Download presentation
Presentation is loading. Please wait.
1
the LIPID MAPS Consortium University Of California San Diego
A systems approach to pathways and networks involved in lipid metabolism in macrophage activation the LIPID MAPS Consortium University Of California San Diego
2
Lipid Metabolic Pathways
Cellular Networks Signaling Pathways Gene expression Protein expression Enzyme activation Lipid Metabolites Lipid Associated Proteins Lipid Metabolic Pathways
3
Macrophage or endothelial Induction of inflammatory and
cell membrane Direct Activation (Proteolysis) MAP3K ACTIVATE RAW CELLS WITH Kdo2-Lipid A Induction of inflammatory and immune response genes Measure time series of Gene, Lipid, protein and Cytokine Responses Cytokines (IL-1b, TNFa), Tissue factor, B7, etc. LIPID MAPS TM
4
Layers of Replications and Measurements
Bio Replicates MS MS MS Tech Replicates Mass Spec Runs
5
EXPERIMENTAL DATA
6
Lipidomics Data Display : Gene array-search by pathway http://www
7
Lipid Pathways and Networks:Visualization tools VANTED: Displaying lipidomic timecourse data Hyperlink to protein DB Hyperlink to lipid DB
8
Integrated lipids, genes, and pathways data across timecourse
experiments for RAW cells treated with Kdo2-lipid A LIPID MAPS funded by Glue Grant from: Overview PLA carboxylase Acetyl CoA Malony-CoA decarboxylase synthase Fatty acid Carnitine Palmitoyl Transferase (CPT-1) KDO2-lipid A DNA cytosol ACS mitochondria Acyltransferases lipases PLC TLR4 Microarray results Metabolic pathway Signaling pathway Energy metabolism HMG-CoA reductase Serine Palmitoyltransferase Rate limiting step Physical interaction Sterol O-Acyltransferases LCAT LDL HDL ABCG1 ABCA1 Receptors Proteins Lipid rafts PPAR Fatty Acid FAT/CD36 FATP Malonyl-CoA Acetyl-CoA Acyl-CoA Citrate Sphingolipids Fatty Acids Glycerolipids Glycerophospholipids Sterols Isoprenoids CE Fatty Acids: Omega-3 and Omega-6 polyunsaturated fatty acids Sterols Glycerophospholipids Fatty Acids: Eicosanoids Fatty Acids: Omega-9 polyunsaturated and straight chain fatty acids Sphingolipids
9
EXPERIMENTAL DATA
10
Ligand Screen – Time Course
Ca++ 10’ cAMP 0.5’ 1’ 3’ 8’ 20’ Phospho Protein 2.5’ 5’ 15’ 30’ Micro Array 30’ 1 hr 2 hr 4 hr
11
Summary of Ligand Screen Responses
Similar presentations
