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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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National Institute on Aging Initial Review Group (NIA)
Program Officer
Kohanski, Ronald A
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University of Minnesota Twin Cities
Physical Medicine & Rehab
Schools of Medicine
United States
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Prochniewicz, Ewa; Lowe, Dawn A; Spakowicz, Daniel J et al. (2008) Functional, structural, and chemical changes in myosin associated with hydrogen peroxide treatment of skeletal muscle fibers. Am J Physiol Cell Physiol 294:C613-26
Prins, Kurt W; Lowe, Dawn A; Ervasti, James M (2008) Skeletal muscle-specific ablation of gamma(cyto)-actin does not exacerbate the mdx phenotype. PLoS One 3:e2419
Landisch, Rachel M; Kosir, Allison M; Nelson, Steven A et al. (2008) Adaptive and nonadaptive responses to voluntary wheel running by mdx mice. Muscle Nerve 38:1290-303
Warren, Gordon L; Moran, Amy L; Hogan, Harry A et al. (2007) Voluntary run training but not estradiol deficiency alters the tibial bone-soleus muscle functional relationship in mice. Am J Physiol Regul Integr Comp Physiol 293:R2015-26
Lund, Troy C; Grange, Robert W; Lowe, Dawn A (2007) Telomere shortening in diaphragm and tibialis anterior muscles of aged mdx mice. Muscle Nerve 36:387-90
Moran, Amy L; Nelson, Steven A; Landisch, Rachel M et al. (2007) Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin dysfunction in mature female mice. J Appl Physiol 102:1387-93
Gorzek, Jeffrey F; Hendrickson, Kaysie C; Forstner, Jeffrey P et al. (2007) Estradiol and tamoxifen reverse ovariectomy-induced physical inactivity in mice. Med Sci Sports Exerc 39:248-56
Zhong, Sheng; Lowe, Dawn A; Thompson, LaDora V (2006) Effects of hindlimb unweighting and aging on rat semimembranosus muscle and myosin. J Appl Physiol 101:873-80
Moran, Amy L; Warren, Gordon L; Lowe, Dawn A (2006) Removal of ovarian hormones from mature mice detrimentally affects muscle contractile function and myosin structural distribution. J Appl Physiol 100:548-59
Lowe, Dawn A; Williams, Brian O; Thomas, David D et al. (2006) Molecular and cellular contractile dysfunction of dystrophic muscle from young mice. Muscle Nerve 34:92-100

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