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.

Abstract

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

Substances

  • 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