Feel the Heat – The Nobel Prize in Physiology or Medicine 2021

This year’s Nobel Prize in Physiology or Medicine is shared by two American scientists for discovering the receptors for touch and temperature. We now know how the physical stimuli of holding a hot cup of tea are converted into electrical signals in the nervous system.

By Dr Jamshed

The recipients of the Nobel Prize 2021 are: David Julius of the University of California, San Francisco, and Ardem Patapoutian of the Scripps Research, La Jolla, CA.

Dr. David – Story of chili peppers

The hot spicy feeling of a chili pepper is primarily because of its active compound, capsaicin. Dr. David knew about capsaicin and its role in eliciting burning sensation. So, he asked: what is in/on a sensory neuron that detects capsaicin? He hypothesized that the detector is a receptor that is encoded by a gene. If it sounds too obvious information to you, consider the fact that he started his experiments in 1990s!

            To work on his hypothesis, he made millions of DNA fragments from the genes of capsaicin-activated sensory neurons. He expected to find one particular fragment/gene responsible for the receptor for capsaicin. Since many cell types do not efficiently respond to capsaicin, he introduced DNA fragments, one by one, into such non-responding cells and recorded the effects of capsaicin on them. Working with millions of DNA fragments, his team finally hit the jackpot. The receptor responsible for capsaicin-induced neuronal activation was a novel protein that they named TRPV1. It is an ion channel on the cell membranes. The team’s further research showed that TRPV1 opens and allows ion movement at temperatures above 43 oC. In other words, it was a heat-sensitive receptor, the activity of which is often perceived as pain.

            After discovering a receptor for heat, they kept looking a receptor for cold sensation. The reason is simple: feeling cold is a distinct sensation, and cold is not just “absence of heat”. Dr. David’s team later discovered a cold-sensitive channel, TRPM8. Interestingly, Dr. Ardem also discovered TRPM8, but independently of Dr. David’s work.

            Now we have a list of different channels for temperature detection, but it was Drs. David and Ardem that pioneered the field.

Dr. Ardem – Story of a refugee under pressure

Beirut of 1960s was a glamorous city of Lebanon. Dr. Ardem was born in 1967 in Beirut. The start of civil war in 1975 and beyond compelled Dr. Ardem’s family to migrate to a stable country. Dr. Ardem moved to Los Angeles, USA, in his youth and completed his PhD in 1996.

            Dr. Ardem focused on touch sensation. He would poke a cell membrane and note the responses. In his award-winning series of experiments, he shortlisted 72 genes behind the response to pressure since these 72 genes were found to be activated by mechanical stimuli. Then, he spent years silencing those 72 genes, one by one, and noticing the response to touch. One day, poking a cell membrane did not produce a response when one particular gene was silenced. In other words, a mechanosensitive receptor had been discovered that responded to pressure. It was named Piezo1 since the Greek word for pressure is pronounced as Piezo. Soon, they found a second receptor, Piezo2, primarily because of its similarity to Piezo1.

            This means that Dr. Ardem’s team had discovered a novel class of ion channel proteins that is activated when we touch something or hug someone.

Implications of knowing molecular basis of somatosensation (touch and temperature)

David Julius’s discovery, especially, of TRPV1 has helped explaining temperature sensation, protective reflexes and various pains (inflammatory, neuropathic and visceral) in our body. Ardem Patapoutian’s findings on Piezo1 and Piezo2 have provided molecular explanation of mechanical pain, blood pressure, respiration, urination and body movements.

            Our survival and interaction with the environment depend on these receptors!

Reference

Press Release: https://www.nobelprize.org/uploads/2021/10/press-medicineprize2021.pdf

Jamshed Arslan

Pharm D (gold medalist); PhD (Neuropharmacology) Skilled in basic and clinical research and scientific writing with over a decade of teaching experience.

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