MRI: Acquisition of an LC-MS Facility for Research and Education in Metabolic Systems Biology

MRI：收购 LC-MS 设施用于代谢系统生物学的研究和教育

• 批准号: 0821381
• 负责人: Kyongbum Lee
• 金额: $ 27.55万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-11-01 至 2011-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0821381&HistoricalAwards=false
• 关键词: MRI; Acquisition; LC; MS; Facility

CBET-0821381LeeIntellectual Merit: A biological entity such as a cell or tissue is increasingly recognized as a complex system with intertwined functions and structural features. These functions and features generally cannot be directly attributed to a specific molecular component of the system; rather, they arise from the many layers of interactions between these components. In this regard, the analysis and design of both natural and engineered bio-systems will benefit from integrated models and measurements that characterize the global behavior of these systems. Given the molecular nature of biological systems, a crucial determinant of their global character is their chemical profile. The goal of this program is to establish a multi-user instrumentation facility for chemical profiling, with emphasis on metabolite analysis. The metabolite profile of a biological system cumulatively reflects the states of gene expression, protein expression, and the cellular environment as well as multidirectional interactions among these elements. Moreover, metabolites are direct intermediates of life-essential biochemical pathways, and, in conjunction with appropriate models, may be used to quantitatively asses the activities of these pathways in intact cells and tissues. The core research projects of this program seek to develop, apply, and validate methods and models for the acquisition and analysis of quantitative metabolite profiling data. These methods and models will be used for the global analysis of cellular metabolism and its interactions with various other specialized biochemical pathways. Three core projects are planned to explore the use of metabolic profile data in the contexts of system description (e.g. biomarker identification) as well as in-depth analysis of both small (natural product) and large molecule (cellulose) biosynthesis. The core projects are: (1) pathway analysis of liver drug toxicity; (2) synthesis and characterization of novel bacterial cellulose-based biomaterials; and (3) metabolic engineering of new routes for natural product synthesis in heterologous hosts. In addition to the project-specific outcomes, we expect to obtain broadly applicable metabolomics technologies, e.g. specific measurement protocols and bioinformatics tools, that will enable future studies seeking to better understand the global regulation of cellular biochemical activity. Broader Impact: Research: The envisioned metabolomics facility is a much needed addition to the instrument infrastructure of Tufts University's main campus that will broadly support research activities at the university and other nearby institutions. We plan to integrate the metabolomics facility with other core laboratories of a newly established, inter-departmental research complex of the school, and provide an easily accessible and affordable analytical technology resource for this research community. Outreach activities are planned to also attract users from nearby academic institutions (e.g. Northeastern University) currently lacking a similar facility. Education: The instrument facility will also extend the educational possibilities at Tufts. The metabolite profiling facility will become an invaluable resource for training young scientists across levels (undergraduates, graduate students, and post-doctoral fellows) in state-of-the-art methods for biochemical data acquisition and analysis. Importantly, the program will recruit and support students to actively engage in peer-training. In addition, the instruments will directly facilitate on-going new course development efforts aimed at promoting interdisciplinary learning. Benefits to courses include: direct participation of students in the generation of real data for a modeling and algorithms class; direct exposure to modern analytical instrumentation by undergraduates in laboratory classes; and generation of a new laboratory unit on field sample analysis for an environmental chemistry class. Outreach: Specific activities are planned to enhance participation by members of under-represented groups and first-generation college students through Tufts' Computer Science, Engineering, and Mathematics Scholars (CSEMS) program.

CBET-0821381 Lee智力优点：生物实体（如细胞或组织）越来越被认为是一个复杂的系统，具有相互交织的功能和结构特征。这些功能和特征通常不能直接归因于系统的特定分子组分;相反，它们来自这些组分之间的多层相互作用。在这方面，自然和工程生物系统的分析和设计将受益于表征这些系统的全球行为的综合模型和测量。鉴于生物系统的分子性质，决定其整体特征的一个关键因素是其化学特征。该计划的目标是建立一个多用户仪器设施，用于化学特征分析，重点是代谢物分析。生物系统的代谢物谱累积地反映了基因表达、蛋白质表达和细胞环境的状态以及这些元素之间的多向相互作用。此外，代谢物是生命必需的生化途径的直接中间体，并且结合适当的模型，可以用于定量评估这些途径在完整细胞和组织中的活性。该计划的核心研究项目旨在开发，应用和验证用于获取和分析定量代谢物分析数据的方法和模型。这些方法和模型将用于细胞代谢及其与各种其他专门的生化途径的相互作用的全球分析。计划开展三个核心项目，探索在系统描述（例如生物标志物识别）以及深入分析小分子（天然产物）和大分子（纤维素）生物合成方面使用代谢概况数据。核心项目是：（1）肝脏药物毒性的途径分析;（2）新型细菌纤维素基生物材料的合成和表征;（3）异源宿主中天然产物合成新途径的代谢工程。除了特定项目的成果外，我们还希望获得广泛适用的代谢组学技术，例如特定的测量方案和生物信息学工具，这将使未来的研究能够更好地了解细胞生化活性的全球调控。更广泛的影响：研究：设想的代谢组学设施是塔夫茨大学主校区仪器基础设施的一个急需补充，将广泛支持大学和附近其他机构的研究活动。我们计划将代谢组学设施与学校新成立的跨部门研究综合体的其他核心实验室整合，并为该研究社区提供易于获取和负担得起的分析技术资源。还计划开展外联活动，以吸引目前缺乏类似设施的附近学术机构（如东北大学）的用户。教育：仪器设施也将扩大塔夫茨的教育可能性。代谢物分析设施将成为培训各级年轻科学家（本科生，研究生和博士后研究员）的宝贵资源，用于生化数据采集和分析的最先进方法。重要的是，该计划将招募和支持学生积极参与同行培训。此外，这些工具将直接促进正在进行的旨在促进跨学科学习的新课程开发工作。课程的好处包括：学生直接参与生成建模和算法课程的真实的数据;本科生在实验室课程中直接接触现代分析仪器;以及为环境化学课程生成一个关于现场样品分析的新实验室单元。外联：计划通过塔夫茨大学的计算机科学、工程和数学学者（CSEMS）计划开展具体活动，以提高代表性不足的群体和第一代大学生的参与。