Biomolecular Feedback Systems

287 Pages·2014·3.838 MB·English

by  Domitilla Del Vecchio, Richard M. Murray

Biomolecular Feedback Systems

Biomolecular Feedback Systems
Domitilla Del Vecchio
Richard M. Murray
Princeton UniversityPress
Princeton and Oxford
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DelVecchio, Domitilla,1975–
Biomolecular feedback systems / Domitilla Del Vecchio and Richard M. Mur-
ray.
pagescm
Includes bibliographical references andindex.
ISBN 978-0-691-16153-2 (hardcover : alk. paper) 1. Biological Control Sys-
tems.2.Systemsbiology. I.Murray,RichardM.II.Title.
QH508.D452015
612.8 233–dc23 2014013061
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Contents
Preface vii
1 IntroductoryConcepts 1
1.1 Systemsbiology: Modeling, analysisandroleoffeedback . . . . . . 1
1.2 Thecellasasystem . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3 Controlanddynamicalsystemstools . . . . . . . . . . . . . . . . . 11
1.4 Input/output modeling . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.5 Fromsystemstosynthetic biology . . . . . . . . . . . . . . . . . . 22
1.6 Furtherreading . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
2 DynamicModelingofCoreProcesses 29
2.1 Modelingchemicalreactions . . . . . . . . . . . . . . . . . . . . . 29
2.2 Transcription andtranslation . . . . . . . . . . . . . . . . . . . . . 44
2.3 Transcriptional regulation . . . . . . . . . . . . . . . . . . . . . . . 55
2.4 Post-transcriptional regulation . . . . . . . . . . . . . . . . . . . . 70
2.5 Cellularsubsystems . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
3 AnalysisofDynamicBehavior 89
3.1 Analysisnearequilibria . . . . . . . . . . . . . . . . . . . . . . . . 89
3.2 Robustness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
3.3 Oscillatory behavior . . . . . . . . . . . . . . . . . . . . . . . . . . 113
3.4 Bifurcations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
3.5 Modelreduction techniques . . . . . . . . . . . . . . . . . . . . . . 127
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
4 StochasticModelingandAnalysis 139
4.1 Stochasticmodeling ofbiochemical systems . . . . . . . . . . . . . 139
4.2 Simulationofstochastic systems . . . . . . . . . . . . . . . . . . . 154
4.3 Input/output linearstochastic systems . . . . . . . . . . . . . . . . 157
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
vi CONTENTS
5 BiologicalCircuitComponents 169
5.1 Introduction tobiological circuitdesign . . . . . . . . . . . . . . . 169
5.2 Negativeautoregulation . . . . . . . . . . . . . . . . . . . . . . . . 171
5.3 Thetoggleswitch . . . . . . . . . . . . . . . . . . . . . . . . . . . 177
5.4 Therepressilator . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
5.5 Activator-repressor clock . . . . . . . . . . . . . . . . . . . . . . . 184
5.6 Anincoherent feedforward loop(IFFL) . . . . . . . . . . . . . . . 189
5.7 Bacterialchemotaxis . . . . . . . . . . . . . . . . . . . . . . . . . 191
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
6 InterconnectingComponents 205
6.1 Input/output modelingandthemodularity assumption . . . . . . . . 205
6.2 Introduction toretroactivity . . . . . . . . . . . . . . . . . . . . . . 206
6.3 Retroactivity ingenecircuits . . . . . . . . . . . . . . . . . . . . . 209
6.4 Retroactivity insignaling systems . . . . . . . . . . . . . . . . . . 214
6.5 Insulation devices: Retroactivity attenuation . . . . . . . . . . . . . 219
6.6 Acasestudyontheuseofinsulation devices . . . . . . . . . . . . . 236
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239
7 DesignTradeoffs 243
7.1 Competitionforsharedcellularresources . . . . . . . . . . . . . . 243
7.2 Stochasticeffects:Designtradeoffsinsystemswithlargegains . . . 253
Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Bibliography 259
Index 267
Preface
This text 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 the textbook Feedback Systems [1] as part of a course
on biomolecular feedback and control systems, or as a stand-alone reference for
readerswhohavehadabasiccourseinfeedbackandcontroltheory.Thefulltextfor
thisbook,alongwithadditionalsupplementalmaterial,isavailableonacompanion
Website:
http://press.princeton.edu/titles/10285.html
The material in this book is intended to be useful to three overlapping audi-
ences:graduatestudentsinbiologyandbioengineering interestedinunderstanding
theroleoffeedbackinnaturalandengineeredbiomolecularsystems;advancedun-
dergraduatesandgraduatestudentsinengineeringdisciplineswhoareinterestedin
the use of feedback inbiological circuit design; and established researchers in the
biological scienceswhowanttoexplorethepotential application ofprinciples and
toolsfromcontroltheorytobiomolecularsystems.Wehavewrittenthetextassum-
ingsomefamiliarity withbasicconcepts infeedback andcontrol, buthavetriedto
provide insights and specific results asneeded, so that thematerial can be learned
inparallel.Wealsoassumesomefamiliaritywithcellbiology,atthelevelofafirst
coursefornon-majors.Theindividualchaptersinthetextindicatetheprerequisites
in more detail, most of which are covered either in Åstro¨m and Murray [1] or in
thesupplemental information availablefromthecompanionWebsite.
Acknowledgments.Manycolleaguesandstudentsprovidedfeedbackandadviceon
the book. We would particularly like to thank Mustafa Khammash, Eric Klavins,
and Eduardo Sontag, who gave detailed comments on some of the early versions
of the text. In addition, wewould like to acknowledge Abdullah Amadeh, Andras
Gyorgy, Narmada Herath, Yutaka Hori, Shridhar Jayanthi, Scott Livingston, Rob
Phillips,YiliQian,PhillipRivera,VipulSinghal,AnandhSwaminathan,EricWin-
free, andEnoch Yeung fortheir support and comments along the way.Finally, we
wouldliketothankCaltech,MITandtheUniversityofMichiganforprovidingthe
manyresources thatwerenecessary tobringthisbooktofruition.
DomitillaDelVecchio RichardM.Murray
Cambridge, Massachusetts Pasadena,California

Biomolecular Feedback Systems