Project Summary Long-range (>10 µm) transport of electrons along networks of G. sulfurreducens protein filaments, known as microbial nanowires, has been invoked to explain a wide range of globally important redox phenomena. The remarkable electronic conduction capability of those nanowires has sparked a great deal of interest in the medical application space, such as building biocompatible materials and biosensors. For over a decade, G. sulfurreducens nanowires were thought to be bacterial type IV pili, supported by many indirect genetic and biochemical observations. Recently we showed that these conductive nanowires are not made of type IV pilins. Instead, these structures are a polymerized multi-heme c-type cytochrome, such as OmcS and OmcE, which have never been characterized before. Currently, our knowledge of cytochrome appendages is still very limited. This study aims to address fundamental scientific questions about cytochrome filaments in respiring prokaryotes and apply our discoveries to the general medical field. Specifically, I will: A) identify and characterize novel cytochrome filaments in bacterial and archaeal strains through bioinformatics searches followed by microscopic validation. B) Study the conduction mechanism of these filaments by high-resolution cryogenic electron microscopy (cryo-EM) and conductivity measurement. C) Design self-assembled conductive nanowires based on structural knowledge. The results have and will continue to advance our understanding of cytochrome nanowires, and self-assembling nanowire products can be used in many future biomedical applications.