CNS-Met Metabolomics Core

CNS-Met 代谢组学核心

• 批准号: 10557544
• 负责人: Patrick G Sullivan
• 金额: $ 40.05万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557544
• 关键词: Address; Alzheimer' s Disease; Area; Behavior; Biochemical; Biochemical Pathway; Bioenergetics; Biological; Biological Sciences; Biomass; Biometry; Brain; Cells; Centers of Research Excellence; Central Nervous System; Cerebrum; Cognition; Communication; Consult; Consultations; Data; Data Analyses; Defect; Diagnosis; Disease; Ensure; Epilepsy; Experimental Designs; Fostering; Foundations; Freezing; Future; Generations; Genus Hippocampus; Glucose; Goals; Grant; Homeostasis; Human Resources; Individual; Infrastructure; Kentucky; Leadership; Libraries; Mass Fragmentography; Mass Spectrum Analysis; Measures; Memory; Mentorship; Metabolic; Metabolic Diseases; Metabolism; Methods; Mitochondria; Modernization; Molecular; Neurons; Ontology; Output; Oxidation-Reduction; Parkinson Disease; Pathway interactions; Patients; Pharmaceutical Preparations; Phase; Pilot Projects; Preparation; Process; Research; Research Personnel; Research Project Grants; Running; Sampling; Scientist; Spinal cord injury; Statistical Data Interpretation; Sustainable Development; Synapses; Talents; Techniques; Technology; Testing; Time; Tissue Microarray; Tissue Sample; Tissues; Training; Training and Education; Traumatic Brain Injury; Treatment outcome; United States National Institutes of Health; Universities; Work; biomarker discovery; brain metabolism; career development; central nervous system injury; clinical translation; cohort; computerized data processing; data acquisition; data reduction; defined contribution; design; disease prognosis; experimental study; glucose metabolism; improved; instrument; instrumentation; interest; mass analyzer; member; metabolome; metabolomics; mitochondrial metabolism; monomer; multidisciplinary; nervous system disorder; neuroinflammation; neurotransmitter biosynthesis; operation; personalized medicine; prospective; response; sample fixation; skills; skills training; success

Neurological disorders and central nervous system (CNS) injuries show clear metabolic defects, which in turn disrupts bioenergetics balances, redox status, and neurotransmitter biosynthesis that are required for maintaining, synaptic activity, neuronal homeostasis, and neuroinflammation. For these reasons, CNS metabolism research has generated interest from those studying Alzheimer’s disease, traumatic brain injury, epilepsy, spinal cord injury, Parkinson’s disease, and others. Modern metabolomics allows for the profiles of hundreds of metabolites from a single sample. It is both informative and transformative, supports both hypothesis-generating and hypothesis-driven research. Current applications of metabolomics include, molecular basis of metabolic diseases, biomarker discovery, disease prediction, drug responses, and personalized medicine. The overarching goal of the CNS-Met Metabolomics Core is to make cutting-edge metabolomics and mitochondrial energetics techniques and analyses available to CNS-Met Research Project Leaders (RPL) and pilot project PIs. The available expertise and instrumentation are well-aligned with the RPL proposals. The core directors have worked with each RPL to generate exciting preliminary data. The core will engage with, assist in experimental design, run samples, train personnel, and analyze brain metabolism data. The CNS-Met Metabolomics Core will support the talented RPLs in the area of CNS metabolism and enhance their success in competing for NIH R-level grants. To achieve these goals, the core will Aim 1: Provide experimental design consultation and project-specific study planning. The core has worked closely with the RPLs, and will continue to do so, on experimental design, data processing, and biostatistical analyses. Proper experimental design and sample preparation will lay the foundation for a successful metabolomics experiment. Aim 2: Provide metabolomics expertise and training. The core will house an Agilent 5977B GCMS, 2) Agilent 6545 quadrupole time of flight LC/CE-QTOF, and 3) a Seahorse Biosciences XF24e and XFe96 Flux Analyzers as well as Oroboros O2KFluorometer. The core will run samples, assist, train, and/or supervise data analysis from basic data reduction, incorporating procedural control, normalization, pathway ontology matching, data interpretation, and offer possible next steps. Aim 3: Perform sample processing, technical analyses, and data reduction-interpretation-presentation. The core will assist users by performing sample preparation, instrument operation, mass spectrometry peak matching to metabolites with a known compound library, sample normalization, and statistical analyses. The core will utilize integrated processes established by core leadership from experimental design though rapid and consistent sample acquisition, sample fixation, sample extraction, data reduction, statistical analysis, data analysis, and biological interpretation to ensure the success of the CNS-Met RPLs and pilot project PIs.

神经系统疾病和中枢神经系统(CNS)损伤表现出明显的代谢缺陷，在 转而破坏生物能量平衡、氧化还原状态和神经递质生物合成，这些都是 维持、突触活动、神经元动态平衡和神经炎症。出于这些原因，CNS 新陈代谢研究引起了研究阿尔茨海默氏症、创伤性脑损伤、 癫痫、脊髓损伤、帕金森氏症等。现代新陈代谢组学允许对 一个样本中有数百种代谢物。它既提供丰富的信息，又具有变革性，支持两者 假设生成和假设驱动的研究。代谢组学目前的应用包括， 代谢性疾病的分子基础、生物标记物的发现、疾病预测、药物反应和 个性化医疗。 CNS-Met代谢组学核心的首要目标是使尖端代谢组学和 线粒体能量学技术和分析可供CNS-Met研究项目负责人(RPL)和 试点项目绩效指标。现有的专业知识和工具与RPL的建议很好地结合在一起。其核心是 董事们已经与每个RPL合作，生成了令人兴奋的初步数据。核心将参与、协助 实验设计，运行样本，培训人员，并分析大脑代谢数据。CNS-Met 代谢组学核心将支持在中枢神经系统代谢领域有才华的RPL并提高他们的成功 在竞争NIH R级拨款时。 为实现这些目标，核心目标1：提供实验设计咨询和具体项目 学习计划。核心已经并将继续在实验设计方面与实验室密切合作， 数据处理和生物统计分析。适当的实验设计和样品制备将为 为新陈代谢组学实验的成功奠定基础。目标2：提供代谢组学专业知识和培训。 核心将容纳安捷伦5977B GCMS，2)安捷伦6545四极飞行时间LC/CE-QTOF，以及3)a) 海马生物科学XF24e和XFe96流量分析仪以及Oroboros O2K荧光仪。核心将会 从基本数据简化开始运行样本、协助、培训和/或监督数据分析，包括程序 控制、标准化、路径本体匹配、数据解释，并提供可能的下一步。目标3： 进行样品处理、技术分析和数据整理-解释-陈述。核心将会 协助用户进行样品准备、仪器操作、质谱峰匹配 已知化合物库的代谢物、样品归一化和统计分析。 核心将利用核心领导层从实验设计建立的集成流程 快速和一致的样品采集、样品固定、样品提取、数据还原、统计分析， 数据分析和生物解释，以确保CNS-Met RPLs和试点项目PIS的成功。