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The Nobel Prize in Physiology or Medicine 2021

The Nobel Prize in Physiology or Medicine 2021 has been awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch.

The work that led to this year’s Nobel Prize is focussed on somatosensation, our ability to feel temperature and touch. Somatosensation is what gives us the ability to feel our body surface and our internal organs. It monitors temperature, pain, touch and the location or movement of our body, called proprioception. It is also essential for tasks we perform effortlessly, such as carrying a cup of coffee.

How are physical stimuli, such as heat and touch, registered by the nervous system? This question has fascinated humankind for thousands of years. It is now known that nerves register changes in our external and internal environments, and there are different types of nerves that detect different types of stimuli.

But how are heat and touch registered by the nervous system? Nerves must convert the physical stimuli of heat and touch into a biological signal. Therefore, molecular receptors must exist that detect and translate heat or touch into nerve impulses. The identity of such receptors remained unknown, until this year’s Nobel Prize winning work…

Discovering TRPV1

Capsaicin is an active component of chilli peppers. When eating a spicy meal filled with chilli peppers, one may begin to sweat. Therefore, it seems that capsaicin can trick the brain into thinking there is an actual change in body temperature.

Historically, it was known that capsaicin could activate sensory neurons, and that this activation is responsible for the burning sensation after eating spicy food. However, the molecular receptor detecting capsaicin remained a mystery.

David Julius and his co-workers set out to identify the capsaicin receptor on sensory neurons. It was assumed that a single gene must be responsible. Therefore, he made millions of DNA fragments corresponding to the active genes in sensory neurons in the hope that at least one would contain the gene for the capsaicin receptor.

The team finally succeeded and identified the capsaicin receptor, which turned out to be a novel protein named TRPV1, an ion channel localised in the cellular outer membrane. It was later found that heat opened the TRPV1 channel for ions. Therefore, Julius had discovered a temperature sensitive ion channel, activated by heat that is perceived as painful.

Years later, Ardem Patapoutian independently discovered a related channel called TRPM8. It is now recognised that several TRP channels, activated at different temperatures, work together to create cold temperature sensations and heat induced pain.

Discovering PIEZ01

The molecular mechanisms for touch also remained a mystery until now. The sensation of touch is initiated by mechanical force on the skin. Patapoutian and his co-workers identified a cell line that was mechanosensitive. In these cells, they identified 72 candidate genes that were suspected to be the critical sensor activated by mechanical force. One by one, each of the genes was silenced and the cells were tested for mechanosensitive.

After almost a year of hard work and 71 genes later, the mechanosensitive receptor was discovered in the 72nd gene after it was silenced. The gene was named PIEZ01, and soon after, a second touch-sensitive gene was found, called PIEZ02.

Patapoutian later demonstrated that PIEZ0 proteins belong to a novel class of proteins that function as ion channels, activated by mechanical force. Importantly, it was then revealed that PIEZ02 was the hugely significant sensor responsible for touch and proprioception. These are senses that are used every day; for example, in a hug.

Patrik Ernfors, member of the Nobel Committee for Physiology or Medicine, summarised:

“The work by David Julius and Ardem Patapoutian has unlocked one of the secrets of nature, by explaining the molecular basis for sensing temperature and mechanical force. This represents a foundation for our perception of temperature, heat pain, touch, and the location and movement of our body, called proprioception.

In further work, TRP and PIEZ0 channels have been found to play key roles in many aspects of physiology, thus establishing far reaching roles of the newly identified temperature and mechanically sensitive ion channels.”

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