David Julius and Ardem Patapoutian won the 2021 Nobel Prize in Physiology and Medicine for their work on temperature and touch
Writer: Denis Duagi
Editor: Chelsea K Tripp
Artist: Lucie Gourmet
On October 4, 2021, the Nobel Assembly at Karolinska Institute jointly awarded David Julius and Ardem Patapoutian the Nobel Prize in Physiology or Medicine for their independent discoveries of receptors responsible for our ability to sense heat, cold, and touch. The Nobel Prize in Physiology and Medicine is the highest honour in the field of neuroscience, and historically, a total of 17 Nobel Prizes have been awarded in the area of neuroscience to no less than 40 laureates. The prize has previously been has been awarded to the fathers of neuroscience, Cajal and Golgi, world-renowned figures in the field such as Bernard Katz and Rita Levi-Montalcini, and more recently to UCL scientist John O’Keefe and scandinavian scientists May-Britt Moser and Edvard I. Moser.
The two scientists are joining in for their discoveries of the receptors for temperature and touch. David Julius and his collaborators identified and cloned the capsaicin receptor, now known as the transient receptor potential vanilloid type 1 (TRPV1) receptor. Patapoutian’s team was responsible for cloning PIEZO1 and PIEZO2, mechanically sensitive ion channels that transduce sensations of touch and sometimes, pain.
These discoveries began in the late 1990s, when David Julius at the University of California, San Francisco, began to systematically interrogate individual proteins expressed by sensory neurons to assess which could respond to capsaicin, the chemical irritant found in chilli peppers. This experimentation identified a gene that encoded a novel ion channel protein which was later named TRPV1. Upon further investigation, it was discovered that the TRPV1 channel is sensitive to heat and opens at temperatures greater than 43°C. The resulting influx of ions through the open channel induces electrical signals in the nerve fibres in our skin, which are then transmitted to the central nervous system where they are perceived as painful. Subsequently, Julius identified and characterized multiple other channels from the same TRP family with roles in pain and somatosensation.
During this time, Ardem Patapoutian, working at the Scripps Research Institute in La Jolla, California, sought to identify receptors activated by mechanical stimuli. Using a cell line that produced a measurable electrical signal when insulted with a micropipette, and a similar systematic approach as that of Julius, Patapoutian discovered an ion channel protein whose knockout rendered the cell line insensitive to mechanical insults. This mechanosensitive ion channel would be named Piezo1, and lead to the discovery of a second protein, named Piezo2, which also responded to mechanical pressure. Similar to the mechanism of the temperature-sensing receptors, both Piezo1 and Piezo2 open following the exertion of mechanical force to the membranes of sensitive cells, and the resulting influx of ions induce electrical signals in the nervous system.
The discoveries of both David Julius and Ardem Patapoutian have impacted the fundamental understanding of how we sense and interact with our environment. Briefly, TRPV1 has been shown to play a role in how we regulate our core body temperature and respond to various types of pain, and Piezo2 is involved in how we regulate our blood pressure and breathing, to name a few. These discoveries continue to inform the development of treatments for a variety of conditions, including chronic pain. In one interview, the two researchers talk about how these molecular targets could be of immense therapeutic value, similarly to how antibodies against Calcitonin Gene Related Peptide (CGRP) and anti Nerve Growth Factor (NGF) have revolutionized the treatments for migraine and arthritis. The work of Julius and Patapoutian altered the trajectory of neuroscience research, and they have been rewarded with the highest honor in their field.