Breakthrough made possible by more than 60 million worms and state-of-the-art imaging only available at Oregon Health & Science University (OHSU) and two other national cryoEM laboratories in the United States.
Researchers at Oregon Health & Science University have, for the first time and in almost atomic detail, revealed the nature of the essential inner ear component that controls hearing.
Eric Gouaux, Ph.D., senior scientist at the OHSU Vollum Institute and a Howard Hughes Medical Institute investigator, who is also the study’s senior author, remarked “this is the last sensory system in which that fundamental molecular machinery has remained unknown.
“The molecular machinery that carries out this absolutely amazing process has been unresolved for decades.”
The finding was made after years of hard research to separate the process that allows the inner ear to transform vibrations into sound, known as the mechanosensory transduction complex.
The discovery, which used cryo-electron microscopy to reveal the structure, was detailed today in the journal Nature. The results could help find new ways to treat hearing problems, which affect more than 460 million people around the world.
The study shows the inner ear complex’s structural layout, which transforms vibrations into electrical impulses that the brain interprets as sound. The process is known as mechanosensory transduction, and it is responsible for the perceptions of balance and sound.
Scientists took use of the roundworm Caenorhabditis elegans’s mechanosensory complex, which is extremely similar to that of humans.
Gouaux says that the first step is to figure out the basic structure.
“It immediately suggests mechanisms by which one might be able to compensate for those deficits,” adds Gouaux. “If a mutation gives rise to a defect in the transduction channel that causes hearing loss, it’s possible to design a molecule that fits into that space and rescues the defect. Or it may mean we can strengthen interactions that have been weakened.”
Hearing loss can be inherited due to gene mutations that change the proteins that make up the mechanosensory transduction complex. It can also happen due to injury, such as long-term exposure to high noise. In any event, the discovery made by OHSU researchers enables scientists to visualize the complex for the first time.
The discovery is a remarkable accomplishment, according to a renowned OHSU neuroscientist who was not directly engaged in the study.
“The auditory neuroscience field has been waiting for these results for decades, and now that they are right here — we are ecstatic,” adds Peter Barr-Gillespie, Ph.D., an OHSU research scientist and national leader in hearing research. “The results from this paper immediately suggest new avenues of research, and so will invigorate the field for years to come.”
Barr-Gillespie is also OHSU’s executive vice president and chief research officer.
Researchers solved the mystery by cultivating and isolating sixty million worms over a period of nearly five years.
“We spent several years optimizing worm-growth and protein-isolation methods, and had many ‘rock-bottom’ moments when we considered giving up,” says co-first author Sarah Clark.
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