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

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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.