High Resolution 1H NMR Metabolomics Using Slow and Ultra Slow Magic Angle Spinning
EMSL Project ID
17497b
Abstract
Recently, we developed new so-called slow-MAS (magic angle spinning) NMR techniques that significantly enhance the spectral information in biofluids, intact excised tissues, organs and live small animals (mice). With 1H PASS, a sample spinning rate as low as 30Hz can be utilized, permitting non-destructive high resolution 1H NMR metabolic profiling in cells, cells attached to solid surfaces, excised tissues and organs. With 1H PHORMAT, a sample spinning rate as low as 1Hz can be utilized, allowing in vivo high resolution 1H NMR metabolic profiling in a small live animal such as mouse. More recently, a localized 1H PHORMAT experiment, namely the LOCMAT experiment, has been developed also in our laboratory, permitting high resolution 1H metabolic profiling in an arbitrarily localized volume inside a live small animal. In this science theme proposal, in addition to a continued effort in improving the performance of our slow and ultra slow-MAS technologies, we will apply our already established NMR metabolomics methods to study a variety of biological problems, including but not limited to those proposed in the following Specific Aims.Specific Aim 1: To conduct a study of mice exposed to F. tularensis, one of the top ten biological agents identified by the US government. Following exposure the metabolic perturbations in the animals global physiology and the subsequent health outcomes will be investigated using key body fluids such as urine, plasma/serum, bronchoalveolar lavage fluids (BALF), excised intact lungs, histopathology, and live animals. We will also determine if functional or structural changes occur in other organs such as heart and liver following aerosol exposure to model systems such as Francisella spp.
Specific Aim 2. To establish the statistical accuracy of slow-MAS methods by focusing on metabolic profiling on excised mouse livers under well controlled conditions and to investigate the impact of underlying disease in obesity mice using comparative metabolic biomarkers.
Specific Aim 3. The long-term goal of this specific aim is to understand the biological pathways and networks in lung inflammatory and fibrotic diseases via discovery and quantitation of key metabolites.
Specific Aim 4. We will perform an integrated, sensitive NMR metabolomics study of the impact of exposing mice and rats to 0, 0.2, 0.5, 2 and 3Gy using both high LET proton and iron ions particle radiation. The metabolic perturbations in the animals global physiology and the subsequent health outcomes will be investigated from two hours to 1 year post irradiation using key body fluids and excised tissues. In parallel we will also investigate the impact of exposing mice and rats to gamma-rays at the same dose and dose rate to address the differences in dose-rate effects between proton, iron ions and gamma-rays. We will elucidate the detailed molecular mechanisms of high LET radiation, with emphasis on understanding the molecular basis of radiation through the discovery of metabolic "signatures". This new knowledge will be translated to benefit human health in radiation therapy as well as in space exploration.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2007-05-23
End Date
2010-09-30
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
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BOBBIE-JO M. WEBB-ROBERTSON, LEE ANN MCCUE, NATHANIAL BEAGLEY, JASON E. MCDERMOTT, DAVID S. WUNSCHEL, SUSAN M. VARNUM, JIAN ZHI HU, NANCY G. ISERN, GARRY W. BUCHKO, KATHLEEN MCATEER, JOEL G. POUNDS
Pacific Symposium on Biocomputing 14:451-463 (2009)
PMID: 19209722
Application of High-Resolution 1H MAS NMR Spectroscopy to the Analysis of Intact Bones from Mice Exposed to Gamma Radiation
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RADIATION RESEARCH 172, 000–000 (2009)
DOI: 10.1667/RR1715.1
Hu JZ, DN Rommereim, KR Minard, A Woodstock, BJ Harrer, RA Wind, RP Phipps, and PJ Sime. 2008. "Metabolomics in Lung Inflammation: A High Resolution ¹H NMR Study of Mice Exposed to Silica Dust ." Toxicology Mechanisms and Methods 18(5):385-398. doi:10.1080/15376510701611032
Hu JZ, Q Zhang, DN Rommereim, NG Isern, DW Hoyt, TO Metz, MK Murphy, K Mcateer, DL Huso, JF Dicello, and RP Phipps. 2008. "Metabolic Changes in Mice Exposed to High let Iron Ion and Proton Radiation." Abstract submitted to 19th Annual NASA Spacce Radiation Investigators Workshop, Philadelphia, PA. PNWD-SA-8187.
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