Clive Morgan, Ph.D.
Meet the Researcher
Morgan received his doctorate in biochemistry from University College London, where he also completed postdoctoral research and at the U.K.’s University of Manchester. He is a senior research associate at Oregon Health & Science University. His 2017 Emerging Research Grant is supported by donors who designated gifts to Hearing Health Foundation (HHF) to fund Usher syndrome research, and by the board of HHF.
Usher syndrome is the most common cause of combined blindness and deafness. To further our knowledge about this genetic disorder, our aim is to understand how the ear works at a molecular level. The hair cells of the inner ear detect sound and vibrations using very fine projections. The
molecules directly responsible for monitoring movement of the hair bundles are located at the very tips of the projections.
During my studies I realized that individual molecules are only as important as the molecules with which they associate. Molecules of the inner ear had been understudied, mostly because of technical limitations. In 2007, Peter Barr-Gillespie, Ph.D. (the scientific director of the Hearing Restoration
Project), pioneered a study of the molecular makeup of the hair bundle using mass spectrometry. Now in his lab we use modern mass-spectrometry methods to detect these
incredibly scarce molecules.
By identifying all of the molecules present, and determining how they associate, we should be able to model the fully assembled mechanosensitive apparatus, or how sound is converted to electrical signals. Ultimately we aim to perform structural studies to better understand, at a mechanistic level, why people with Usher syndrome are deaf and why blindness is delayed.
We also want to learn how in healthy individuals the ear is able to discern specific sounds in a sea of noise. This is because it could be that some Usher mutations make the hair bundle more sensitive to noise-induced damage. There is evidence in mice that mutations in one particular Usher gene, USH1C, result in hair bundles that are less sensitive to mechanical stimulation.
As a child I always watched science shows on British TV—“Horizon” and “Tomorrow’s World”—and I read New Scientist and Scientific American. The first scientist in the family, I was inspired by my high school chemistry and biology teachers, who introduced me to the British Science Association.
Through the group I was able to visit the University of Oxford to attend the yearly British Science Festival. I saw demonstrations of some of the first high-temperature superconductors, sat on a Cray supercomputer the size of a hippo, and watched detectors being built for the European particle accelerator. All made deep impressions on me on the power of science, research, and technology.
I value high-quality data and am respectful of hard work and determination and of research that pushes our knowledge forward. I personally try to adhere to these values. I think this is an exciting time for hearing research, and that our understanding is rapidly improving.
Clive Morgan, Ph.D.’s grant was generously supported by donors who designated gifts to Hearing Health Foundation (HHF) to fund Usher syndrome research, and by the board of HHF. We thank these donors for funding research to improve the understanding of Usher syndrome.
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The Research
Oregon Health & Science University
Characterization of Usher syndrome 1F protein complexes
Much of our current knowledge on the molecular makeup of the hair bundle has origins in genetic studies. Several key genes have been discovered but are limited to those genes that are absolutely required for hearing and dispensable in other systems. Many independent genetic mutations also occur in a handful of genes, so that finding new genes can be quite difficult and expensive. My colleague Peter Barr-Gillespie, Ph.D., has pioneered the use of hair bundle isolation techniques to allow studies of the hair bundle proteome, allowing us to uncover many of the features of the hair bundle in single experiments. The next step is to look at how these proteins interact to fulfill the functions of a mechanically sensitive hair bundle and the effects of genetic abnormalities on the whole bundle proteome (set of proteins). In this project I will analyze individual protein complexes using a new hair bundle isolation strategy that allows us to isolate and analyze protein complexes from the hair bundle. I will perform a comparative analysis of the makeup of all Usher syndrome protein complexes. This will shed new light on the proteins involved directly in mechanotransduction.
Long-term goal: To understand the molecular architecture of the hair bundle and to decipher the molecular basis for genetic abnormalities leading to deafness, in order to decipher the functioning of the auditory and vestibular system in greater clarity.