The Biomolecular NMR facility at The Scripps Research Institute is one of the foremost in the United States. Scripps has made an extraordinary investment over the past two decades in building and equipping this facility but the electronics consoles on many of the spectrometers are now obsolete and need to be replaced. This proposal requests funding to replace the obsolete 1997-vintage DRX console on our most sensitive instrument, an 800 MHz spectrometer equipped with a cryogenic probe, with a state-of- the-art Avance III console. The new electronics console is expected to increase the sensitivity of the instrument by as much as 25%, provide enhanced radiofrequency generation and phase stability to improve the performance of demanding pulse experiments, and enable the implementation of new 2H relaxation and non-linear sampling experiments that simply cannot be performed with our existing instrumentation. The upgraded electronics will directly benefit the NIH-funded research programs of four major user groups (Dyson, Williamson, Wright, and W|thrich) and two minor users (Kelly and Otomo). These research programs are probing fundamental questions in structural biology and are addressing key issues related to human health and disease. The enhanced capabilities of the instrument will facilitate ongoing and future research on the underlying molecular basis of cancer, myotonic dystrophy, neurodegeneration, amyloid diseases, and infectious disease.