Yesterday, Prof Rubel delivered a public talk at the Med School: ’The 21st Century: A New Era for Hearing Habilitation’.
Ed Rubel has a long trajectory, and has contributed to many aspects of neuroscience, ranging from how brains are put together in the embryo, how and when auditory processing is set up, how the way that neurons are connected determine how information is coded, and much more.
But among all his contributions one stands out: the discovery that the sensory hair cells in the inner ear of birds can regenerate after damage. His team found this, as he describes, serendipitously in the mid 1980’s. In mammals, once the sensory hair cells are damaged due to noise exposure or chemical toxicity (like exposure to certain antibiotics), the cells are not replaced, and as a result, the hearing loss is permanent. Thus, the question is: what is different between birds and mammals that allows one, but not the other to repair their damaged ears?
This answer has eluded us since then. There are basically two possibilities: One, that damage induces the mechanisms of repair in birds, but not mammals. The other is that the repair mechanisms are inhibited in mammals (and that damage removes this inhibition in birds). In order to get to the bottom of this, one would need to understand what are the cellular mechanisms that are either inhibiting or inducing hair cell replacement.
And here is where the Rubel group in Seattle came up with a rather clever solution: Let’s look in the zebrafish. One reason to do this is that zebrafish, like many other fishes, have hair cells on the lateral line on the surface of the body in structures called neuromasts. And like in birds, fishes are able to replace these cells.There are two advantages to the zebrafish approach. First, because the neuromasts are on the surface of the body it is possible to load the sensory hair cells and support cells with fluorescent molecules and monitor what is happening over time with different treatments. Second, the genetics of zebrafish are well-known, which facilitates the identification and manipulation of genes to see what their effects are on the ability to regenerate those cells.
Ed Rubel teamed up with David Raible’s group, and examined genes that may be involved in different susceptibility to induced hair cell death by neomycin, as well as what drugs that may confer protection to the hair cells. Their work was published in PLoS Genetics (doi:10.1371/journal.pgen.1000020) and you can go and read it thanks to the magic of Open Access.
Their ultimate goal is to use this approach to screen for genes and pharmaceutical compounds that protect hair cells from damage in the zebrafish and, once identified, determine whether their findings apply to mammals as well. As the authors state in their summary:
Variation in the genetic makeup between individuals plays a major role in establishing differences in susceptibility to environmental agents that damage the inner ear. […] The combination of chemical screening with traditional genetic approaches offers a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders.
You can also read more about the project in a feature by Shirley S Wang in the Wall Street Journal.About Professor Ed Rubel: Professor Rubel is the Virginia Merrill Bloedel Professor of Hearing Science at the University of Washington. He was the founding Director of the Virginia Merrill Bloedel Hearing Research Center and is currently the Scientific Director. Professor Rubel’s work is geared towards understanding the development, plasticity, pathology and potential repair of the inner ear and auditory pathways in the brain. His work throughout the years has focused on the cellular processes underlying the development of the auditory system and how these processes are influenced by early experience.