Biological Clocks, Rhythms, and Oscillations

The Theory of Biological Timekeeping

An introduction to the mathematical, computational, and analytical techniques used for modeling biological rhythms, presenting tools from many disciplines and example applications.

All areas of biology and medicine contain rhythms, and these behaviors are best understood through mathematical tools and techniques. This book offers a survey of mathematical, computational, and analytical techniques used for modeling biological rhythms, gathering these methods for the first time in one volume. Drawing on material from such disciplines as mathematical biology, nonlinear dynamics, physics, statistics, and engineering, it presents practical advice and techniques for studying biological rhythms, with a common language.

The chapters proceed with increasing mathematical abstraction. Part I, on models, highlights the implicit assumptions and common pitfalls of modeling, and is accessible to readers with basic knowledge of differential equations and linear algebra. Part II, on behaviors, focuses on simpler models, describing common properties of biological rhythms that range from the firing properties of squid giant axon to human circadian rhythms. Part III, on mathematical techniques, guides readers who have specific models or goals in mind. Sections on “frontiers” present the latest research; “theory” sections present interesting mathematical results using more accessible approaches than can be found elsewhere. Each chapter offers exercises. Commented MATLAB code is provided to help readers get practical experience.

The book, by an expert in the field, can be used as a textbook for undergraduate courses in mathematical biology or graduate courses in modeling biological rhythms and as a reference for researchers.

Daniel B. Forger is Professor in the Department of Mathematics and in the Department of Computational Medicine and Bioinformatics at the University of Michigan.
Preface xiii
Notation xvii
1 Basics 1
PART I MODELS 35
2 Biophysical Mechanistic Modeling: Choosing the Right Model Equations 37
3 Functioning in the Changing Cellular Environment 73
4 When Do Feedback Loops Oscillate? 101
PART II BEHAVIORS 131
5 Systems-Level Modeling 133
6 Phase Response Curves 171
7 Eighteen Principles of Synchrony 195
PART III ANALYSIS AND COMPUTATION 225
8 Statistical and Computational Tools for Model Building: How to Extract Information from Timeseries Data 227
9 How to Shift an Oscillator Optimally 261
10 Mathematical and Computational Techniques for Multiscale Problems 291
Glossary 323
Bibliography 329
Index 341

About

An introduction to the mathematical, computational, and analytical techniques used for modeling biological rhythms, presenting tools from many disciplines and example applications.

All areas of biology and medicine contain rhythms, and these behaviors are best understood through mathematical tools and techniques. This book offers a survey of mathematical, computational, and analytical techniques used for modeling biological rhythms, gathering these methods for the first time in one volume. Drawing on material from such disciplines as mathematical biology, nonlinear dynamics, physics, statistics, and engineering, it presents practical advice and techniques for studying biological rhythms, with a common language.

The chapters proceed with increasing mathematical abstraction. Part I, on models, highlights the implicit assumptions and common pitfalls of modeling, and is accessible to readers with basic knowledge of differential equations and linear algebra. Part II, on behaviors, focuses on simpler models, describing common properties of biological rhythms that range from the firing properties of squid giant axon to human circadian rhythms. Part III, on mathematical techniques, guides readers who have specific models or goals in mind. Sections on “frontiers” present the latest research; “theory” sections present interesting mathematical results using more accessible approaches than can be found elsewhere. Each chapter offers exercises. Commented MATLAB code is provided to help readers get practical experience.

The book, by an expert in the field, can be used as a textbook for undergraduate courses in mathematical biology or graduate courses in modeling biological rhythms and as a reference for researchers.

Author

Daniel B. Forger is Professor in the Department of Mathematics and in the Department of Computational Medicine and Bioinformatics at the University of Michigan.

Table of Contents

Preface xiii
Notation xvii
1 Basics 1
PART I MODELS 35
2 Biophysical Mechanistic Modeling: Choosing the Right Model Equations 37
3 Functioning in the Changing Cellular Environment 73
4 When Do Feedback Loops Oscillate? 101
PART II BEHAVIORS 131
5 Systems-Level Modeling 133
6 Phase Response Curves 171
7 Eighteen Principles of Synchrony 195
PART III ANALYSIS AND COMPUTATION 225
8 Statistical and Computational Tools for Model Building: How to Extract Information from Timeseries Data 227
9 How to Shift an Oscillator Optimally 261
10 Mathematical and Computational Techniques for Multiscale Problems 291
Glossary 323
Bibliography 329
Index 341