The goal of this proposal is to provide a high resolution Field Emission Scanning Electron Microscope (FE- SEM) that is dedicated to research in the biomedical sciences. This instrument will support interdisciplinary investigations in many areas, including critical NIH roadmap initiatives in nanotechnology and medicine. All of the major user projects described in this grant will definitely benefit from a modern high resolution SEM that can operate over a large range of accellerating voltages. This proposal represents a major, institution-wide effort to upgrade scanning electron microscopy infrastructure. The institution has pledged continued support for the housing, maintenance, and utilization of the proposed FE-SEM well into the future. The new SEM will provide capabilities not currently available in a shared resource laboratory at UNC-CH. Other SEMs at UNC- CH are either over 10 years old or not in open facilities. The new FE-SEM will be placed in the Microscopy Services Laboratory (MSL) - a long-standing, excellently-run microscopy facility that is dedicated solely to the provision of advanced microscopy resources to the research community. Based on increasing usage of the MSL's SEM over the past four years, on the number of investigator inquiries about using SEM in research, and on the types of research questions being asked, this is the appropriate time to seek funding for an advanced SEM that will cover current research needs and will provide new techniques and opportunities for the future. Relevance Modern high resolution scanning electron microscopy will be used for many medically related research purposes such as: the study of nanoparticles created for drug delivery and their interaction with host cells (Dr. Fischer), the structure of the blood clotting protein fibrin (Dr. Wolberg), examination of how disease causing bacteria associate with human cells to cause disease (Dr. Kawula), the interaction of pollutant particles with the human airway (Dr. Carson), tiny variations of the cell surface of the gonorrhea-causing organism and how these variations lead to resistance to antibiotics (Dr. Nicholas), examining the way cells form thin filaments in order to move - a feature important in the spread of cancer cells (Dr. Cheney), variations in cell structures involved in detecting sugar molecules and how these changes affect a cell's growth and behavior - important in diabetes research (Dr. Jones), how specific genes in a plant (Arabidopsis, all of whose genes are known), affect embryonic development - important in understanding development in all eukaryotes, including humans (Dr. Reed), and the detailed structure of injured blood vessels and how several blood components interact to heal the vessels (Dr. Whinna). New, high resolution scanning electron microscopes make it possible to study the ultra-fine structural details of big molecules, such as fibrin, and the tiny variations in the surfaces of micro- organisms, cells, and tissues in a way that can enhance our knowledge of these structures and lead to improvements in our understanding and treatment of disease. ? ? ?
