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How we feel temperature and touch: Research that won US scientists Nobel Prize in medicine

David Julius and Ardem Patapoutian were jointly awarded the Nobel Prize in Physiology or Medicine for 2021 Monday for their discoveries of receptors for temperature and touch.

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Bengaluru: The 2021 Nobel Prize in Physiology or Medicine has been awarded jointly to American scientists David Julius and Ardem Patapoutian for their “discoveries of receptors for temperature and touch”.

The duo’s work together has been key to deciphering the molecular process behind how heat, cold and touch initiate signalling pathways in our nervous systems, which help us understand sensation, pressure and temperature.

The research conducted by Julius, at the University of California-San Diego, involved capsaicin, the spicy compound found in chillies that induces the burning sensation in the mouth, to recognise the sensors in human nerve endings that are receptive to heat.

Meanwhile, Patapoutian, from the California-based facility Scripps Research, utilised pressure-sensitive cells that respond to mechanical stimuli to identify the group of sensors responsible for the response.

“These breakthrough discoveries launched intense research activities leading to a rapid increase in our understanding of how our nervous system senses heat, cold, and mechanical stimuli,” said the Nobel Committee in its official release Monday.

“The laureates identified critical missing links in our understanding of the complex interplay between our senses and the environment,” it added.

ThePrint explains Julius and Patapoutian’s research and its importance in understanding the human body’s nervous system.

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Capsaicin and heat

The compound capsaicin, found in chillies, was known to cause the sensation of pain and burning among nerve cells, but the molecular mechanism behind this was a mystery.

To solve the riddle, Julius and his team built a library of millions of fragments of DNA containing genes that are expressed when the functions of pain, heat and touch are activated in our nerve cells.

In its database, the team started to hunt for a gene that codes for (or produces) a protein that reacts to capsaicin.

For this, the researchers used cultures of cells that don’t naturally respond to capsaicin and are insensitive to it. They then started to express (or turn on) individual genes within these cell cultures and identified the genes that caused the cells to become sensitive to the chemical.

The gene that sensed capsaicin encoded a novel protein that was previously unidentified, called TRPV1. The capsaicin receptor is also sensitive to heat and activates at temperatures thought to be painful. The discovery of this heat-sensing receptor led to the discovery of additional such receptors.

Later, both Julius and Patapoutian, independently, utilised methanol to identify another receptor called TRPM8 that was activated by cold.

These receptors function because of an “ion channel”, which is a specialised protein in the plasma membrane of the cell that provides a passage for charged ions to cross and thus transmit signals.

The discovery of TRPV1 and TRPM8 led to subsequent and further research on thermal sensation.

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Touch and pressure

Meanwhile, Patapoutian and his team were working on identifying receptors that are activated by and respond to the mechanical stimulus of push and pressure.

They used micropipettes (laboratory equipment used to aspirate liquids) to poke cells, to look for electrical signals that can transmit between lines of cells when stimulated by pressure.

The team then shortlisted 72 candidate genes that encoded possible receptors for pressure.

They also followed an approach similar to Julius and tested each gene in a cell culture — this time a mechanosensitive cell culture where the cells were naturally receptive to mechanical sensitivity.

The team inactivated the genes one by one till they identified one where turning off the gene made the cells insensitive to mechanical pressure when poked with a micropipette. This ion channel or receptor is called Piezo1.

A similar gene called Piezo2 was later discovered, which is also activated by applying pressure on cell membranes.

Further research following these breakthrough findings determined that the Piezo2 ion channel is essential for touch and also plays an important role in our body’s ability to understand position, orientation and motion.

Both these ion channels have also been shown to play key roles in controlling physiological processes like blood pressure, bladder control and respiration.

The Nobel prizes

The discovery of TRPV1, TRPM8, Piezo1 and Piezo2 channels have collectively been instrumental in understanding the cellular-level processes behind how our body understands, interprets and responds to heat, cold, touch, and pressure.

“Intensive ongoing research originating from this year’s Nobel Prize awarded discoveries focusses on elucidating their functions in a variety of physiological processes,” said the Nobel committee’s statement. “This knowledge is being used to develop treatments for a wide range of disease conditions, including chronic pain.”

The Nobel Prizes are awarded every year in the subjects of physiology or medicine, physics, chemistry, literature and peace. A sixth Nobel Memorial Prize in Economic Sciences, not established in Alfred Nobel’s will in 1895, is also awarded by the Karolinska Institutet.

Winners are selected by committees in Sweden and Norway, and receive a gold medal and 10 million Swedish kronor (approximately Rs 8.3 crore).

The Nobel prizes have also been a subject of ongoing criticism for their lack of recognition of women, people of colour, and scientists from the global south or middle- and low-income countries.

Of the 224 winners of the Nobel in physiology or medicine since 1901, 12 have been women while only six were not citizens of the US, European Union or Australia-New Zealand.

(Edited by Rachel John)

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