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

Tufts University, Medford MA

Investigators

Abstract

CBET-0821381 Lee Intellectual 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.