SysMO Sulfolobus (Schleper)-WesterhoffManchester

大多数生物体在面对环境的大量变化时都相当健壮。哺乳动物和鸟类通过让不同的器官和细胞以高度协调的方式处理不同的任务来实现这种鲁棒性。单细胞微生物可能从细胞内网络中获得其大部分鲁棒性。对于生命的三个领域中的两个，这在某种程度上是可以理解的，但对于最近发现的生命形式，即古生物，这还完全不清楚。然而，正是这些海洋生物受到环境的最极端挑战，因为其中一些生活在超热喷口或盐中，并受到突然和极端变化的影响。直到最近，科学才发展起来，分析细胞内网络如何产生这些网络组件所不存在的重要特性。同样的道理，一群人比同样数量的人单独行动要有效得多。）这个“系统生物学”将在这里部署和调整，以分析目前适合这种研究的最极端的古菌之一，即硫磺硫化叶菌的鲁棒性机制。该研究项目汇集了来自四个欧洲国家的最合适的专业知识。它将集中在所有生物体中可能最重要和最大的生化功能的稳健性，即它们的主要碳和能量代谢。它将着眼于可能是微生物细胞经历的最普遍的扰动，即温度的变化。一个中央碳和能量代谢的计算机“复制品”将被制作出来。在协调良好的实验和计算机复制中，生物体实现鲁棒性的各种机制将被识别和量化。如果其中一个机制被取消，这些机制可以在多大程度上相互替代，这一点将得到确定。系统生物学的这一新方面将提出设计针对寄生细胞的药物的新方法，其中考虑到这些细胞的适应性。所取得的理解也将有助于开发这些生物体，使其成为化学品的理想生物工厂，包括需要从极端环境中收获的能源燃料。

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.