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ArmitageIM_MartinBL

Research Abstracts Online
January 2009 - March 2010

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University of Minnesota Twin Cities
College of Biological Sciences
Medical School
Department of Biochemistry, Molecular Biology, and Biophysics

PI: Ian M. Armitage
Co-PI: Bruce L. Martin

Structure/Function of Biomolecules: NMR-based Differential Metabolic Profiling of Microglia and Astrocytes

These researchers used MSI resources for two projects during this period. In the first, they use multi-nuclear/dimensional NMR methods to forge new inroads into the following areas: the structure and metal exchange properties of proteins involved in the maintenance of metal homeostasis in vivo; structural/functional studies of select molecules involved in Alzheimer’s disease; and the structure, dynamics, and mechanism of activation of specific zinc finger DNA transcription factors upon zinc binding. The researchers use the BSCL to process the multidimensional NMR datasets, to calculate the three-dimensional structures of the biomolecules, and to visualize those calculated structures.

The second project deals with neurological disorders that involve differentially activated microglia and astrocytes. The researchers are bringing together two Academic Health Center Centers of Excellence to apply proton NMR spectroscopy of cell culture extracts to distinguish the metabolic profile of microglia from that of astrocytes in both their quiescent and activated states. Successful completion of this ex vivo characterization would stage the University research community well for NIH support of follow-up in vivo spectroscopy of murine models of central nervous system disorders to track the temporal sequence of glial activation. These studies will in turn support the eventual development of noninvasive NMR metabolomic profiling of patients with neurologic disorders. This project makes extensive use of the Chenomx software in the BSCL for the assignment of the metabolite 1H NMR spectra.

Group Members

Issam El Ghazi, Research Associate
Brian Reilly, Undergraduate Student
Di Wu, Undergraduate Student