This is a re-submission application for a request for a new transmission electron microscope (TEM) to replace an existing one that was purchased in 1979. Our current TEM has been operating for 28 years. It is failing and is wholly inadequate to serve the research needs of our large active and expanding research community in the Department of Neurology at Massachusetts General Hospital. Many of our researchers work in neurodegenerative diseases including Alzheimer disease, Huntington's disease, and Parkinson's disease. Some of the current exciting topics we work on include the role of autophagy in clearance of disease proteins from neurons, the effects of disease proteins on organization and recycling of neurotransmitter receptors in animal models of disease, membrane permeability changes in traumatic brain injury, and the mechanisms underlying axonal demyelination. These and other research areas will be greatly enhanced by having a new TEM in our department. Some of us have long track records in using electron microscopy to study the nervous system. The lack of a reliably functioning TEM hinders our ability to plan new directions involving EM analysis and in training our young investigators in EM applications. Advances in TEMs have greatly improved especially in capability for self-alignment and digital imaging, which we lack in our TEM. We do not have access to other modern instruments at our institution. Since the first submission, I have received an institutional commitment of $141,000 to be used toward the purchase of a new TEM. We have also improved our application by making the recommended revisions suggested by the reviewers.
