Nature Biotechnology
23, 975 - 982 (2005)
Published online: 17 July 2005; | doi:10.1038/nbt1114
There is a Corrigendum (October 2006) associated with this Article.
Integrative model of the response of yeast to osmotic shockEdda Klipp1, 5, Bodil Nordlander2, 5, Roland Krüger3, Peter Gennemark4
& Stefan Hohmann21
Berlin Center for Genome Based Bioinformatics (BCB), Max-Planck Institute for Molecular Genetics, Dept. Vertebrate Genomics, Ihnestr. 73, 14195 Berlin, Germany. 2
Department of Cell and Molecular Biology/Microbiology, Göteborg University, Box 462, S-40530 Göteborg, Sweden. 3
Humboldt University Berlin, Institute for Biology, Invalidenstr. 43, 10115 Berlin, Germany. 4
Department of Computer Science and Engineering, Chalmers University of Technology, S-41296 Göteborg, Sweden. 5
These authors contributed equally to this work.
Correspondence should be addressed to Edda Klipp klipp@molgen.mpg.de or Stefan Hohmann hohmann@gmm.gu.se 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.
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