Case study in systematic modelling: thiamine uptake in the yeast Saccharomyces cerevisiae

In recent years, with important advances in molecular biology, experimental and measurement technologies, it has become possible to generate the quantitative data that are needed for building mathematical models of complex biochemical processes. Cartoon-like diagrams of biological pathways can be turned into dynamical models, allowing simulation and analysis to gain an insight into the underlying control mechanisms and the behaviour of the overall system. This kind of system-level understanding has not been reachable from the study of the components of pathways in isolation. However, mathematical modelling does not only integrate the available knowledge about a certain system with newly generated experimental results. During the process of modelling, questions need to be addressed that lead to an increased quantitative understanding of the system. Models can be used to optimize experimental approaches and protocols and to test different hypotheses about the underlying biological mechanisms. Finally, a validated mathematical model can be used to perform in silico experiments that might be hard or impossible to do in the laboratory. In this chapter we present a case study of a systematic modelling approach applied to the thiamine uptake system of the yeast Saccharomyces cerevisiae. This example is part of our broader effort to model the whole of thiamine metabolism in yeast, which involves several additional processes such as thiamine utilization, biosynthesis and gene regulation. Our main goal is to describe how systematic modelling has improved the knowledge about the system under study.