Study finds a gene that enables touch plays a role in the sense of smell


March 05, 2022 23:03 IS

Texas [US]MARCH 5 (ANI): Researchers at SMU (Southern Methodist University) have found that a gene linked to the sensation of touch could appear as an olfactory gene in the moonlight.

The conclusion was drawn from studying a very small, transparent worm that shares many similarities with the human nervous system. The study was published in the journal Nucleic Acids Research.

“This gene was previously identified as a potential therapeutic target for chronic pain. Now that we know the gene is also involved in the sense of smell, it could offer a way to treat or understand olfactory disorders, such as the mysterious loss of smell that many COVID-19 patients have reported,” said Adam D. Norris from SMU, co-author of the study.

Norris is the Floyd B. James Assistant Professor in the Department of Biological Sciences at SMU. He collaborated with SMU graduate students Xiaoyu Liang and Canyon Calovich-Benne, who are the study’s lead authors.

Touch is one of the human body’s most important senses, but there’s a lot we still don’t understand, Norris said.

Scientists know that when we touch something, our nervous system converts the mechanical input it receives from touch receptors in our skin into electrical signals to the brain. This is known as mechanosensation and allows the brain to tell us a variety of things about that touch, such as: B. whether the object we touched was hot or cold, or—in the case of a rose thorn—sharp.

But the exact mechanics of “what’s going on under the hood” during this electrical response to touch are poorly understood because the human nervous system is so complex.

Scientists often study the nervous system of the worm Caenorhabditis elegans because it is a much simpler species. This worm has 302 neurons in its nervous system compared to the billions of neurons found in the human brain, but many of the genes that make these neurons in C. elegans have functional counterparts in humans.

The SMU research team started with solid knowledge – that a gene called mec-2 was critical for activating touch neurons in C. elegans. What the SMU research team found, however, is that activating touch isn’t its only role.

“Besides turning genes on and off, another way to control a neuron’s function is to create different (but functionally similar) versions of a single gene, called isoforms. We looked for different neurons that contain different isoforms of important genes,” Norris said. “This led us to the fundamental discovery outlined in this paper, namely that different isoforms of a single gene (mec-2) work to enable both mechanosensing and olfaction.”

Specifically, they learned that the mec-2 isoform responsible for mechanosensation requires activation of the activity of a gene called mec-8, Norris explained. Neurons have the ability to express multiple genes within themselves. Those expressing the mec-8 gene instead produce the olfactory isoform of mec-2.

“Mec-8 ensures that mec-2 is made in the mechanosensory isoform,” he said.
Without them, mec-2 genes instead produce isoforms necessary for odor in C. elegans, SMU researchers found using cutting-edge techniques called “deep single cell sequencing.”
“Single cell sequencing allows researchers to look at all of the genes that are activated in a single cell.
Deep single-cell sequencing allows them to see the entirety of each gene, and not just a small fragment from the end of the gene,” Norris explained. “Together, deep single-cell sequencing reveals all genes and all isoforms of those genes expressed in a single cell.

“Our use of this technology allowed us to determine isoforms in single sensory neurons with unprecedented sensitivity, which led directly to these discoveries,” he said.

Now that they know mec-2’s role in smell, the next step for Norris Lab is to investigate whether a human gene called stomatin can do the same.

The mec-2 gene is found in worms, not humans. But stomatin is a human-produced gene and has been shown to be very similar to mec-2 in relation to human touch.

If it turns out that smell is the same, then similar methods currently being studied to treat chronic pain could potentially be used to treat the loss of smell in people with COVID-19, Norris said.

Therapeutic drugs work by identifying a molecular target that plays a role in an adverse biological effect. Once that target is identified, the next step is to find a chemical key that can bind to the target and modify its behavior so it doesn’t produce its usual negative effect. This chemical key can then be used to create a therapeutic drug. In the case of the Norris team’s research, scientists want to see if they might be able to modify mec-2 in worms – and possibly stomatin in humans – in a way that stimulates or dulls certain senses.

“The idea in preclinical studies is to decrease the sensitivity of mechanosensory neurons without gluing the sensory channels themselves, by instead modulating the activity of mec-2 to relieve chronic pain,” Norris said. “In this way, mec-2 can perhaps be used as a ‘sensory thermostat’ to regulate sensory activity up or down.”

However, Norris stressed that this theory needs more research.

“So far, experiments have been conducted with C. elegans and mice that are consistent with each other. It’s natural to assume that similar results hold in humans,” he said. “But that has to be proven.” (ANI)


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