A long-term goal of systems biology, to be discussed in Chapter 8, is the complete elucidation of the gene regulatory networks of a living organism. Indeed, this has been a Holy Grail of molecular biology for several decades. Today, with the availability of complete genome sequences and new genomic technologies, this goal is within our reach. As a first step, DNA microarrays can be used to produce a comprehensive list of the genes involved in defined regulatory sub-circuits in well-studied model organisms such as E. coli. In this chapter we describe the use of DNA microarrays to identify the target genes of regulatory networks in E. coli controlled by global regulatory proteins that allow E. coli cells to respond to their nutritional and physical environments. We begin by describing the design and analysis of experiments to examine differential gene expression profiles between isogenic strains differing only by the presence or absence of a single global regulatory protein which controls the expression of a gene regulatory circuit (regulon) composed of many operons.

Before we can identify the genes of any given regulatory circuit we need to be able to measure their behaviors with accuracy and confidence under various treatment conditions. However, because of the influences of experimental and biological errors inherent in high-dimensional DNA microarray experiments, discussed in Chapter 4, this is not a simple task.