MOSES - MicroOrganism Systems Biology: Energy and Saccharomyces cerevisiae-Kell

为了补充现有的自顶向下和自底向上的合成酶策略，本文开发了一种多米诺骨牌、面向问题的合成酶方法，该方法遵循与选定的高度连接的分子特性相关的规则。选择的属性是ATP（“能量”）。这种方法是在最合适的、定义明确的、工业上最相关的生物——面包酵母中发展起来的。MOSES项目连接了SYSMO国家的酵母系统生物学中心，并与酵母系统生物学网络和HepatoSys相关联。它将向新的团体开放。酵母帮助我们生产面包、葡萄酒和啤酒。它也是生长最快的生物之一：当有多余的食物供给时，它会尽可能快地利用这些食物。在这种“盛宴”的条件下，生物体利用能量的效率非常低。在“饥荒”的条件下，酵母改变了它的策略。它降低了它生长和产生酒精的速度，试图转变为只产生二氧化碳（温室气体）。然后，它恢复增长，但效率要高得多，速度也慢得多。所有这些都需要同时对许多过程进行微妙的调节。以前人们认为，这种类型的调节是由单个“关键”分子实现的，这些分子要么处于“开”状态，要么处于“关”状态。最近，人们已经清楚地认识到，在生物体中，调控往往涉及许多分子的网络。这使得生物调控变得更加难以理解，也可能是科学仍然难以找到有效治疗困扰我们的复杂疾病（如癌症、糖尿病和关节炎）的原因之一。一种新型的科学正在发展，其重点是研究生物体的这种网络方面。它被称为“系统生物学”。到目前为止，大多数系统生物学要么是从同时研究生物体的许多分子开始的，要么是从同时研究生物体的许多分子开始的，要么是只研究其中的几个。前一种方法往往是如此复杂，它导致混淆而不是理解。后者可能会导致与整个生物体无关的理解。在此，我们建议发展一种新型的系统生物学，称为多米诺系统生物学。它首先评估网络中最强的调控途径和分子，然后首先研究这些。然后，它就有了一种机制，可以转移到下一个重要的调节途径和分子上，等等。细胞的能量状态可以从细胞内ATP分子的浓度中读出。已知这种分子ATP为许多重要的细胞内过程提供所需的能量。我们在此建议从涉及ATP的调控途径开始发展酵母的多米诺骨牌系统生物学。该项目是五个欧洲国家中最合适的小组之间的合作。这可能会让我们了解酵母是如何更有效地为我们做这些事情的。多米诺骨牌系统生物学的发展应该是一个宝贵的工具，也为分析病变细胞和发现更好的药物靶点。

To complement existing top-down and bottom-up SB strategies, here a domino, problem oriented SB approach is developed, which follows the lines of regulation, pertinent to a selected highly connected molecule property. The selected property is ATP ('energy'). The approach is developed in the most suitable, well-defined, industrially most relevant organism, baker's yeast. The MOSES program connects yeast Systems Biology nuclei in SYSMO countries and is associated with the Yeast Systems Biology Network and HepatoSys. It will be open to new groups. Yeast helps us produce bread, wine and beer. It is also one of the fastest growing organisms: When provided with an excess of food it utilizes this as quickly as it can. Under such conditions of 'feast', the organism uses the energy very inefficiently. Under conditions of 'famine' yeast changes its strategy. It reduces the rate at which it grows and produces alcohol, tries to switch to producing carbon dioxide (the greenhouse gas) only. It then resumes growth but much more efficiently and more slowly. All of this involves subtle regulation of many processes at the same time. It was previously thought that regulation of this type is achieved by single 'key' molecules that would either be in an 'on' state or in an 'off' state. Recently, it has become clear that in living organisms, regulation tends to involve networks of many molecules. This makes biological regulation much more difficult to understand and may be one reason why the sciences still have a hard time to find effective treatments for the complex diseases that plague us, such as cancer, diabetes and arthritis. A new type of science is being developed that focuses on this network aspect of living organisms. It is called 'Systems Biology'. Until now most Systems Biology has either begun by looking at all of the many, many molecules of living organisms at the same time, or by looking at just a very few of them. The former approach tends to be so complex that it leads to confusion more than understanding. The latter may lead to understanding that may not be relevant to the living organism as a whole. Here we propose to develop a new type of Systems Biology, called domino systems biology. It begins by assessing what are the strongest regulatory routes and molecules in the network and then studies these first. It then has a mechanism to move to the next important regulatory routes and molecules, etc. The energy state of the cell may be read from the intracellular concentration of the molecule ATP. This molecules ATP is known to provide many important intracellular processes with the energy they require. We here propose to develop domino systems biology for yeast starting with the regulatory routes that involve ATP. The project is a collaboration between the most appropriate groups of five European countries. It is likely to result in understanding of how yeast can be made to do the things it does for us more efficiently. The domino systems biology developed should be an invaluable tool also for the analysis of diseased cells and the discovery of better drug targets.