ShEEP Request for Seahorse Analyzer for Measuring Mitochondrial Respiration

ShEEP 请求使用 Seahorse 分析仪来测量线粒体呼吸

• 批准号: 9908873
• 负责人: JOSEPH F QUINN
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908873
• 关键词: Afghanistan; Alzheimer' s Disease; Alzheimer' s disease model; Animal Model; Antimalarials; Antiparasitic Agents; Auditory; Award; Basic Science; Brain; Cell Culture Techniques; Cell model; Cells; Clinic; Clinical; Clinical Research; Clinical Trials; Communicable Diseases; Conflict (Psychology); Consumption; Cultured Cells; Development; Drug Evaluation; Ensure; Enzymes; Epilepsy; Equipment; Evaluation; Exposure to; Funding; Future; Genus Hippocampus; Goals; Health; Health Services; Health Services Research; Healthcare Systems; Home environment; Injury; Intervention; Iraq; K-Series Research Career Programs; Laboratories; Lead; Malaria; Malignant Neoplasms; Measurement; Measures; Methodology; Methods; Mission; Mitochondria; Modeling; Multiple Sclerosis; Mutation; Neck; Neurodegenerative Disorders; Neuroprotective Agents; Neurosciences; Organelles; Outcome Measure; Outcomes Research; Oxygen Consumption; Parasites; Parkinson Disease; Pharmacotherapy; Proteins; Recording of previous events; Rehabilitation therapy; Reproducibility; Research; Research Personnel; Research Project Grants; Research Support; Resource Sharing; Respiration; Role; Scientist; Services; Sheep; Site; Source; Stromal Cells; Succinate Dehydrogenase; Technology; Tissues; Toxic effect; Toxoplasmosis; Training; Translating; Translations; Traumatic Brain Injury; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; Universities; Veterans; Work; agent orange; alcohol research; alpha Toxin; animal tissue; base; brain cell; brain tissue; cancer cell; cell type; clinical application; clinical translation; clinically relevant; cooperative study; design; epidemiology study; experience; improved; instrument; interest; microorganism; neurorestoration; oncology; pre-clinical; preclinical study; programs; recruit; square foot; targeted cancer therapy; user-friendly

Objectives: The objective of this equipment request is to obtain a state-of-the-art instrument to measure mitochondrial function in order to serve the research needs of investigators at the VA Portland Health Care System facility (VAPORHCS). In fiscal year 2018, VAPORHCS scientists were successful in competing for over $32 million in research grants from the VA, NIH, DOD and other sources. The VAPORHCS ranks 7th among all VAs nationwide in total research funding. There are 10 career development award or K-award recipients currently being trained here. Research is conducted in a total of 96,000 square feet of wet and dry lab space that supports programs in basic science, clinical research, rehabilitation, health services, cooperative studies, epidemiology and outcomes research. VAPORHCS is home to Centers of Excellence funded by the VA in Auditory Research and Health Services Research, and an NIH- funded Alcohol Research Center. Clinical programs awarded to the VAPORHCS include a NODES, NAVIGATE, MVP recruiting site, MIRECC, PADRECC, Centers for Multiple Sclerosis and Epilepsy, and Centers funded by QUERI and AHRQ. Plan: The plan is to obtain a Seahorse analyzer and locate it in the Portland VA facility to serve as a shared resource for VA investigators whose research involves measurement of mitochondrial respiration. Planned studies by the six VA-funded investigators include: measurement of mitochondrial respiration for: 1) the evaluation of candidate therapies in cell culture and animal models of Alzheimer’s disease, 2) evaluation of antimalarial drugs, 3) evaluation of drugs for the treatment of toxoplasmosis, 4) evaluation of the functional significance of succinate dehydrogenase mutations in stromal cell cancer cells, 5) evaluation of candidate therapies in a toxin model of Parkinson’s disease, and 6) evaluation of the effects of traumatic brain injury upon brain cell mitochondria. Once the instrument is in place, additional investigators are expected to take advantage of it. Methods: The tissue source for the measurements will vary across the respective laboratories, with mitochondrial respiration measured in cultured cells, in parasites, and in mitochondria isolated from brain tissue, depending on the research program. The Seahorse analyzer measures basal and maximum mitochondrial energy consumption and a number of other metrics are calculated from these values. Clinical relevance: The investigators participating in this request perform research which is intended to be translated to clinical application, and several have advanced their preclinical work to clinical trials, including treatments for Alzheimer’s disease, cancer, malaria, toxoplasmosis, and traumatic brain injury. The research supported by this instrument consequently has a high likelihood of leading to interventions to improve the health of veterans. Relevance to the VA’s mission: The treatment of neurodegenerative disease, cancer, infectious disease, and traumatic brain injury are all important for the VA’s mission. Two of the conditions under study are especially relevant to the VA: Parkinson’s disease is a service- connected illness for veterans with a history of exposure to Agent Orange exposure and traumatic brain injury is the signature injury for veterans of recent conflicts in Iraq and Afghanistan.

目的：本设备申请的目的是获得最先进的仪器， 测量线粒体功能，以满足VA研究人员的研究需求 波特兰卫生保健系统机构（VAPORHCS）。在2018财年，VAPORHCS科学家 成功地从退伍军人管理局、国家卫生研究院、国防部获得了超过3200万美元的研究赠款 和其他来源。VAPORHCS在全国所有VA中的总研究排名第七 经费目前正在培训10名职业发展奖或K奖获得者 这里.研究在总共96，000平方英尺的干湿实验室空间中进行， 支持基础科学，临床研究，康复，卫生服务， 合作研究、流行病学和成果研究。VAPORHCS是家庭中心， 卓越由VA资助的听觉研究和卫生服务研究，以及NIH- 酒精研究中心。授予VAPORHCS的临床项目包括 NODES、NAVIGATE、MVP招募网站、MIRECC、PADRECC、多发性硬化中心 以及由QUERI和AHRQ资助的中心。 计划：计划是获得一台Seahorse分析仪，并将其放置在波特兰VA设施中， 作为VA调查人员的共享资源，其研究涉及测量 线粒体呼吸由VA资助的六名研究人员计划进行的研究包括： 线粒体呼吸的测量用于：1）评估细胞中的候选疗法 阿尔茨海默病的培养和动物模型，2）抗疟药物的评价，3） 用于治疗弓形虫病的药物的评价，4）用于治疗弓形虫病的药物的功能评价， 间质细胞癌细胞中琥珀酸脱氢酶突变的意义，5）评估 在帕金森病的毒素模型中的候选疗法，和6）评价 创伤性脑损伤对脑细胞线粒体的影响。一旦文书到位， 调查人员将利用这一点。 方法：用于测量的组织来源将在各个实验室中有所不同， 在培养细胞、寄生虫和线粒体中测量线粒体呼吸 从脑组织中分离出来，这取决于研究项目。Seahorse分析仪 测量基础和最大线粒体能量消耗以及一些其他 从这些值计算度量。 临床相关性：参与本申请的研究者进行的研究 旨在转化为临床应用，有几个已经推进了其临床前 致力于临床试验，包括治疗阿尔茨海默病，癌症，疟疾， 弓形虫病和脑外伤该仪器支持的研究 因此，很有可能采取干预措施，改善退伍军人的健康。 与退伍军人事务部的使命的相关性：神经退行性疾病，癌症， 传染病和创伤性脑损伤对退伍军人事务部的使命都很重要。两 研究中的条件与VA特别相关：帕金森病是一种服务- 有接触过橙子剂的退伍军人的相关疾病， 创伤性脑损伤是最近伊拉克冲突中退伍军人的标志性损伤， 阿富汗