Derivation, identification and validation of a computational model of a novel synthetic regulatory network in yeast

J Math Biol. 2011 May;62(5):685-706. doi: 10.1007/s00285-010-0350-z. Epub 2010 Jun 12.


Systems biology aims at building computational models of biological pathways in order to study in silico their behaviour and to verify biological hypotheses. Modelling can become a new powerful method in molecular biology, if correctly used. Here we present step-by-step the derivation and identification of the dynamical model of a biological pathway using a novel synthetic network recently constructed in the yeast Saccharomyces cerevisiae for In-vivo Reverse-Engineering and Modelling Assessment. This network consists of five genes regulating each other transcription. Moreover, it includes one protein-protein interaction, and its genes can be switched on by addition of galactose to the medium. In order to describe the network dynamics, we adopted a deterministic modelling approach based on non-linear differential equations. We show how, through iteration between experiments and modelling, it is possible to derive a semi-quantitative prediction of network behaviour and to better understand the biology of the pathway of interest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Computer Simulation*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Deoxyribonucleases, Type II Site-Specific / genetics
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Gene Regulatory Networks / physiology*
  • Models, Genetic*
  • Nonlinear Dynamics
  • Organisms, Genetically Modified / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Reproducibility of Results
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Synthetic Biology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • ASH1 protein, S cerevisiae
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CBF1 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • GAL4 protein, S cerevisiae
  • GAL80 protein, S cerevisiae
  • Repressor Proteins
  • SWI5 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • HO protein, S cerevisiae
  • Deoxyribonucleases, Type II Site-Specific