An introduction to systems biology : design principles of biological circuits

INTRODUCTION TRANSCRIPTION NETWORKS, BASIC CONCEPTS Introduction The Cognitive Problem of the Cell Elements of Transcription Networks Dynamics and Response Time of Simple Gene Circuits AUTO-REGULATION, A NETWORK MOTIF Introduction Patterns, Randomized Networks and Network Motifs Autoregulation is a Network Motif Negative Auto-Regulation Speeds the Response Time of Gene Circuits Negative Auto-Regulation Promotes Robustness to Fluctuations in Production Positive auto-regulation speeds responses and widens cell-cell variability Summary THE FEEDFORWARD LOOP NETWORK MOTIF Introduction The Number of Appearances of a Subgraph in Random Networks The Feedforward Loop (FFL) is a Network Motif The Structure of the Feedforward Loop Circuit Dynamics of the Coherent FFL with AND-Logic The C1-FFL is a Sign-Sensitive Delay Element The Incoherent FFL: a pulse generator and response accelerator Why Are Some FFL Types Rare? Convergent Evolution of FFLs Summary TEMPORAL PROGRAMS AND THE GLOBAL STRUCTURE OF TRANSCRIPTION NETWORKS Introduction The Single-Input Module (SIM) Network Motif SIMs Can Generate Temporal Expression Programs Topological Generalizations of Network Motifs The Multi-Output FFL Can Generate FIFO Temporal Order Signal Integration and Combinatorial Control: Bi-Fans and Dense-Overlapping Regulons Network Motifs and the Global Structure of Sensory Transcription Networks NETWORK MOTIFS IN DEVELOPMENTAL, SIGNAL-TRANSDUCTION AND NEURONAL NETWORKS Introduction Network Motifs in Developmental Transcription Networks: Positive feedback loops and bistability Motifs in Signal Transduction Networks Information Processing Using Multi-Layer Perceptrons Composite Network Motifs: Negative Feedback and Oscillator Motifs Network Motifs in the Neuronal Network of C. Elegans Summary ROBUSTNESS OF PROTEIN CIRCUITS, THE EXAMPLE OF BACTERIAL CHEMOTAXIS The Robustness Principle Bacterial Chemotaxis, or How Bacteria 'Think' The Chemotaxis Protein Circuit of E. coli Two Models Can Explain Exact Adaptation, One is Robust and the Other Fine Tuned The Barkai-Leibler model Individuality and Robustness in Bacterial Chemotaxis ROBUST PATTERNING IN DEVELOPMENT Introduction to Morphogen Gradients Exponential Gradients Are Not Robust Increased Robustness by Self-Enhanced Morphogen Degradation Network Motifs That Provide Robust Patterning The Robustness Principle Can Distinguish Between Mechanisms of Fruit Fly Patterning KINETIC PROOFREADING Introduction Kinetic Proofreading of the Genetic Code Can Reduce Error Rates of Molecular Recognition Recognition of Self and Non-Self by the Immune System Kinetic Proofreading May Occur in Diverse Recognition Processes in the Cell OPTIMAL GENE CIRCUIT DESIGN Introduction Cost and Benefit Analysis of Gene circuits Optimal Expression Level of a Protein Under Constant Conditions To Regulate or Not to Regulate: Optimal Regulation in Variable Environments Environmental Selection of the Feedforward Loop Network Motif Summary RULES FOR GENE REGULATION BASED ON ERROR MINIMIZATION Introduction The Savageau Demand Rules Rules for Gene Regulation Based on Minimal Error Load Demand Rules for Genes with Multiple Regulators Summary EPILOGUE: Simplicity in Biology APPENDIX A: The Input-Function of a Gene, Michaelis-Menten and Hill Equations APPENDIX B: Multi-Dimensional Input-Functions APPENDIX C: Graph Properties of Transcription Networks APPENDIX D: Cell-Cell Variability in Gene Expression GLOSSARY BIBLIOGRAPHY