In a study published on February 29 in the open-access journal PLoS Genetics, researchers at the University of Washington have developed a research method that relies on a zebrafish’s lateral line—the faint line running down each side of a fish that enables it to sense its surroundings—to quickly screen for genes and chemical compounds that protect against hearing loss from some medications. The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health.
“The fish’s lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fish’s body, making them more easily accessible,” said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD. “This means that scientists can very efficiently analyze the sensory structures under different conditions to find out what is likely to cause damage to these structures and, conversely, what can protect them from damage.”
When people are exposed to some antibiotics and chemotherapy agents, the sensory structures in the inner ear, called hair cells, can be irreversibly damaged, resulting in hearing loss and balance problems. These are known as ototoxic medications. People vary widely in their susceptibility to these agents as well as to damage caused by other chemical agents, loud sounds and aging.
To find out why this is so, senior scientists Edwin Rubel, David Raible, and their research team developed a screening strategy that uses hair cells in the lateral line of zebrafish larvae to signal how hair cells in a person’s inner ear might respond under similar conditions. Hair cells are named for small bristly extensions, or stereocilia, jutting from their tops. Movement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fish’s environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.
The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.
Using genetic techniques, the group then examined the larvae’s DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutations—each located on different genes—that, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.
Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening technique—exposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cells—the researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouse’s inner ear against the drug, indicating that the same compound may be protective for other mammals as well.
“One of the pluses about working with zebrafish is that, like other fish, they produce hundreds of offspring. We can look at lots of animals and we can look at many hair cells per animal, which means that we can get good quantitative data,” said Dr. Raible.
The authors suggest that their research technique, which combines chemical screening with traditional genetic approaches, offers a fast and efficient way to identify potential drugs and drug targets that may one day provide therapies for people with hearing loss and balance disorders.
Other sponsors of the study include the American Academy of Otolaryngology—Head and Neck Surgery Foundation, the University of Washington Royalty Research Fund and the V.M. Bloedel Hearing Research Center.
Andrew Hyde | alfa
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine