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的理解。它们也带来了一些惊喜。一个事实是，看起来非常不同的有机体在它们的分子方面相当相似。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近的相似之处，它们之间存在很大的差异，例如在它们与人类相互作用的方式上(见下文)。虽然这有助于科学发现分子的行为方式，但它也向我们展示了一个巨大的悖论：可以肯定的是，人类和蠕虫在几乎所有重要的事情上都有显著的不同。一项名为系统生物学的最新科学发展认识到，生物有机体的功能也取决于其组成部分之间的相互作用，就像足球运动员的得分不仅取决于球员自己，而且往往更取决于球队其他成员如何合作，在正确的时刻将球传给她。在这里，我们建议检验我们的假设，即有机体之间的大部分差异源于其组成部分之间相互作用的差异。四种密切相关的微生物将被比较，即一种生产奶酪的微生物，一种是食物的粪便污染物，一种会导致喉咙痛和更糟的微生物，以及一种促进消化的食品添加剂。四种细菌中的网络将被拆解，通过这些网络的碳和能量的流动将被确定，细菌能够在多大程度上调整其网络以适应变化的环境将被测量。结果将被组装到计算机模型中，然后应该可以重现细菌的行为。它将研究这些生物体的计算机版本是否以及如何解释它们导致疾病的程度或作为帮助我们生产食物的有机体的功能的差异。这些对功能差异的解释将在实验中得到验证。由一个国际联盟与曼彻斯特部分参与大部分计算机建模的工作，不仅将帮助我们找到上述悖论的解决方案，而且它还将展示数学和实验生物学方法之间强相互作用的力量，以解决生命中的重大问题。所获得的经验，以及模型本身，对于帮助理解生命、健康和疾病的分子基础应该更广泛地有用。

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.