Science in Rochester – A new tool for understanding ear damage

By Emma Grygotis

Our ears are finely tuned instruments – intricate assemblies of cells, bones, and tissue that convert sound from the environment into electrical signals that are perceived by the brain. However, there is a downside to this sensitivity: ears are highly susceptible to damage.

Many every day experiences, like loud music or treatment with certain antibiotics, risk serious, even permanent, damage to the ear. In most of the body, specialized blood cells are constantly patrolling, ready to defend against injury, but the neurons connecting the ear to the brain are protected behind the blood-brain barrier.

That’s a good thing, most of the time. Except when damage or infection does occur. Then, the sensitive neurons of the inner ear are cut off from the repair crews.

Instead, a specialized class of brain cells, called microglia, performs all the myriad functions of the immune system. They’re highly versatile, the main line of defense against many different types of threats. But even as the importance of microglia has become more apparent, we still know very little about them.

Gail Seigel, Ph.D., is a principal investigator in the Center for Hearing & Deafness of the University at Buffalo. She hopes a new tool developed in her lab will help to shed light on these shapeshifting immune cells.

Part of the challenge of studying microglia lies in their versatility. A microglial cell from the ear may behave very differently from the microglia of the brain or the spinal cord. They’re also highly plastic, changing rapidly to adapt to their surroundings. This means any given microglial cell may behave very differently from another.

To combat this problem, Seigel’s team set out to create an immortalized cell line, a population of nearly identical cells that can replicate indefinitely. They began with rat cochlea, the snail-shaped part of the inner ear that serves as the connection to the brain. After isolating the microglia, they next infected them with a virus that directs the cells to divide rapidly.

The result is a population of cells that can be easily grown outside of the body, but otherwise look and act just like microglia. For example, in response to a bacterial toxin, they produce chemical signals to alert nearby cells of the threat. They’re also able to devour foreign substances, which the investigators tested by photographing them as they engulfed microscopic plastic beads.

Seigel has named the cells “Mocha,” short for “microglia of the cochlea,” and published the results in the December 2017 issue of Molecular and Cellular Neuroscience.

Now, they’re gearing up to use the cells to study how microglia in the ear behave under different situations. For Seigel, who has spent much of her career studying eye cancers, venturing into the realm of the auditory system is an exciting new challenge. She plans to use Mocha cells as a screening tool, to identify drugs that are safe and effective in treating diseases of the ear.

The value of Mocha cells is not limited to hearing disorders, however. Microglia are critical players throughout the nervous system, beginning in the earliest stages of brain development. Their importance persists throughout a person’s entire lifetime, even helping to counteract age-related neurodegenerative disorders like Alzheimer’s’ and Parkinson’s’ diseases. In order to maximize the potential of Mocha cells, the team has made them widely available to other researchers through the laboratory-sharing service, Kerafast. They hope that the cells will be useful for studying a wide range of conditions, with far-reaching impacts.

“I can’t do everything,” Seigel says. “There are so many experiments I could do, and never enough time.”

Indeed, in addition to running her research program, Seigel dedicates an enormous amount of energy to scientific advocacy. As the Diversity Chair for the Rochester NY March for Science, she is an outspoken supporter of continued public funding and the accessibility of scientific research. The development of Mocha cells would not have been possible without grants from both the National Institutes of Health (NIH) and the National Institute for Occupational Safety and Health (NIOSH). Continued support for these and other publicly funded research programs is essential for taking the next step: translating the results into medical practice.

Seigel is now setting her sights forward, with many new projects on the horizon. This includes planning the second annual March for Science, to be held this coming April 14th 2018. She is motivated by the central role of science in driving both economic development and new life-saving medicines.

“We are losing a generation of scientists,” Seigel says, “and with them, the future of science in America.”

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