Our understanding of Noise-Induced Hearing Loss is rather rudimentary, despite the importance of this problem to human occupational and recreational health. The damage is permanent because mammals cannot regenerate their auditory hair cells once they die. Studies of the underlying causes of noise-induced hearing loss have focused on mechanical damage to cells, and molecular studies centered around oxidative damage and cytoskeletal disruptions. Mammalian studies are challenged by difficult access to the inner ear inside the temporal bone, and expensive animal care costs. In this proposal we seek to capitalize on the genetic model organism, Drosophila, to systematically characterize gene expression changes induced by acute or chronic over-exposure to sound. Our preliminary results show that there are strong immediate effects on auditory function after acute exposure. We propose first to study the immediate and longer-term morphological and physiological consequences of these forms of noise trauma. Second, we will identify genome-wide responses to acoustic stress using microarray analysis. These studies will provide insight into possible pathways through which to increase resistance to noise damage as a preventative measure, or to reduce the deleterious effects of noise damage after the fact as a therapeutic measure. They will also inform the individual genetic differences in susceptibility to noise damage.

Public Health Relevance

Over-exposure to noise is a serious problem in today's industrial and technological world, especially with increasing age structure in human populations. The proposed project uses the genetic model organism Drosophila to investigate functional and structural consequences to the auditory organ upon acute or chronic over-exposure to sound, and to understand gene expression changes evoked by this treatment. The results of our studies will facilitate identification of putative preventative and therapeutic targets for human noise-induced hearing loss and age-related hearing loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC011397-01
Application #
8031513
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2010-12-01
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
1
Fiscal Year
2011
Total Cost
$225,500
Indirect Cost
Name
University of Iowa
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Christie, Kevin W; Eberl, Daniel F (2014) Noise-induced hearing loss: new animal models. Curr Opin Otolaryngol Head Neck Surg 22:374-83
Christie, Kevin W; Sivan-Loukianova, Elena; Smith, Wesley C et al. (2013) Physiological, anatomical, and behavioral changes after acoustic trauma in Drosophila melanogaster. Proc Natl Acad Sci U S A 110:15449-54
Jacobs, Julie S; Hong, Xiaojing; Eberl, Daniel F (2011) A ""mesmer""izing new approach to site-directed mutagenesis in large transformation-ready constructs: Mutagenesis via Serial Small Mismatch Recombineering. Fly (Austin) 5:162-9
Fritzsch, Bernd; Eberl, Daniel F; Beisel, Kirk W (2010) The role of bHLH genes in ear development and evolution: revisiting a 10-year-old hypothesis. Cell Mol Life Sci 67:3089-99