MOSES - MicroOrganism Systems Biology: Energy and Saccharomyces cerevisiae: Coordination plus WPs 1 and 7 and contributions to 5 and 6

MOSES - 微生物系统生物学：能量和酿酒酵母：协调以及 WP 1 和 7 以及对 5 和 6 的贡献

• 批准号: BB/F003528/1
• 负责人: Hans Westerhoff
• 金额: $ 42.4万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF003528%2F1
• 关键词: MOSES; MicroOrganism; Systems; Biology; Energy

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.

为了补充现有的自上而下和自下而上的SB策略，这里开发了多米诺骨牌，面向问题的SB方法，其遵循与所选择的高度连接的分子性质相关的调节线。所选属性为ATP（“能量”）。该方法是在最合适的，定义明确的，工业上最相关的生物体，面包酵母中开发的。MOSES计划连接SYSMO国家的酵母系统生物学核心，并与酵母系统生物学网络和HepatoSys相关。它将向新的群体开放。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体之一：当提供过量的食物时，它会尽可能快地利用这些食物。在这种“盛宴”的条件下，生物体非常低效地使用能量。在“饥荒”的条件下，酵母改变了策略。它降低了生长和生产酒精的速度，试图只生产二氧化碳（温室气体）。然后，它恢复增长，但效率更高，速度更慢。所有这些都涉及到同时对许多过程的微妙调节。以前认为，这种类型的调节是通过单一的“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。这使得生物调节更加难以理解，可能是科学界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，重点是生物体的网络方面。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所有许多分子开始的，要么是从只研究其中的一小部分开始的。前一种方法往往过于复杂，导致混淆而不是理解。后者可能会导致理解，可能不相关的生物有机体作为一个整体。在这里，我们建议开发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节途径和分子，然后首先研究这些。然后，它有一个机制，移动到下一个重要的调节途径和分子等。细胞的能量状态可以从ATP分子的细胞内浓度读取。这种分子ATP已知提供许多重要的细胞内过程所需的能量。在这里，我们建议开发多米诺骨牌系统生物学酵母开始的监管路线，涉及ATP。该项目是由五个欧洲国家组成的最适当小组之间的合作。它可能会导致了解如何使酵母更有效地为我们做事情。多米诺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。

项目成果

Targeting pathogen metabolism without collateral damage to the host.

• DOI: 10.1038/srep40406
• 发表时间: 2017-01-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Haanstra JR;Gerding A;Dolga AM;Sorgdrager FJH;Buist-Homan M;du Toit F;Faber KN;Holzhütter HG;Szöör B;Matthews KR;Snoep JL;Westerhoff HV;Bakker BM
• 通讯作者: Bakker BM

Systems biology of HIF metabolism in cancer

• 发表时间: 2012-10
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Emily G. Armitage;H. Westerhoff;Helen L. Kotze;R. Goodacre;N. Lockyer;K. Williams

Structural and dynamic features of the eukaryotic translation initiation pathway

真核翻译起始途径的结构和动态特征

• 发表时间: 2008
• 期刊: Febs Journal
• 影响因子: 5.4
• 作者: Bryant, H.

Engineering of self-sustaining systems: Substituting the yeast glucose transporter plus hexokinase for the Lactococcus lactis phosphotransferase system in a Lactococcus lactis network in silico

• DOI: 10.1002/biot.201100314
• 发表时间: 2012-07-01
• 期刊: BIOTECHNOLOGY JOURNAL
• 影响因子: 4.7
• 作者: Adamczyk, Malgorzata;Westerhoff, Hans V.
• 通讯作者: Westerhoff, Hans V.

Systems biology of chemotherapy in hypoxia environments

• 发表时间: 2012-11
• 期刊: Mutagenesis
• 影响因子: 2.7
• 作者: Helen L. Kotze;H. Westerhoff;N. Lockyer;R. Goodacre;Emily G. Armitage;K. Williams