The American David Julius discovered receptors for spicy food and heat on the skin, as well as receptors for the freshness of mint and cold. Armenian Ardem Patapoutian’s receptors are related to mechanical stress and pain. Today, they shared the Frontier Knowledge Award in the biology and biomedical categories.
This year, the BBVA Foundation awarded its Research Frontier Award in Biology and Biomedicine to researchers David Julius From the University of California, San Francisco Ardem Patapoutian La Jolla Scripps Institute (both in the United States)’ Recipient Enables us to perceive temperature, pain and stress”.
According to the jury minutes, these three characteristics are part of our sense of touch. “Perhaps the five human senses are the least understood, and Julius and Pataptian have revealed the molecular and neural basis of thermal and mechanical senses.”
Your research offers Potential medical implicationsBecause it “explains how to reduce chronic and acute pain associated with a variety of diseases, injuries and their treatment.” In fact, several pharmaceutical laboratories are looking for molecules that act on these receptors to treat different forms of chronic pain, such as those associated with inflammatory processes such as arthritis.
Óscar Marín, secretary of the Center’s jury, emphasized: “Although we have not yet seen the practical application of these findings, their potential is so great that there is no doubt that this is a transformative milestone worthy of recognition. “The neurodevelopmental disorders of King’s College London (UK), in addition to “from a basic point of view, the great value of understanding, How we see the world“.
In any case, the laureates’ discoveries have opened up a field of research that can change the way in which key physiological processes in biological functions are understood, so that relevant medical applications can be derived.
This new field is called “mechanobiology”. It is the first to study the role of pressure receptors in the excretion system to remind the bladder that the bladder is full, or to regulate pressure through the circulatory system. In the blood vessels.
Sensors with the same spiciness and heat
In the history of investigation David Julius (New York, 1955), The first surprise was when he discovered the receptors that caused a burning sensation in the mouth when the substance was ingested Capsaicin (The pungent ingredient in hot peppers or Padrón peppers) can also detect calories.
Julius used capsaicin to identify the first gene TRPV1 protein that encodes a receptor for a temperature sensor. He found that TRPV1 was also activated at high temperatures. The signal sent by this receptor is integrated into the brain and calibrated in the following way: If the heat is so high that it can burn tissue, it is interpreted as pain.
Upon learning of the ruling, the winner explained that although “in hindsight” the connection between pungency and high temperature seemed “obvious”, it was not the case at the time.His research began with his use of Natural compounds in society, Which ultimately leads to The molecular basis of pain.
“Julius said: “Plants defend themselves by producing substances that cause pain to carnivores. We have discovered that we use these tools to try to understand the feeling of pain on a molecular scale.
His research group focused on studying the molecular basis of capsaicin perception, and through the work of other groups, he learned that it may be related to pain. This is how they identified the genes for the spicy component receptor in peppers, but when they asked about the function of this protein in humans, the real surprise came. Julius pointed out: “It’s impossible. Only it can appreciate spicy food.”
In the cultured cells, they found that heat can also activate the capsaicin receptor: “We realized that heating the cell would strongly activate the receptor. The award-winning scientist recalled that this was an exciting time.
Mint and cold receiver, mustard receiver
Then, they continued to search for cold receptors to conduct this research. They have begun to track the relationship between temperature and certain flavors, and they resort to the menthol present in mint. mint, Accompanied by a sense of freshness. In fact, they found that the receptors for menthol and low temperature are the same. To Julius’ surprise, it is similar to capsaicin.
He said: “The most fascinating thing about this discovery is that the molecule is genetically very similar to capsaicin and capsaicin-activated receptors in capsicum.” Therefore, these findings reveal to us that nature uses a common Strategy that makes us Nervous system finds changes Through a series of temperature changes of similar molecules”.
Later, Julius also discovered receptors for pungent compounds mustard,belong mustard, Back to nature: “Mustard extract has been used for pain testing for many years: apply it on the skin of patients to stimulate the skin and check its response to pain; this can also cause inflammation and increase sensitivity to temperature and touch. This is the survey Inflammatory painJust like arthritis joints. After investigating how the process works, we identified the receptors in nerve cells, which is the mechanism by which mustard and other mustard plants cause the tingling sensation. “
The same mustard receptor has been found to be related to the cause of skin itching. Cry when cutting onions, Also by Some animal poison, Just like a scorpion. But Julius explained that the “most relevant” of this mechanism is that “understanding the pain of inflammatory lesions is very important” and that it is possible to “understand how the lesions cause inflammation.” pain Not only acute, but also persistent, leading to chronic pain syndrome.”
Complement each other from competing scientists
The discovery of the capsaicin receptor gene was published in 1997.then Ardem Patapoutian (Lebanon, 1967)Immigration Armenian Who came to the United States to flee the Lebanon war to become a doctor, although he soon “fell in love with research,” he has also begun to study the molecular basis of sensory perception.
The two winners met yesterday at the University of California in San Francisco during the Patapoutian postdoctoral stay. They described the beginning of their relationship as “competitors” yesterday, but because they investigated different recipients, they quickly became “complementers” “.
Patapoutian identified the genes of receptors that are activated by tension (stretching mechanical force).These receptor proteins are called Piezoelectric And they are responsible for sensing the pressure in the skin and blood vessels, so their importance to health goes beyond the sense of touch.
Tactile, neuropathic pain and mechanobiology
The minutes of the meeting said, “These discoveries opened the way to MechanobiologyThis is an emerging research field that combines biology, engineering and physics.”
The starting point of Patapoutian’s research is to observe that touch is the only sensation, based on the conversion of physical signals such as pressure into chemical language that the body can understand. “When researching nerve Make us feel touched and painful, we realize that they have done something unusual: they have the ability Perceive physical force, Just like mechanical force and temperature. Little is known about how the human body converts these physical signals into chemical language. “
Patapoutian and his team are looking for cells grown in the laboratory. These cells will pressure. When they found them, they used interfering RNA to systematically cancel the expression of the candidate gene until they identified the receptor. They did not expect to discover the relationship with other physiological processes at that time.
“We know that proteins are involved in the perception of pain, touch, hearing, or blood pressure, but no one knows a family, the receptors we found, Piezoelectric 1 and Piezoelectric 2 pcsIt will explain all these processes,” Patapoutian said yesterday.
After the initial discovery, discoveries were made in this field of research. Patapoutian team unveiled Three-dimensional structure of the receptor Piezoelectric, Which also helps to understand their mechanical function: they are large proteins that enter and leave the cell membrane dozens of times, just like they are elastic threads that pass through the cell membrane, and can stretch and contract.Last October, in natural Describes how Piezoelectric 2 alarms, indicating that the bladder is full.Also Piezoelectric 2 Perceive the friction on the skin, stroke it. Or, you can warn people with skin inflammation after sunburn.
“Piezoelectric 2 involves a specific type of pain,” Patapoutian explained. “The hammer has nothing to do with the receiver, but if I get a sunburn and feel pain just by touching my shoulder, it does work.This may be related to treatment Neuropathic pain (For example, the part that persists after the original lesion disappears). I think the next five to ten years will be very interesting to discover the medical potential of these discoveries.”
Scripps Institute researchers also found that these sensors are in “Proprioception“Refers to the ability to feel the relative position of various parts of the body, “a feeling that we are not paying attention, because we can’t close it”, but we completely rely on it to stand up or learn to walk.
Patapoutian also firmly believes that mechanobiology will reveal another way of communication between cells, which may have a huge impact on biomedical research: “Until now, we have understood life as a group of chemical substances that talk to each other through chemical synthesis. , But I think we are more and more aware of In the process from cell division to hearing, touch and pain, mechanobiology, mechanical force plays an important role.. The results we have found so far are important, but this is only the tip of the iceberg of this new science. “