Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism

哺乳动物冬眠研究——通往代谢转化研究中心的道路

• 批准号: 10207672
• 负责人: KELLY L DREW
• 金额: $ 230.77万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207672
• 关键词: Address; Adopted; Adult; Alaska; Animals; Arctic Regions; Arousal; Basal metabolic rate; Basic Science; Biology; Biomedical Research; Black Bear; Body Composition; Body Temperature; Cardiovascular Diseases; Centers of Research Excellence; Cessation of life; Clinical; Clinical Research; Clinical Trials; Complex; Desire for food; Diet; Eating; Elderly; Essential Amino Acids; Fasting; Foundations; Funding; Genetic; Goals; Health; Health Care Costs; Heart Arrest; Hibernation; Homeostasis; Hospitalization; Hour; Human; Impairment; Individual; Institutes; Interdisciplinary Study; Knowledge; Laboratories; Leadership; Legal patent; Life; Link; Mammals; Metabolic; Metabolic Diseases; Metabolism; MicroRNAs; Modeling; Muscular Atrophy; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Patients; Phase; Phase 0 Study; Physiological; Pilot Projects; Play; Population; Post-Transcriptional Regulation; Pre-Clinical Model; Prophylactic treatment; Protein Biosynthesis; Regulation; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Role; Scientist; Seizures; Skeletal Muscle; Source; Spermophilus; Stroke; Temperature; Time; Transcript; Translating; Translations; United States National Institutes of Health; Universities; arctic ground squirrel; career; career development; design; differential expression; disability risk; druggable target; experience; flexibility; gut microbiota; improved; indexing; insight; interest; metabolic rate; microbial; multidisciplinary; muscle form; muscle strength; obese person; organizational structure; preservation; research and development; response; sarcopenia; skeletal muscle growth; skeletal muscle metabolism; skeletal preservation

Project Summary - Overall This application is in response to PAR-16-415, Centers of Biomedical Research Excellence (COBRE) (P20). The proposed phase 1 center (P1C) is built on a strong foundation and long-term commitment to hibernation research at the University of Alaska's Institute of Arctic Biology (IAB). The objective of the P1C is to use the expertise at IAB, in particular that of Dr. Kelly Drew, the PI, to build and strengthen the University of Alaska's hibernation research infrastructure. The plan involves guiding the career development of three investigators, experienced in research, but who have yet to receive R01s from NIH, and to guide the career development of new investigators currently showing an interest in hibernation research. The long-term goal, likely beyond the life of the P1C, is to apply what is learned about the mechanisms underlying the physiological changes in hibernation to as yet unresolved issues relevant to metabolism and metabolic diseases such as disuse muscle atrophy, sarcopenia, obesity, type 2 diabetes and cardiovascular diseases in humans. The center will support the research and career development of both experienced scientists and those getting their start in research. The center will have a focus on all stages of research from basic through translational. By defining translational paths for discoveries in hibernation, the P1C will contribute to the career development of the investigators. Strong administrative and scientific leadership will accomplish the goals of this P1C through the following four Specific Aims (SA): SA1. Establish an organizational structure and research infrastructure that will support and promote a multidisciplinary framework to define mechanisms of metabolic adaptations in hibernating mammals. SA 2. Enhance the careers of P1C project PIs as well as new investigators leading pilot projects through the P1C in order to allow them to compete successfully for NIH individual research grants. SA3. Support research projects and pilot projects aimed at developing an understanding of physiological, genetic and gut microbial mechanisms in hibernation and how these mechanisms may play a role in treating disuse muscle atrophy or sarcopenia. SA 4. Support clinical research projects related to the theme of the center. Seasonal hibernators arguably display the most dramatic natural alterations in metabolism, appetite, diet, body composition and body temperature of any mammal across their annual cycle. Such extremes offer insight into regulatory mechanisms, and druggable targets that would be less obvious in traditional pre-clinical models. This P1C focuses on genetic and gut microbial mechanisms related to protein synthesis and preservation of skeletal muscle during prolonged disuse and fasting in hibernating mammals. Once completed new investigators will be equipped to identify and translate treatments to promote anabolic sensitivity and preservation of muscle mass and strength. Such discoveries have the potential to save $1 billion per year in health-care costs in the US by reducing risk for disability, hospitalization, and death in older and mobility impaired adults.

项目摘要 - 总体 该应用是针对生物医学研究卓越中心（Cobre）（P20）的16-415 PAR-16-415。 拟议的第一阶段中心（P1C）建立在坚强的基础和长期致力于冬眠的基础上 阿拉斯加大学北极生物学研究所（IAB）的研究。 P1C的目的是使用 IAB的专业知识，尤其是PI凯利·德鲁（Kelly Drew）博士，以建立和加强阿拉斯加大学 冬眠研究基础设施。该计划涉及指导三名调查人员的职业发展， 在研究方面经验丰富，但尚未从NIH获得R01，并指导职业发展 新的研究人员目前对休眠研究表现出兴趣。长期目标，可能超出 P1C的生命是应用有关生理变化基础机制的知识 尚未解决与新陈代谢和代谢疾病有关的尚未解决的问题，例如废除肌肉 人类萎缩，肌肉减少症，肥胖，2型糖尿病和心血管疾病。中心将支持 经验丰富的科学家和开始研究的研究和职业发展。 该中心将重点关注从基本到翻译的所有研究阶段。通过定义翻译 冬眠中发现的途径，P1C将有助于调查人员的职业发展。 强大的行政和科学领导将通过以下四个实现该P1C的目标 具体目标（SA）：SA1。建立一个组织结构和研究基础架构，以支持和 促进多学科框架来定义冬眠哺乳动物中代谢适应的机制。 SA 2。提高P1C Project PIS的职业以及新的研究人员领导飞行员项目通过 P1C为了使他们能够成功竞争NIH个人研究补助金。 SA3。支持研究 项目和试点项目旨在发展对生理，遗传和肠道微生物的理解 冬眠的机制以及这些机制如何在治疗肌肉萎缩或 肌肉减少症。 SA 4。支持与中心主题有关的临床研究项目。季节性冬眠 可以说表现出代谢，食欲，饮食，身体成分和 在其年度周期中，任何哺乳动物的体温。这样的极端提供了有关监管的洞察力 在传统的临床前模型中，机制和可药物目标将不太明显。这个P1C 着重于与蛋白质合成和骨骼保存有关的遗传和肠道微生物机制 长时间废弃和禁食的肌肉在冬眠的哺乳动物中。完成后，新调查人员将 能够识别和翻译治疗以促进代谢敏感性和肌肉质量的保留 和力量。这些发现有可能每年节省美国的医疗保健费用10亿美元 降低年龄较大和流动性的成年人的残疾，住院和死亡的风险。