1. GTL User Facilities Facility IV: Analysis and Modeling of Cellular Systems Jim K. Fredrickson

2. Genomes to Life Facilities for 21 st Century Biology Facility IV Analysis and Modeling of Cellular Systems Measure & predict dynamic events within cells. Spatial & temporal variations in cell “state” – individual microbes to multi-cellular systems. Facility I Production and Characterization of Proteins Facility II Whole Proteome Analysis Facility IV Modeling and Analysis of Cellular Systems Facility III Characterization and Imaging of Molecular Machines

3. Molecular Machine Dynamics Reveal Function dynamic changes in cellular localization of the DivK protein reveal insights into the cell cycle of Caulobacter crescentus

4. 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

5. Genome sequence High- Throughput Cultivation Data Analysis Data Interpretation Data Archival Modeling Facility I Facility III Facility II New tools & infrastructure for unprecedented analyses of cell state Cell & multi-cell models Systems level understanding of microbes & communities Proteomics, Regulatory networks Reagents, probes Machines for dynamic analysis Cultures, communities Cultures Facility IV: Final Component of an Integrated Network for Systems Biology Spatial, Temporal Analyses (imaging) Small Molecule Analyses Controlled Experimental Systems Cultures, genes Single Cell Expression

6. Spatially Resolved NMR Microspectroscopy Spatially localized spectroscopy 3-D µ-MRI of water distribution in a 600-µm- diameter tumor spheroid Combined optical/ MR microscope Environmentally regulated sample chamber In situ analysis of environment, metabolites in living cells

7. 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