SysMO Sulfolobus (Schleper)-WesterhoffManchester

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Most living organisms are rather robust vis-à-vis a great number of changes in their environment. Mammals and birds achieve much of this robustness by having different organs and cells process different tasks in a highly coordinated fashion. Unicellular microrganisms may derive much of their robustness from intracellular networks. This is somewhat understood for two of the three domains of Life, but not yet at all for the most recently discovered life form, i.e. Archaea. Yet it is these Archaea that are subject to the most extreme challenges from the environment as some of them live in hyperthermal vents or in salt and are subject to sudden and extreme variations. Only recently, the science has been developed that analyzes how intracellular networks generate important properties that are absent from the components of those networks. In much the same way groups of people can be much more effective than the same number of people all operating individually.) This 'Systems Biology' will here be deployed and tuned to analyze mechanisms of robustness in one of the most extreme Archae that is presently amenable to such studies, i.e. Sulfolobus solfataricus. The research program brings together much of the most appropriate expertise from four European countries. It will focus in the robustness of perhaps the most vital and massive biochemical functions of all organisms, i.e. their main carbon and energy metabolism. It wll look at perhaps the most pervasive perturbations cells of microorganisms experience, i.e. variations in temperature. A computer 'replica' of central carbon and energy metabolism will be made. Both in well-coordinated experiments and in the computer replica the various mechanisms through which the organisms achieve robustness will be identified and quantified. The extent, to which the mechanisms can stand in for each other should one of them be eliminated, will be determined. This new aspect of Systems Biology will suggest new ways to design drugs against parasytic cells, where adaptation of those cells is taken into account. The understanding achieved will also help develop these organisms as perhaps ideal biological factories for chemicals, including energy-fuel that needs to be harvested from extreme environments.