David Julius Receives $3M Breakthrough Prize for Work on Pain Sensation

From Spider Venom to Chili Peppers, Julius Explores All Avenues to Understand the Neuroscience of Pain

By Jason Alvarez

David Julius, PhD

David Julius, PhD, professor and chair of the Department of Physiology at UC San Francisco, is a winner of the 2020 Breakthrough Prize in Life Sciences.

Julius, 63, received the prize “for discovering molecules, cells, and mechanisms underlying pain sensation,” according to the Breakthrough Prize Foundation. He is one of four researchers honored with this year’s life sciences award.

Now in its eighth year, the Breakthrough Prize was founded by Silicon Valley pioneers Sergey Brin, Yuri and Julia Milner, Mark Zuckerberg and Priscilla Chan, and Anne Wojcicki. The annual prize recognizes “achievements in the Life Sciences, Fundamental Physics and Mathematics, disciplines that ask the biggest questions and seek the deepest explanations.” Each Breakthrough Prize includes a $3 million cash award.

A biochemist and molecular biologist, Julius has made great strides in deciphering what’s behind our ability to sense heat, cold and chemical irritants – work that has offered new insights to scientists who aim to better understand and treat pain. One of Julius’ drivers has been the need for new drugs that could effectively treat pain without the side effects and addictive potential of opioid drugs.

“As a scientist, you want to understand the basics,” Julius said. “Ultimately, from the therapeutic perspective, identifying signaling molecules within pain pathways has relevance for drug design, because those are potential targets for the development of new treatments.”

“The work of David Julius demonstrates once again that curiosity-driven research into the fundamental workings of biology not only elevates our understanding of the human condition but also leads to new discoveries with major implications for advancing medicine,” said UCSF Chancellor Sam Hawgood, MBBS. “It is a source of pride for all of us at UCSF that David’s unique and seminal work, which has inspired scientists worldwide, has been recognized with the Breakthrough Prize.”

The work of David Julius demonstrates once again that curiosity-driven research into the fundamental workings of biology not only elevates our understanding of the human condition but also leads to new discoveries with major implications for advancing medicine.

UCSF Chancellor Sam Hawgood

Through decades of research, Julius has homed in on a class of ion channel proteins called TRP (pronounced “trip”) receptors, and his work has stimulated intense interest in TRP channels as potential targets for new painkillers.

For example, since joining the UCSF faculty in 1989, Julius has sought, along with his students and postdoctoral fellows, to understand how the chemical compound responsible for the spicy heat of chili peppers – called capsaicin – elicits a burning sensation when eaten or touched. The research has led to the detailed characterization of the specific protein responsible, named TRPV1.

TRPV1 is a specialized ion channel located at the outer tips of sensory nerves, which transmit electrical signals to the brain, where the sensation of heat or pain is generated.

Julius has shown that “hot” chili peppers are aptly named, since TRPV1 is triggered not only by capsaicin, but also by “real” heat greater than 110 degrees Fahrenheit. This ion channel also contributes to the hypersensitivity to heat felt in injured tissue, such as sunburned skin, in which the brain perceives mild stimuli as burning hot.

In recent years, Julius has turned his attention to better understanding the structure of TRPV1 and related molecules, in hopes that this information could aid the design of new pain drugs. In a scientific tour de force in 2013, he and UCSF colleague Yifan Cheng, PhD, used a technique called cryo-electron microscopy, or cryoEM, to determine the structure of TRPV1 at near-atomic scale.

Julius has also applied these approaches to identify the molecular source of the icy sensation triggered by menthol from mint. Just as heat acts on TRPV1 similarly to capsaicin, Julius’ lab found that a related channel called TRPM8 can be activated either by menthol or by cold temperatures. A third TRP channel, TRPA1, responds to the pungent compounds that give wasabi its punch, and is also involved in inflammatory pain. In 2015, Julius and Cheng used cryo-EM to determine the structure of this “wasabi receptor.”

wasabi receptor show in microscopic detail

David Julius and Yifan Cheng used cryo-EM to determine the structure of the “wasabi receptor.”

Julius and his fellow awardees will be recognized at the eighth annual Breakthrough Prize gala awards ceremony on Sunday, Nov. 3, at NASA Ames Research Center in Mountain View, Calif., which will be broadcast live on the National Geographic channel. The awards will be followed by the Breakthrough Prize Symposium on Monday, Nov. 4. The symposium is being hosted at UCSF’s Mission Bay campus.

Julius, the Morris Herzstein Chair in Molecular Biology and Medicine at UCSF, has received numerous honors and awards, including the Canada Gairdner International Award, the Shaw Prize in Life Science and Medicine, the Dr. Paul Janssen Award for Biomedical Research, the Passano Award, the Prince of Asturias Award for Technical and Scientific Research, the Scolnick Prize from the McGovern Institute for Brain Research, the Unilever Science Prize, and the Klaus Joachim Zülch Neuroscience Prize. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.