Dynamics of Hair Bundle Proteins

描述(由申请人提供)：我在加里·勒文博士的实验室获得博士学位，在那里我研究皮肤中的触摸感受器。我对机械转导的普遍兴趣将我带到了彼得·吉莱斯皮博士的实验室，他是毛细胞研究领域的领先研究人员之一。在我的博士后培训期间，我使用了各种技术参与了几个项目，包括离子通道TRPN1的本地化研究和基于质谱学的发束蛋白质鉴定。目前，我正在鉴定最初的蛋白质组学研究产生的感兴趣的束蛋白。在我未来的研究中，我对毛细胞蛋白质的动态周转感兴趣，特别是在应对氧化应激和噪音损害等有害影响时。我目前的K99/Roo提案的目标是使用代谢标记蛋白质的质谱分析和束蛋白的体内成像来研究发束蛋白的周转和动力学。我目前研究所的研究环境非常出色：吉莱斯皮实验室与俄勒冈州听力研究中心和世界著名的Vollum研究所有联合预约。然而，为了实施拟议的项目，我将需要在各种新技术方面进行进一步的培训，包括先进的质谱学应用和产生转基因非洲爪哇的方法。该领域的领先研究人员已经同意在他们的实验室接待和培训我。毛细胞研究充满了技术困难，需要应用创新的方法来解决既定的问题，尽管过去接受了广泛的培训，但我仍然缺乏独立进行所需研究的实验技能。因此，独立之路奖非常适合我目前的职业情况，它同时强调培训和独立。内容提要：听力器官的健康有赖于其分子成分的不断更换。这项拟议的研究使用质谱学和成像技术来解决这样一个问题，即噪音损害等有害环境刺激是否会影响对听力重要的蛋白质的周转。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.