We aim to greatly extend our existing studies in the two current R01s (Actin and Nucleoprotein Complexes) in the proposed period, capitalizing on the advances in electron cryo-microscopy that have only recently become possible with direct electron detectors. In addition, we will work on a number of projects that are outside the scope of the present R01s, but involve bacterial pathogenesis and thus have great relevance to human health: Type IV pili, Type II Secretion System, bacterial and archaeal flagellar filaments. 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.
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 cholera, while others will have longer range impact, including new tools for biotechnology.
