Humans rely on our senses to tell us about the world. Which side is this waterfall on? Is it day or night? Is this food fresh or spoiled?
Such questions are more difficult to answer if our sensory systems cannot detect the sound of flowing water, the shimmer of moonlight, or the smell of spoiled milk. Before this week, the Nobel Committee for Physiology or Medicine recognized important advances in our understanding of how sensations are detected in three sensory systems: audience, vision and feel.
Today, the Nobel Committee awarded this year’s Medicine Prize to two scientists who have advanced our understanding of this process of detecting “somatosensation”, the sense responsible for perceptions of touch, temperature, vibration. , pain, and proprioception – the body’s ability to sense its own movements and position in space.
October 4, 2021, David Jules, professor of physiology at the University of California, San Francisco, and Patapoutien Ardem, neuroscientist at Howard Hughes Medical Institute and Scripps Research, received the Nobel Prize in Physiology or Medicine for their pioneering work identifying the proteins the body uses to sense temperature and pressure. These two scientists led teams that deciphered the key steps in the processes by which temperature and pressure are recognized by sensory cells and converted into signals that can be interpreted by the brain as perceptions such as heat, cold or heat. texture.
My own research has long focused on understanding these types of processes with respect to the senses of smell and taste. Using the tools of molecular biology and neuroscience – much like some of those employed by Julius and Patapoutian – my collaborators and I are working to understand how smell and taste receptors allow us to detect the various chemicals that make up smells and tastes.
The work of Julius and Patapoutian has dramatically broadened scientists’ views on how the nervous system reads the external and internal worlds by introducing us to entirely new classes of sensory receptors. Their findings have provided critical and new information on the physiology of temperature, pain, and tactile sensation.
Bring the heat
Scientific inquiry is an attempt to answer questions about the processes that people observe in nature. Some of the greatest advances come from taking a new perspective – and applying new techniques to – a long-studied question.
The path to the discovery of a heat-sensing receiver by Julius and his colleagues began with a simple observation that many people made during a meal – that chili peppers can cause a burning sensation and pain. This is because we often describe spicy foods as “hot” even though the food itself is cold. Many plants, including peppers, herbs and spices, produce compounds which can be irritating when encountered in excess, but add complexity to foods in moderation.
Nociceptors are special sensory neurons that carry information about pain, including pain caused by potentially damaging heat levels. Scientists studying pain have known for years that capsaicin – the chemical in chili peppers responsible for their perceived heat – activates nociceptors. However, the mechanism by which this happens was still unknown when Julius and his colleagues tackled the problem in the mid-1990s.
The important innovation of the Julius Group was to use capsaicin itself as a tool to isolate the sensory receptor that detects capsaicin, a feat they reported in 1997. To do this, they tested thousands of different proteins produced by rodent sensory neurons until they found one that responded to capsaicin and its chemical cousins. As expected, this protein also responded to high temperatures, indicating that it was the long-sought heat sensor in these neurons.
This protein, named TRPV1, was the first in a group of related proteins discovered by Julius’ lab and other groups that respond to various plant chemicals and different temperatures. For example, the TRPM8 protein is activated by both cold and menthol, the chemical that causes mint to feel cool, while the TRPA1 protein is activated by pungent compounds found in garlic.
While Patapoutian and his colleagues also investigated this family of heat-sensitive proteins, they quickly turned their attention to another aspect of somatosensation: touch.
But they were faced with a unique challenge: All cells seem to respond to physical pressure. The question therefore became: how were the researchers able to differentiate the function of a specific pressure sensor from this more general response?
They took a smart approach. Instead of testing single gene products for their ability to respond to pressure – a strategy that has worked so well to identify the capsaicin receptor – Patapoutian and his team instead unique genes silenced, one by one, in a touch cell until the cell loses its ability to respond.
They then confirmed in nerve cells that two related proteins, named Piezo1 and Piezo2, mediate responses to physical stimulation. Later on Patapoutien group and others have shown more directly that Piezo proteins are essential to touch itself.
Open the doors to new scientific discoveries
The findings of Julius and Patapoutian have given sensory researchers fundamental information about how people interact with their world. But they will almost certainly lead to important medical breakthroughs as well.
For example, red blood cells also express Piezo1, which can help them change shape to fit tiny capillaries. However, certain mutations in Piezo1 can lead to deformed red blood cells and rare type of anemia, in which the number of red blood cells is depleted.
Topical capsaicin creams are already used by many people as an over-the-counter treatment for the relief of minor muscle pain. But this family of heat-sensitive proteins could also prove to be interesting targets for new drugs aimed at treating debilitating diseases, chronic pain.
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Temperature sensitive proteins of the Trp family remain important for the detection of compounds present in a variety of edible plants such as chili peppers, mint and garlic. For people with impaired smell or taste, stimulating these pathways can help improve the palatability of foods that might otherwise appear tasteless. Identifying new aromatic compounds that specifically target these new proteins may help increase the enjoyment of food and drink by the millions of people with odor or taste disorders, including those caused by COVID-19.
Nature has let us know that a whole new world of biology is waiting to be discovered. Julius and Patapoutian have now shown the way.