The mission of the Boston University Mass Spectrometry Research Resource for Biology and Medicine is the development and application of advanced, mass spectrometry-based methods for the characterization of biopolymers that are relevant to human health and disease. Its steady progress has been fostered by close working relationships between basic scientists, clinicians and trainees at the student and postdoctoral levels. During the next grant period, the Resource will carry out Technological Research and Development (TR&D) projects that are designed to address the needs of major collaborators with whom it has identified Driving Biological Projects (DBPs) and will also use the tools and approaches that result from these efforts to solve challenging biological questions raised by additional collaborators and the wider community. The TR&D goal of the BUSM MS Resource is to advance MS methods and instrumentation to meet the short- and long-term needs of medicine. The selection of DBPs aims to identify new areas appropriate for MS in the health sciences, develop new MS-based approaches to meet the requirements of these fields and apply cutting-edge MS to the solution of critical questions in the life sciences. The Resource will focus on the needs of glycobiology for detailed structural elucidations and the profiling of complex mixtures of glycans. In particular, glycan fragmentation pathways will be thoroughly explored using novel electron-based and established dissociation methods and new bioinformatics tools will be developed for glycan analysis. Methods for 2-D analysis of glycans, lipids and proteins on surfaces and in tissues will be developed. Ion mobility mass spectrometry will be investigated for the analysis of glycans, glycoconjugates and complex peptide mixtures and for the characterization of noncovalent complexes. Top-down analysis of variant and post-translationally modified proteins will be pursued to establish relationships among PTMs on individual proteins, to provide straightforward clinical analyses, and to probe protein-glycan and protein-protein interactions. The Resource will train students, postdoctoral fellows and practicing scientists in mass spectrometry, and educate the local, national and international community about modern MS to encourage its wide and appropriate use.

Public Health Relevance

Biological projects will include glycoform profiling of influenza strains, characterization of N- and O-linked glycans and lipopolysaccharides on infectious bacteria and parasites, structural determinations of glycolipids and glycosaminoglycans in human milk that have anti-AlDS activity, protein misfolding disorders, immunology, extracellular matrix biology, cancer and cardiovascular disease; all impact human health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM104603-19
Application #
8911347
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (40))
Program Officer
Sheeley, Douglas
Project Start
1997-07-01
Project End
2017-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
19
Fiscal Year
2015
Total Cost
$1,559,777
Indirect Cost
$578,832
Name
Boston University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Tang, Yang; Pu, Yi; Gao, Jinshan et al. (2018) De Novo Glycan Sequencing by Electronic Excitation Dissociation and Fixed-Charge Derivatization. Anal Chem 90:3793-3801
Tang, Yang; Wei, Juan; Costello, Catherine E et al. (2018) Characterization of Isomeric Glycans by Reversed Phase Liquid Chromatography-Electronic Excitation Dissociation Tandem Mass Spectrometry. J Am Soc Mass Spectrom 29:1295-1307
Khatri, Kshitij; Pu, Yi; Klein, Joshua A et al. (2018) Comparison of Collisional and Electron-Based Dissociation Modes for Middle-Down Analysis of Multiply Glycosylated Peptides. J Am Soc Mass Spectrom 29:1075-1085
Wu, Jiandong; Wei, Juan; Hogan, John D et al. (2018) Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides. J Am Soc Mass Spectrom 29:1262-1272
Klein, Joshua A; Meng, Le; Zaia, Joseph (2018) Deep Sequencing of Complex Proteoglycans: A Novel Strategy for High Coverage and Site-specific Identification of Glycosaminoglycan-linked Peptides. Mol Cell Proteomics 17:1578-1590
van Eijk, Martin; Rynkiewicz, Michael J; Khatri, Kshitij et al. (2018) Lectin-mediated binding and sialoglycans of porcine surfactant protein D synergistically neutralize influenza A virus. J Biol Chem 293:10646-10662
Hogan, John D; Klein, Joshua A; Wu, Jiandong et al. (2018) Software for Peak Finding and Elemental Composition Assignment for Glycosaminoglycan Tandem Mass Spectra. Mol Cell Proteomics 17:1448-1456
Irani, Seema; Naowarojna, Nathchar; Tang, Yang et al. (2018) Snapshots of C-S Cleavage in Egt2 Reveals Substrate Specificity and Reaction Mechanism. Cell Chem Biol 25:519-529.e4
Raghunathan, Rekha; Polinski, Nicole K; Klein, Joshua A et al. (2018) Glycomic and Proteomic Changes in Aging Brain Nigrostriatal Pathway. Mol Cell Proteomics 17:1778-1787
Jarugumilli, Gopala Krishna; Choi, Jong-Ryoul; Chan, PuiYee et al. (2018) Chemical Probe to Identify the Cellular Targets of the Reactive Lipid Metabolite 2- trans-Hexadecenal. ACS Chem Biol 13:1130-1136

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