Touching Down on the 2021 Nobel Prize in Physiology or Medicine

blog / News October 15 2021

Last week, the Nobel assembly at the Karolinska Institute in Sweden announced the Nobel Prize in Physiology or Medicine to two scientists whose work ultimately solved the ancient mystery of how the human body perceives temperature and pressure.

And the 2021 Nobel Prize in Physiology or Medicine goes to …

This year’s award went to David Julius and Ardem Patapoutian, both based in the US, for their outstanding work in identifying sensors in the nerve endings of our skin and internal organs that allow us to perceive and respond to heat and mechanical stimuli.  David Julius is a professor and group leader at University of California, San Francisco School of Medicine, and Ardem Patapoutian is a neuroscience professor and Howard Hughes Medical Institute investigator at Scripps Research in La Jolla, California.

Breakthrough discoveries made by Julius and Patapoutian over the course of their careers were the catalysts for what would become an intense research field that would eventually answer fundamental questions about how the human nervous system senses heat, cold, and touch, filling big gaps in our understandings about the complex interplay between our senses and the environment, which is critical for our survival.

Watch the announcement of the 2021 Nobel Prize in Physiology or Medicine

Source: Nobel Prize

Turning up the heat in David Julius’ lab

David Julius obtained a PhD from UC Berkeley, followed by a postdoc at Columbia University in the 1980’s. During his postdoc, he cloned and characterised the human serotonin 1c receptor, which yielded new insights into the how the roles of serotonin, the so-called ‘happy hormone’, are mediated in the central nervous system.

Julius’ faculty career began at the University of California, San Francisco in 1989, where he continued to study the serotonin 1c receptor throughout the 1990s with many significant publications in this field. Towards the end of that decade, his attention shifted to chilli peppers when he saw the possibility to make massive strides in research by studying how the chemical compound capsaicin causes the burning sensation that occurs when we eat a chilli dish.

At this point, other researchers in the field had already figured out that capsaicin activates certain nerve cells that cause pain sensations, but how this actually happened remained a conundrum.

To solve the mystery, Julius and his group members created a large complementary DNA (cDNA) library representing the genes expressed by the sensory neurons that respond to heat, pain and touch. They rationalised that the gene(s) that mediated the nerve response to capsaicin would be represented in that cDNA pool, and they were right!

Eventually, and after many cell culture experiments to study the function of these cDNAs one by one, the group identified a single gene whose expression could make otherwise non-responsive cells respond to capsaicin. This gene encodes a new ion channel protein that they later called TRPV1. They had found a capsaicin receptor that becomes activated at temperatures perceived by cells as being painful.

The hot-cold code had been cracked

 The groundbreaking findings on TRPV1 were published in Nature in 1997, paving the way for discoveries of additional temperature-sensing receptors in the years to follow.

The discovery of the cold-sensitive receptor TRPM8, which was made independently but simultaneously by David Julias and Ardem Patapoutian who published their findings in Nature and Cell, respectively, was another important piece in the puzzle, and soon many different ion channels were uncovered that were shown to be activated by a range of different temperatures.

Other labs around the world quickly hopped on the bandwagon to explore the roles of these channels in sensing heat, using genetically-engineered animal models that lacked the newly uncovered genes.

Ardem Patapoutian comes into the picture

As well as having an interest in temperature sensing, Ardem Patapoutian was also on a mission to elucidate the receptors that are activated by mechanical stimuli. Patapoutian obtained a PhD in biology from the California Institute of Technology in 1996 and then completed a postdoc at the University of California, San Francisco, before assuming his faculty role at Scripps Research Institute, where he has been based since 2000.

Alongside research in thermal sensing, Patapoutian and collaborators began searching for genes involved in touch perception. They had noticed that individual cells of a particular cell line emitted a measurable electric signal when they were prodded with a pipette. To dig into the reason for this, they began inactivating a panel of 72 candidate genes that putatively encoded ion channels, one by one to see if inactivation of any of these genes eliminated the electrical reaction to the pipette. They identified one gene, which they named Piezo1, which was soon followed by the discovery of another similar gene called Piezo2.

Patapoutian and his team found that the Piezo1 and Piezo2 genes were highly expressed by sensory neurons and further characterization revealed them to encode ion channels that were activated directly upon the exertion of pressure on cell membranes. These key findings were published in Science in 2010, which opened the floodgates to many publications from Patapoutian’s group and others who showed that Piezo2 is indispensable for the sense of touch, as well as additional roles for Piezo1 and Piezo2 in mechanical perception as well as in fundamental physiological processes.

The future is bright – can you feel it?

Julias’ and Patapoutian’s remarkable achievements have not only solved the age-old puzzle of how temperature and mechanical stimuli trigger nerve impulses, but they have also set the stage for further research and efforts to develop treatments for a range of diseases, including chronic pain. Only the future will reveal the full potential of their accomplishments!

Further Reading: