An Introduction to Systems Biology: Design Principles of Biological Circuits, 1st Edition (Paperback) book cover

An Introduction to Systems Biology

Design Principles of Biological Circuits, 1st Edition

By Uri Alon

Chapman and Hall/CRC

320 pages | 110 B/W Illus.

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Description

Thorough and accessible, this book presents the design principles of biological systems, and highlights the recurring circuit elements that make up biological networks. It provides a simple mathematical framework which can be used to understand and even design biological circuits. The textavoids specialist terms, focusing instead on several well-studied biological systems that concisely demonstrate key principles.

An Introduction to Systems Biology: Design Principles of Biological Circuits builds a solid foundation for the intuitive understanding of general principles. It encourages the reader to ask why a system is designed in a particular way and then proceeds to answer with simplified models.

Reviews

"[This text deserves] serious attention from any quantitative scientist or physicist who hopes to learn about modern biology. [It is] well written. … Alon’s book is the better place for physicists to start. It assumes no prior knowledge of or even interest in biology. Yet right from chapter 1, the author succeeds in explaining in an intellectually exciting way what the cell does and what degrees of freedom enable it to function. … The book proceeds with detailed discussions of some of the key network motifs, circuit-element designs … [and] focuses on concrete examples such as chemotaxis and developmental pattern formation. … He draws the detailed strands together into an appealing and inspiring overview of biology. … One final aspect that must be mentioned is the wonderful set of exercises that accompany each chapter. … Alon’s book should become a standard part of the training of graduate students in biological physics… ."

—Nigel Goldenfeld, University of Illinois at Urbana-Champaign, Physics Today, June 2007

"…a superb, beautifully written and organized work that takes an engineering approach to systems biology. Alon provides nicely written appendices to explain the basic mathematical and biological concepts clearly and succinctly without interfering with the main text. He starts with a mathematical description of transcriptional activation and then describes some basic transcription-network motifs (patterns) that can be combined to form larger networks. … Alon investigates networks at a higher level, including genomic regulatory networks. He does an excellent job of explaining and motivating a useful toolbox of engineering models and methods using network-based controls. … will be a valuable and non-overlapping addition to a systems-biology curriculum."

—Eric Werner, Department of Physiology, Anatomy and Genetics, University of Oxford, Nature, Vol. 446, No. 29, March 2007

"I read Uri Alon’s elegant book almost without stopping for breath. He perceives and explains so many simple regularities, so clearly, that the novice reading this book can move on immediately to research literature, armed with a grasp of the many connections between diverse phenomena."

—Philip Nelson, Professor of Physics, University of Pennsylvania, Philadelphia, USA

"… Beyond simply recounting recent results, Alon boldly articulates the basic principles underlying biological circuitry at different levels and shows how powerful they can be in understanding the complexity of living cells. For anyone who wants to understand how a living cell works, but thought they never would, this book is essential."

—Michael B. Elowitz, California Institute of Technology, Pasadena, USA

"Uri Alon offers a highly original perspective on systems biology, emphasizing the function of certain simple networks that appear as ubiquitous building blocks of living matter. The quest for simplicity — without losing contact with complex reality — is the only way to uncover the principles organizing biological systems. Alon writes with uncommon lucidity…"

—Boris Shraiman, University of California, Santa Barbara, USA

"This is a remarkable book that introduces not only a field but a way of thinking. Uri Alon describes in an elegant, simple way how principles such as stability, robustness and optimal design can be used to analyze and understand the evolution and behavior of living organisms. Alon’s clear intuitive language and helpful examples offer — even to a mathematically naive reader — deep mathematical insights into biology. The community has been waiting for this book; it was worth the wait."

—Galit Lahav, Harvard Medical School, Boston, Massachusetts, USA

Table of Contents

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

About the Series

Chapman & Hall/CRC Mathematical and Computational Biology

Learn more…

Subject Categories

BISAC Subject Codes/Headings:
MAT003000
MATHEMATICS / Applied
SCI010000
SCIENCE / Biotechnology
SCI055000
SCIENCE / Physics