Our research focuses on using evolutionary techniques to engineer biopolymers and cells. We select binding species (aptamers) and ribozymes from random sequence populations. We then attempt to apply the selected species to solve real-world problems. For example, we have selected aptamers that can interact tightly and specifically with the Rev protein of HIV-1, and are exploring how these aptamers can be used to block viral replication. Similarly, we have selected ribozymes that can be allosterically activated by a variety of effectors, including proteins, and are using these ribozymes to design and build biosensors that may be useful in diagnosing disease. We also have developed methods for evolving proteins with novel functions, and are similarly attempting to use the evolved proteins in medical or biotechnological applications. Finally, we have extended our evolutionary research approaches to whole organisms, and are attempting to evolve ‘unnatural’ E. coli (unColi) that can augment their genetic codes with unnatural amino acids. It is hoped that strains of unColi will allow us to generate enzymes with previously unknown or inaccessible structures or activities. While we have largely used evolutionary engineering to effect these changes, we are increasingly relying upon bioinformatics, modeling, and rational design to accelerate evolutionary processes.