PROJECT SUMMARY/ABSTRACT Funding is requested to obtain a 900 MHz NMR Bruker Avance Neo console and cryoprobes to replace our obsolete Varian/Agilent system at the University of Colorado School of Medicine. The existing console and probes are over 17 years old and are now obsolete as Agilent has withdrawn from the NMR business. This 900 MHz instrument functions as a regional ultra high field NMR facility that serves the needs of users at multiple institutions through the Rocky Mountain West region of the United States. There is no other NMR instrument like it within 800 miles of Denver. In the last 10 years it has been used by 55 investigators from 20 institutions. The long term objectives of this application are 1) to ensure access to state-of-the-art NMR instrumentation and expertise in NMR spectroscopy for NIH funded researchers in the region, for the structural analysis of biological macromolecules and their interactions; 2) to provide training in state-of-the art NMR approaches to the next generation of biomedical researchers. The requested instrumentation provides enhanced sensitivity and technical capabilities that will allow the implementation of modern NMR experiments for the study of biological macromolecules in solution. This upgrade is essential to support the specific aims of NIH funded research of the users of this instrument that include fundamental studies of biological macromolecular structure and function, discovery of novel lead compounds for therapeutic interventions, to development of novel techniques for NMR spectroscopy studies. The requested instrumentation meets our long-term objectives by ensuring continued access for NIH funded researcher to the instrumentation required for their projects. This new instrumentation will dramatically enhance research capabilities and research productivity, and provide outstanding training opportunities to the next generation of biomedical scientists.