David Julius, PhD, professor and chair of the Department of Physiology at UC San Francisco, was named on March 28 to receive the 2017 Canada Gairdner International Award, one of the most prestigious prizes in biomedicine. The award, accompanied by a $100,000 honorarium, is given annually to five scientists who have made significant contributions to understanding human biology and disease.
Julius received the prize “for determining the molecular basis of somatosensation – how we sense heat, cold and pain,” according to the award citation. His work has stimulated intense interest among pharmaceutical companies interested in finding new classes of drugs that could effectively treat pain without the side effects and addictive potential of opioids.
“Dr. Julius’s research is fundamental and has been critical to the development of novel pain-relieving drugs. We are pleased to bring him into the Gairdner family of more than 360 laureates,” said Janet Rossant, PhD, president and scientific director of the Gairdner Foundation, which bestows the award each year. According to the Foundation’s website, 84 previous Gairdner Award recipients have gone on to win a Nobel Prize.
Distinctive Molecules from the Natural World
In his work, Julius and his lab team have used distinctive molecules from the natural world – including toxins from tarantulas and coral snakes, as well as capsaicin, the molecule that produces the “heat” in chili peppers – to understand how signals responsible for temperature and pain sensation are detected and transmitted by neural circuits to the brain.
For example, TRPV1 (“trip vee one”) is a remarkable protein found on the outer tips of sensory nerves. Julius and colleagues have shown that the hot chili pepper is aptly named: TRPV1 is triggered not only by the application of capsaicin, but also by “real” heat greater than 110 degrees Fahrenheit.
Whether triggered by real heat or tricked by capsaicin, TRPV1 changes the electrical potential of the sensory nerves in which it resides, sending a signal that travels through these cells’ branching connections to neighboring nerve cells, and ultimately to the brain, where the sensation of heat or pain is generated. The TRPV1 channel also contributes to the hypersensitivity to heat felt in injured tissue, such as sunburned skin, in which even mild stimuli are interpreted by the brain as burning heat.
Julius’s lab also discovered that a molecule called TRPM8, which is structurally similar to TRPV1, is responsible for sensing cool temperatures – and can similarly be “tricked” by menthol and related compounds, which explains mints’ cooling effects. A third TRP channel studied by the Julius lab, called TRPA1, responds to inflammatory pain, such as the pain of arthritis, but also reacts to the pungent compounds that give wasabi and mustard their punch.
Understanding the Molecules in Detail
In recent years, Julius has turned his attention to better understanding the structure of TRPV1 and related molecules in detail, in hopes that this information could drive the design of new pain drugs. In 2013, in a scientific tour de force, members of the Julius lab and that of UCSF colleague Yifan Cheng, PhD, used a technique called cryo-electron microscopy, or cryoEM, to determine the structure of TRPV1 at near-atomic scale. Two years later, the Julius and Cheng labs accomplished the same feat with TRPA1.
This video shows a three-dimensional model of the TRPV1 protein at 3.4 Angstroms, bound by both spider toxin (pink) and resiniferatoxin (red spheres). Resiniferatoxin occupies the same binding sites as capsaicin, the compound that gives chilies their “heat.” The protein’s four subunits are colored light yellow, blue, green and red. As the model rotates to show top and bottom views, the central channel through which ions pass into the cell is visible. Courtesy of Cheng lab
“David’s work demonstrates that fundamental biological research can lead researchers to surprising and powerful new discoveries with major implications for advancing medicine,” said UCSF Chancellor Sam Hawgood, MBBS. “I want to congratulate David for this great honor, which reflects the values of creativity paired with scientific rigor that UCSF takes great pride in fostering.”
Julius, the Morris Herzstein Chair in Molecular Biology and Medicine at UCSF, has received numerous honors and awards, including the Dr. Paul Janssen Award for Biomedical Research, the Shaw Prize in Life Science and Medicine, 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 Science, the National Academy of Medicine (formerly the Institute of Mediine), and the American Academy of Arts and Sciences.
“We spend so much of our time looking ahead to the next study or the next approach to cracking the mysteries of the biology of pain, but an award like this is an opportunity to turn around and take stock,” Julius said. “It’s wonderful recognition for the lab and all the talented people who have contributed to this work over the years that everything we have been pulling towards is exciting to society as well. If anything I hope we’ve inspired people to think about pain as a process that can be understood and eventually controlled.”
Past UCSF recipients of the Gairdner Award include Nobel Laureates J. Michael Bishop, MD; Elizabeth Blackburn, PhD; Shinya Yamanaka, MD, PhD; Stanley Prusiner, MD; and Harold Varmus, MD; as well as prominent researchers John Clements, MD; YW Kan, MD, FRS; and Peter Walter, PhD.
The other 2017 Gairdner Award recipients were Akira Endo, PhD, of Tokyo University of Agriculture and Technology; Lewis E. Kay, PhD, of the University of Toronto; Rino Rappouli, PhD, of GlaxoSmithKlein Vaccines; and Huda Y. Zoghbi, MD of Baylor College of Medicine.
UC San Francisco (UCSF) is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy; a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences; and a preeminent biomedical research enterprise. It also includes UCSF Health, which comprises three top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospitals in San Francisco and Oakland, and other partner and affiliated hospitals and healthcare providers throughout the Bay Area.