GTL User Facilities

Facility IV: Analysis and Modeling of Cellular Systems

Jim K. Fredrickson

Genomes to Life Facilities for 21st 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

Molecular Machine Dynamics Reveal Function

dynamic changes in cellular localization of the DivKprotein 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

Genomesequence

High-ThroughputCultivation

Data AnalysisData Interpretation

Data ArchivalModeling

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

Machinesfor dynamic

analysisCultures,communities

Cultures

Facility IV: Final Component of an Integrated Network for Systems Biology

Spatial, TemporalAnalyses (imaging)

Small MoleculeAnalyses

Controlled Experimental

Systems

Cultures,genes

Single Cell Expression

Spatially Resolved NMR Microspectroscopy

Spatially localized

spectroscopy

3-D µ-MRI of water distribution

in a 600-µm- diameter tumor

spheroidCombined

optical/ MR microscope

Environmentally regulated sample chamber

In situ analysis of environment, metabolites in living cells

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