? We are requesting funds to purchase an electron microscope to replace our current 17-year-old one that has become increasingly unreliable. The proposed microscope will be used by a group of 11 users primarily from the Departments of Otolaryngology-Head & Neck Surgery and Ophthalmology at the Johns Hopkins University School of Medicine. A total of 13 projects will be supported by 8 RO1, 2 KO8, 1 K23, and several nonfederal grants. The purchase of this microscope is crucial for the continued progress of research supported by NIH programs. The breadth of the projects is broad but unified by a foundation in structural neurobiology. Projects include (a) studies of the synaptic organization and plasticity of the mammalian auditory system; (b) histopathologic studies of the human eye; (c) ultrastructural examinations of sensory receptors and associated structures of the eyes and ears in normal, pathologic, and/or genetically altered animals; (d) localization of molecules (cytoskeletal and synaptic proteins, growth factors, or ion channels) in eyes and ears that pertain to normal function; (e) identification of growth factors that enhance photoreceptor growth; and (f) gene transfer experiments involving factors that influence laryngeal nerve growth, reinnervation, and muscle development. Conceptual and technical approaches utilized by the different research groups emphasize the common themes that link these various projects. Our work is highly dependent upon electron microscopy, and the proposed purchase will provide its users with a reliable instrument that is equipped with a number of advanced features that are currently unavailable anywhere at our institution. Award of this instrument will have an immediate and positive effect on the productivity of these projects. It will serve to catalyze interdisciplinary discussions among users, provide a valuable teaching tool for our trainees, and enhance the progress of biomedical research on hearing, vision, and voice. ? ?