Comparative systems biology of lactic acid bacteria (SYSMOLAB2; Teusink-Westerhoff)

分子和基因组学方法极大地促进了我们对生物体的理解。它们也导致了一些意外。其中之一是，看似高度不同的生物体在分子方面相当相似。事实上，人类的许多分子成分与蠕虫甚至细菌的成分相似。在细菌物种之间发现了更接近的相似性，这些细菌物种之间存在很大差异，例如它们如何与人类相互作用（见下文）。虽然这一直在帮助科学发现分子的行为，但它也给我们带来了一个巨大的悖论：毫无疑问，人类和蠕虫在几乎所有重要的事情上都有巨大的差异。科学的最新发展，称为系统生物学，认识到生物体的功能也是由其组成部分之间的相互作用决定的，就像足球运动员的得分不仅取决于球员本人，而且往往更多地取决于团队的其他成员如何合作，在正确的时刻将球传给她。在这里，我们建议测试我们的假设，即生物体之间的差异大多来自其组件之间的相互作用的差异。将比较四种密切相关的生物，即一种生产我们的奶酪，一种是食物的粪便污染物，一种是导致喉咙痛和更糟的，一种是促进消化的食品添加剂。四种细菌中每一种的网络都将被解开，碳和能量通过这些网络的流动将被确定，细菌能够在多大程度上调整其网络以适应改变的环境将被测量。这些结果将被整合到计算机模型中，然后再现细菌的行为。将研究这些计算机版本的生物体是否以及如何解释它们引起疾病或作为帮助生产我们食物的生物体发挥作用的程度的差异。这些功能差异的解释将通过实验进行检验。一个国际财团与曼彻斯特部分从事大部分计算机建模的工作，不仅有助于我们找到上述悖论的解决方案，而且还将展示数学和实验生物学方法之间强有力的相互作用对生命大问题的影响。所获得的经验，以及模型本身，应该是有用的更广泛地帮助理解生命的分子基础，健康和疾病。

Molecular and genomics approaches have contributed greatly to our understanding of living organisms. They have also led to a number of surprises. One is the fact that organisms that appear to be highly different are rather similar in terms of their molecules. In fact, many of the molecular components of humans are similar to components of worms and even bacteria. Even closer similarities have been found between bacterial species that differ greatly between themselves, e.g. in how they interact with human beings (see below). Whilst this has been helping Science discover how molecules behave, it also presents us with a great paradox: for sure, humans and worms differ dramatically in almost anything that is important. A recent development in the sciences, called Systems Biology, recognizes that the functioning of living organisms is also determined by the interactions between their components, just like the scoring by a football player is not just determined by that player himself, but often more by how the rest of the team has cooperated to deliver the ball to her at the right moment. Here we propose to test our hypothesis that most of the differences between organisms derives from differences in the interactions between their components. Four strongly related organisms will be compared, i.e. one that produces our cheese, one that is a fecal contaminant of food, one that causes sore throats and worse, and one that is a food additive promoting digestion. The networks in each of the four bacteria will be unraveled, the flow of carbon and energy through those networks will be determined, and the extent to which the bacteria are able to adjust their networks to altered environments will be measured. The results will be assembled into computer models that should then reproduce the behaviour of the bacteria. It will be examined whether and how these computer versions of the organisms explain the differences in the extent to which they cause disease or function as organisms that help produce our food. These explanations of the functional differences will then be tested experimentally. The work by an international consortium with the Manchester part engaged in much of the computer modelling, will not only help us in finding resolutions of the above-mentioned paradox, but it will also demonstrate the power of strong interactions between mathematical and experimental biology approaches to big questions of Life. The experience gained, as well as the models themselves, should be useful much more widely for helping understand the molecular basis of Life, of health and of disease.