700 MHz NMR console and probe upgrade for biomolecular and 19 F NMR studies at theUniversity of Minnesota - This Shared Instrumentation Grant application requests funds to upgrade the 700 MHz NMR spectrometer at the Minnesota NMR Center (MNMR), a University of Minnesota core facility that serves as a hub for high-field NMR spectroscopy. The existing instrument is currently equipped with a 22-year-old Bruker Avance I console and TXI cryoprobe that are now obsolete, increasingly unreliable, and no longer capable of supporting many state-of-the- art experimental experiments. Hardware failures, including cryoplatform instability, auto-tuning issues, and console communication problems, have significantly reduced instrument availability and limited its utility, even as user demand continues to grow. The manufacturer no longer guarantees part availability or technical support for this aging platform, posing an ongoing risk to research continuity. The proposed upgrade includes a Bruker Avance NEO console and QCI-F CryoProbe. This combination will restore the instrument to full operational capacity and provide a significant technical leap in sensitivity, stability, and experimental flexibility. Specifically, the upgraded system will deliver improvements in 13C sensitivity, enable simultaneous 1H decoupling during 19F detection, and support 19F-detected experiments. These capabilities will open new experimental avenues for investigators studying conformational exchange, ligand screening, protein- small molecule interactions, intrinsically disordered proteins, and macromolecular dynamics on the µs–ms timescale. In addition, the system will support automation features, as well as compatibility with TopSpin 4.x software and the existing autosampler, further improving efficiency, reproducibility, and throughput. MNMR currently supports 32-36 active research groups each year, whose work results in 30-40 peer-reviewed publications annually and is supported by 16-20 NIH-funded projects. The user base spans five colleges and includes researchers from more than a dozen departments across the Twin Cities campus. Current users apply NMR to a broad spectrum of biomedical problems, including DNA repair, cancer signaling, infectious disease, metabolism, and drug discovery. The MNMR Center is also an important training resource, providing hands-on experience in high-field NMR methods for graduate students, postdoctoral fellows, and technical staff. The requested upgrade will alleviate the significant pressure currently placed on the Center’s two 600 MHz instruments, which are nearing full capacity due to users shifting away from the outdated 700 MHz instrument. By restoring this underutilized instrument to full functionality and enabling advanced biomolecular and small molecule NMR experiments, the upgrade will enhance access, expand capacity, and improve data quality for a broad and growing community of NIH-funded investigators. This investment will not only strengthen ongoing research programs but also attract new users to the MNMR Center. Thus, this proposal addresses an urgent instrumentation need and will have immediate and lasting impact on NIH-supported research across structural biology, chemical biology, and biomedical sciences at the University of Minnesota.