Tandem mass spectrometry for flux analysis
Ph.D. Student: Jung Choi
Tandem mass spectrometry is a powerful tool for obtaining structural information of molecules and has been used previously to elucidate the structure of a variety of small to medium sized molecules, including organic molecules, lipids and fatty acids, peptides, carbohydrates, as well as DNA and RNA adducts. However, its application for analysis of labeling distributions and flux determination is yet to be fully explored. The goal of this project is therefore to fully develop the application of tandem mass spectrometry (GC-MS/MS) for the analysis of stable-isotope labeling and estimation of fluxes.
Specific aims of this research are: (i) optimize GC-MS/MS analysis conditions for accurate and precise detection of mass isotopomer distributions of cellular metabolites; (ii) develop novel modeling methods for simulating labeling distributions in biochemical networks and estimating fluxes from GC-MS/MS data; (iii) experimentally demonstrate the advantages of the GC-MS/MS approach for in vivo flux analysis in cell culture experiments.
Antoniewicz MR, Kelleher JK, Stephanopoulos G.