Dynamics of Hair Bundle Proteins

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DESCRIPTION (provided by applicant): I obtained my Ph.D. degree in the lab of Dr. Gary Lewin, where I worked on touch receptors in the skin. My general interest in mechanotransduction then lead me to the lab of Dr. Peter Gillespie, one of the leading researchers in the field of hair cell research. During my postdoctoral training, I have used a variety of techniques to work on several projects, including localization studies on the ion channel TRPN1 and mass spectrometry based identification of hair bundle proteins. At present, I am characterizing bundle proteins of interest that resulted from the initial proteomics study. For my future studies, I am interested in the dynamic turnover of hair cell proteins, especially in response to harmful impacts such as oxidative stress and noise damage. The goal of my present K99/ROO proposal is to use mass spectrometry analysis of metabolically labeled proteins and in vivo imaging of bundle proteins to study turnover and dynamics of hair bundle proteins. The research environment of my present research institute is outstanding: The Gillespie lab has a joint appointment with the Oregon Hearing Research Center and the world-renowned Vollum institute. To conduct the proposed projects, however, I will need further training in a variety of new techniques, including advanced mass spectrometry applications and methods to generate transgenic Xenopus laevis. Leading researchers in the field have agreed to host and train me in their labs. Hair cell research is full of technical difficulties and demands the application of innovative approaches to established problems, and despite extensive past training, I am still lacking experimental skills to conduct the desired research independently. The Pathway to Independence award, with its dual emphasis on training and independence, is therefore a great fit for my present career situation. 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 will help to develop methods to prevent and restore hearing losses in humans.