Group Contacts
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Improving metabolomic measurement and analysisMetabolomics, the study of small molecule biochemical components associated with metabolism, can greatly enhance researchers’ fundamental understanding of how cells operate. This approach has a wide range of potential uses, from gaining insight into how a single-cell microorganism uses carbon and nitrogen, to identifying differences between cancer cells and healthy cells. Metabolomics technologies, in particular mass spectrometry (MS), are rapidly maturing and nearing high throughput status, when one would be able to measure the concentrations of a large fraction of metabolites with high precision, high temporal resolution, and low per-experiment cost. However, the experimental techniques, as well as data analysis protocols, are still far from perfection. In particular, the sensitivity of high throughput metabolic techniques currently allows determination of the concentrations of relatively abundant species only. Taking advantage of Los Alamos expertise in stable isotope labeling and MS analysis, as well as in reverse engineering of biochemical interaction networks from metabolic data; researchers in B, CCS, ISR and T Divisions are developing a set of coordinated experimental and computational tools and protocols for improving the quality of high throughput metabolomic measurements and analysis. They will use this data for reconstruction of both small-scale metabolic pathways and system-wide metabolic networks. Specifically, they are working to improve MS metabolic profiling by developing stable isotope-enhanced metabolome analysis methods and improving the unique reverse engineering metabolic network inference software developed at Los Alamos. These methods will be applied to an evolving series of experimental studies using in vitro models of malignant tumor progression in standard 2-D and more complex 3-D cell culture systems. In addition to enhancing the technologies used in this area of research, the Los Alamos team will provide a large set of metabolic profiles to improve the basic understanding of the metabolomics of human cancer, a necessary step before such technologies will be applicable in diagnostics and therapy monitoring. The National Institutes of Health recently funded this research for five years in conjunction with the National Cancer Institute. James Freyer (B-9) and Ilya Nemenman (CCS-3) lead the project; other researchers include includes Pat Unkefer (B-DO) and Cliff Unkefer (B-8), Steven Brumby (ISR-2), and William Hlavacek and Fangping Mu (both in T-10). |
B-8 Teams
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