title: Derivation, identification and validation of a computational model of a novel synthetic regulatory network in yeast.
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.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), 80131 Naples, Italy. marucci@tigem.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Marucci
authors.forename: Stefania
authors.initials: S
authors.lastname: Santini
authors.forename: Mario
authors.initials: M
authors.lastname: di Bernardo
authors.forename: Diego
authors.initials: D
authors.lastname: di Bernardo
mesh_terms: D000465:Algorithms; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism; D053263:Gene Regulatory Networks / Q000502:physiology*; D008957:Models, Genetic; D017711:Nonlinear Dynamics; D030781:Organisms, Genetically Modified / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D058615:Synthetic Biology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C098733:ASH1 protein, S cerevisiae; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C064042:CBF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; C055002:GAL80 protein, S cerevisiae; D012097:Repressor Proteins; C080218:SWI5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C530845:HO protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific