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 #
8P41GM103483-14
Application #
8299450
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
2012-06-01
Budget End
2013-05-31
Support Year
14
Fiscal Year
2012
Total Cost
$1,709,225
Indirect Cost
$661,713
Name
Lawrence Livermore National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
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
Zhao, Chunqing; Hwang, Sung Hee; Buchholz, Bruce A et al. (2014) GABAA receptor target of tetramethylenedisulfotetramine. Proc Natl Acad Sci U S A 111:8607-12
Malfatti, Michael A; Lao, Victoria; Ramos, Courtney L et al. (2014) Use of microdosing and accelerator mass spectrometry to evaluate the pharmacokinetic linearity of a novel tricyclic GyrB/ParE inhibitor in rats. Antimicrob Agents Chemother 58:6477-83
Dingley, Karen H; Ubick, Esther A; Vogel, John S et al. (2014) DNA isolation and sample preparation for quantification of adduct levels by accelerator mass spectrometry. Methods Mol Biol 1105:147-57
Cappuccio, Jenny A; Falso, Miranda J Sarachine; Kashgarian, Michaele et al. (2014) 14C Analysis of protein extracts from Bacillus spores. Forensic Sci Int 240:54-60
Etminan, Nima; Dreier, Rita; Buchholz, Bruce A et al. (2014) Age of collagen in intracranial saccular aneurysms. Stroke 45:1757-63
Etminan, Nima; Buchholz, Bruce A; Dreier, Rita et al. (2014) Cerebral aneurysms: formation, progression, and developmental chronology. Transl Stroke Res 5:167-73
Thomas, Avi T; Stewart, Benjamin J; Ognibene, Ted J et al. (2013) Directly coupled high-performance liquid chromatography-accelerator mass spectrometry measurement of chemically modified protein and peptides. Anal Chem 85:3644-50
Sarachine Falso, Miranda J; Buchholz, Bruce A (2013) Bomb Pulse Biology. Nucl Instrum Methods Phys Res B 294:666-670
Alkass, Kanar; Saitoh, Hisako; Buchholz, Bruce A et al. (2013) Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents. PLoS One 8:e69597

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