Difference between revisions of "Supplement: Biomolecular Feedback Systems"

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{{supheader|Biological Systems}}
 
{{supheader|Biological Systems}}
<font size="+1">Domitilla Del Vecchio (U. Michigan) and Richard M. Murray (Caltech)</font>
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<font size="+1">Domitilla Del Vecchio (MIT) and Richard M. Murray (Caltech)</font>
  
{{righttoc}}
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{{warning|This page is out of dateSee http://www.cds.caltech.edu/~murray/BFSwiki for the latest version}}
This supplement is intended for researchers interested in the application of feedback and control to biomolecular systemsThe material has been designed so that it can be used in parallel with ''Feedback Systems'' as part of a course on biomolecular feedback and control systems, or as a standalone reference for readers who have had a basic course in feedback and
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control theory.  The supplement is being written by [http://www.eecs.umich.edu/~ddv/ Domitilla Del Vecchio] and [[User:Murray|Richard Murray]] based on a variety of presentations, lectures and notes.
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<font color=red>This page contains working notes for the material that is being prepared for the supplementWe anticipate that a preliminary version of the notes will be available by July 2009.</font>
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__NOTOC__
 +
This textbook is intended for researchers interested in the application of feedback and control to biomolecular systems.  The material has been designed so that it can be used in parallel with ''Feedback Systems'' as part of a course on biomolecular feedback and control systems, or as a standalone reference for readers who have had a basic course in feedback and
 +
control theoryThis book is being written by [[http:www.mit.edu/~ddv/|Domitilla Del Vecchio]] and [[Richard Murray]] based on a variety of presentations, lectures and notes.
  
=== Audience ===
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'''Note:''' These notes are in draft form and may contain errors.  Permission is granted to download and print a copy for individual use, but this material may not be reproduced, in whole or in part, without written consent from the author.
The supplement is intended to be useful to three distinct audiences:
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* First year PhD students in biology and bioengineering interested in feedback and control mechanisms in cells
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* Juniors through graduate students in engineering who are interested in biological circuit design
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* More senior researchers in the biological sciences who want to understand the application of principles and tools from feedback systems as applied to biomolecular systems
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The pre-requisites for the supplement are a basic understanding of probability, differential equations and some linear algebra at an undergraduate level, along with a first course in feedback and control systems at the level of the main text (can be taken concurrently).
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=== Outline ===
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<!-- {{BFS quick links}} -->
The current plan for the supplement is based on the following draft outline.  Comments are welcome on topics that are missing.
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===== News ([[BFS:Archived news|archive]]) =====
 +
* 14 Sep 2014: The contents of this page have been moved to http://www.cds.caltech.edu/~murray/BFSwiki.
 +
* 19 Jan 2014: Updated chapters on circuits, modules and tradeoffs (Ch 5-7) + bibliography.  A {{BFS pdf|complete manuscript|bfs-public|19Jan14}} is also available.
 +
* 6 Jan 2014: Updated chapter on stochastic modeling and analysis (Ch 4)
 +
* 11 Dec 2013: Updated chapter on dynamic behavior (Ch 3)
 +
* 7 Dec 2013: Updated chapter on core processes (Ch 2)
 +
* 5 Dec 2013: Updated contents, preface, introduction (Ch 1) and references
 +
* 12 Jul 2012: Updated outline; new PDFs postedA {{BFS pdf|complete manuscript|bfs-public|11Jul12}} is also available.
 +
<p>
  
{|
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=== Contents ===
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{| width=100% border=1
 
|- valign=top
 
|- valign=top
 
| width=50% |
 
| width=50% |
<ol type="I">
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* {{BFS pdf|Preface and Contents|bfs-frontmatter|05Dec13}}
<li> Review of Core Processes
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* Chapter 1: {{BFS pdf|Introductory Concepts|bfs-intro|05Dec13}}
* Modeling of transcription and translation
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** Systems Biology: Modeling, Analysis and the Role of Feedback
** ODE models (coming from chemical reactions and thermodynamics)
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** The Cell as a System
** time constants
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** Control and Dynamical Systems Tools
** cell affects (dilution, degradation)
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** Input/Output Modeling
* Transcriptional Regulation
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** From Systems to Synthetic Biology
** repression
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* Chapter 2: {{BFS pdf|Core Processes|bfs-coreproc|07Dec13}}
** activation
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** Modeling Techniques
** (Thermodynamics &rarr; chemical kinetics &rarr;Hill functions, Michaelis-Menten)
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** Transcription and Translation
* Intracellular sensing
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** Transcriptional Regulation
* Intracellular communication
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** Post-Transcriptional Regulation
* Intracellular computation
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** Cellular Subsystems
</li>
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* Chapter 3: {{BFS pdf|Dynamic Behavior|bfs-dynamics|11Dec13}}
<li> Dynamic behavior
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** Analysis Near Equilibria
* Steady state analysis (log/log diagrams)
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** Robustness
* Phase plane analysis
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** Oscillatory Behavior
* Time response
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** Bifurcations
* Limit cycles
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** Model Reduction Techniques
</li>
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* Chapter 4: {{BFS pdf|Stochastic Modeling and Analysis|bfs-stochastic|06Jan14}}
<li> Feedback examples
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** Stochastic Modeling of Biochemical Systems
* Lactose metabolism
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** Simulation of Stochastic Systems
* Heat shock
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** Input/Output Linear Stochastic Systems
* Chemotaxis
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<!--
</li>
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* Chapter 5: {{BFS pdf|Feedback Examples|bfs-fbkexamps|11Jul12}}
</ol>
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** The ''lac'' Operon
|  
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** Bacterial chemotaxis|bfs-chemotaxis
<ol type="I" start=4>
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-->
<li> Stochastic behavior 
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* Noise modeling (intrinsic/extrinsic), spectrum
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* Stochastic simulation analysis (SSA)
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* Markov modeling and analysis
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* Linearized modeling and analysis: include disturbance attenuation in freq domain (?)
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</li>
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<li> Biological  circuit design
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* DNA-protein, vs protein-protein, etc.
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* Feedforward loops
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* PID in biocircuits
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* Activation vs repression (demand theory)
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* Modularity and retroactivity
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* Logical functions: AND, switches, inverters, toggles, etc.
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</li>
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<li> Design examples
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</li>
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<li> Robustness and evolvability
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</li>
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<li> Multicellular systems
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* Additional core processes
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* Quorum Sensing
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* Development
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</li>
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</ol>
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|}
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=== Examples ===
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The material above is intended to be useful in analyzing a large variety of natural and engineered biomolecular feedback systems.  Some of these examples will be included in the text, while others may be mentioned in exercises or simply left for the reader to explore on their own.
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{|
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|- valign=top
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| width=50% |
 
| width=50% |
* Repressilator: eqs, simulations, limit cycle stability using PB+ and Hastings 
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* Chapter 5: {{BFS pdf|Biological Circuit Components|bfs-circuits|19Jan14}}
* Toggle switch: eqs, nullclines and equilibria, stability, Lyapunov
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** Introduction to Biological Circuit Design
* Self repression: frequency response, time response
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** Negative Autoregulation
* Self activation: dynamics plus Lyapunov
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** The Toggle Switch
* Activator-repressor clock (two implementations): eqs, simulations, PB for the 2D model reduction, Hopf Bifurcation for the 4D (singular perturbation for the 2D reduction?)  
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** The Repressilator
* Chemotaxis: integral feedback (Iglesias), modeling (incl methylation)
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** Activator-repressor Clock
* Input adaptation: MAPK with feedback? (Kholodenko?)
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** An Incoherent Feedforward Loop (IFFL)
* Biochemical circuits (in vitro)
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** Bacterial Chemotaxis
| width=50% |
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* Chapter 6: {{BFS pdf|Interconnecting Components|bfs-modules|19Jan14}}
* Development/differentiation: signal switching (Tomlin, Ashthagiri)
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** Input/Output Modeling and the Modularity Assumption
* Sporalation, fate choice (Elowitz)
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** Introduction to Retroactivity
* MAPK cascades (Sauro, Kholodenko)
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** Retroactivity in Gene Circuits
* Quorum Sensing (Weiss, ?), synchronization
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** Retroactivity in Signaling Systems
* Methabolic Pathways/engineering (yeast demand analysis, Hoffmeyer)
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** Insulation Devices: Retroactivity Attentuation
* Hemoglobin (Kirshner) for allostery feedback?
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** A Case Study on the Use of Insulation Devices
* Glucose/Lactose (Jacob and Monod)
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* Chapter 7: {{BFS pdf|Design Tradeoffs|bfs-tradeoffs|19Jan14}}
* Anti-sense switches (Smolke)
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** Competition for Shared Cellular Resources
* FFL (Alon)?
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** Stochastic Effects: Design Tradeoffs in Systems with Large Gains
* Heat Shock (El Samad)
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* Appendix A: A Primer on Control Theory
* Calcium Regulation (Khammash)
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<!--
 +
* Appendix A: Cell Biology Primer (from NCBI)
 +
** [http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html What is a Cell]
 +
** [http://www.ncbi.nlm.nih.gov/About/primer/genetics_genome.html What is a Genome]
 +
** [http://www.ncbi.nlm.nih.gov/About/primer/genetics_molecular.html Molecular Genetics: Piecing It Together]
 +
** [http://www.genome.gov/Glossary/ NHGRI Talking Glossary]
 +
* Appendix C: {{BFS pdf|Random Processes|bfs-random|11Jul12}}
 +
** Random Variables
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** Continuous-State Random Processes
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** Discrete-State Random Processes
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-->
 +
* {{BFS pdf|Bibliography and Index|bfs-backmatter|19Jan14}}
 
|}
 
|}
 
=== Additional Information ===
 
 
* [http://meetings.cshl.edu/meetings/engine06.shtml Engineering Principles in Biological Systems]: 6-8 December 2006, Cold Spring Harbor Laboratory
 
* [http://www.ima.umn.edu/2007-2008/W4.21-25.08/ Design Principles in Biological Systems]: 24-28 April 2008, Institute for Mathematics and Its Applications (IMA)
 

Latest revision as of 22:01, 14 September 2014

Domitilla Del Vecchio (MIT) and Richard M. Murray (Caltech)

WARNING: This page is out of date. See http://www.cds.caltech.edu/~murray/BFSwiki for the latest version


This textbook is intended for researchers interested in the application of feedback and control to biomolecular systems. The material has been designed so that it can be used in parallel with Feedback Systems as part of a course on biomolecular feedback and control systems, or as a standalone reference for readers who have had a basic course in feedback and control theory. This book is being written by Domitilla Del Vecchio and Richard Murray based on a variety of presentations, lectures and notes.

Note: These notes are in draft form and may contain errors. Permission is granted to download and print a copy for individual use, but this material may not be reproduced, in whole or in part, without written consent from the author.

News (archive)
  • 14 Sep 2014: The contents of this page have been moved to http://www.cds.caltech.edu/~murray/BFSwiki.
  • 19 Jan 2014: Updated chapters on circuits, modules and tradeoffs (Ch 5-7) + bibliography. A complete manuscript (PDF) is also available.
  • 6 Jan 2014: Updated chapter on stochastic modeling and analysis (Ch 4)
  • 11 Dec 2013: Updated chapter on dynamic behavior (Ch 3)
  • 7 Dec 2013: Updated chapter on core processes (Ch 2)
  • 5 Dec 2013: Updated contents, preface, introduction (Ch 1) and references
  • 12 Jul 2012: Updated outline; new PDFs posted. A complete manuscript (PDF) is also available.

Contents

  • Preface and Contents (PDF)
  • Chapter 1: Introductory Concepts (PDF)
    • Systems Biology: Modeling, Analysis and the Role of Feedback
    • The Cell as a System
    • Control and Dynamical Systems Tools
    • Input/Output Modeling
    • From Systems to Synthetic Biology
  • Chapter 2: Core Processes (PDF)
    • Modeling Techniques
    • Transcription and Translation
    • Transcriptional Regulation
    • Post-Transcriptional Regulation
    • Cellular Subsystems
  • Chapter 3: Dynamic Behavior (PDF)
    • Analysis Near Equilibria
    • Robustness
    • Oscillatory Behavior
    • Bifurcations
    • Model Reduction Techniques
  • Chapter 4: Stochastic Modeling and Analysis (PDF)
    • Stochastic Modeling of Biochemical Systems
    • Simulation of Stochastic Systems
    • Input/Output Linear Stochastic Systems
  • Chapter 5: Biological Circuit Components (PDF)
    • Introduction to Biological Circuit Design
    • Negative Autoregulation
    • The Toggle Switch
    • The Repressilator
    • Activator-repressor Clock
    • An Incoherent Feedforward Loop (IFFL)
    • Bacterial Chemotaxis
  • Chapter 6: Interconnecting Components (PDF)
    • Input/Output Modeling and the Modularity Assumption
    • Introduction to Retroactivity
    • Retroactivity in Gene Circuits
    • Retroactivity in Signaling Systems
    • Insulation Devices: Retroactivity Attentuation
    • A Case Study on the Use of Insulation Devices
  • Chapter 7: Design Tradeoffs (PDF)
    • Competition for Shared Cellular Resources
    • Stochastic Effects: Design Tradeoffs in Systems with Large Gains
  • Appendix A: A Primer on Control Theory
  • Bibliography and Index (PDF)