Legacy Support During Closure of the Mass Spectrometry Resource for Biology and Medicine

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The mission of the Boston University Mass Spectrometry 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. Because NIGMS has now imposed a time limit for P41 grants, the grant P41 GM104603 cannot be renewed. This proposal requests the funding essential to avoid a disruptive sudden closedown of the Resource's activities and afford a smooth transition period to enable the orderly completion of ongoing driving biomedical and collaborative projects that depend on methods and expertise uniquely available in the Resource, finalizing of ongoing software development, sharing of software, databases and protocols to meet the needs of the community, and the identification and implementation of alternative mechanisms to address the future needs of the user community and enable further technology developments that should evolve from the accomplishments of the Resource over the last 20 years. The Resource will focus on the needs of glycobiology for detailed structural elucidations and the profiling of complex mixtures of glycans. Reference data that illuminates glycan fragmentation pathways using multiple dissociation methods will be compiled and deposited into public databases; the new, user-friendly bioinformatics tools that the Resource is creating for glycan analysis will be completed, tested and shared. Protocols and sets of reference data for Ion mobility-tandem mass spectrometry will be compiled for the analysis of glycans and complex peptide mixtures, for characterization of noncovalent complexes, and for evaluation of new ExD cell designs being constructed by a small industry collaborator. In-house in developed software for glycan structural determinations and top-down analysis of variant and post-translationally modified proteins, that can establish relationships among PTMs on individual proteins, will be completed and shared; it should provide means for straightforward clinical analyses, and for probing protein-glycan and protein-protein interactions. Translational projects to be completed will include characterization of N- and O-linked glycans and lipopolysaccharides on infectious bacteria and parasites, structural determinations of glycolipids and glycosaminoglycans in human milk, protein misfolding disorders, immunology, extracellular matrix biology and cardiovascular disease. The Resource will transfer its experience in training students, postdoctoral fellows and practicing scientists to other educational institutions and industry.