NOBEL PRIZE IN PHYSIOLOGY AND MEDICINE | RECEPTORS OF SOMATOSENSATION

         

           The modern man started invading the planet a few 300,000 years ago. Since then, the act of new ideas came to play. Started from scratch, from the stone, bronze, and iron age to the modern and contemporary time, tons of discoveries had been made and continuing. The field of research and technology is accelerating with tremendous facilities. In the present time, more futuristic ideas are taking place in day-to-day life. 

          The only thing that remained constant, is this human body. Although small changes like some parts are vestige, all in all, it's still the same. Humans also wondered knowing its framework and mechanism, and also took 300,000 years and ended up with no conclusion. And it's still in progress. It's been just 4 days since the newly discovered receptors of touch and temperature, which took place by the immense work of 2 researchers of the US, that lead them to the most prestigious prize of the world.

          The Nobel Assembly of Karolinsk Institute had announced the Nobel prize in physiology and medicine jointly to David Julius and Ardem Patapoutian for the discoveries of receptors for temperature and touch. David(1955) is working at the University of California, San Francisco, and Ardem(1967) is from Lebanon, working in Scripps Research La Jolla, California. Let's dive into the topic in detail.

CONCEPT OF SENSES 

         We all know that we have five sense organs: eyes, ears, nose, tongue, and skin, and their functions are vision, hearing, smell, taste, and touch respectively. These sense organs possess receptors of their own type, which react to the external stimulus. The receptors generate electrical signals which are further transferred to the brain through neurons where the action is generated. In this way, the brain, nerve cells, and receptors work in a coordinated manner. 

         Out of the five sense organs, the skin serves for touch as well as temperature sensation. The skin has touch or thermoreceptors. The novel works are based on Somatosensation. So let me elaborate on it.

SOMATOSENSATION AND ITS MECHANISM   

           As we know that touch receptors are present in our skin, which makes us feel something when we get in contact with it. This ability to feel our body surface or internal organs with the outside world is referred to as Somatosensation. Feeling of temperature, touch and movement are feelings relying on it. The receptors result in the continuous flowing of information that connects our internal body with the external world.

 

           Since these receptors are involuntary in nature, it also works efficiently in our subconscious state of mind. You must be familiar with the word "Reflex Action", which explains the situation these receptors work in this state. In general, the whole system works like the pathway depicted below.

           You can see the sensory endings present at the skin that receives the stimulus. These are the sensory neurons and are of varying types for different stimuli. The physical stimuli of heat and touch are converted into biological signals which leads the process. 

           Besides all these known facts, the scientist workers wonder that several molecular receptors must exist on nerve cells that are responsible for converting heat and touch signals into nerve impulses. The identification of these receptors was actually unknown till now, which was then discovered by David Julius. Let's have a look at his scientific work.

THE NEW DISCOVERY

            From the 17th century, the stimulus of pain, the temperature was explained and the mechanism behind the neuro-signal transfer was known,  defined the working between skin and brain. Thereafter, neurons act as units for signal transfer was also discovered that is responsible for the conversion of physical stimuli of heat and touch to biological signals. But, as I had mentioned earlier, that the molecular receptors are unknown, which has been done now by the novelists.

           David Julius and his co-workers took the help of a chemical named "Capsaicin", which is present actively in chilly pepper. When we eat something with chilly pepper, it gives a burning or sometimes a painful sensation, as a result, we start sweating.

           This Capsaicin can trick the brain into thinking there is an actual change in body temperature. It was known that capsaicin activates sensory neurons and this activation is responsible for the burning sensation while eating chilly pepper. But the molecule that detects capsaicin remained unknown. 

           Julius assumed that a single gene active in sensory neurons is responsible for the sensation. Therefore he took millions of DNA fragments that were active in sensory neurons hoping that one of them would contain genes for capsaicin receptors. He then introduced single DNA fragments into cells that are insensitive to capsaicin, and then added capsaicin and recorded the activity. It was a high-risk project that needed lots of DNA fragments to be recorded but finally came to an end. The capsaicin receptor was identified and it turn out to be the novel protein named "trpv1" which is present at the outer membrane of the cell. The protein trpv1 acts as a channel for ions. Julius tested that how trpv1 reacted to the warm temperature and opens the ion channel. Later, he fixed the protein for a temperature-sensitive ion channel activated by heat that is perceived as painful.

           

          

           A few years later, David Julius and Ardem Patapoutian independently search for a cold-sensitive channel and discovered a related channel "trpm8" soon after this additional related channels were shown to contribute to touch sensation. We all know that the number of different channels is activated at different temperatures at different time intervals. Then they act together to code in temperature sensation and heat-induced pain.

AN OUTLOOK

            After the mechanism for temperature sensation was revealed, the molecular mechanism for the sensation of touch remained a mystery. The sensational touch is started by mechanical force such as when pocking on the skin. Here the activity of the cell membrane reacts first to the touch. Ardem and his co-workers used this system and identified a cell line that is mechanosensitive. In these cells, Ardem identified 72 candidate genes that he thought could be the critical sensor activated by mechanical force. One-by-one each of the 72 candidate genes were silenced and the cells were tested for mechanical sensitivity. 

           71 of 72 genes had been tested without result. But when 72 number gene was silenced, sensitivity to pocking was lost. The mechanosensitive receptors had been discovered and was named "PSO1". Though it was similar to PSO1, a second gene was found and named "PSO2". Ardem demonstrated that PSO protein belongs to an entirely novel class of protein and functions as ion channels activated by mecahnical force. Importantly, PSO2 was then found to be the sensor for touch.

           So to summarize, the work of Julius and Ardem has unlocked one of the secrets of nature by explaining the molecular basis of sensing temperature and mechanical forces. This represents a foundation for our perception of temperature, heat pain and touch, and the location and movement of our body called Proprioception. In further work, TRP and PSO 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.

 

SOURCE: Announcement of the 2021 Nobel Prize in Physiology or Medicine | https://youtu.be/01T0yOyD808