Biomolecular Feedback Systems

Domitilla Del Vecchio is associate professor of mechanical engineering at the Massachusetts Institute of Technology. Richard M. Murray is professor of control and dynamical systems and bioengineering at the California Institute of Technology. His books include Feedback Systems: An Introduction for Scientists and Engineers (Princeton).

"The authors did superbly in combining the biophysical processes and corresponding mathematics... This book serves both as a primer and a reference for constructing synthetic biological circuits with special focus on biomolecular feedback. It nicely bridges the gap between fields with a concise biological introduction, and approachable mathematics."--Harold Bien and Gabor Balazsi, Quarterly Review of Biology "This book promises much for the reader with a background in both biochemistry and mathematics. Such a reader will not only learn how to analyse models for bioengineered bimolecular systems but they will have the insights to both build these systems and to 'tune' the biochemistry to obtain desired parameter values."--Mark Nelson, Gazette of the Australian Mathematical Society

• Preface vii 1 Introductory Concepts 1 1.1 Systems biology: Modeling, analysis and role of feedback 1 1.2 The cell as a system 8 1.3 Control and dynamical systems tools 11 1.4 Input/output modeling 18 1.5 From systems to synthetic biology 22 1.6 Further reading 28 2 Dynamic Modeling of Core Processes 29 2.1 Modeling chemical reactions 29 2.2 Transcription and translation 44 2.3 Transcriptional regulation 55 2.4 Post-transcriptional regulation 70 2.5 Cellular subsystems 81 Exercises 86 3 Analysis of Dynamic Behavior 89 3.1 Analysis near equilibria 89 3.2 Robustness 103 3.3 Oscillatory behavior 113 3.4 Bifurcations 124 3.5 Model reduction techniques 127 Exercises 133 4 Stochastic Modeling and Analysis 139 4.1 Stochastic modeling of biochemical systems 139 4.2 Simulation of stochastic systems 154 4.3 Input/output linear stochastic systems 157 Exercises 164 5 Biological Circuit Components 169 5.1 Introduction to biological circuit design 169 5.2 Negative autoregulation 171 5.3 The toggle switch 177 5.4 The repressilator 180 5.5 Activator-repressor clock 184 5.6 An incoherent feedforward loop (IFFL) 189 5.7 Bacterial chemotaxis 191 Exercises 203 6 Interconnecting Components 205 6.1 Input/output modeling and the modularity assumption 205 6.2 Introduction to retroactivity 206 6.3 Retroactivity in gene circuits 209 6.4 Retroactivity in signaling systems 214 6.5 Insulation devices: Retroactivity attenuation 219 6.6 A case study on the use of insulation devices 236 Exercises 239 7 Design Tradeoffs 243 7.1 Competition for shared cellular resources 243 7.2 Stochastic effects: Design tradeoffs in systems with large gains 253 Exercises 257 Bibliography 259 Index 267