An Introduction to Systems Biology: Design Principles of Biological Circuits

Note: Supplemental materials are not guaranteed with Rental or Used book purchases.

ISBN: 9781584886426 | 1584886420
Cover: Nonspecific Binding
Copyright: 7/7/2006

Sorry, this item is currently not available.

Thorough and accessible, this book presents the design principles of biological systems, and highlights the recurring circuit elements that make up biological networks. It provides a simple mathematical framework which can be used to understand and even design biological circuits. The text avoids specialist terms, focusing instead on several well-studied biological systems that concisely demonstrate key principles.An Introduction to Systems Biology: Design Principles of Biological Circuits builds a solid foundation for the intuitive understanding of general principles. It encourages the reader to ask why a system is designed in a particular way and then proceeds to answer with simplified models.

CHAPTER 1 Introduction

(4)

CHAPTER 2 Transcription Networks: Basic Concepts

(22)

2.1 Introduction

(1)

2.2 The Cognitive Problem of the Cell

(2)

2.3 Elements of Transcription Networks

(11)

2.3.1 Separation of Timescales

(3)

2.3.2 The Signs on the Edges: Activators and Repressors

(1)

2.3.3 The Numbers on the Edges: The Input Function

(2)

2.3.4 Logic Input Functions: A Simple Framework for Understanding Network Dynamics

(1)

2.3.5 Multi-Dimensional Input Functions Govern Genes with Several Inputs

(2)

2.3.6 Interim Summary

(1)

2.4 Dynamics and Response Time of Simple Gene Regulation

(4)

2.4.1 The Response Time of Stable Proteins Is One Cell Generation

(1)

Further Reading

(1)

Exercises

(5)

CHAPTER 3 Autoregulation: A Network Motif

(14)

3.1 Introduction

(1)

3.2 Patterns, Randomized Networks, and Network Motifs

(3)

3.2.1 Detecting Network Motifs by Comparison to Randomized Networks

(1)

3.3 Autoregulation: A Network Motif

(1)

3.4 Negative Autoregulation Speeds the Response Time of Gene Circuits

(3)

3.5 Negative Autoregulation Promotes Robustness to Fluctuations in Production Rate

(3)

3.5.1 Positive Autoregulation Slows Responses and Can Lead to Bi-Stability

(1)

3.6 Summary

(1)

Further Reading

(1)

Exercises

(3)

CHAPTER 4 The Feed-Forward Loop Network Motif

(34)

4.1 Introduction

(1)

4.2 The Number of Appearances of a Subgraph in Random Networks

(3)

4.3 The Feed-Forward Loop Is a Network Motif

(1)

4.4 The Structure of the Feed-Forward Loop Gene Circuit

(3)

4.5 Dynamics of the Coherent Type-1 FFL with AND Logic

(1)

4.6 The C1-FFL Is a Sign-Sensitive Delay Element

(7)

4.6.1 Delay Following an ON Step of Sx

(1)

4.6.2 No Delay Following an OFF Step of Sx

(1)

4.6.3 The C1-FFL Is a Sign-Sensitive Delay Element

(1)

4.6.4 Sign-Sensitive Delay Can Protect against Brief Input Fluctuations

(2)

4.6.5 Sign-Sensitive Delay in the Arabinose System of E. coli

(2)

4.6.6 The OR Gate C1-FFL Is a Sign-Sensitive Delay for OFF Steps of Sx

(1)

4.6.7 Interim Summary

(1)

4.7 The Incoherent Type-1 FFL

(8)

4.7.1 The Structure of the Incoherent FFL

(1)

4.7.2 Dynamics of the I1-FFL: A Pulse Generator

(4)

4.7.3 The I1-FFL Speeds the Response Time

(1)

4.7.4 Response Acceleration Is Sign Sensitive

(1)

4.7.5 Experimental Study of the Dynamics of an I1-FFL

(1)

4.7.6 Three Ways to Speed Your Responses (An Interim Summary)

(1)

4.8 Why Are Some FFL Types Rare?

(3)

4.8.1 Steady-State Logic of the I1-FFL: Sy Can Turn on High Expression

(1)

4.8.2 I4-FFL, a Rarely Selected Circuit, Has Reduced Functionality

(3)

4.9 Convergent Evolution of FFLs

(1)

4.10 Summary

(1)

Further Reading

(1)

Exercises

(4)

CHAPTER 5 Temporal Programs and the Global Structure of Transcription Networks

(22)

5.1 Introduction

(1)

5.2 The Single-Input Module (SIM) Network Motif

(1)

5.3 SIMs Can Generate Temporal Expression Programs

(4)

5.4 Topological Generalizations of Network Motifs

(2)

5.5 The Multi-Output FEL Can Generate FIFO Temporal Order

(5)

5.5.1 The Multi-Output FFL Can Also Act as a Persistence Detector for Each Output

(1)

5.6 Signal Integration and Combinatorial Control: Bi-Fans and Dense Overlapping Regulons

(1)

5.7 Network Motifs and the Global Structure of Sensory Transcription Networks

(3)

Further Reading

(1)

Exercises

(4)

CHAPTER 6 Network Motifs in Developmental, Signal Transduction, and Neuronal Networks

(38)

6.1 Introduction

(1)

6.2 Network Motifs in Developmental Transcription Networks

(6)

6.2.1 Two-Node Positive Feedback Loops for Decision Making

(2)

6.2.2 Regulating Feedback and Regulated Feedback

101

(1)

6.2.3 Long Transcription Cascades and Developmental Timing

102

(1)

6.2.4 Interlocked Feed-Forward Loops in the B. subtilis Sporulation Network

102

(2)

6.3 Network Motifs inSignal Transduction Networks

104

(2)

6.4 Information Processing Using Multi-Layer Perceptrons

106

(9)

6.4.1 Toy Model for Protein Kinase Perceptrons

106

(5)

6.4.2 Multi-Layer Perceptrons Can Perform Detailed Computations

111

(4)

6.5 Composite Network Motifs: Negative Feedback and Oscillator Motifs

115

(3)

6.6 Network Motifs in the Neuronal Network of C elegans

118

(9)

6.6.1 The Multi-Input FFL in Neuronal Networks

122

(3)

6.6.2 Multi-Layer Perceptrons in the C. elegans Neuronal Network

125

(2)

6.7 Summary

127

(1)

Further Reading

128

(1)

Exercises

129

(6)

CHAPTER 7 Robustness of Protein Circuits: The Example of Bacterial Chemotaxis

135

(24)

7.1 The Robustness Principle

135

(1)

7.2 Bacterial Chemotaxis, or How Bacteria Think

136

(4)

7.2.1 Chemotaxis Behavior

136

(1)

7.2.2 Response and Exact Adaptation

137

(3)

7.3 The Chemotaxis Protein Circuit of E. coli

140

(2)

7.3.1 Attractants Lower the Activity of X

141

(1)

7.3.2 Adaptation Is Due to Slow Modification of X That Increases Its Activity

142

(1)

7.4 Two Models Can Explain Exact Adaptation: Robust and Fine-Tuned

142

(7)

7.4.1 Fine-Tuned Model

143

(3)

7.4.2 The Barkai-Leibler Robust Mechanism for Exact Adaptation

146

(2)

7.4.3 Robust Adaptation and Integral Feedback

148

(1)

7.4.4 Experiments Show That Exact Adaptation Is Robust, Whereas Steady-State Activity and Adaptation Times Are Fine-Tuned

149

(1)

7.5 Individuality and Robustness in Bacterial Chemotaxis

149

(2)

Further Reading

151

(1)

Exercises

152

(7)

CHAPTER 8 Robust Patterning in Development

159

(16)

8.1 Introduction

159

(2)

8.2 Exponential Morphogen Profiles Are Not Robust

161

(2)

8.3 Increased Robustness by Self-Enhanced Morphogen Degradation

163

(2)

8.4 Network Motifs That Provide Degradation Feedback for Robust Patterning

165

(1)

8.5 The Robustness Principle Can Distinguish between Mechanisms of Fruit Fly Patterning

166

(6)

Further Reading

172

(1)

Exercises

172

(3)

CHAPTER 9 Kinetic Proofreading

175

(18)

9.1 Introduction

175

(1)

9.2 Kinetic Proofreading of the Genetic Code Can Reduce Error Rates of Molecular Recognition

176

(6)

9.2.1 Equilibrium Binding Cannot Explain the Precision of Translation

177

(3)

9.2.2 Kinetic Proofreading Can Dramatically Reduce the Error Rate

180

(2)

9.3 Recognizing Self and Non-Self by the Immune System

182

(5)

9.3.1 Equilibrium Binding Cannot Explain the Low Error Rate of Immune Recognition

183

(2)

9.3.2 Kinetic Proofreading Increases Fidelity of T-Cell Recognition

185

(2)

9.4 Kinetic Proofreading May Occur in Diverse Recognition Processes in the Cell

187

(1)

Further Reading

188

(1)

Exercises

188

(5)

CHAPTER 10 Optimal Gene Circuit Design

193

(22)

10.1 Introduction

193

(1)

10.2 Optimal Expression Level of a Protein under Constant Conditions

194

(7)

10.2.1 The Benefit of the LacZ Protein

195

(1)

10.2.2 The Cost of the LacZ Protein

196

(1)

10.2.3 The Fitness Function and the Optimal Expression Level

197

(2)

10.2.4 Laboratory Evolution Experiment Shows That Cells Reach Optimal LacZ Levels in a Few Hundred Generations

199

(2)

10.3 To Regulate or Not to Regulate: Optimal Regulation in Variable Environments

201

(2)

10.4 Environmental Selection of the Feed-Forward Loop Network Motif

203

(4)

10.5 Summary

207

(1)

Further Reading

207

(1)

Exercises

208

(7)

CHAPTER 11 Demand Rules for Gene Regulation

215

(18)

11.1 Introduction

215

(2)

11.2 The Savageau Demand Rule

217

(3)

11.2.1 Evidence for the Demand Rule in E. coli

217

(2)

11.2.2 Mutational Explanation of the Demand Rule

219

(1)

11.2.3 The Problem with Mutant-Selection Arguments

220

(1)

11.3 Rules for Gene Regulation Based on Minimal Error Load

220

(2)

11.4 The Selection Pressure for Optimal Regulation

222

(1)

11.5 Demand Rules for Multi-Regulator Systems

223

(5)

11.6 Summary

228

(2)

Further Reading

230

(1)

Exercises

230

(3)

CHAPTER 12 Epilogue: Simplicity in Biology

233

(8)

APPENDIX A The Input Function of a Gene: Michaelis—Menten and Hill Equations

241

(12)

A.1 Binding of a Repressor to a Promoter

241

(3)

A.2 Binding of a Repressor Protein to an Inducer: Michaelis—Menten Equation

244

(1)

A.3 Cooperativity of Inducer Binding and the Hill Equation

245

(2)

A.4 The Monod, Changeux, and Wymann Model

247

(1)

A.5 The Input Function of a Gene Regulated by a Repressor

247

(1)

A.6 Binding of an Activator to Its DNA Site

248

(2)

A.6.1 Comparison of Dynamics with Logic and Hill Input Functions

250

(1)

A.7 Michaelis—Menten Enzyme Kinetics

250

(1)

Further Reading

251

(1)

Exercises

251

(2)

APPENDIX B E Multi-Dimensional Input Functions

253

(4)

B.1 Input Function That Integrates an Activator and a Repressor

253

(2)

Exercises

255

(2)

APPENDIX C Graph Properties of Transcription Networks

257

(4)

C.1 Transcription Networks Are Sparse

257

(1)

C.2 Transcription Networks Have Long-Tailed Output Degree Sequences and Compact Input Degree Sequences

257

(2)

C.3 Clustering Coefficients of Transcription Networks

259

(1)

C.4 Quantitative Measures of Network Modularity

259

(2)

APPENDIX D Cell-Cell Variability in Gene Expression

261

(4)

Further Reading

264

(1)

GLOSSARY

265

(6)

BIBLIOGRAPHY

271

(24)

INDEX

295

Please wait while the item is added to your bag...

FREE SHIPPING

Rent More, Save More! Use code: BBRENTAL

5% off 1 book, 7% off 2 books, 10% off 3+ books

An Introduction to Systems Biology: Design Principles of Biological Circuits

Summary

Author Biography

Table of Contents

Supplemental Materials

FREE SHIPPING

Rent More, Save More! Use code: BBRENTAL

5% off 1 book, 7% off 2 books, 10% off 3+ books

An Introduction to Systems Biology: Design Principles of Biological Circuits

Summary

Author Biography

Table of Contents

Supplemental Materials

Digital License