Nobel Prize-winning research

Today the Nobel Laureates in Medicine or Physiology. This year, the winners have been David julius and Ardem Patapoutian for his discoveries of the receptors of the temperature and the touch. The ability to perceive heat, cold and touch is essential for survival and sustains interaction with the world around us, but how do nerve impulses start to be able to perceive temperature and pressure?

This question has been answered by this year's two laureates. First, the American biochemist David Julius (New York, 1955) used the capsaicin, a spicy compound in chili that induces a burning sensation, to identify a sensor in the nerve endings of the skin that responds to heat.

The awardees identified critical links that were missing in our understanding of the complex interplay between our senses and the environment.

For his part, Ardem Patapoutian (Lebanon, 1967) used pressure-sensitive cells to discover a new class of sensors that respond to mechanical stimuli in the skin and internal organs. These discoveries rapidly increased understanding of how our nervous system perceives heat, cold, and mechanical stimuli.

Additionally, the awardees identified critical links that were missing in our understanding of the complex interplay between our senses and the environment.

The importance of perceiving the environment

Appreciating temperature, touch, and movement is essential to our adaptation to the ever-changing environment. As early as the seventeenth century, the philosopher Rene Descartes he imagined threads connecting different parts of the skin to the brain. In this way, a foot touching an open flame would send a mechanical signal to the brain.

Later discoveries revealed the existence of specialized sensory neurons that record changes in our environment. Joseph Erlanger and Herbert Gasser received the Nobel Prize in Physiology or Medicine in 1944 for their discovery of different types of sensory nerve fibers that react to different stimuli, for example, in responses to painful and non-painful touch.

Before the discoveries of Julius and Patapoutian, it was not known how temperature and mechanical stimuli are converted into electrical impulses in the nervous system.

Since then, it has been shown that nerve cells are highly specialized in the detection and transduction of different types of stimuli, allowing a nuanced perception of our environment.

For example, our ability to feel differences in surface texture through our fingertips, or to discern between pleasant and unpleasant heat.

The capsaicin gene

Before the discoveries of Julius and Patapoutian, it was not known how temperature and mechanical stimuli are converted into electrical impulses in the nervous system. In the late 1990s, David Julius, a researcher at the University of California, San Francisco (USA), saw the possibility of making great advances by analyzing how the chemical compound capsaicin causes the burning sensation that we feel when we come into contact with peppers.

At that time it was already known that this compound activated the nerve cells that cause the sensation of pain, but the way in which this chemical substance actually exerted this function was an unsolved puzzle.

The discovery of TRPV1 was the breakthrough that made it possible to understand how temperature differences can induce electrical signals in the nervous system.

Julius and his companions created a library of millions of DNA fragments corresponding to genes that are expressed in sensory neurons that react to pain, heat, and touch. And they hypothesized that the library would include a DNA fragment that would encode the protein capable of reacting to capsaicin. Finally, they identified a single gene capable of making cells sensitive to the compound.

Further experiments revealed that the identified gene encoded a new ion channel protein, and this newly discovered receptor was later named TRPV1. When Julius investigated the protein's ability to respond to heat, he realized that he had discovered a heat sensor that activated at temperatures perceived as painful.

The discovery of TRPV1 was a breakthrough that paved the way for unraveling other temperature sensors. Julius and Patapoutian independently used menthol to identify TRPM8, a receptor that is activated by cold. Other ion channels related to TRPV1 and TRPM8 were also identified and found to be activated at different temperatures.

Touch and pressure sensors

However, it remained unclear how mechanical stimuli could be converted into senses of touch and pressure. The researchers had already found mechanical sensors in bacteria, but the mechanisms underlying touch in vertebrates remained unknown.

Patapoutian, a scientist at Scripps Research in La Jolla (California, USA), wanted to identify the receptors that are activated by mechanical stimuli. Thus, his team identified for the first time a cell line that emitted a measurable electrical signal when individual cells were punctured with a micropipette.

In later work, the Piezo1 and Piezo2 channels have been shown to regulate other important physiological processes, such as blood pressure, respiration, and urinary bladder control.

The receptor activated by mechanical force was assumed to be an ion channel and in a next step, 72 candidate genes encoding potential receptors were identified. These genes were inactivated one by one to discover the person responsible for the mechanosensitivity in the cells studied.

Finally, they managed to describe a single gene whose silencing made cells insensitive to micropipette punctures: Piezo1. Because of its similarity with Piezo1, a second gene called Piezo2 was discovered.

Patapoutian's breakthrough led to a series of works that demonstrated that the Piezo2 ion channel is essential for the sense of touch. Furthermore, it was shown that Piezo2 plays a critical role in sensing body position and movement, known as proprioception.

In later work, the Piezo1 and Piezo2 channels have been shown to regulate other important physiological processes, such as blood pressure, breathing and urinary bladder control.

In short, the discovery of the TRPV1, TRPM8 and Piezo channels has made it possible to understand how heat, cold and mechanical force can initiate the nerve impulses that facilitate perception and adaptation to the world around us.