The Egelman laboratory uses structural biology to understand the function and evolution of protein and nucleoprotein polymers. The main method employed is cryo-electron microscopy, which now allows for near-atomic resolution of biological polymers almost routinely. While I started as a graduate student looking at F-actin, the methods I helped develop have allowed for high resolution structural studies of many other polymers. I have been working on pili of pathogenic bacteria, which are an essential virulence factor. What has been surprising is that small numbers of amino acid changes can lead to large variations in quaternary structure, something that I have termed the lability of quaternary structure. This can be seen as a mechanism in evolution for the amplification of relatively small numbers of substitutions in the primary sequence of proteins. I have gone on using in vitro systems with peptides to show how dramatic these changes in quaternary structure can be. My laboratory has also been interested in protein polymers that resist the most extreme environments, such as pili on the surface of archaea that live in nearly boiling acid. Our studies of viruses that infect such hyperthermophilic acidophiles have revealed a packing of DNA in the A-form which appears to afford protection against such harsh conditions.