New Delhi: The Nobel Assembly at the Karolinska Institute decided to award the 2021 Nobel Prize in Physiology or Medicine to David Julius and Ardem Patapoutian for "their discoveries of receptors for temperature and touch".
Their discoveries led to the identification of additional temperature-sensing receptors, which are important for several physiological processes and disease conditions.
The Nobel Laureates discovered the TRPV1, TRPM8, and Piezo channels, which allow us to understand how nerve impulses that help us perceive and adapt to the world can be initiated by heat, cold and mechanical force.
A sensor in the nerve endings of the skin that responds to heat was identified by David Julius using capsaicin, which is a compound present in chilli peppers that induces burning sensation.
A novel class of sensors that respond to mechanical stimuli in the skin and internal organs was discovered by Ardem Patapoutian, using pressure-sensitive cells.
There were many missing links in our understanding of the complex interplay between our senses and the environment, which the laureates identified through their discoveries.
How Temperature, Mechanical Stimuli Convert Into Electrical Impulses
The mechanism of electrical impulses being generated from temperature and mechanical stimuli was not understood prior to the discoveries of David Julius and Ardem Patapoutian, according to a statement issued by the Nobel Committee for Physiology or Medicine.
Philosopher René Descartes, in the 17th century, thought that different threads connect the skin to the brain. Further discoveries found that changes in the environment are interpreted by specialised sensory neurons.
The responses to painful and non-painful touch can be attributed to sensory nerve fibres which react to distinct stimuli, a discovery by Joseph Erlanger and Herbert Gasser, which made them win the Nobel Prize in Physiology or Medicine in 1944.
These discoveries helped people understand that nerve cells are responsible for detecting and transducing stimuli, but the conversion of such stimuli to electrical impulses was not known.
The Discoveries By David Julius and Ardem Patapoutian
The burning sensation felt when one comes into contact with chilli peppers was analysed by David Julius at the University of California, San Francisco, USA, in the late 1990s.
Julius and his team then created a library of millions of DNA fragments corresponding to genes that direct the functioning of sensory neurons reacting to pain, heat, and touch, and hypothesised that the library would consist of a DNA fragment that has the genetic code for the protein that can react to capsaicin.
Extensive research helped them identify a single gene that had the ability to make cells capsaicin sensitive. They also found that a novel ion channel protein was encoded by the gene, and named it TRPV1. They found that the channel is a heat-sensing receptor activated by painful heat.
Julius and Patapoutian worked independently of one another.
A chemical substance named methanol was used by them to identify TRPM8, which is a receptor activated by cold. TRPV1 is an ion channel activated by inflammatory pain, neuropathic pain, visceral pain, and protective reflexes.
These discoveries led to the identification of additional temperature-sensing receptors.
Discoveries Could Get Cure For Conditions Like Chronic Pain
David Julius' discovery of TRPV1 is extremely important because it helped us understand how electrical signals in the nervous system are induced by temperature differences.
Ardem Patapoutian, who worked at Scripps Research in La Jolla, California, USA, conducted research to identify receptors activated by mechanical stimuli.
Patapoutian and his team of researchers poked individual cultured cells with a micropipette, and identified a cell line releasing a measurable electric signal, for the first time. They assumed that this receptor, which was activated by mechanical stimuli, is an ion channel. In subsequent steps, they identified 72 candidate genes encoding possible receptors.
In order to identify the gene responsible for sensitivity to mechanical stimuli, they started inactivating the genes one by one. Intensive research helped them identify a single gene whose inactivation caused the cells to become insensitive to poking with the micropipette. The researchers thus discovered a novel mechanosensitive ion channel, and named it Piezo1, originating from the Greek Word piesi, meaning pressure.
A second gene similar to Piezo1 was discovered, and was named Piezo2. Subsequent studies found that the exertion of pressure on cell membranes directly activated these ion channels, which are present in high amounts in sensory neurons.
The discovery by Patapoutian was the breakthrough which helped demonstrate that Piezo2 is essential for the sense of touch, and played an important role in sensing of body position and motion, and a phenomenon known as proprioception.
Mechanical pain, urination, respiration, blood pressure, skeletal remodelling are also regulated by Piezo1 and Piezo2.
The discoveries help us understand that the initiation of nerve impulses by heat, cold, and mechanical force is caused due to ion-channels such as TRPV1, TRPM8, Piezo1 and Piezo2. Our ability to perceive temperature can be attributed to the TRP channels.
The sense of touch and the regulation of important physiological processes dependent on sensing temperature or mechanical stimuli can be attributed to TRP and Piezo channels.
The applications of these discoveries are being explored in intensive ongoing research and to find the cure for disease conditions like chronic pain.