This is an application for an analytical transmission electron microscope (TEM) to replace obsolete equipment in the Core Electron Microscopy Research Facility (CEMRF) at the University of Nebraska Medical Center (UNMC). The current TEM was obtained through a Shared Instrumentation Grant in 1985. The equipment has been maintained on a service contract but the support company is no longer able to guarantee replacement parts and operation. The microscope serves not only UNMC, but projects from the University of Nebraska at Omaha and at Lincoln, Creighton University, Boys Town National Research Hospital and local industry. A new electron microscope is essential for completion of numerous research projects funded by grants from NIH as well as NSF, DOD and other agencies. The most extensive use is focused on nanotechnology and its applications to drug delivery systems. This research group is headed by Dr. Alexander Kabanov, College of Pharmacy, who is a Co- Investigator on this grant. Other Co-Investigators on this grant and members of the campus- wide Users Committee are from the Eppley Cancer Institute and the Colleges of Dentistry and Medicine. Other on-going projects utilizing ultrastructural techniques involve: 1) role of mucins in the progression and metastasis of pancreatic and ovarian cancer cells;2) the mechanisms of separation and gene regulation of metastasis of cancer cells;3) cellular and synaptic mechanisms underlying the pathogenesis of HIV-1-associated dementia;4) ultrastructural analysis of umbilical cord blood derived dendritic cells compared with bone marrow and peripheral blood derived dendritic cells;and 5) ultrastructural examination of bronchial biopsies and stem cell therapy for epithelial repair. The proposed microscope as a key component of the CEMRF will continue to support the entire campus under the supervision of a multi- departmental Users Committee to insure its availability, maintain its productivity and continue to enhance the research capabilities available on this campus. Public Health Relevance: This research grant is for the purchase of a transmission electron microscope to replace very old equipment that is part of a Core Research Facility at the University of Nebraska Medical Center (UNMC). This is an essential piece of major equipment that is required to support a number of federal, state and locally-funded research projects at UNMC as well as other institutions in the region. Many of these projects dealing with nanomedicine, cancer biology, and stem cell therapy will have direct benefit to improving patient care and public health in general.