Biomolecular Feedback Systems

This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, this comprehensive book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources. Featuring numerous exercises and illustrations throughout, Biomolecular Feedback Systems is the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems. Provides a user-friendly introduction to essential concepts, tools, and applications Covers the most commonly used modeling methods Addresses the modular design problem for biomolecular systems Uses design examples from both natural systems and synthetic circuits Solutions manual (available only to professors at press,princeton.edu) An online illustration package is available to professors at press.princeton.edu Machine Generated Contents Note: 1. Introductory Concepts -- 1.1. Systems Biology: Modeling, Analysis And Role Of Feedback -- 1.2. Cell As A System -- 1.3. Control And Dynamical Systems Tools -- 1.4. Input/output Modeling -- 1.5. From Systems To Synthetic Biology -- 1.6. Further Reading -- 2. Dynamic Modeling Of Core Processes -- 2.1. Modeling Chemical Reactions -- 2.2. Transcription And Translation -- 2.3. Transcriptional Regulation -- 2.4. Post-transcriptional Regulation -- 2.5. Cellular Subsystems -- Exercises -- 3. Analysis Of Dynamic Behavior -- 3.1. Analysis Near Equilibria -- 3.2. Robustness -- 3.3. Oscillatory Behavior -- 3.4. Bifurcations -- 3.5. Model Reduction Techniques -- Exercises -- 4. Stochastic Modeling And Analysis -- 4.1. Stochastic Modeling Of Biochemical Systems -- 4.2. Simulation Of Stochastic Systems -- 4.3. Input/output Linear Stochastic Systems -- Exercises -- 5. Biological Circuit Components -- 5.1. Introduction To Biological Circuit Design -- 5.2. Negative Autoregulation -- 5.3. Toggle Switch -- 5.4. Repressilator -- 5.5. Activator-repressor Clock -- 5.6. Incoherent Feed Forward Loop (iffl) -- 5.7. Bacterial Chemotaxis -- Exercises -- 6. Interconnecting Components -- 6.1. Input/output Modeling And The Modularity Assumption -- 6.2. Introduction To Retroactivity -- 6.3. Retroactivity In Gene Circuits -- 6.4. Retroactivity In Signaling Systems -- 6.5. Insulation Devices: Retroactivity Attenuation -- 6.6. Case Study On The Use Of Insulation Devices -- Exercises -- 7. Design Tradeoffs -- 7.1. Competition For Shared Cellular Resources -- 7.2. Stochastic Effects: Design Tradeoffs In Systems With Large Gains -- Exercises. Domitilla Del Vecchio, Richard M. Murray. Includes Bibliographical References And Index. This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, the book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources. Featuring numerous exercises and illustrations throughout, the book is the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems. Provides an introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. This book begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes.