Complex coordination of multi-scale cellular responses to environmental stress.

Cells and organisms are regularly exposed to a variety of stresses, and effective responses are a matter of survival. The article describes a multi-scale experimental and dynamical modeling analysis that clearly indicates concerted stress control in different temporal and organizational domains, and a strong synergy between the dynamics of genes, proteins and metabolites. Specifically, we show with in vivo NMR measurements of metabolic profiles that baker's yeast responds to a paradigmatic stress, heat, at three organizational levels and in two time regimes. At the metabolic level, an almost immediate response is mounted. However, this response is a "quick fix" in comparison to a much more effective response that had been pre-organized in earlier periods of heat stress and is an order of magnitude stronger. Equipped with the metabolic profile data, our modeling efforts resulted in a crisp, quantitative separation of response actions at the levels of metabolic control and gene regulation. They also led to predictions of necessary changes in protein levels and clearly demonstrated that formerly observed temperature profiles of key enzyme activities are not sufficient to explain the accumulation of trehalose as an immediate response to sudden heat stress.