This application requests funds for an intermediate voltage cryo- electron microscope for the imaging of biological molecules and macromolecular assemblies. This instrument, with its 500-1000-fold increased brightness over other available microscopes enables operation in a high-coherence mode that virtually eliminates the damping of the contrast transfer function at high resolutions, and greatly enhances the resolution to which images can be made. The microscope will be used for studies that include the structure of prokaryotic and eukaryotic ribosomes; mitochondrial outer membrane pore; skeletal fast twitch calcium release channel; and cytoplasmic dynein motion. For all these projects this microscope will produce significantly improved images, providing a much more highly detailed vision of the structures of these biological systems.
