? The North Dakota State University-COBRE (NDSU-COBRE) program is focused on the study of proteases in disease. The scientific focus of the NDSU-COBRE Center is the development of therapeutic inhibitors for a family of zinc-dependent enzymes, matrix metalloproteinases (MMPs). On the non-scientific side, the NDSU COBRE Center has dedicated a large part of its budget to Human Resources. The center aims to increase the number of faculty with biomedical research interests. Research activities in the Center are also designed to bring qualified technicians, postdoctoral associates, and students to North Dakota. ? ? Improvements in the area of equipment will allow the center to better address some of its major goals. The purchase of three key pieces of equipment is being proposed. Structural characterization of small organic molecules and biomolecules under investigation as part of the COBRE program require access to a modern mass spectrometer and a circular dichroism spectrometer. The existing nearly obsolete 12 year old mass spectrometer (electron impact, direct insertion probe, mass range of 600) is inadequate for the tasks at hand. Similarly, the center does not have routine access to a circular dichroism spectrometer, a key technique for analyzing conformation of the polypeptides to be used in the targeting project. The third instrument, a confocal laser scanning fluorescence microscope, will greatly enhance productivity of biological research in the COBRE program. Main directions include tracking MMPs in liposomes as delivery vehicles, cells, and tissues using immuno-fluorescence or quenched fluorescent substrates and monitoring subcellular disposition of fluorescent MMP inhibitors. The requested system uses multiple low energy high frequency laser beams to allow analyses in living cells. ? ?
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