Models in biology: lessons from modeling regulation of the eukaryotic cell cycle.

John J Tyson,Béla Novák

doi:10.1186/s12915-015-0158-9

Abstract

In this essay we illustrate some general principles of mathematical modeling in biology by our experiences in studying the molecular regulatory network underlying eukaryotic cell division. We discuss how and why the models moved from simple, parsimonious cartoons to more complex, detailed mechanisms with many kinetic parameters. We describe how the mature models made surprising and informative predictions about the control system that were later confirmed experimentally. Along the way, we comment on the ‘parameter estimation problem’ and conclude with an appeal for a greater role for mathematical models in molecular cell biology.

Highlights

In this essay we illustrate some general principles of mathematical modeling in biology by our experiences in studying the molecular regulatory network underlying eukaryotic cell division
Focus on the biology by asking a specific question We focus in this review on the molecular mechanisms controlling entry into and exit from mitosis (M phase) in the natural cell cycles of frog embryos and fission yeast cells and in the artificial mitotic cycles exhibited by frog egg extracts
For larger concentrations of maturation promoting factor’ (MPF), 24 U/μl and 48 U/μl, cyclin is degraded at the same high rate, but the time lag decreases to ~10 minutes model, on the other hand, cyclin is a stoichiometric activator of Cdc2; i.e., cyclin binds with phosphorylated Cdc2 to form preMPF (Fig. 2c, left). preMPF is converted into active MPF by the phosphatase activity of Cdc25

Summary

Introduction

In this essay we illustrate some general principles of mathematical modeling in biology by our experiences in studying the molecular regulatory network underlying eukaryotic cell division. Focus on the biology by asking a specific question We focus in this review on the molecular mechanisms controlling entry into and exit from mitosis (M phase) in the natural cell cycles of frog embryos and fission yeast cells and in the artificial mitotic cycles exhibited by frog egg extracts.

Results

Conclusion