Peter G. Barr-Gillespie, Ph.D.

Research

We study mechanotransduction by hair cells, the sensory cells of the inner ear. Being interested in what molecules make up the transduction apparatus, the collection of channels, linker molecules, and motors that mediate transduction, we take a frank reductionist approach. We start with physiology: when you mechanically stimulate a hair cell, what are the characteristics of the resulting receptor current? Studying transduction currents, we learn how transduction channels open and close in response to mechanical forces, and how the adaptation motor responds to sustained forces and allows channels to close. These experiments have suggested candidate families for the transduction channel and the adaptation motors, for example, and we use these clues to identify, clone, and characterize the responsible molecules. Because the scarcity of hair cells prevent extensive biochemical characterization, we express transduction molecules in vitro and determine properties that can be compared with the physiology of transduction. This approach has proven highly successful for identification of the adaptation motor, myosin-1c, the tip link, cadherin-23, and the calcium pump, PMCA2a. We hope to soon identify the transduction channel, then determine how the cell assembles these and other molecules to make a sensory cell that can responds to deflections of one nanometer or less.