Abstract We aim to greatly extend our existing studies in the proposed period, capitalizing on the great advances in electron cryo-microscopy that have been due to improved direct electron detectors, better software, and faster computers. The studies will include pili and flagellar filaments from pathogenic bacteria, mating pili, type III and IV secretion systems, and archaeal viruses infecting hosts living in the most extreme environments. In addition, we will continue studies of small molecules and peptides that self-assemble into tubes and filaments, many with anticipated biomedical applications. Our work on actin and why the sequence has been so highly conserved will continue. By working on many disparate polymers, we expect to develop more general methods that can be applied by others to helical polymers in biology. Since large numbers of such polymers exist, ranging from cytoskeletal filaments to amyloid to helical viruses (such as Ebola) the potential significance of this work is enormous and likely to have a great impact.

Narrative This project is aimed at understanding the structure and function of a large number of helical protein and nucleoprotein filaments, ranging from actin in human muscle to helical viruses that infect organisms living in nearly boiling acid. Some of the studies are likely to have a direct and immediate impact on human health, such as those involving the bacteria responsible for meningitis and food poisoning, while others will have longer range impact including new tools for biotechnology.