Hearing Health Summer 2015 Issue Summer 2015 | Page 22

research Distilling the Data The burgeoning field of bioinformatics allows the Hearing Restoration Project to analyze and compare large genomics datasets and identify the best genes for more testing. This sophisticated data analysis will help speed the way toward a cure for hearing loss and tinnitus. ince its launch in 2011, the Hearing Restoration Project (HRP) is focused on identifying new therapies that will restore inner ear hair cell function, and hence hearing. Within the consortium, smaller research groups engage in separate projects over the course of the year, to move the science along more quickly. Over the past decade my group, and the group led by my collaborator Mark Warchol, Ph.D., have worked to identify genes that are potential targets for drug development or for gene therapies to cure hearing loss. Our approach has been to determine the exact mechanisms that some vertebrates—in our case, birds— use to regenerate their hair cells and thus spontaneously restore their hearing. We have been comparing this genetic “tool kit” with the mechanisms that mammals normally use to make hair cells. Unlike birds, mammals cannot regenerate adult hair cells when they are damaged, which is a leading cause of human hearing and balance disorders. Our working hypothesis is that birds have regeneration mechanisms that mammals are missing—or that mammals have developed a repressive mechanism that prevents hair cell regeneration. In either case, our strategy has been to get a detailed picture of what transpires during hair cell regeneration in birds by using cutting-edge technologies developed during the Human Genome Project (the international research collaboration whose goal was the complete 22 | hearing health | a publication of hearing health foundation mapping of all the nuclear DNA in humans). These nextgeneration (NextGen) DNA sequencing methods have allowed us to accurately measure changes in every single gene as chick sensory hair cells regenerate. The good news is that this gives us, for the first time, an exquisitely detailed and accurate description of all of the genes that are potential players in the process. The bad news is that this is an enormous amount of information; thousands of genes change over the course of seven days of regeneration. Some of these will be the crucially important—and possibly game-changing—genes that we want to explore in potential therapies, but most will be downstream effects of those upstream formative events.The challenge is to correctly identify the important causative needles in the haystack of later consequences. We already know some important genetic players, but we are still far from understanding the genetic wiring of hair cell development or regeneration. For example, after decades of basic research, we know that certain signaling pathways, such as those termed Notch and Wnt, are important in specifying how hair cells develop. These chemical signaling pathways are made of multiple protein molecules, each of which is encoded by a single gene. However, the Notch and Wnt pathways together comprise fewer than 100 genes and, despite being intensively studied for years, we do not completely understand every nuance of how they fit together. Photo credit: istockphoto.com/Magnilion S By Michael Lovett, Ph.D.