• American scientists David Julius and Ardem Patapoutian won the 2021 Nobel Prize for Physiology or Medicine for their discoveries of receptors for temperature and touch. 

• Julius utilised capsaicin, a pungent compound from chili peppers that induces a burning sensation, to identify a sensor in the nerve endings of the skin that responds to heat. 

• Patapoutian used pressure-sensitive cells to discover a novel class of sensors that respond to mechanical stimuli in the skin and internal organs. 

• The Nobel Committee said that their discoveries have unlocked one of the secrets of nature by explaining the molecular basis for sensing heat, cold and mechanical force, which is fundamental for our ability to feel, interpret and interact with our internal and external environment.

• Last year’s Prize went to three scientists who discovered the liver-ravaging Hepatitis C virus.

Sensing temperature

In the latter part of the 1990’s, David Julius at the University of California, San Francisco saw the possibility for major advances by analysing how the chemical compound capsaicin causes the burning sensation we feel when we come into contact with chili peppers. 

Capsaicin was already known to activate nerve cells causing pain sensations, but how this chemical actually exerted this function was an unsolved riddle. 

Julius and his coworkers created a library of millions of DNA fragments corresponding to genes that are expressed in the sensory neurons which can react to pain, heat, and touch. Julius and colleagues hypothesized that the library would include a DNA fragment encoding the protein capable of reacting to capsaicin. They expressed individual genes from this collection in cultured cells that normally do not react to capsaicin. 

After a laborious search, a single gene was identified that was able to make cells capsaicin sensitive. The gene for capsaicin sensing had been found.

Further experiments revealed that the identified gene encoded a novel ion channel protein and this newly discovered capsaicin receptor was later named TRPV1. When Julius investigated the protein’s ability to respond to heat, he realised that he had discovered a heat-sensing receptor that is activated at temperatures perceived as painful.

Julius and Patapoutian used the chemical substance menthol to identify TRPM8, a receptor that was shown to be activated by cold. Additional ion channels related to TRPV1 and TRPM8 were identified and found to be activated by a range of different temperatures.

Julius’ discovery of TRPV1 was the breakthrough that allowed us to understand how differences in temperature can induce electrical signals in the nervous system.

Sensing mechanical stimuli

Ardem Patapoutian, working at Scripps Research in La Jolla, California wished to identify the elusive receptors that are activated by mechanical stimuli.

Patapoutian and his collaborators first identified a cell line that gave off a measurable electric signal when individual cells were poked with a micropipette. It was assumed that the receptor activated by mechanical force is an ion channel and in a next step 72 candidate genes encoding possible receptors were identified. 

These genes were inactivated one by one to discover the gene responsible for mechanosensitivity in the studied cells. After an arduous search, Patapoutian and his co-workers succeeded in identifying a single gene whose silencing rendered the cells insensitive to poking with the micropipette. 

A new and entirely unknown mechanosensitive ion channel had been discovered and was given the name Piezo1, after the Greek word for pressure. Through its similarity to Piezo1, a second gene was discovered and named Piezo2. Sensory neurons were found to express high levels of Piezo2 and further studies firmly established that Piezo1 and Piezo2 are ion channels that are directly activated by the exertion of pressure on cell membranes.

The breakthrough by Patapoutian led to a series of papers from his and other groups, demonstrating that the Piezo2 ion channel is essential for the sense of touch.

Unlocking one of the secrets of nature

• The groundbreaking discoveries of the TRPV1, TRPM8 and Piezo channels by this year’s Nobel laureates have allowed us to understand how heat, cold and mechanical force can initiate the nerve impulses that allow us to perceive and adapt to the world around us. 

• The TRP channels are central for our ability to perceive temperature. The Piezo2 channel endows us with the sense of touch and the ability to feel the position and movement of our body parts. 

• TRP and Piezo channels also contribute to numerous additional physiological functions that depend on sensing temperature or mechanical stimuli.

Nobel Prize

Alfred Nobel, an inventor, entrepreneur, scientist and businessman, laid the foundation for the prize in 1895 when he wrote his last will, leaving much of his wealth to the establishment of the prize. Since 1901, the Nobel Prize has been honoring men and women from around the world for outstanding achievements in physics, chemistry, physiology or medicine, literature and for work in peace.

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