RUI: Genetic Control of Sensory Hair Cell Membrane Channels in Zebrafish

Mount Saint Mary'S University, Los Angeles CA

Investigators

Abstract

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Sensory neurons in the ears of vertebrates--called hair cells--detect and transduce sound, gravitational and vibrational stimuli from the environment into electrical signals. They pass on this information to higher order neurons in the brain by releasing chemical neurotransmitters at synapses. The long-term goal of this project is to understand how the genome specifies the instructions that control the release of neurotransmitters from hair cells in auditory and vestibular structures. The present project involves studying isolated wild type and mutant hair cells from zebrafish using electrophysiological methods to characterize the membrane channels and receptors that mediate transmitter release. The use of this animal model is appropriate as it provides a simple, accessible preparation that will shed light on the genetic and physiological control of hearing and balance in vertebrates. Several lines of research will be pursued. First, because of the importance of calcium and potassium ions in the electrical and chemical events triggering neurotransmitter release, the channels that regulate the flux of these ions across hair cell membranes will be characterized. Next, as transmitter release from hair cells can be modulated by factors released by other cells, the presence of receptors for these agents will be documented and the effects of receptor activation explained. Finally, the changes in the properties of hair cell channels and receptors that result from auditory and vestibular mutants that affect hearing and balance will be analyzed. It is hoped that through the study of both wild type and mutant animals in this model system, a clearer understanding of the roles sensory hair cells play in mediating hearing and balance in vertebrates will emerge. Broader Impacts: Hearing and balance in vertebrates are reliant on the electrical activity of sensory hair cells in the inner ear. The present project is designed to discover the role the genome plays in controlling the activity of these cells. This research will provide a much needed investigation of the biophysical properties of hair cells in a model species that is ideally suited to genetic manipulation and analysis. A major goal of the project is to train women scientists. Mount St. Mary's College undergraduates are all women nearly 75% of whom are the first in their families to attend college. Furthermore, more than half are from underrepresented minorities. This project will provide a mentoring environment to train and educate these women in performing high quality independent research.