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Biomolecular Feedback Systems

Biomolecular Feedback Systems

Domitilla Del Vecchio
Richard M. Murray
Copyright Date: 2015
Edition: STU - Student edition
Pages: 286
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  • Book Info
    Biomolecular Feedback Systems
    Book Description:

    This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, this comprehensive book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources.

    Featuring numerous exercises and illustrations throughout,Biomolecular Feedback Systemsis the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems.

    Provides a user-friendly introduction to essential concepts, tools, and applicationsCovers the most commonly used modeling methodsAddresses the modular design problem for biomolecular systemsUses design examples from both natural systems and synthetic circuitsSolutions manual (available only to professors at press, online illustration package is available to professors at

    eISBN: 978-1-4008-5050-1
    Subjects: Biological Sciences, Mathematics, Technology

Table of Contents

  1. Front Matter
    (pp. i-iv)
  2. Table of Contents
    (pp. v-vi)
  3. Preface
    (pp. vii-viii)
    Domitilla Del Vecchio and Richard M. Murray
  4. Chapter 1 Introductory Concepts
    (pp. 1-28)

    This chapter provides a brief introduction to concepts from systems biology, tools from differential equations and control theory, and approaches to modeling, analysis and design of biomolecular feedback systems. We begin with a discussion of the role of modeling, analysis and feedback in biological systems. This is followed by a short review of key concepts and tools from control and dynamical systems theory, intended to provide insight into the main methodology described in the text. Finally, we give a brief introduction to the field of synthetic biology, which is the primary topic of the latter portion of the text. Readers...

  5. Chapter 2 Dynamic Modeling of Core Processes
    (pp. 29-88)

    The goal of this chapter is to describe basic biological mechanisms in a way that can be represented by simple dynamical models. We begin the chapter with a discussion of the basic modeling formalisms that we will utilize to model biomolecular feedback systems. We then proceed to study a number of core processes within the cell, providing different model-based descriptions of the dynamics that will be used in later chapters to analyze and design biomolecular systems. The focus in this chapter and the next is on deterministic models using ordinary differential equations; Chapter 4 describes how to model the stochastic...

  6. Chapter 3 Analysis of Dynamic Behavior
    (pp. 89-138)

    In this chapter, we describe some of the tools from dynamical systems and feedback control theory that will be used in the rest of the text to analyze and design biological circuits. We focus here on deterministic models and the associated analyses; stochastic methods are given in Chapter 4.

    As in the case of many other classes of dynamical systems, a great deal of insight into the behavior of a biological system can be obtained by analyzing the dynamics of the system subject to small perturbations around a known solution. We begin by considering the dynamics of the system near...

  7. Chapter 4 Stochastic Modeling and Analysis
    (pp. 139-168)

    In this chapter we explore stochastic behavior in biomolecular systems, building on our preliminary discussion of stochastic modeling in Section 2.1. We begin by reviewing methods for modeling stochastic processes, including the chemical master equation (CME), the chemical Langevin equation (CLE) and the Fokker-Planck equation (FPE). Given a stochastic description, we can then analyze the behavior of the system using a collection of stochastic simulation and analysis tools. This chapter makes use of a variety of topics in stochastic processes; readers should have a good working knowledge of basic probability and some exposure to simple stochastic processes.

    Biomolecular systems are...

  8. Chapter 5 Biological Circuit Components
    (pp. 169-204)

    In this chapter, we describe some simple circuit components that have been constructed inE. colicells using the technology of synthetic biology and then consider a more complicated circuit that already appears in natural systems to implement adaptation. We will analyze the behavior of these circuits employing mainly the tools from Chapter 3 and some of the tools from Chapter 4. The basic knowledge of Chapter 2 will be assumed.

    In Chapter 2 we introduced a number of core processes and models for those processes, including gene expression, transcriptional regulation, post-translational regulation such as covalent modification of proteins, allosteric...

  9. Chapter 6 Interconnecting Components
    (pp. 205-242)

    In Chapter 2 and Chapter 5 we studied the behavior of simple biomolecular modules, such as oscillators, toggles, self-repressing circuits, signal transduction and amplification systems, based on reduced-order models. One natural step forward is to create larger and more complex systems by composing these modules together. In this chapter, we illustrate problems that need to be overcome when interconnecting components and propose a number of engineering solutions based on the feedback principles introduced in Chapter 3. Specifically, we explain how loading effects arise at the interconnection between modules, which change the expected circuit behavior. These loading problems appear in several...

  10. Chapter 7 Design Tradeoffs
    (pp. 243-258)

    In this chapter we describe some of the design tradeoffs arising from the interaction between synthetic circuits and the host organism. We specifically focus on two issues. The first issue is concerned with the effects of competition for shared cellular resources on circuits’ behavior. In particular, circuits (endogenous and exogenous) share a number of cellular resources, such as RNA polymerase, ribosomes, ATP, enzymes, and nucleotides. The insertion or induction of synthetic circuits in the cellular environment changes the for these resources, with possibly undesired repercussions on the functioning of the circuits. Independent circuits may become coupled when they share common...

  11. Bibliography
    (pp. 259-266)
  12. Index
    (pp. 267-276)