The Nobel Prize in Physiology or Medicine 2021 has been awarded jointly to
- David Julius, University of California, San Francisco (UCSF), USA, and
- Ardem Patapoutian, Howard Hughes Medical Institute, Scripps Research, La Jolla, CA, USA,
“for their discoveries of receptors for temperature and touch”.
Research
Our ability to sense heat, cold, and touch is essential for survival. David Julius and Ardem Patapoutian discovered how nerve impulses are initiated so that temperature and pressure can be perceived.
Temperature-Sensing
David Julius used capsaicin, a compound from chili peppers that induces a burning sensation. It was already known that capsaicin activates nerve cells that trigger pain sensations, but how it exerts this function was unknown. Julius and his team created a library of millions of DNA fragments corresponding to genes expressed in sensory neurons that can react to pain, heat, and touch. They expressed individual genes from this collection in cultured cells that normally do not react to capsaicin and identified a single gene that was able to make the cells sensitive to capsaicin. The identified gene encoded an ion-channel protein, and this newly discovered capsaicin receptor was later named TRPV1.
The discovery of TRPV1 was a breakthrough that paved the way for deciphering other temperature-sensing receptors. Related ion channels were identified, leading to an understanding of how different temperatures can trigger electrical signals in the nervous system. Independently, David Julius and Ardem Patapoutian used menthol to identify TRPM8, a receptor that is activated by cold. Additional ion channels related to TRPV1 and TRPM8 were identified and found to be activated by a range of different temperatures.
Pressure-Sensing
Ardem Patapoutian used pressure-sensitive cells to discover a new class of sensors that respond to mechanical stimuli in the skin and internal organs. The team first identified a cell line that emitted a measurable electrical signal when individual cells were poked with a micropipette. 72 candidate genes encoding possible receptors were identified and inactivated one by one to discover the gene responsible for mechanosensitivity.
The team identified a single gene whose silencing rendered the cells insensitive to impact with the micropipette. It was named Piezo1, after the Greek word for pressure. Through its similarity to Piezo1, a second gene was discovered and named Piezo2. Piezo1 and Piezo2 are ion channels that are directly activated by the exertion of pressure on cell membranes.
Patapoutian’s breakthrough led to further research showing that the Piezo2 ion channel is essential for the sense of touch. Moreover, Piezo2 was shown to play a key role in the sensing of body position and motion, known as proprioception. Piezo1 and Piezo2 channels have been shown to regulate additional important physiological processes, including blood pressure, respiration, and urinary bladder control.
Laureates
David Julius, born November 4, 1955, in Brighton Beach, Brooklyn, NY, USA, studied at the Massachusetts Institute of Technology (MIT) in Cambridge, MA, USA, and received his Ph.D. from the University of California, Berkeley, USA, in 1984, under joint supervision of Jeremy Thorner and Randy Schekman. As a postdoctoral fellow, Julius worked with Richard Axel at Columbia University, New York City, NY, USA. In 1990, he joined the faculty at the University of California, San Francisco (UCSF), where he currently is the Chair of the Department of Physiology.
Among many other awards, David Julius received the Shaw Prize in Life Science and Medicine in 2010, the Breakthrough Prize in Life Sciences in 2020, and the 2020 Kavli Prize in Neuroscience (together with Ardem Patapoutian).
Ardem Patapoutian, born in Beirut, Lebanon, in 1967, studied chemisty at the American University of Beirut before emigrating to the United States in 1986. He earned a bachelor’s degree in cell and developmental biology from the University of California, Los Angeles, USA, in 1990 and a Ph.D. in biology from the California Institute of Technology (Caltech), Pasadena, CA, USA, in 1996. As a postdoctoral fellow, Patapoutian worked with Louis F. Reichardt at the University of California, San Francisco. In 2000, he became an Assistant Professor at the Scripps Research Institute. Between 2000 and 2014, he held another research position at the Novartis Research Foundation, and since 2014, he has been a Researcher for the Howard Hughes Medical Institute (HHMI).
Among many other awards, Ardem Patapoutian received the W. Alden Spencer Award in 2017, the Rosenstiel Award in 2019, the Kavli Prize for Neuroscience in 2020 (together with David Julius), and the BBVA Foundation Frontiers of Knowledge Award in Biology/Biomedicine. He is a Fellow of the American Association for the Advancement of Science since 2016, a Member of the National Academy of Sciences since 2017, and Member of the American Academy of Arts and Sciences since 2020.
Award Ceremony
Traditionally, the award ceremonies take place in Stockholm, Sweden, on December 10—the anniversary of Alfred Nobel’s death. This year, the Laureates will receive their medals and diplomas in their home countries, and the traditional banquet will not take place due to the coronavirus pandemic. Last year was the first time since 1956 that the banquet was canceled, also because of the pandemic. In 1956, the banquet was suspended to avoid having to invite the Soviet ambassador after the USSR invaded Hungary.
Selected Publications by David Julius
- The capsaicin receptor: a heat-activated ion channel in the pain pathway,
Michael J. Caterina, Mark A. Schumacher, Makoto Tominaga, Tobias A. Rosen, Jon D. Levine, David Julius,
Nature 1997, 389, 816–824.
https://doi.org/10.1038/39807 - The Cloned Capsaicin Receptor Integrates Multiple Pain-Producing Stimuli,
Makoto Tominaga, Michael J. Caterina, Annika B. Malmberg, Tobias A. Rosen, Heather Gilbert, Kate Skinner, Brigitte E. Raumann, Allan I. Basbaum, David Julius,
Neuron 1998, 21, 531–543.
https://doi.org/10.1016/S0896-6273(00)80564-4 - Impaired Nociception and Pain Sensation in Mice Lacking the Capsaicin Receptor,
M. J. Caterina, A. Leffler, A. B. Malmberg, W. J. Martin, J. Trafton, K. R. Petersen-Zeitz, M. Koltzenburg, A. I. Basbaum, D. Julius,
Science 2000, 288, 306–313.
https://doi.org/10.1126/science.288.5464.306 - Identification of a cold receptor reveals a general role for TRP channels in thermosensation,
David D. McKemy, Werner M. Neuhausser, David Julius,
Nature 2002, 416, 52–58.
https://doi.org/10.1038/nature719
Selected Publications by Ardem Patapoutian
- A TRP Channel that Senses Cold Stimuli and Menthol,
Andrea M. Peier, Aziz Moqrich, Anne C. Hergarden, Alison J. Reeve, David A. Andersson, Gina M. Story, Taryn J. Earley, Ilaria Dragoni, Peter McIntyre, Stuart Bevan, Ardem Patapoutian,
Cell 2002, 108, 705–715.
https://doi.org/10.1016/S0092-8674(02)00652-9 - Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels,
B. Coste, J. Mathur, M. Schmidt, T. J. Earley, S. Ranade, M. J. Petrus, A. E. Dubin, A. Patapoutian,
Science 2010, 330, 55–60.
https://doi.org/10.1126/science.1193270 - Piezo2 is the major transducer of mechanical forces for touch sensation in mice,
Sanjeev S. Ranade, Seung-Hyun Woo, Adrienne E. Dubin, Rabih A. Moshourab, Christiane Wetzel, Matt Petrus, Jayanti Mathur, Valérie Bégay, Bertrand Coste, James Mainquist, A. J. Wilson, Allain G. Francisco, Kritika Reddy, Zhaozhu Qiu, John N. Wood, Gary R. Lewin, Ardem Patapoutian,
Nature 2014, 516, 121–125.
https://doi.org/10.1038/nature13980 - Piezo2 is the principal mechanotransduction channel for proprioception,
Seung-Hyun Woo, Viktor Lukacs, Joriene C de Nooij, Dasha Zaytseva, Connor R Criddle, Allain Francisco, Thomas M Jessell, Katherine A Wilkinson, Ardem Patapoutian,
Nat. Neurosci. 2015, 18, 1756–1762.
https://doi.org/10.1038/nn.4162
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