How can we understand the complexity of genes, RNAs, and proteins and the associated regulatory networks? One approach is to look for recurring types of dynamical behavior. Mathematical models prove to be useful, especially models coming from theories of biochemical reactions such as ordinary differential equation models. Clever, careful experiments test these models and their basis in specific theories. This textbook aims to provide advanced students with the tools and insights needed to carry out studies of signal transduction drawing on modeling, theory, and experimentation. Early chapters summarize the basic building blocks of signaling systems: binding/dissociation, synthesis/destruction, and activation/inactivation. Subsequent chapters introduce various basic circuit devices: amplifiers, stabilizers, pulse generators, switches, stochastic spike generators, and oscillators. All chapters consistently use approaches and concepts from chemical kinetics and nonlinear dynamics, including rate-balance analysis, phase plane analysis, nullclines, linear stability analysis, stable nodes, saddles, unstable nodes, stable and unstable spirals, and bifurcations. This textbook seeks to provide quantitatively inclined biologists and biologically inclined physicists with the tools and insights needed to apply modeling and theory to interesting biological processes. Key Features: Full-color illustration program with diagrams to help illuminate the concepts Enables the reader to apply modeling and theory to the biological processes Further Reading for each chapter High-quality figures available for instructors to download

An introduction to the mathematical concepts and techniques needed for the construction and analysis of models in molecular systems biology. Systems techniques are integral to current research in molecular cell biology, and system-level investigations are often accompanied by mathematical models. These models serve as working hypotheses: they help us to understand and predict the behavior of complex systems. This book offers an introduction to mathematical concepts and techniques needed for the construction and interpretation of models in molecular systems biology. It is accessible to upper-level undergraduate or graduate students in life science or engineering who have some familiarity with calculus, and will be a useful reference for researchers at all levels. The first four chapters cover the basics of mathematical modeling in molecular systems biology. The last four chapters address specific biological domains, treating modeling of metabolic networks, of signal transduction pathways, of gene regulatory networks, and of electrophysiology and neuronal action potentials. Chapters 3–8 end with optional sections that address more specialized modeling topics. Exercises, solvable with pen-and-paper calculations, appear throughout the text to encourage interaction with the mathematical techniques. More involved end-of-chapter problem sets require computational software. Appendixes provide a review of basic concepts of molecular biology, additional mathematical background material, and tutorials for two computational software packages (XPPAUT and MATLAB) that can be used for model simulation and analysis.

This textbook contains the essential knowledge in modeling, simulation, analysis, and applications in dealing with biological cellular control systems. In particular, the book shows how to use the law of mass balance and the law of mass action to derive an enzyme kinetic model - the Michaelis-Menten function or the Hill function, how to use a current-voltage relation, Nernst potential equilibrium equation, and Hodgkin and Huxley's models to model an ionic channel or pump, and how to use the law of mass balance to integrate these enzyme or channel models into a complete feedback control system. The book also illustrates how to use data to estimate parameters in a model, how to use MATLAB to solve a model numerically, how to do computer simulations, and how to provide model predictions. Furthermore, the book demonstrates how to conduct a stability and sensitivity analysis on a model.

Aimed at postgraduate students in a variety of biology-related disciplines, this volume presents a collection of mathematical and computational single-cell-based models and their application. The main sections cover four general model groupings: hybrid cellular automata, cellular potts, lattice-free cells, and viscoelastic cells. Each section is introduced by a discussion of the applicability of the particular modelling approach and its advantages and disadvantages, which will make the book suitable for students starting research in mathematical biology as well as scientists modelling multicellular processes.

For decades biology has focused on decoding cellular processes one gene at a time, but many of the most pressing biological questions, as well as diseases such as cancer and heart disease, are related to complex systems involving the interaction of hundreds, or even thousands, of gene products and other factors. How do we begin to understand this complexity? Fundamentals of Systems Biology: From Synthetic Circuits to Whole-cell Models introduces students to methods they can use to tackle complex systems head-on, carefully walking them through studies that comprise the foundation and frontier of systems biology. The first section of the book focuses on bringing students quickly up to speed with a variety of modeling methods in the context of a synthetic biological circuit. This innovative approach builds intuition about the strengths and weaknesses of each method and becomes critical in the book’s second half, where much more complicated network models are addressed—including transcriptional, signaling, metabolic, and even integrated multi-network models. The approach makes the work much more accessible to novices (undergraduates, medical students, and biologists new to mathematical modeling) while still having much to offer experienced modelers--whether their interests are microbes, organs, whole organisms, diseases, synthetic biology, or just about any field that investigates living systems.

An introduction and overview of system modeling in biology that is accessible to researchers from different fields, including biology, computer science, mathematics, statistics, physics, and biochemistry. Research in systems biology requires the collaboration of researchers from diverse backgrounds, including biology, computer science, mathematics, statistics, physics, and biochemistry. These collaborations, necessary because of the enormous breadth of background needed for research in this field, can be hindered by differing understandings of the limitations and applicability of techniques and concerns from different disciplines. This comprehensive introduction and overview of system modeling in biology makes the relevant background material from all pertinent fields accessible to researchers with different backgrounds. The emerging area of systems level modeling in cellular biology has lacked a critical and thorough overview. This book fills that gap. It is the first to provide the necessary critical comparison of concepts and approaches, with an emphasis on their possible applications. It presents key concepts and their theoretical background, including the concepts of robustness and modularity and their exploitation to study biological systems; the best-known modeling approaches, and their advantages and disadvantages; lessons from the application of mathematical models to the study of cellular biology; and available modeling tools and datasets, along with their computational limitations.

The emerging, multi-disciplinary field of systems biology is devoted to the study of the relationships between various parts of a biological system, and computer modeling plays a vital role in the drive to understand the processes of life from an holistic viewpoint. Advancements in experimental technologies in biology and medicine have generated an enormous amount of biological data on the dependencies and interactions of many different molecular cell processes, fueling the development of numerous computational methods for exploring this data. The mathematical formalism of Petri net theory is able to encompass many of these techniques. This essential text/reference presents a comprehensive overview of cutting-edge research in applications of Petri nets in systems biology, with contributions from an international selection of experts. Those unfamiliar with the field are also provided with a general introduction to systems biology, the foundations of biochemistry, and the basics of Petri net theory. Further chapters address Petri net modeling techniques for building and analyzing biological models, as well as network prediction approaches, before reviewing the applications to networks of different biological classification. Topics and features: investigates the modular, qualitative modeling of regulatory networks using Petri nets, and examines an Hybrid Functional Petri net simulation case study; contains a glossary of the concepts and notation used in the book, in addition to exercises at the end of each chapter; covers the topological analysis of metabolic and regulatory networks, the analysis of models of signaling networks, and the prediction of network structure; provides a biological case study on the conversion of logical networks into Petri nets; discusses discrete modeling, stochastic modeling, fuzzy modeling, dynamic pathway modeling, genetic regulatory network modeling, and quantitative analysis techniques; includes a Foreword by Professor Jens Reich, Professor of Bioinformatics at Humboldt University and Max Delbrück Center for Molecular Medicine in Berlin. This unique guide to the modeling of biochemical systems using Petri net concepts will be of real utility to researchers and students of computational biology, systems biology, bioinformatics, computer science, and biochemistry.

This book discusses the mathematical simulation of biological systems, with a focus on the modeling of gene expression, gene regulatory networks and stem cell regeneration. The diffusion of morphogens is addressed by introducing various reaction-diffusion equations based on different hypotheses concerning the process of morphogen gradient formation. The robustness of steady-state gradients is also covered through boundary value problems. The introduction gives an overview of the relevant biological concepts (cells, DNA, organism development) and provides the requisite mathematical preliminaries on continuous dynamics and stochastic modeling. A basic understanding of calculus is assumed. The techniques described in this book encompass a wide range of mechanisms, from molecular behavior to population dynamics, and the inclusion of recent developments in the literature together with first-hand results make it an ideal reference for both new students and experienced researchers in the field of systems biology and applied mathematics.

What every neuroscientist should know about the mathematical modeling of excitable cells, presented at an introductory level.

The dynamic development of various processes is a central problem of biology and indeed of all the sciences. The mathematics describing that development is, in general, complicated, because the models that are realistic are usually nonlinear. Consequently many biologists may not notice a possible application of theory. They may be unable to decide whether a particular model captures the essence of a system, or to appreciate that analysis of a model can reveal important aspects of biological problems and may even describe in detail how a system works. The aim of this textbook is to remedy the situation by adopting a general approach to model analysis and applying it several times to problems (drawn primarily from molecular and cellular biology) of gradually increasing biological and mathematical complexity. Although material of considerable sophistication is included, little mathematical background is required - only some exposure to elementary calculus; appendixes supply the necessary mathematics and the author concentrates on concepts rather than techniques. He also emphasizes the role of computers in giving a full picture of model behavior and complementing more qualitative analysis. Some problems suitable for computer analysis are also included. This is a class-tested textbook suitable for a one-semester course for advanced undergraduate and beginning graduate students in biology or applied mathematics. It can also be used as a source book for teachers and a reference for specialists.