Gene allowing humans to feel touch may play a role in sense of smell
Research could lead to treatment for common COVID side effect

Date:
February 23, 2022
Source:
Southern Methodist University
Summary:
Researchers have determined that a gene linked to feeling touch
may moonlight as an olfactory gene. That's the conclusion drawn
from studying a very small, transparent worm that shares many
similarities with the human nervous system.



FULL STORY ==========================================================================
Can you smell those roses? There's a real possibility that the gene
that helps you experience their heavenly fragrance may also help you
feel the prick of their thorns.


========================================================================== Researchers from SMU (Southern Methodist University) have determined that
a gene linked to feeling touch may moonlight as an olfactory gene. That's
the conclusion drawn from studying a very small, transparent worm that
shares many similarities with the human nervous system.

"This gene has previously been identified as a potential therapeutic
target for chronic pain. Now that we know the gene is also involved in olfaction, it might present an opportunity for treating or understanding olfactory defects, such as the mysterious loss of smell that many COVID-19 patients have reported," said SMU's Adam D. Norris, co-author of a study published in the journal Nucleic Acids Research.

Norris is the Floyd B. James Assistant Professor in the Department
of Biological Sciences at SMU. He worked with SMU graduate students
Xiaoyu Liang and Canyon Calovich-Benne, who are the lead authors of the
study. Both are studying to get a Ph.D. in Biological Sciences.

Touch is one of the human body's most important senses, yet there is a
lot we still don't understand, Norris says.

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



==========================================================================
But the exact mechanics of "what's going on beneath the hood" during
this electrical response to touch is poorly understood, because the
human nervous system is so complex.

What can worms tell us about human senses? Scientists frequently study
the nervous system of the worm Caenorhabditis elegansbecause it is a much simpler species. This worm has 302 nerve cells in its nervous system
compared to the billions of nerve cells found in the human brain, yet
many of the genes that create these neurons in C. elegans have functional counterparts in humans.

The SMU research team started with established knowledge -- that a gene
called mec-2 was crucial to activating touch neurons in C. elegans. What
the SMU research team found, though, is that activating touch isn't its
only role.

"In addition to turning genes on and off, another way to control a
neuron's function is to generate 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,
which is that different isoforms of a single gene (mec-2) work to enable
both mechanosensation and olfaction." Specifically, they learned that
the mec-2 isoform responsible for mechanosensation requires the activity
of a gene called mec-8 to be turned on, Norris explained. Neurons have
the ability to express multiple genes inside of them. Those that express
the mec-8 gene produce the olfactory isoform of mec- 2 instead.



========================================================================== "Mec-8 makes sure that mec-2 is made in the mechanosensory isoform,"
he said.

Without it, mec-2 genes instead produce isoforms that are necessary for
smell 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 turned on in a single cell. Deep
single cell sequencing allows them to see the entirety of each gene,
rather than just a small fragment from the end of the gene," Norris
explained. "Together, deep single cell sequencing reveals all of the
genes and all of the 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, directly leading to
these discoveries," he said.

Could this lead to a therapeutic drug to treat loss of smell? Now that
they know mec-2's role in the sense of smell, Norris Lab's next step is
to investigate whether a human gene called stomatin can do the same thing.

The mec-2 gene is found in worms, not humans. But stomatin is a gene
produced by humans and has been proven to be highly similar to mec-2
with regard to touch sensation in humans.

If that is found to be true for smell as well, Norris said perhaps similar methods that are currently being studied to treat chronic pain could
also be used to address loss of smell for people who have had COVID-19.

Therapeutic drugs work by identifying a molecular target that plays a
role in a negative 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 create its usual negative effect. A therapeutic drug can then be created using this chemical key. In the
case of the Norris team's research, scientists want to see if they can potentially modify mec-2 in worms -- and eventually possibly stomatin
in humans -- so they can turn certain senses up or down.

"The idea in preclinical trials is to turn down the sensitivity of mechanosensory neurons without gumming up the sensory channels themselves
by instead modulating the activity of mec-2 to relieve chronic pain,"
Norris said.

"By doing so perhaps mec-2 can be used as a "sensory thermostat" to turn sensory activity up or down." Norris stressed, though, that this theory
needs more research.

"Thus far experiments have been done in C. elegansand mice that
agree with each other. It is natural to hypothesize that similar
results will hold in humans," he said. "But that needs to be proven."
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by Southern_Methodist_University. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Xiaoyu Liang, Canyon Calovich-Benne, Adam Norris. Sensory neuron
transcriptomes reveal complex neuron-specific function and
regulation of mec-2/Stomatin splicing. Nucleic Acids Research,
2021; DOI: 10.1093/nar/ gkab1134 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220223103054.htm

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