Cryo-EM of Helical Protein and Nucleoprotein Polymers at Near Atomic Resolution

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Abstract 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.