Design and Analysis of Biomolecular Circuits: Engineering Approaches to Systems and Synthetic Biology

Cover......Page 1
  Fluorescent Proteins......Page 5
  Applications......Page 9
   Microscopy Samples and Microfluidic Devices......Page 11
Design and Analysis of Biomolecular Circuits......Page 2
   Single Cell Measurements......Page 4
 Preface......Page 6
  SLIC......Page 7
  Image Analysis......Page 13
  Applications......Page 14
  DNA Synthesis, RNA Replication, Protein Synthesis......Page 15
Part I Analysis and Simulation......Page 16
 Chapter 1: Continuous Time Markov Chain Models for Chemical Reaction Networks......Page 17
  Fluorescence Correlation Spectroscopy......Page 19
   Equivalence of Stochastic Equations and Martingale Problems......Page 23
   Thinning of Counting Processes......Page 25
 Concluding Remarks......Page 26
  Scaling Species Numbers and Rate Constants......Page 28
   Simulation......Page 29
   Rates for the Law of Mass Action......Page 31
  Hybrid Limits......Page 34
   First Order Reaction Networks......Page 35
 References......Page 38
   Cellular Noise......Page 3
  Instrumentation......Page 8
 Contributors......Page 12
  Introduction......Page 18
   Poisson Processes......Page 20
 Contents......Page 10
  Biophysical Aspects of Minimal Cell Construction......Page 24
 Outlook......Page 21
   Continuous Time Markov Chains......Page 22
   The Martingale Problem and Forward Equation for Markov Chains......Page 27
   Stationary Distributions......Page 30
   General Form for the Classical Scaling......Page 32
   Diffusion/Langevin Approximations......Page 33
   Product Form Stationary Distributions......Page 39
   Models with Delay......Page 41
   Derivation of the Michaelis-Menten Equation......Page 42
   Scaling Species Numbers and Rate Constants......Page 44
   Determining the Scaling Exponents......Page 45
   An Application of the Balance Conditions......Page 47
   Hybrid Limits......Page 50
   Central Limit Theorems and Diffusion Approximations......Page 51
  References......Page 54
   Why Do We Need Spatial Models of a Cell?......Page 57
   Why Do We Need Stochastic Models?......Page 58
   Simulation Toolkits......Page 59
  Temporal Models of Chemical Kinetics......Page 60
  Monte-Carlo Approaches......Page 62
   Lattice Versus Off-Lattice Methods......Page 64
   The Next Subvolume Method and Its Coarse-Grained Version, Bτ-SSSA......Page 67
   Capturing Spatial Attributes......Page 68
   Spatial Simulation Software......Page 69
   RDME-Based Methods......Page 70
   Methods Based on Microscopic Lattices......Page 71
   Off-Lattice Particle Methods......Page 72
   Greens-Function Reaction Dynamics (GFRD) Methods......Page 73
  Introduction......Page 77
   Dynamical Systems Derived from Chemical Reaction Networks......Page 78
  The Main Results......Page 81
  Discussion......Page 84
  References......Page 85
  Introduction......Page 87
  Qualitative Models from Biology......Page 88
   Interaction Networks......Page 90
   Jacobian Factorisations and Generalised Graphs......Page 91
   Qualitative Classes and Qualitative Rules......Page 93
  Mathematical Background......Page 94
   Generalised Mass-Action Kinetics......Page 97
   Structural Conditions for Local Stability of Equilibria......Page 99
   Monotonicity in General CRNs......Page 100
  Conclusions......Page 104
  References......Page 105
  Introduction......Page 107
   Basic Results......Page 108
   Outline......Page 110
   Entrainment of Transcriptional Modules......Page 112
   Synchronization of Biological Systems......Page 113
  Generic Quorum Sensing Networks......Page 117
   Controlling Synchronization of Genetic Oscillators......Page 120
  Conclusions......Page 126
Part II Modularity and Abstraction......Page 129
  Introduction......Page 130
   Modules as Physically Interacting Molecules......Page 131
   Modules as Temporally Interacting Genes......Page 132
   Modules as Design Patterns......Page 133
  Modules in Synthetic Systems......Page 135
   Mapping Between a MIP and an RC-Circuit......Page 136
   Gene Circuit Fan-Out......Page 140
   Gene Circuit Fan-Out in more General Interfaces......Page 142
   Noise Correlation Time......Page 144
  Fan-Out/Retroactivity Estimation......Page 148
  Summary......Page 149
  Introduction......Page 152
  The Absence of Retroactivity as a Criterion to Demarcate Modules......Page 154
   Network Theory and Retroactivity......Page 155
   An Algorithm to Identify Modules Minimizing Retroactivity......Page 159
  Domain Oriented Modeling and Retroactivity......Page 164
   Thermodynamic Constraints......Page 166
   Thermodynamic Restrictions on Process Interactions......Page 167
   Unidirectionality and Futile Cycles......Page 168
  Conclusion......Page 170
  References......Page 171
  Introduction......Page 173
  Modeling Retroactivity......Page 175
  Example: A Transcriptional System......Page 176
   Quantification of the Retroactivity to the Output......Page 178
   Retroactivity and Noise......Page 179
   Model......Page 180
   Steady State Effects......Page 181
   Dynamic Effects......Page 185
   Experimental Results......Page 189
  Discussion and Conclusion......Page 191
  Introduction......Page 194
   Precise Problem Formulation......Page 198
   Mathematical Details......Page 200
  Retroactivity at Steady States......Page 205
   Appendix: Chemical Reaction Network Formalism......Page 210
  References......Page 211
Part III Design and Standardization......Page 212
 Chapter 10: Computer-Aided Design for Synthetic Biology......Page 213
  Introduction......Page 214
  Methodology......Page 215
  Design: Stage 2......Page 219
   The Role of Modularity in Design......Page 220
  Mathematical Analysis: Stage 3......Page 222
   Programming Languages for Mathematical Analysis......Page 223
   Systems Biology Software Applications......Page 224
  Biological Part Composition: Stage 4......Page 226
   Sequence Refinement......Page 228
  Design by Evolution......Page 229
  Education......Page 231
  References......Page 232
  Overview......Page 235
   Formal Language & Syntactic Model......Page 237
   GenoCAD Web Service......Page 240
  Eugene......Page 241
   Eugene Constructs......Page 242
   Eugene Rules......Page 243
   XOR Design Example......Page 244
  GEC......Page 246
   Amorphous Medium and Proto......Page 251
   Motif-Based Compilation and Optimization......Page 254
  Other High-Level Design Tools for Biological Computation......Page 258
  Summary......Page 260
  Introduction......Page 263
  Robustness of Biological Systems......Page 264
   Methods for Robustness Analysis......Page 266
   Inverse Problems......Page 267
   Formal Specification Languages......Page 269
   Parameter Sampling......Page 274
   Regularizing the Design Problem......Page 279
   Optimizing Robustness......Page 280
   Two Cyanobacterial Clock Models......Page 282
   Specified Systemic Properties......Page 283
   Robustness Results......Page 284
  Conclusion......Page 285
  References......Page 286
 Chapter 13: Data Model Standardization for Synthetic Biomolecular Circuits and Systems......Page 290
  Introduction......Page 291
   Early Examples of Success: PDB......Page 292
   Standards for Models – SBML and CellML......Page 293
  Standards for Synthetic Biology......Page 294
   The Registry of Standard Biological Parts......Page 295
   Software Data Models......Page 296
  References......Page 300
  The DNA Assembly Challenge......Page 303
   The Traditional Multiple Cloning Site Approach......Page 304
   The BioBrick Approach......Page 306
   BioBrick Limitations and Obstacles......Page 308
   SLIC......Page 309
   Gibson......Page 310
   CPEC......Page 311
   SLIC, Gibson, and CPEC Similarities......Page 312
   SLIC, Gibson, and CPEC Limitations and Obstacles......Page 313
  The Golden Gate Assembly Method......Page 314
   Golden Gate Limitations and Obstacles......Page 317
  Conclusion......Page 318
  Glossary......Page 320
  References......Page 321
Part IV Enabling Technologies......Page 323
 Chapter 15: Gene Synthesis … Enabling Technologies for Synthetic Biology......Page 324
  Several Technological Developments Enabled Gene Synthesis......Page 325
  Historical Overview of Gene Synthesis Milestones......Page 327
  Development of Commercial Services Providing Synthetic Genes......Page 328
  Technological Background of de novo Gene Synthesis......Page 331
  Fields of Application for Synthetic Genes......Page 337
   Origin and Reliability......Page 338
   Cost, Capacity and Speed......Page 339
   Flexibility of Design: Artificial Genes, Operons and Genomes......Page 340
  Why Minimal Cells?......Page 343
  Autopoiesis and Minimal Life......Page 345
   Self-reproduction of Liposomes......Page 348
   Vesicle-Based Minimal Synthetic Cells: From the Origins of Life to Synthetic Biology......Page 351
   Relevance in Basic Science, Biotechnology, Drug Delivery......Page 353
   Enzyme Reactions Inside Liposomes......Page 355
    Multi-enzyme Reactions Inside Liposomes......Page 356
   DNA Synthesis, RNA Replication, Protein Synthesis......Page 357
    Two Selected Cases of Pioneering Research......Page 358
    Working for the Production of Nucleic Acids and Proteins Inside Liposomes......Page 361
   Toward Self-reproduction of Core and Shell Components......Page 364
   What Next?......Page 365
   Biophysical Aspects of Minimal Cell Construction......Page 366
  Concluding Remarks......Page 368
  Abbreviations......Page 369
  Introduction......Page 375
   Single Cell Analysis......Page 376
    Cellular Noise......Page 377
    Single Cell Measurements......Page 378
   Fluorescent Proteins......Page 379
   Budding Yeast As a Model Organism......Page 380
   Instrumentation......Page 382
   Applications......Page 383
    Microscopy Samples and Microfluidic Devices......Page 385
    Microscope Light-Path......Page 387
   Applications......Page 388
  Functional Microscopy......Page 390
   Förster Resonance Energy Transfer......Page 391
   Fluorescence Correlation Spectroscopy......Page 393
  Outlook......Page 395
  References......Page 396
Index......Page 400