Abstract Boston University School of Medicine (BUSM), a high-ranking medical school and research institution, has a long history of leadership and excellence in the study of the ultrastructure of the nervous system and the eye in normal and pathological conditions. Currently, 14 NIH-funded investigators from 6 departments/centers (Anatomy & Neurobiology, Pharmacology, Ophthalmology, Medicine, Biochemistry, and the Center for Regenerative Medicine) at BUSM need access to a transmission electron microscope (TEM). These investigators' research projects span multiple fields, including aging, neurodegenerative disease (Alzheimer's, Huntington's and Parkinson's), brain injury, cortical connectivity, diabetes, glaucoma, uveitis, tissue repair and inflammation. Each of these projects employ modern, high-throughput EM techniques to link ultrastructure and subcellular mechanisms to studies using other behavioral, molecular, and confocal and light microscopy techniques. However, although there are two TEMs currently available at BUSM, one is used primarily for clinical diagnostic purposes, and the other is optimized for cryogenic-EM and heavily prioritized for intra-departmental and structural biology research group use. Thus, the availability of these TEMs for use by other NIH-funded researchers at BUSM is very limited, and their TEM work must either be done at TEM facilities in nearby institutions with limited availability or be outsourced to other institutions at high cost, which significantly hinders the productivity of current-NIH funded investigators and the training of graduate students and post-doctoral fellows in TEM techniques. Therefore, there is a very significant need for a TEM optimized for high-throughput imaging of large tissue blocks in multiple research labs and departments at BUSM. The requested instrument will significantly increase and accelerate the productivity of NIH-funded projects and also enable these expert investigators to obtain pilot data for new proposals. Investigators' expertise in this proposal span multiple disciplines and scales of techniques, garnering the ability to gather multi-scale data at the systems and cellular levels. Given the highly-collaborative environment at BUSM, the requested TEM will facilitate the much-needed collaborative multidisciplinary studies to make significant advancements within each of the respective fields represented by the investigators in this proposal. The purchase of the JEOL JEM1400S-Flash equipped with accessories that enable high-throughput, high-contrast, semi-automated image montaging, and 3D serial imaging will also facilitate the much-needed training of the next generation of biomedical scientists proficient in EM. This will greatly benefit both BUSM, an institution committed to high quality graduate education, and the biomedical research workforce nationally, by allowing expert investigators to continue to be highly productive in ultrastructure and related research while continui...