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After receiving his B.S. in Cell and Molecular Biology at Texas Tech University, Richard Walker received his Ph.D. in Neuroscience in 1995 from the University of Texas Southwestern Medical Center. He then trained as a postdoctoral fellow at the University of California, San Diego. In 2000, Walker was appointed as an assistant professor in the Oregon Hearing Research Center with a joint appointment in the Vollum Institute. Research InterestsThe umbrella of mechanical senses covers a diverse set of sensory modalities, including touch, hearing, balance, and proprioception. While very different cells perform the task of collecting information about the mechanical world for each mechanosensory system, they all appear to do it in the same way, directly converting energy in a mechanical stimulus—be it a whisper or a hammer blow to your thumb—to an electrical signal that is passed on to the central nervous system. How do sensory cells transduce mechanical stimuli into electrical signals? To answer this question, research in the Walker lab takes advantage of the ease and elegance of the Drosophila system and can be divided into two parts: a molecular-genetic path to identify the genes involved in mechanosensory transduction and an electrophysiological approach to understanding both wild-type and mutant mechanosensory responses. While each of these approaches is powerful in its own right, combining them gives a comprehensive set of tools both to identify the molecules of mechanosensation and to show how they work together to convert mechanical stimuli into electrical signals. Understanding mechanosensation requires identification of the molecules comprising the transduction machinery. To identify the components of the Drosophila machinery, Walker and colleagues examined mechanosensory mutants for electrophysiological aberrations that hint at defects in transduction molecules. One of the mutants, no mechanoreceptor potential C (nompC), showed intriguing phenotypes that strongly suggested that the gene played an important role in the transduction process. Identification and analysis of the nompC gene revealed that it encodes a novel ion channel. Both Drosophila nompC and a homologous C. elegans gene are selectively expressed in ciliated mechanosensory organs. The expression profile of nompC supports the physiological and behavioral phenotypes of nompC mutants, and substantiates NOMPC as a mechanosensory transduction channel. A surprising finding of these experiments was that the nompC null mutants still showed a small, non-adapting current, suggesting the presence of an additional mechanically-gated channel. The NOMPC channel might, therefore, participate in a transduction complex with another, perhaps related, channel. The cloning of the NOMPC mechanosensory transduction channel represents the first peek into the molecules that make up the transduction machinery in flies. Using NOMPC as a toehold into the transduction cascade gives a tremendous advantage over traditional genetic screens; the proteins that interact with NOMPC either genetically or biochemically can now be precisely targeted. While identifying other transduction components will be necessary to comprehend mechanosensation, an in-depth understanding will require a great deal more biophysical experimentation, particularly on isolated mechanosensory neurons. The Walker lab is therefore developing an isolated-cell preparation to record whole-cell, voltage-clamped transduction currents. This preparation will allow simultaneous manipulation of both the interior and exterior of the mechanoreceptor neuron and its transduction machinery. This precise control will be key for identifying transduction molecules and understanding how they transform a mechanical force into electrical information. Selected PublicationsWalker, R.G. (2003) More whistles and bells for fly hearing. Proc. Natl. Acad. Sci. USA 100:5581-5582. Gillespie, P.G. and Walker, R.G. (2001) Molecular basis of mechanosensory transduction. Nature 413:194-202. Walker, R. G., Willingham, A. T., and Zuker, C. S. (2000) A Drosophila mechanosensory transduction channel. Science 287:2229-2234. Barolo, S. Walker, R. G., Polyanovsky, A. D., Freschi, G., Keil, T., and Posakony, J. W. (2000) A novel notchindependent activity of Suppressor of Hairless is required for normal mechanoreceptor physiology. Cell 103:957-969.
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