Dynamics of Hair Bundle Proteins

描述（由申请人提供）：我在Gary Lewin博士的实验室获得博士学位，在那里我从事皮肤触觉感受器的研究。我对机械转导的普遍兴趣将我带到了Peter Gillespie博士的实验室，他是毛细胞研究领域的主要研究人员之一。在我的博士后培训期间，我使用了多种技术进行了多个项目的工作，包括离子通道TRPN1的定位研究和基于质谱的头发束蛋白鉴定。目前，我正在表征从最初的蛋白质组学研究中产生的感兴趣的蛋白质束。对于我未来的研究，我感兴趣的是毛细胞蛋白质的动态周转，特别是在应对有害影响，如氧化应激和噪音损伤。我目前的K99/ROO提案的目标是使用代谢标记蛋白的质谱分析和束蛋白的体内成像来研究头发束蛋白的周转和动力学。我目前所在的研究所的研究环境非常优秀：Gillespie实验室与俄勒冈听力研究中心和世界知名的Vollum研究所有联合任命。然而，为了进行拟议的项目，我需要进一步接受各种新技术的培训，包括先进的质谱应用和产生转基因非洲爪蟾的方法。该领域的顶尖研究人员已经同意在他们的实验室里接待和培训我。毛细胞研究充满了技术上的困难，需要用创新的方法来解决已有的问题，尽管我过去受过广泛的训练，但我仍然缺乏独立进行所需研究的实验技能。独立之路奖强调培训和独立，因此非常适合我目前的职业状况。听力器官的健康依赖于其分子成分的不断更新。这项拟议的研究使用质谱和成像技术来解决有害的环境刺激（如噪音损伤）是否会影响对听力重要的蛋白质的转换的问题。这项研究的结果将有助于开发预防和恢复人类听力损失的方法。

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.