BRIDGE A: LIPID MAPS NETWORKS The main objective of this Bridge Project is the reconstruction and modeling of lipidomic networks in macrophages. In the first part of this objective, a combination of inference and statistical learning based methods will be used to reconstruct networks from lipid and gene expression data obtained by the Lipidomics Core laboratories of LIPID MAPS. The statistical learning approach includes use of principal component regression and temporal analysis of modules. The LIPID MAPS project will also carry out experiments with stable isotope metabolite precursors. These include CIS-labeled arachidonate, acetate, palmitate, and mevalonate. Bridge A will develop quantitative methods for modeling and analysis of isotopomeric data and will provide kinetic analyses of derived models. From the latter developments, it will be possible to design novel experiments and conceive quantitative hypotheses to predict the consequences of pharmacological and genetic perturbations on lipid networks. In addition, the isotopomer data will be used to elucidate pathways of catabolism versus anabolism of lipids. Unlike protein networks, little is known about the lipid networks of mammalian cells. Development of lipid networks requires a systems biology approach involving large scale measurements of network players followed by mathematically intensive integrative analyses of the data to develop interaction models. These models serve as frameworks for understanding cellular function in normal and pathological conditions. Bridge A will lead the development of new methods for reconstruction and modeling of lipid networks and will provide the scientific community with tools for pathway-based approaches to study cellular function.
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