On October 4, the Nobel Committee announced that the 2021 Nobel Prize in Biomedical Sciences - the first prize of the Nobel season - belonged to two American biologists David Julius and Ardem Patapoutian for their discoveries of mechanisms, body temperature, and touch sensors.

Professor David Julius is an American physiologist at the University of California at San Francisco, and Professor Ardem Patapoutian is an Armenian-American molecular biologist with the Scripps Research Institute in La Jolla, California.

The two biologists previously received the BBVA Foundation's Prize in Biology and Medicine for their work. You can find out more about the Nobel Prize in Medicine 2021 at Medicinecontact.com

How do humans perceive temperature and pressure?

The human ability to sense heat, cold, and touch is essential to survival and underlies our interactions with the world around us.

In everyday life, we take these sensations for granted, but how do nerve impulses begin to sense temperature and pressure? This question has been solved by this year's Nobel Prize winners in Biomedical Sciences.

Biologist David Julius used capsaicin - a spicy compound from chili peppers that causes the sensation of heat - to identify a sensor in the skin's nerve endings that responds to heat. Biologist Ardem Patapoutian, using sensitive cells, discovered a sensor that responds to mechanical stimuli in the skin and internal organs.

These groundbreaking discoveries have ignited extensive research, giving us a rapid understanding of how the human nervous system perceives hot, cold, and mechanical stimuli. These biologists have identified extremely important relationships in the complex interplay between the human senses and the environment.

One of the great mysteries facing humanity is how humans perceive their environment. The mechanisms inside the human body's senses have piqued our curiosity for thousands of years, such as how light is detected by the eye, how sound waves affect our inner ear, and how Various chemical compounds interact with receptors in the nose and mouth to produce odors and tastes. . .

Humans also have countless other ways of perceiving the world around them, like walking barefoot on the grass on a hot summer day can help people feel the heat of the sun, the caress of the wind, and grass underfoot. These sensations of temperature, touch, and movement are essential for human adaptation to ever-changing surroundings.

In the 17th century, the philosopher René Descartes envisioned threads connecting different parts of the skin to the brain. Accordingly, a foot that touches an open flame sends a mechanical signal to the brain. Subsequent discoveries revealed the existence of specialized sensory neurons that record changes in the human environment.

In 1944, two scientists Joseph Erlanger and Herbert Gasser received the Nobel Prize in Biomedical Sciences that year for discovering different types of sensory nerve fibers that respond to different stimuli, for example to painful and painless touch.

Since then, it has been shown that neurons are highly specialized to detect and transmit different types of stimuli, allowing for the nuanced perception of human surroundings. Specifically, the human ability to feel the difference in the texture of a surface through the fingertips, or the ability to distinguish between both pleasant warmth and painful heat….

Unknown discoveries

In the late 1990s, biologist David Julius of the University of California, San Francisco (USA) analyzed how the chemical compound capsaicin causes the burning sensation that people feel when exposed to chili peppers.

Capsaicin has been known to activate the nerve cells that cause pain, but how this chemical function is an unanswered question.

Julius and colleagues created a library of millions of DNA fragments that correspond to genes expressed in sensory neurons that can respond to pain, heat, and touch.

Julius and colleagues hypothesized that the library would include a DNA fragment encoding a protein capable of reacting with capsaicin. They mimicked individual genes in cultured cells that would normally not respond to capsaicin. After a painstaking search, scientists have identified a single gene that can make cells sensitive to capsaicin. This gene, identified to encode a novel ion channel protein and capsaicin receptor, was named TRPV1.

The discovery of TRPV1 is a major breakthrough, leading the way towards the discovery of additional temperature-sensing receptors.

Acting independently, biologists David Julius and Ardem Patapoutian both used the chemical menthol to identify TRPM8, a receptor-activated in cold. Additional ion channels associated with TRPV1 and TRPM8 were identified and activated by a range of different temperatures.

David Julius' discovery of TRPV1 is a breakthrough that allows people to understand how temperature differences can generate electrical signals in the nervous system.

And Ardem Patapoutian and colleagues have identified for the first time a cell line that emits measurable electrical signals when individual cells are poked with a micropipette.

The scientists assumed that the receptor activated by mechanical force was an ion channel, and in the next step, 72 candidate genes encoding possible receptors were identified. These genes were in turn inactivated to reveal the gene responsible for mechanosensitivity in the cells studied.

After an arduous search, Patapoutian and his colleagues succeeded in identifying a single gene that silences cells that render cells insensitive to micropipette probing. A new and completely unknown mechanically induced ion channel has been discovered and named 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 have firmly established that Piezo1 and Piezo2 are ion channels that are directly activated when pressure is applied to the cell membrane.

The Patapoutian breakthrough led to a series of demonstrations that the Piezo2 ion channel is essential for touch. Furthermore, Piezo2 has been shown to play an important role in the all-important sensing of body position and movement, known as proprioception. In a further study, Piezo1 and Piezo2 channels have been shown to regulate other important physiological processes including blood pressure, respiration, and urinary bladder control.