It’s the start of November, which means another year of Nobel Prizes have been awarded! This year, the Nobel Prize in Medicine or Physiology went to Dr. David Julius of University of California in San Francisco and Dr. Ardem Patapoutain of Scripps Research Institute for their discovery of the receptors in the human body that are responsible for touch and temperature. Many of us are already familiar with the five senses, taught to us by teachers since elementary school: taste, touch, sight, sound, and smell. These senses are actually the result of mechanical and chemical reactions that our body uses to send information to the brain to tell us about our environment.
Each one of these senses detects distinct characteristics. For example, your taste sensors detect bitterness or sweetness. When you touch something it can feel hot, cold, rough, or smooth. The cell responsible for this response is the nerve cell.
Nerve cells typically send signals using proteins that live within its membrane. The protein’s job is to protrude from the cell surface and sense environmental stimuli, such as light, pressure, or chemicals. Then, upon sensing the stimulus, the cell responds, typically by changing the amount of ions in the cell. This produces a current that travels down tracks of nerves and delivers the information to your brain so that we can formulate a response. Up until the work of Dr. Julius and Dr. Patapoutain, how the temperature- and pressure-sensing proteins converted their unique stimuli into electrical signals was unknown. In fact, no one had isolated or identified the proteins responsible for this critical process.
The boom of research focused on the chemistry and biology behind the senses began with Dr. Julius’ work in 1997. He and his research team sequenced the messenger RNA (mRNA) in the nerves of the human central nervous system. Messenger RNA is the genetic material our cells use to “read” our DNA and make proteins. They hypothesized that our nerve cells produce proteins that respond to temperature, and that there must be a detectable mRNA strand corresponding to this protein’s gene. The group used this mRNA to figure out the original DNA sequence. Then, they manufactured this piece of DNA in the lab and put it into non-nerve cells.
They generated thousands of strands of DNA, designed to represent genes from neurons that responded to temperature, pain, and touch. They then inserted each piece of genetic material into different, non-nerve cells for testing, in hopes that the cells would make the proteins encoded by the DNA. Next, the researchers exposed the thousands of cells to a compound called capsaicin. This organic compound is responsible for the sensation you get from spicy food. Using fluorescence imaging, they observed how calcium flowed in and out of the cell, which is a measure of the cell’s electrical activity. When cells were stimulated by capsaicin, they absorbed a lot more calcium, and began to fluoresce (glow) during the experiments. They concluded from this evidence that capsaicin-sensing proteins were made by the cell.
The researchers then selected the active cells in the capsaicin trials and exposed them to high temperatures. Researchers were surprised to find that the same cells that responded to capsaicin, which creates a burning sensation in your mouth, were also responding to actual rises in temperature. From these results, they concluded that they had discovered a temperature-sensing protein, named TRP.
In 2015, inspired by this style of experiment, Dr. Patapoutain’s group worked with mice to find the protein responsible for pressure sensation. The researchers had already identified a type of mouse cell which responded to touch with an electrical signal. They hypothesized that the protein responsible would be an ion channel, much like the temperature receptor. They conducted a survey of genes responsible for ion proteins in the cell, and tested the cells with and without each one of the 72 genes they identified.
They created 144 different cells, each one genetically different, and exposed them to the mechanical force by poking them with a micropipette.They measured the electrical activity by monitoring the ions in and out of the nerve cells. Eventually, they discovered a single gene responsible for a single protein, which they named Piezo1, which changed in shape when a force was applied to the cell membrane. When the cell without the Pizeo1 gene was poked, no electrical signal was seen, so the researchers deduced that the protein was responsible for our pressure sensation. Researchers from this project went on to identify an additional protein, Piezo2, which showed similar behavior when being poked and prodded.
The researchers then tested how well the mouse nerves responded to stretching stimuli, and found that mouse muscle cells without the Pizeo2 protein produced fewer nerve signals. They took this to mean that Pizeo2 was involved in sensing mechanical stimulation and converting it into nerve signals.
Thanks to Dr. Julius and Dr. Patapoutain and the research fields their work has sparked, we can now explain why sunlight on our skin feels warm, and how we are able to tell if our seat belt is across our chest. But most importantly, why taking a bite of a habanero lights your mouth on fire! These two milestones represent just how far neuroscience and biochemistry has come in the last two decades.