March 20, 2008

March of Dimes award to aid in finding how genes malfunction to cause deafness

Brian M. McDermott

Schools of zebrafish dart back and forth in tanks in the research lab of Brian M. McDermott, assistant professor from otolaryngology and head and neck surgery at the Case Western Reserve University School of Medicine. He will study thousands of fish with a $150,000 Basil O'Connor Starter Scholar Award from the March of Dimes to understand deafness.

McDermott will produce zebrafish with genetic mutations that result in deafness. He hopes this research will help him understand how similar mutations cause deafness in humans and why one in 1,000 people are born deaf.

"Many forms of deafness result from defects that perturb the development of the hair cells found in the internal ear," said McDermott.

Hair cells have an integral function in hearing and balance. They act as a mechanical device that converts stimuli or sound waves into electrical signals that travel to the brain. The brain processes these signals, and humans can interpret them as sounds for communication. In aquatic animals, hair cells also permit hearing, but they can additionally use these cells to detect water movement to evade predators.

Humans have approximately 16,000 hair cells that line the inner ear's spiral-shaped cochlea and allow for the detection of low- through high-frequency sounds.

When genes mutate, deafness can result, said McDermott, who has identified 6,000 genes in the hair cell's genetic map. He started this research project as a postdoctoral fellow at The Rockefeller University in New York City and has continued it since coming to the medical school a year ago.

He originally determined the genes by probing DNA oligonucleotide microarrays with RNA amplified from hair cells. He compared the genes from the hair cell with those of the liver to distinguish the hair cell's unique genetic blueprint. Of those genes identified, 1,037 form a subgroup that may specifically promote hearing.

He will further investigate one gene that may be mutated in a form of human deafness called DFNB47. The gene is KIDINS220 and there is a corresponding gene in the fish's genome. The functions of the human and fish genes will be studied and how they contribute to hearing investigated by Dr. Geoffrey Deschenes, a medical resident in the McDermott laboratory.

Learning the function in hearing that each key hair-cell gene performs holds the potential to find ways to restore hearing to the deaf.

Some 80 types of non-syndromic deafness have no gene assigned. Once the genes are identified for these forms of deafness, it will be necessary to determine their function using a suitable model system.

"Zebrafish are a superlative model to study the molecular basis of disease," he said, noting his lab will be home to about 10,000 fish when in full operation. He added that the transparency of the fish is an advantage over a mouse model because it allows researchers to see the development of the ear in real time.

The zebrafish's hearing apparatus is different from humans, but the hair cells in both hearing systems are similar. "The hair cells in all vertebrates are likely to have the same genetic blueprint," said McDermott. "Genes that cause deafness in humans will similarly be expected to cause deafness in zebrafish when the genes are mutated."

Among McDermott's research group, which includes graduates students, medical students and medical residents, is Case Western Reserve undergraduate biology major Nathan Klingensmith.

For more information contact Susan Griffith, 216.368.1004.

Posted by: Heidi Cool, March 20, 2008 10:28 AM | News Topics: HeadlinesMain, Healthcare, Provost Initiatives, Research, School of Medicine, news

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