National User Resource for Biological Accelerator Mass Spectrometry

生物加速器质谱国家用户资源

• 批准号: 10239048
• 负责人: Graham Bench
• 金额: $ 121.89万
• 依托单位: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10239048
• 关键词: Address; Animal Model; Area; Award; Biochemistry; Biological; Biological Models; Biological Sciences; Biomedical Research; Biomedical Technology; Biophysics; Budgets; C14 isotope; Cells; Cellular biology; Code; Communities; Complex; Computer software; Data Analyses; Data Reporting; Development; Developmental Biology; Disease; Drug Kinetics; Etiology; Funding; Gases; Genetic; Goals; Grant; Health; Human; Isotopes; Label; Laboratories; Lipids; Mass Spectrum Analysis; Measurement; Measures; Metabolic; Metabolic Pathway; Metabolism; Methods; Modeling; Modification; Molecular; Molecular Biology; National Institute of General Medical Sciences; Organism; Pathway interactions; Pharmacology; Physiological; Physiology; Property; Proteins; Radioisotopes; Radiolabeled; Research; Research Personnel; Research Support; Resource Development; Resources; Risk Assessment; Safety; Sampling; Science; Scientist; Services; System; Technology; Therapeutic; Toxicology; Training; United States; United States National Institutes of Health; Work; Workforce Development; Xenobiotic Metabolism; accelerator mass spectrometry; base; carcinogenesis; detection limit; drug development; improved; in vivo; ion source; mass spectrometer; metabolic abnormality assessment; metabolic rate; nutrition; operation; programs; research study; tool; toxicant

PROJECT SUMMARY The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide ultra- sensitive isotopic analysis (primarily radiocarbon or Carbon-14) by accelerator mass spectrometry (AMS) for NIH-funded and other researchers. It will be the only User Resource of its type in the United States. The User Resource will leverage 20 years of expertise in the development and application of AMS in broad-based biomedical research through the Biomedical Technology Research Resource for the Development of Biomedical Accelerator Mass Spectrometry (BTRRAMS): a NIGMS Biomedical Technology Center (P41GM103483 09/01/2000 – 05/31/2020) that is in its final year of operation. Since June 2014, the BTRRAMS has measured over 20,000 samples (4,000 a year) a year for its user community. The User Resource will continue to meet the needs of current users as well as provide a capability for new users who would benefit from incorporating AMS as a measurement tool into their research programs. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies continue to be an important tool for addressing many complex problems in the biomedical sciences. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and relevant other isotopes with limits of detection in real samples on the order of a few attograms/mg sample. As a National Resource, the most significant work enabled by AMS is likely to be quantification of metabolic pathways in human health states and comparison to ex vivo and in vivo animal models. The technology made available will enable a deeper understanding of the etiology of human health concerns by (1) enabling the ability to quantify pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles. The User Resource has three goals: (1) provide high throughput, ultra-sensitive 14C analysis for the NIH user community ; (2) improve the efficiency of ultra-sensitive 14C analysis through installation of new interfaces to our AMS systems, improvements in ion source efficiency and upgrades to our data analysis codes; and (3) increase the accessibility and visibility of ultra-sensitive 14C measurements for the biomedical research community by training new investigators and expanding the National user base of researchers requiring ultra-sensitive 14C analysis.

项目总结 国家生物加速器质谱学用户资源(用户资源)将提供超 用加速器质谱仪(AMS)进行灵敏的同位素分析(主要是放射性碳或碳14) NIH资助的研究人员和其他研究人员。它将是美国唯一的同类用户资源。用户 资源将利用20年来在AMS的开发和应用方面的专业知识 生物医学研究通过生物医学技术研究资源的开发 生物医学加速器质谱仪(BTRRAMS)：NIGMS生物医学技术中心 (P41GM103483 09/01/2000-05/31/2020)，这是其运营的最后一年。自2014年6月以来， BTRRAMS每年为其用户社区测量超过20,000个样本(每年4,000个)。用户 资源将继续满足当前用户的需求，并为以下新用户提供功能 将AMS作为一种测量工具纳入他们的研究计划将会受益。用户 资源的长处将是放射性碳和选定的其他放射性同位素的超高灵敏度定量 需要同位素的研究。放射性同位素标记研究仍然是一个重要的工具。 以解决生物医学科学中的许多复杂问题。AMS是一种特殊而独特的 有限度地提供放射性碳和相关其他同位素绝对定量的质谱仪 在实际样品中检测的数量级为几个阿特克/毫克样品。作为国家资源，最 由AMS实现的重要工作可能是量化人类健康状态下的代谢途径 并与体外和体内动物模型进行比较。提供的技术将使更深层次的 通过以下方式理解人类健康问题的病因学：(1)能够量化 直接在人体内的药代动力学和其他分子终点；(2)提供进行 使用蛋白质或脂类等生物制剂进行定量研究；以及(3)使更相关的研究成为可能。 健康和疾病中的代谢途径，通过使用低得多的，与生物更相关的， 细胞和完整生物体中代谢底物的浓度。这些研究支持NIGMS的基本理论 有助于理解细胞和生理基础的生物医学研究领域 原则。用户资源有三个目标：(1)为以下项目提供高吞吐量、超灵敏的14C分析 NIH用户社区；(2)通过安装新的 与我们的AMS系统的接口，离子源效率的提高和数据分析的升级 代码；以及(3)提高生物医学超灵敏14C测量的可及性和可见性 通过培训新的研究人员和扩大研究人员的全国用户基础来建立研究社区 需要超灵敏的14C分析。