Our research group focuses on understanding complex protein machines involved in the biogenesis of the bacterial cell envelope in E. coli. We study these machines because they are fundamentally important to the biology of bacteria and they may provide new antibiotic targets. They also present enormous intellectual and experimental challenges. In order to understand these machines, we must bring to bear a wide range of scientific approaches, from bacterial genetics to biochemistry to complex organic synthesis. Genetics combined with biochemistry initially allowed us to identify key components of some of these machines, while others we study have been established several years. Our challenge now is to determine how these machines function at a detailed chemical level and to explore their potential as antibiotic targets. Sophisticated organic synthesis to make very large and complex substrates and to design inhibitors will be required in that effort.