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

智力优势：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成分；相反，它们产生于这些组件之间的许多交互层。在这方面，自然和工程生物系统的分析和设计将受益于这些系统的整体行为特征的综合模型和测量。鉴于生物系统的分子性质，决定其全局特征的一个关键因素是它们的化学特征。该项目的目标是建立一个多用户仪器设备，用于化学分析，重点是代谢物分析。生物系统的代谢物谱累积反映了基因表达、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，代谢物是生命必需生化途径的直接中间体，与适当的模型相结合，可用于定量评估这些途径在完整细胞和组织中的活性。该项目的核心研究项目旨在开发、应用和验证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生化途径的相互作用的全局分析。计划进行三个核心项目，以探索代谢谱数据在系统描述（例如生物标志物鉴定）以及小分子（天然产物）和大分子（纤维素）生物合成的深入分析中的使用。核心项目有：(1)肝脏药物毒性途径分析；(2)新型细菌纤维素基生物材料的合成与表征；(3)异源寄主天然产物合成新途径的代谢工程。除了项目特定的结果外，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理解细胞生化活动的全球调控。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急需补充，将广泛支持大学和其他附近机构的研究活动。我们计划将代谢组学设施与学校新建立的跨部门研究综合体的其他核心实验室整合，并为这个研究社区提供一个易于获取和负担得起的分析技术资源。还计划开展外展活动，以吸引目前缺乏类似设施的附近学术机构（例如东北大学）的用户。教育：仪器设备也将扩大塔夫茨大学的教育可能性。代谢物分析设施将成为培养不同层次的年轻科学家（本科生、研究生和博士后）的宝贵资源，用于最先进的生化数据采集和分析方法。重要的是，该项目将招募并支持学生积极参与同伴培训。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类的真实数据；本科生在实验课上直接接触现代分析仪器；并为环境化学课堂设计了一个新的现场样品分析实验单元。外展：计划开展具体活动，通过塔夫茨大学的计算机科学、工程和数学学者（cems）项目，提高代表性不足群体成员和第一代大学生的参与度。

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.