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Canonical Modeling of the Multi-Scale Regulation of the Heat Stress Response in Yeast
Instituto de Tecnologia Quıímica e Biológica, Universidade Nova de Lisboa / Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal
Integrative BioSystems Institute and The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 313 Ferst Drive, Suite 4103, Atlanta, GA 30332, USA
* Author to whom correspondence should be addressed.
Received: 30 December 2011; in revised form: 8 February 2012 / Accepted: 10 February 2012 / Published: 27 February 2012
Abstract: Heat is one of the most fundamental and ancient environmental stresses, and response mechanisms are found in prokaryotes and shared among most eukaryotes. In the budding yeast Saccharomyces cerevisiae, the heat stress response involves coordinated changes at all biological levels, from gene expression to protein and metabolite abundances, and to temporary adjustments in physiology. Due to its integrative multi-level-multi-scale nature, heat adaptation constitutes a complex dynamic process, which has forced most experimental and modeling analyses in the past to focus on just one or a few of its aspects. Here we review the basic components of the heat stress response in yeast and outline what has been done, and what needs to be done, to merge the available information into computational structures that permit comprehensive diagnostics, interrogation, and interpretation. We illustrate the process in particular with the coordination of two metabolic responses, namely the dramatic accumulation of the protective disaccharide trehalose and the substantial change in the profile of sphingolipids, which in turn affect gene expression. The proposed methods primarily use differential equations in the canonical modeling framework of Biochemical Systems Theory (BST), which permits the relatively easy construction of coarse, initial models even in systems that are incompletely characterized.
Keywords: biochemical systems theory; canonical modeling; dynamical model; heat stress; metabolic regulation; multi-scale control; sphingolipid metabolism; systems biology; trehalose
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Fonseca, L.L.; Chen, P.-W.; Voit, E.O. Canonical Modeling of the Multi-Scale Regulation of the Heat Stress Response in Yeast. Metabolites 2012, 2, 221-241.
Fonseca LL, Chen P-W, Voit EO. Canonical Modeling of the Multi-Scale Regulation of the Heat Stress Response in Yeast. Metabolites. 2012; 2(1):221-241.
Fonseca, Luis L.; Chen, Po-Wei; Voit, Eberhard O. 2012. "Canonical Modeling of the Multi-Scale Regulation of the Heat Stress Response in Yeast." Metabolites 2, no. 1: 221-241.