Introduction

In Chapter 7, we studied three global regulatory proteins in E. coli (Lrp, IHF, and Fnr). These proteins are responsible for the direct regulation of scores of genes, and through the use of DNA microarrays we were able to establish a fairly comprehensive list of the genes each protein regulates with good confidence. These results have an intuitive graphical representation where nodes represent proteins and directed edges represent direct regulation. Intuitively these simple graphs should capture a portion of the complete “regulatory network” of E. coli. Within this network, Lrp, IHF, and Frn are like “hubs”, to use an analogy with the well-connected airports of airline flight charts, three of the two dozen or so hubs in the E. coli regulatory chart. In spite of their simplicity, these diagrams immediately suggest a battery of questions. How can one represent more complex indirect interactions or interactions involving multiple genes at the same time? Is there any large-scale “structure” in the network associated with, for instance, control hierarchies, or duplicated circuits, or plain feedback and robustness? What is the relationship between the global regulatory proteins (i.e., the hubs) and the less well connected nodes? How are the edges of the hubs distributed with respect to a functional pie chart classification (biosynthesis, catabolism, etc.) of all the genes?

These questions point towards an ever broader set of problems and ultimately whether we can model and understand regulatory and other complex biological processes from the molecular level to the systems level.