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GTL User Facilities. Facility IV: Analysis and Modeling of Cellular Systems. Jim K. Fredrickson. Facility I Production and Characterization of Proteins. Facility II Whole Proteome Analysis. Facility III Characterization and Imaging of Molecular Machines.
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GTL User Facilities Facility IV: Analysis and Modeling of Cellular Systems Jim K. Fredrickson
Facility IProduction and Characterization of Proteins Facility IIWhole Proteome Analysis Facility IIICharacterization and Imaging of Molecular Machines Facility IVModeling and Analysis of Cellular Systems Genomes to Life Facilities for 21st Century Biology Facility IVAnalysis and Modeling of Cellular Systems • Measure & predict dynamic events within cells. • Spatial & temporal variations in cell “state” – individual microbes to multi-cellular systems.
Molecular Machine Dynamics Reveal Function dynamic changes in cellular localization of the DivK protein reveal insights into the cell cycle of Caulobacter crescentus
Capabilities Required for Measuring Individual Cells • Single microbe populations exhibit variation • Can arise from noise in gene expression • Microbial communities will be more complicated Elowitz et al. 16 AUGUST 2002
Facility IV: Final Component of an Integrated Network for Systems Biology Facility I Reagents, probes Cultures, genes Controlled Experimental Systems High-Throughput Cultivation Single Cell Expression Genome sequence • New tools & infrastructure for unprecedented analyses of cell state • Cell & multi-cell models • Systems level understanding of microbes & communities Data Analysis Data Interpretation Data Archival Modeling Spatial, Temporal Analyses (imaging) Small Molecule Analyses Machines for dynamic analysis Proteomics, Regulatory networks Cultures, communities Cultures Facility II Facility III
Spatially Resolved NMR Microspectroscopy In situ analysis of environment, metabolites in living cells 3-D µ-MRI of water distribution in a 600-µm- diameter tumor spheroid Environmentally regulated sample chamber Combined optical/ MR microscope Spatially localized spectroscopy
Facility IV: Analysis and Modeling of Cellular Systems • Enable the final ascent to a systems level understanding of microbes, communities & multi-cellular organisms • Next generation biology facility to measure dynamic state of living cells – machines, metabolites, signaling… • Couple experiment, analysis, and theory in a recursive fashion to reveal networks, function