Integrative model of the response of yeast to osmotic shock.
Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and-with appropriate modifications-other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.
Klipp
Edda
E
Berlin Center for Genome Based Bioinformatics, Max-Planck Institute for Molecular Genetics, Dept. Vertebrate Genomics, Ihnestr. 73, 14195 Berlin, Germany. klipp@molgen.mpg.de
Nordlander
Bodil
B
Krüger
Roland
R
Gennemark
Peter
P
Hohmann
Stefan
S
D002462:Cell Membrane / Q000502:physiology*; D003198:Computer Simulation; D015966:Gene Expression Regulation, Fungal / Q000502:physiology*; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014882:Water-Electrolyte Balance / Q000502:physiology*
D029701:Saccharomyces cerevisiae Proteins