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Outline

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Heat-Shock Response

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Mechanisms Modeled

"Competition among DnaK and RNAP..."

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Stochastic vs. Deterministic

Stochastic Simulation Algorithm

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Analysis of the HS System

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Effect of Sequestration on Sensitivity

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Role of the degradation loop in attenuating stochastic fluctuations

Linearized Heat Shock Models

H2 norm (variance) Computations

Comparison of the Two Models

SSA Results and Comparison of the Two Modes of Regulation

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Model Reduction: General Principles for Biological Systems

The Reduced Heat Shock Model

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Known Biology vs. Phenotype

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Missing Players?

Model Invalidation

Model Invalidation using SOStools

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Is the WT Response optimal?

"Cost function:"

Pareto Optimal Design of the Heat Shock System

New Tools

Control Theory in Biological Systems

"New understanding of regulation in..."

Acknowledgements