Molecular Biophysics of Myosin and Actin in Aged Muscle

描述（申请人提供）：申请人：申请人，黎明A。Lowe是一位生理学家，其研究重点是年龄引起的肌肉退化的分子机制。Lowe博士虽然接受过肌肉生理学培训，但在肌肉生物化学和分子生物学方面获得了经验，并在当前的应用中提出学习和利用分子生物物理技术来完善用于研究衰老肌肉的多学科方法。她的职业目标是发展a）在学术环境中的独立研究路线，B）一个额外资助的实验室和c）指导研究生和博士后研究员在研究和学术界所需的指导技能。指导研究科学家发展奖将为申请人提供必要的支持和培训，以实现这些职业目标。 职业发展/培训计划：该计划的主要内容将是通过指导培训获得先进的分子生物物理技术。大部分培训将来自申办者，但也将从由生物物理学和老龄化领域的知名研究人员组成的咨询委员会获得关键指导。进一步的职业和研究发展的结构化活动将包括参加关于老龄化的夏季研究研讨会，正式的课程工作，出席和参加国家科学会议，定期参加期刊俱乐部和研讨会，并继续与明尼苏达大学的老龄化中心和肌肉和肌肉疾病中心联系。 研究计划：该提案的总体目标是让Lowe博士学习和应用分子生物物理技术来探索与年龄相关的肌肉收缩性变化。肌肉功能下降是衰老的常见但不希望的后果，为了建立逆转或预防下降的方法，必须首先阐明潜在的分子机制。Lowe博士将使用电子顺磁共振光谱（Aim 1）和单分子生物物理（Aim 2）技术研究年龄对肌肉中两种基本收缩蛋白质肌球蛋白和肌动蛋白的结构，功能和相互作用的影响。 环境：Lowe博士的培训计划环境非常出色。发起人大卫托马斯博士是肌肉生物物理学领域的国际知名科学家，是上述两个中心的董事会成员，也是NIH资助的两个培训项目的负责人，一个是肌肉，另一个是生物物理学。

DESCRIPTION (provided by applicant): Applicant: The applicant, Dawn A. Lowe, is a physiologist whose research is focused on molecular mechanisms underlying age-induced deterioration of muscle. Although trained in muscle physiology, Dr. Lowe has acquired experience in muscle biochemistry and molecular biology, and in the current application proposes to learn and utilize molecular biophysical techniques to round out a multidisciplinary approach to be used in studying aging muscle. Her career goal is to develop a) an independent line of research in an academic setting, b) an extramurally-funded laboratory and c) mentoring skills needed to guide graduate students and post-doctoral fellows in research and academia. The Mentored Research Scientist Development Award will provide the necessary support and training for the applicant to reach these career goals. Career Development/Training Plan: The primary element of the plan will be the acquisition of advanced molecular biophysical techniques from mentored training. The majority of the training will come from the sponsor but key mentoring will also be obtained from an advisory committee composed of established investigators in the fields of biophysics and aging. Structured activities for further career and research development will include attendance at a summer research workshop on aging, formal course work, attendance and participation at national scientific meetings, regular involvement in journal clubs and seminars, and continued affiliation with The Center on Aging and The Center for Muscle and Muscle Disorders at the University of Minnesota. Research Plan: The overall aim of this proposal is for the Dr. Lowe to learn and apply molecular biophysical techniques to explore age-related alterations in muscle contractility. A decline in muscle function is a common yet undesired consequence of aging and in order to establish methods to reverse or prevent the decline, the underlying molecular mechanisms must first be elucidated. Dr. Lowe will use electron paramagnetic resonance spectroscopy (Aim 1) and single molecule biophysical (Aim 2) techniques to study the effects of age on the structure, function, and interaction of two fundamental contractile proteins in muscle, myosin and actin. Environment: The environment for Dr. Lowe's training plan is outstanding. The sponsor, Dr. David Thomas, is an internationally known scientist in the field of muscle biophysics, is on the Board of Directors for both of the Centers mentioned above, and is the director of two NIH-funded training programs, one in muscle and the other in biophysics.