Hair cell mechanotransduction is the process that underlies our senses of hearing and balance. The focus of the Shin lab is the study of proteins that mediate the exquisitely sensitive mechanotransduction process. Stress factors such as reactive radicals and mechanical overstimulation can damage hair cell proteins, raising the question how these proteins are repaired or replaced. Our hypothesis is that the main strategy for maintaining integrity of hair ceil proteins is a constant turnover of proteins. I am therefore interested in the dynamic turnover of hair ceil proteins, especially in response to harmful impacts such as oxidative stress and noise damage. The goal of my present ROO proposal is to use mass spectrometry analysis of metabolically labeled proteins and in vivo imaging of hair bundle proteins to study turnover and dynamics of hair cell proteins. Lay summary: The health of the hearing organ depends on the constant replacement of its molecular components. The proposed study uses mass spectrometry and imaging technologies to address the question whether harmful environmental stimuli such as noise damage can influence the turnover of proteins important for hearing. The results of this study wiii help to develop methods to prevent and restore hearing losses in humans.
Hearing loss is America's leading disability, and for developing preventative and restorative approaches, it is crucial to understand how the integrity of the hearing organ is maintained. Our hypothesis is that the turnover of damaged proteins is cmcial for the health of the hair cell. Owing to technical innovations in the field of proteomics and live-cell imaging, we are now able to attack these questions in a comprehensive way.
|Shin, Jung-Bum; Krey, Jocelyn F; Hassan, Ahmed et al. (2013) Molecular architecture of the chick vestibular hair bundle. Nat Neurosci 16:365-74|
|Francis, Shimon P; Katz, Joshua; Fanning, Kathryn D et al. (2013) A novel role of cytosolic protein synthesis inhibition in aminoglycoside ototoxicity. J Neurosci 33:3079-93|
|Shin, Jung-Bum; Longo-Guess, Chantal M; Gagnon, Leona H et al. (2010) The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice. J Neurosci 30:9683-94|