Investigating and Utilizing Microbial Appendages - Project Summary This research program seeks to understand the fundamental mechanisms underlying the production, regulation, and function of microbial appendages, such as flagella and pili, and to use this knowledge to design self-assembled nanofibers for various biochemical applications. Microbial appendages, including flagella and pili, are essential structures that prokaryotic cells invest significant energy in producing. These appendages extend microns from the cell surface and play crucial roles in bacterial survival, adaptation, and virulence. Our recent work has focused on elucidating the structural and functional diversity of flagellar outer domains, revealing their roles in diverse functions such as surface attachment, colonization, and biofilm formation. We have also discovered new types of appendages, such as the extracellular cytochrome nanowires in both bacteria and archaea, which expands our understanding of microbial electron transfer mechanisms. Additionally, we have made progress in understanding the dynamics of pili production, demonstrating how a single pilin subunit can assemble into distinct pilus structures under different conditions, highlighting the adaptability of these structures. In the next five years, we plan to investigate several key areas that align with the overall vision of this project. One focus will be to uncover the interaction between the membranous sheath and a particular class of flagella outer domains in H. pylori. Understanding this interaction could lead to novel strategies for disrupting bacterial colonization and reducing the risk of severe complications. We also aim to discover and characterize a new class of pili in cyanobacteria, exploring their role in colony formation, toxin interactions, etc. Finally, we will combine our knowledge of cytochrome nanowires with self-assembled peptides to design self-assembled conductive nanowires. Our research program has the potential to significantly advance our understanding of microbial appendages and their roles in bacterial physiology and pathogenesis. Furthermore, the development of self-assembled peptide nanofibers could lead to innovative biomaterials with broad applications in biomedicine, opening new avenues for treatment and technological advancement.