Silicon Cell Model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

Temperature changes are not only most difficult to deal with for organisms, it is also unclear how biological networks can withstand and respond to such changes. Even slight differences between the rates of individual reactions in metabolic pathways shoul d cause rapid accumulation or depletion of intermediates with various deleterious effects. With a change in temperature, the rates of individual reactions in metabolic pathways must therefore change by precisely the same extent. Organisms could adapt by ( i) having identical temperature coefficients of the enzymes, (ii) metabolic regulation, (iii) adjusting Vmax-s (e.g. through enzyme phosphorylation), (iv) adjusting translation or protein stability, (v) adjusting transcription or mRNA stability, (vi) rero uting the metabolic flow, (vii) formation of compatible solutes, (viii) export of ?overflow? metabolites or (ix) going into dormancy. We hypothesize that several of these mechanisms contribute to different extents and propose to quantify each of these ada ptation in a systems biology approach. As the issue should be most acute for thermophiles, we suggest to study this with a thermophilic archaeon. We will study the central carbohydrate metabolism (CCM) of Sulfolobus and its regulation under temperature va riation. The archaeal CCM is characterized by unusual pathways and enzymes that often differ from their bacterial or eukaryotic counterparts. Details of regulation and energetic of the CCM will be revealed while we will assemble the data required for inte gration of genomic, transcriptomic, proteomic, metabolomic, kinetic and biochemical information on the effects of temperature changes. Our long term goal is to use our proposed Analysis, Modelling and Experimental Design Platform as a nucleus for building a sufficiently precise replica for this part of the living cell (a Silicon Cell) to enable computation of life, particular its robustness to changes in temperature, at the system level.