tell, very surprised and a little bit shocked,” he said. 

Delivering the good news to Patapoutian required a little help from his family, though. Patapoutian’s phone was in “do not disturb” mode, so he didn’t receive Perlmann’s phone calls. Perlmann finally reached Patapoutian’s 92-year-old father, who was able to connect with Patapoutian. “I heard it from him, which was very special,” Patapoutian said. 

The sense of touch

Touch provides us with crucial information about our environment, yet it remains poorly understood at the molecular level. Touch-sensitive cells can warn of danger from hot, cold, and toxic substances. These cells can also tell us when we experience a gentle touch or when a hammer accidentally hits our finger. The sensing of mechanical forces and their translation into chemical signals influence a variety of biological processes. Hearing depends on mechanosensation, and the sensory modality also controls the function of the heart, blood vessels, lungs, and kidney.

Patapoutian was born in 1967 in Beirut, Lebanon. He has advanced the understanding of thermosensation with the discovery of ion channels in touch-sensitive cells that respond to changes in temperature. He calls these channels the body’s molecular thermometers. For example, one of them preferentially responds to cool temperatures and the cooling compound menthol. Another, which also responds to cold, is a general sensor of noxious chemicals, including ingredients in garlic and wasabi. Its activation causes pain and inflammation.

How cells sense mechanical forces, like pressure and stretching, is one of the last big unsolved questions in vertebrate sensory research, Patapoutian says. It has proven difficult to pinpoint the molecules underlying cells’ sensitivity to mechanical forces, but here Patapoutian has broken new ground, identifying two novel ion channels, Piezo1 and Piezo2, that are responsible for that sensitivity.

Patapoutian’s team used a simple cellular technique to mimic the sensation of touch. They directly poked a cell’s membrane while also recording its activity, Ernfors explained in the Nobel press conference. 

For their award-winning research, the team used this technique to test the effect of silencing each of 72 genes they had previously identified as potential sensors of mechanical force. After nearly a year of experimenting, the team had tested 71 of the genes, “without any promising results,” Ernfors said. Then came gene number 72. When the researchers switched off this gene, the cell was suddenly no longer sensitive to poking. “The mechanosensitive receptor had been discovered,” Ernfors said. 

Patapoutian’s team named the receptor Piezo1 after the Greek word for pressure and later discovered a related receptor, Piezo2. “Patapoutian demonstrated that Piezo proteins belong to an entirely novel class of proteins and function as ion channels activated by mechanical force,” Ernfors said. 

Prior to this work, finding receptors for sensing touch and pain had been “kind of the big elephant in the room,” Patapoutian said. Scientists knew such receptors existed, but finding them had been difficult.

Piezo channels are present in a wide variety of tissues, and Patapoutian plans to investigate how they function to regulate various biological processes and how they may contribute to disease. One of the exciting things about this work, he says, is that it has revealed aspects of biology where the team didn’t know pressure sensing was important. For example, they’ve found that red blood cells can sense pressure and adjust their volume accordingly.

Feeling the heat

Julius was born in 1955 in New York. A biochemist and molecular physiologist, he studies the molecular mechanisms underlying sensations such as heat, cold, and pain. His lab has examined menthol, wasabi, capsaicin (the ingredient that makes chili peppers hot), and other natural products to discover how sensory nerves detect temperature, itch, and other sensations.

Julius and his coworkers wanted to identify the receptor for capsaicin on sensory neurons and assumed that a single gene was responsible.

In the lab, Julius’s team added single fragments of DNA into cells that were not sensitive to capsaicin. Then, they added the chemical to the cells and recorded their activity. By testing millions of DNA fragments, Julius was able to identify the gene that made the cells able to detect capsaicin. “This was a high-risk project,” Ernfors said, “but after looking through large amounts of DNA fragments, the team finally succeeded and identified the capsaicin receptor.”

The gene encoded a protein called TrpV1, an ion channel located in cells’ outer membrane. When the team exposed the protein to heat, the ion channel opened. “He had discovered a temperature-sensitive ion channel activated by heat that is perceived as painful,” Ernfors said.

Julius considers mentorship an essential and fulfilling aspect of his career. In his 30 years on the faculty at UCSF, Julius has trained more than 40 graduate students and postdocs. Prior to 1990, Julius worked as a postdoc in the lab of HHMI Investigator Richard Axel at Columbia University. Julius earned his doctoral degree from the University of California, Berkeley in 1984, and his bachelor’s degree from the Massachusetts Institute of Technology in 1977.

Julius and Patapoutian will split the 10 million Swedish kronor (roughly $1.1 million) for this year’s prize.

Patapoutian is now one of 33 current or former HHMI scientists who have won the Nobel Prize. Last year, HHMI Investigator Jennifer Doudna shared the Nobel Prize in Chemistry with Emmanuelle Charpentier for developing a method of genome editing known as CRISPR-Cas9.

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