In a study published in the Feb. 29 issue of the 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. Such medications are called ototoxic. 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, Ph.D., David Raible, Ph.D. 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.
Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
Identified the component that allows a lethal bacteria to spread resistance to antibiotics
27.07.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.
Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
27.07.2017 | Life Sciences
27.07.2017 | Life Sciences
27.07.2017 | Health and Medicine