PROJECT SUMMARY/ABSTRACT We request support to replace our aging and obsolete Varian Inova 600 MHz NMR console and failed cold probe. The 600 MHz NMR instrument at the University of Colorado School of medicine has been in operation for over 20 years, and in that time it has supported over 30 different federally funded research groups from five research institutions, including from local biotechnology companies. The products of this research have results in over 100 publications, many in high impact journals. However, the electronics console and probes have come to the end of their life, and are suffering from an increasing number of potentially fatal breakdowns, such that it can no longer perform critical experiments required by the current generation of NIH funded researchers. Further, Agilent/Varian have withdrawn from the NMR market and are winding down their support operations for NMR spectroscopy. At this time there is no clear mechanism to maintain operation of this spectrometer in the long term. A recent failure of the existing Varian coldprobe has accelerated the necessity to replace and upgrade this equipment. Purchase of a new Bruker Avance Neo console with the latest generation of cryoprobes will restore full operation of this spectrometer, allow researchers to take advantage of the latest development in NMR methods and hardware, and accelerate the pace of scientific discovery. This new console and probe will be installed on the existing Oxford Instruments 14T NMR magnet, and restore the spectrometer to full operations. The new console will ensure that the NMR Core facility is able to continue to provide essential services to its users into the future. The research and educational programs supported by the CU NMR facility cover a broad range of topics from cancer biology, infectious disease, neuro-degeneration and epigenetics through to more basic investigations into the role of protein dynamics, and fundamental NMR methods development. Many of the systems under investigation are high priority targets for drug discovery. The NMR core also supports the work of synthetic chemists in a range of fields including drug development, bioengineering, and biopolymers for medical devices and dental applications. Almost all of these research programs will benefit dramatically from the enhanced capabilities of the new system. The dramatic increase in sensitivity (~70%) improved salt tolerance and the ability to directly detect 13C, will permit study of more challenging systems, reduce costs and enhance research productivity. The critical importance of this instrument to the University of Colorado research community has been recognized with the commitment of substantial matching funds in support of this instrument.

PROJECT NARRATIVE NMR spectroscopy is widely used to study the structure, function and interactions of biological macromolecules implicated in diseases, and to discover new approaches to combat these diseases .The NMR equipment requested here will support a group of NIH funded researchers who have a wide range of interests in understanding and combating cancer, diabetes, neurogeneration and microbial infections. Additionally, it will be used to develop novel cutting edge methodology for the analysis of protein structure and dynamics, and to understand fundamental concepts of how proteins function.