BBS Program
Yale University
P.O. Box 208084
New Haven, CT 06520-8084
Tel: 203.785.3735
Fax: 203.785.3734
bbs@yale.edu
Assistant Professor of Neurology and Neurobiology
M.D. University of Colombo 1986
Ph.D. University of Oxford 1991
We work on the molecular basis of a number of physiological phenomena related to the hearing and balance organs. Phenomenon of electrical resonance. Electrical tuning is a phenomenon by which certain vertebrates discriminate between different frequencies of sound. Electrical resonance results when the inherent oscillation in the membrane potential of hair cells corresponds to sound of a particular frequency. This gives rise to a resonance and amplification of signal with consequent transmitter release from these cells. The inherent oscillation in membrane potential in a hair cell is brought about by an inward Calcium current and an outward Potassium current (calcium dependent). Inherent to this view is that the two proteins are physically proximate. We had previously erroneously believed that the range in BK channel currents was brought about by alternative splicing. We now hypothesize that this variation in current is brought about by association with other proteins. We have isolated several binding partners using the yeast two hybrid technique and are in the process of evaluating their ability to alter BK kinetics and bring about channel clustering and co-localization. The role of Prestin (in Collaboration with Dr. Joseph Santos-Sacchi). Prestin is a recently described protein in outer hair cells that is responsible for the sharp tuning seen in the hearing organ of mammals. It is critical for normal hearing. Knocking out of this protein results in the loss of hearing in mice. Prestin is a “motor” protein that gives rise to electromotility in outer hair cells. It’s an unusual phenomenon in that motility in outer hair cells can be rapid, upto 20KHz, which is orders of magnitude faster than conventional motor proteins like myosin. Broadly, we are seeking to understand how prestin acts as a “motor” using mutagenesis and other techniques such as FRET/?FLIM.