Nobel Prize in Medicine 2021

 

The Nobel Prize in Physiology or Medicine 2021

David Julius of USA and Ardem Patapoutian of Lebanon were jointly awarded the Nobel Prize in Physiology or Medicine in 2021 "for their discovery of temperature and touch receptors." David Julius was born on 4 November 1955, New York, NY, USA. He is currently affiliated with University of California, San Francisco, CA, USA. Ardem Patapoutian was born in 1967, Beirut, Lebanon. Current affiliation at the time of the award is at Howard Hughes Medical Institute, Scripps Research, La Jolla, CA, USA.

Our capacity to feel warmth, coldness, and touch is critical for life and supports how we engage with the environment. We take these sensations for granted in our everyday lives, but how do nerve impulses originate temperature and pressure perception? The Nobel Laureates for this year have answered those questions.

David Julius used capsaicin, a pungent substance found in chilli peppers that causes a burning sensation, to find a heat-sensitive sensor in the skin's nerve endings. Ardem Patapoutian discovered a new class of sensors that react to mechanical stimuli in the skin and interior organs using pressure-sensitive cells. These groundbreaking discoveries sparked a flurry of study, resulting in a fast improvement in our knowledge of how our nervous system perceives heat, cold, and mechanical stimuli. The laureates discovered important gaps in our knowledge of the complicated interplay between our senses and our surroundings.

By examining how the chemical component capsaicin creates the burning sensation we feel when we come into touch with chilli peppers, David Julius of the University of California, San Francisco, recognised the potential for huge breakthroughs. Capsaicin was already known to stimulate nerve cells, creating pain feelings, but exactly how this molecule did so remained a mystery. Julius and his colleagues constructed a database of millions of DNA fragments belonging to genes expressed in sensory neurons that respond to pain, heat, and touch. Julius and colleagues expected that the library would contain a DNA fragment encoding a capsaicin-reactive protein. Individual genes from this collection were expressed in cultivated cells that do not ordinarily react to capsaicin. After a long search, a single gene was discovered that may make cells sensitive to capsaicin. The capsaicin-sensing gene had been discovered! Further research found that the identified gene encoded an unique ion channel protein, which was dubbed TRPV1 after the recently discovered capsaicin receptor. Julius identified a heat-sensing receptor that is activated at temperatures that are felt as painful when he looked into the protein's capacity to respond to heat.

Study under pressure

Whereas the processes for temperature sensation were being discovered, it was still unknown how mechanical impulses might be transformed into our tactile and pressure perceptions. Mechanical sensors had already been discovered in bacteria, but the processes that underpin touch in vertebrates were unclear. Ardem Patapoutian, a researcher at Scripps Research in La Jolla, California, wanted to find out which receptors are triggered by mechanical stimulation.

As individual cells were pushed with a micropipette, Patapoutian and his coworkers discovered a cell line that gave off a quantifiable electric signal. The receptor triggered by mechanical force was considered to be an ion channel, and 72 candidate genes encoding potential receptors were discovered as a further step. To find the gene responsible for mechanosensitivity in the cells tested, these genes were inactivated one after another. Patapoutian and his colleagues identified a single gene whose silencing rendered the cells unresponsive to pushing with the micropipette after a long search.

 Patapoutian's revelation sparked a flurry of studies from his and other organisations revealing that the Piezo2 ion channel is critical for touch perception. Furthermore, Piezo2 has been demonstrated to play a fundamental part in the crucial sense of body position and motion known as proprioception. Piezo1 and Piezo2 channels have also been demonstrated to govern other essential physiological processes such as blood pressure, respiration, and urine bladder control in subsequent studies.

This year's Nobel Laureates' significant discoveries of the TRPV1, TRPM8, and Piezo channels have helped us to better grasp how heat, cold, and mechanical force may trigger nerve impulses which permit us to detect and adapt to new environments around us. Our capacity to detect temperature is largely dependent on TRP channels. The Piezo2 channel gives us the capacity to feel touch as well as the location and movement of our body parts.

TRP and Piezo channels also play a role in a variety of other physiological activities that rely on temperature or mechanical inputs for detection. Intensive continuing research centred on clarifying their involvement in a number of physiological processes stemming from this year's Nobel Prize-winning findings. This understanding is being applied to the development of medicines for a variety of diseases, including chronic pain.