Scientists Discover Mechanism of Hearing in Near-Atomic Detail HEAD TOPICS
Scientists Discover Mechanism of Hearing in Near-Atomic Detail
10/21/2022 8:17:00 PM Scientists Discover Mechanism of Hearing in Near-Atomic Detail
Source SciTechDaily
Scientists Discover Mechanism of Hearing in Near-Atomic Detail Discovery made possible by state-of-the-art imaging and more than 60 million worms. For the first time and in near-atomic detail, scientists at Oregon Health & Science University (OHSU) have revealed the structure of the key part of the inner ear responsible for hearing. “This is the last Discovery made possible by state-of-the-art imaging and more than 60 million worms.Until now.NaturePeter Barr-Gillespie, Ph.D.Caenorhabditis elegans“It immediately suggests mechanisms by which one might be able to compensate for those deficits,” Gouaux said. “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.” Read more:
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Oregon Health & Science University October 21, 2022 Scientists have revealed, for the first time and in near-atomic detail, the structure of the key part of the inner ear responsible for hearing.October 20th, 2022 at 3:20 PM By Joshua Hawkins Scientists working at Yale and the University of Rhode Island (URI) have discovered a new molecular cancer treatment that can home in on cancer cells and eradicate tumors in mice.on Wednesday in the journal Nature.. Discovery made possible by state-of-the-art imaging and more than 60 million worms. For the first time and in near-atomic detail, scientists at Oregon Health & Science University (OHSU) have revealed the structure of the key part of the inner ear responsible for hearing. The new molecular cancer treatment relies on a specific molecule, which can seek out the acidic environments that surround cancer cells. “This is the last sensory system in which that fundamental molecular machinery has remained unknown,” said senior author Eric Gouaux, Ph. But this protection came with a price: People who inherit the plague-resistant mutations run a higher risk of immune disorders such as Crohn’s disease.D. This is where drugs known as STING agonists come into play. He is a senior scientist with the OHSU Vollum Institute and a Howard Hughes Medical Institute investigator. “The molecular machinery that carries out this absolutely amazing process has been unresolved for decades. However, finding “cold” cancer cells can be difficult. Although the plague has been infecting people for , it struck medieval Europe with intense ferocity that led scientists to wonder if the Black Death had changed the genetic makeup of Europe.” Until now. Through years of meticulous research to isolate the process that enables the inner ear to convert vibrations into sound, known as the mechanosensory transduction complex, scientists were about to painstakingly piece together the structure. Researchers published a study on the molecule in the journal this month. Published on October 12 in the journal Nature , the study revealed the structure of the key part of the inner ear responsible for hearing through cryo-electron microscopy. The idea makes basic evolutionary sense: When a lot of organisms die off, the survivors will pass down mutations that protected them from death. This discovery could point the way toward developing fresh treatments for hearing impairments, which affect more than 460 million people worldwide. Image source: filin174 / Adobe By using the molecule to guide the drug to the tumors and cancer cells, they’re able to kick them out of the “cold” tumor range and push the immune system to fight back. “The auditory neuroscience field has been waiting for these results for decades, and now that they are right here — we are ecstatic.” — Peter Barr-Gillespie, Ph. This molecular cancer treatment lets the immune system fight cancer for longer periods. Dark moths were better able to hide from birds and survived to pass on their genes.D. Revealed in the study is the detailed architecture of the inner ear complex that converts vibrations into electrical impulses that the brain translates as sound. We’ve seen more and more targeted options like this new molecule cancer treatment popping up in recent years. Known as mechanosensory transduction, the process is responsible for the sensations of balance and sound. Credit. To make the discovery, scientists exploited the fact that the roundworm Caenorhabditis elegans harbors a mechanosensory complex very similar to that of humans. Resolving the basic structure is the first step, according to Gouaux. “It immediately suggests mechanisms by which one might be able to compensate for those deficits,” Gouaux said. National Gallery of Art When the Black Death struck, there were no evolutionary biologists to document its impact. “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 through gene mutations that alter the proteins comprising the mechanosensory transduction complex. In 1998, researchers proposed that the gene might have offered protection during the Black Death. Or it can occur from damage, including sustained exposure to loud noise. In either case, OHSU researchers’ discovery allows scientists to visualize the complex for the first time. The finding is an extraordinary achievement, said one leading neuroscience researcher at OHSU who was not directly involved in the research. Instead of studying living people, Dr. “The auditory neuroscience field has been waiting for these results for decades, and now that they are right here — we are ecstatic,” said Peter Barr-Gillespie, Ph. D., an OHSU research scientist and national leader in hearing research. They found fragments of DNA in 318 skeletons that had lived between 1000 and 1500. “The results from this paper immediately suggest new avenues of research, and so will invigorate the field for years to come.” Barr-Gillespie also serves as the chief research officer and executive vice president at OHSU. Researchers resolved the puzzle through careful cultivation and isolation techniques involving 60 million worms over almost five years. This shift was not proof on its own that the mutations conferred some evolutionary advantage. “We spent several years optimizing worm-growth and protein-isolation methods, and had many ‘rock-bottom’ moments when we considered giving up,” co-first author Sarah Clark, Ph.D., a postdoctoral fellow in the Gouaux lab, wrote in a research brief published by Nature . One way to tell the difference is speed: Under extreme conditions, natural selection can make a mutation spread far faster than genetic drift can. Reference: “Structures of the TMC-1 complex illuminate mechanosensory transduction” by Hanbin Jeong, Sarah Clark, April Goehring, Sepehr Dehghani-Ghahnaviyeh, Ali Rasouli, Emad Tajkhorshid and Eric Gouaux, 12 October 2022, Nature DOI: 10.1038/s41586-022-05314-8 Hanbin Jeong, Ph. D. They took advantage of the fact that large stretches of our DNA contain no working genes., a postdoc fellow in the Gouaux lab, is co-first author with Clark. Co-authors included April Goehring, senior research associate in the Gouaux lab; and, Sepehr Dehghani-Ghahnaviyeh, Ali Rasouli, and Emad Tajkhorshid of the University of Illinois at Urbana-Champaign. Acknowledgments: Initial cryoEM grids were screened at the Pacific Northwest Cryo-EM Center, or PNCC, which is supported by NIH grant U24GM129547 and performed at the PNCC at OHSU, accessed through EMSL (grid. They only spread thanks to genetic drift.436923. 9), a DOE Office of Science User Facility sponsored by the Office of Biological and Environmental Research. The large single-particle cryo-EM dataset was collected at the Janelia Research Campus of the Howard Hughes Medical Institute, or HHMI. But 35 of the mutations in immune genes spread far faster than the neutral ones — so fast that only natural selection could account for their success. The OHSU Proteomics Shared Resource is partially supported by NIH core grants P30EY010572 and P30CA069533. This work was supported by NIH grant 1F32DC017894 to S.C.. E.G. is an investigator of the HHMI. Credit. The simulations were supported by the NIH grants, P41-GM104601 and R01-GM123455 to E.T. Simulations were performed using allocations on Anton at Pittsburgh Supercomputing Center (award MCB100017P to E. Museum of London Archaeology Image Researchers at McMaster University extracted DNA from fragments of bone dating back centuries to look for genes that provided protection against the Black Death.T.), and XSEDE resources provided by the National Science Foundation Supercomputing Centers (XSEDE grant number MCA06N060 to E.T..). .