The National Resource for Accelerator Mass Spectrometry (AMS) was established in 1999 to enable biomedical researchers to accurately quantify very low levels of radioisotopes while exploring fundamental issues in biology. In this renewal, we will expand our present capabilities by developing a fully integrated HPLC AMS to increase our capabilities for metabolic measurements which our collaborators require. We will develop methods to study biochemical pathways and cellular processes down to the level of the single cell. Finally we will develop and validate methods for the application of AMS in human translational research which is a growing area of demand by collaborators and service users. Throughout the tenure of the grant we will continue to provide a resource to the research community that will include service to investigators familiar with AMS, training of investigators in the technology and dissemination of the Resource. Towards these goals, our specific aims are to: 1.) Increased throughput of AMS through direct coupling to separatory instruments. 2.) Increase the value and information content of AMS measurements by combining molecular identities with quantitation of defined isolates for pathway analysis from very small cellular, animal, and human samples. 3.) Provide quantitation of biological systems using multiple isotopic tracers within sampled materials. 4.) Provide high throughput precision quantitation for collaborative and service clients.

Public Health Relevance

This Center provides new technology for filling the unique niche of ultra-high sensitivity isotope quantitation in biomedical studies. The technology is ideal for quantifying endpoints without perturbing the natural metabolism in model systems so that results are relevant and it allows studied to be done in humans to assure that models represent the human situation and for translational research. This technology supports over 60funded investigators.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Biotechnology Resource Grants (P41)
Project #
5P41GM103483-15
Application #
8474795
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Program Officer
Sheeley, Douglas
Project Start
2000-09-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
15
Fiscal Year
2013
Total Cost
$1,654,246
Indirect Cost
$638,413
Name
Lawrence Livermore National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
Tong, T; Ondov, J M; Buchholz, B A et al. (2016) Contemporary carbon content of bis (2-ethylhexyl) phthalate in butter. Food Chem 190:1064-8
Mortimer, Monika; Petersen, Elijah J; Buchholz, Bruce A et al. (2016) Separation of Bacteria, Protozoa and Carbon Nanotubes by Density Gradient Centrifugation. Nanomaterials (Basel) 6:
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Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M et al. (2016) Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer. PLoS One 11:e0146256
Kim, Jeffrey; Stewart, Benjamin; Weiss, Robert H (2016) Extraction and Quantification of Tryptophan and Kynurenine from Cultured Cells and Media Using a High Performance Liquid Chromatography (HPLC) System Equipped with an Ultra-Sensitive Diode Array Detector. Bio Protoc 6:
Mortimer, Monika; Petersen, Elijah J; Buchholz, Bruce A et al. (2016) Bioaccumulation of Multiwall Carbon Nanotubes in Tetrahymena thermophila by Direct Feeding or Trophic Transfer. Environ Sci Technol 50:8876-85
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Malfatti, Michael A; Kuhn, Edward A; Turteltaub, Kenneth W et al. (2016) Disposition of the Dietary Mutagen 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Healthy and Pancreatic Cancer Compromised Humans. Chem Res Toxicol 29:352-8
Madeen, Erin; Corley, Richard A; Crowell, Susan et al. (2015) Human in Vivo Pharmacokinetics of [(14)C]Dibenzo[def,p]chrysene by Accelerator Mass Spectrometry Following Oral Microdosing. Chem Res Toxicol 28:126-34
Maze, Ian; Wenderski, Wendy; Noh, Kyung-Min et al. (2015) Critical Role of Histone Turnover in Neuronal Transcription and Plasticity. Neuron 87:77-94

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