Loss of sensory hair cells is a major cause of hearing impairment and can arise from both genetic and environmental causes including noise trauma, aging, and drug exposure. The overall objective of this application is to investigate the mechanism of aminoglycoside drug toxicity in hair cells. This research will test the hypothesis that perturbation of proteins which are direct or indirect targets of aminoglycosides will alter the degree of hair cell death using the zebrafish lateral line as a model system. Two approaches are used to define components modulating aminoglycoside toxicity: physiological alteration of hair cells in wildtype zebrafish and isolation of mutants with altered aminoglycoside response.
The specific aims of this application are to: 1) test whether disruption of mitochondrial function alters aminoglycoside response; 2) determine the molecular nature of the zebrafish sentinel mutation that exhibits aminoglycoside resistance; and 3) identify new mutations with sensitivity or resistance to aminoglycoside hair cell loss. The long term goal of this research to identify pathways which may underlie other less experimentally tractable forms of hair cell loss, such as age or noise related hair cell loss, and to suggest targets for intervention during drug treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DC006998-01
Application #
6836732
Study Section
Communication Disorders Review Committee (CDRC)
Program Officer
Sklare, Dan
Project Start
2004-06-25
Project End
2006-06-24
Budget Start
2004-06-25
Budget End
2005-06-24
Support Year
1
Fiscal Year
2004
Total Cost
$56,536
Indirect Cost
Name
University of Washington
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195