MSACL Conference Schedule

Drug Target Identification Via Systems-Level Metabolic Flux Profiling
Wed 8:30 AM - Session: Metabolomics
Josh Rabinowitz
Metabolic enzymes are among the most important drug targets. Recent advances in monitoring metabolic activity via mass spectrometry are opening new avenues to identifying the targets of existing drugs, as well as to finding novel targets for therapeutic intervention. This talk will present methodology for monitoring metabolite concentrations and fluxes in cultured cells. A key experimental technique involves monitoring the kinetics of assimilation of isotope-labeled nutrient into cellular metabolites (kinetic flux profiling). The power of modern mass spectrometry enables such experiments to generate highly specific information about a broad spectrum of metabolic pathways in parallel. The ability to use the resulting data to identify drug targets will be demonstrated via two examples. The first will involve the identification of a novel metabolic target of the antibiotic trimethoprim in Escherichia coli. The second will involve identification of fatty acid biosynthetic enzymes as novel targets for the treatment of cytomegalovirus infection.