This NSF MRI award funds the acquisition of a quadruple inverse (QCI) cryoprobe to substantially increase the sensitivity of the high-resolution 600 MHz NMR instrument in the NMR Facility at the Medical University of South Carolina (MUSC). The proposed QCI has all the capabilities of state-of-the-art probes for biomolecular NMR including optimized direct detection of 1H, 13C and 31P frequencies, simultaneous irradiation at 1H, 2H, 31P, 13C, and 15N frequencies, and actively shielded z-axis gradient. The versatile QCI configuration permits investigations of nucleic acids and proteins without changing probes and without compromising flexibility. The three- to four-fold increase in sensitivity afforded by cryoprobes over conventional room temperature probes translates into nine- to sixteen-fold reduction in acquisition times, thereby significantly enhancing throughput. An added benefit of increased sensitivity of the cryoprobe is the lowered sample concentration requirements. Thus, studies of samples that are expensive to produce, prone to aggregate at high concentrations, or are otherwise chemically unstable are readily facilitated, thereby opening up the possibility of tackling research problems previously inaccessible using existing NMR instrumentation. The QCI facilitates novel avenues for NMR methods development. Phosphorylated metabolites have been difficult to study through direct 31P detection because of low sample concentrations. With the increased sensitivity available with the requested cryoprobe featuring a cooled 31P preamplifier, studies on such metabolites will provide new information not available using current technology. The successful acquisition of a QCI-cryoprobe opens new opportunities for fundamental studies that are important for RNA-protein recognition and corresponding underlying principles of affinity and specificity.

The impact of the QCI acquisition reaches across many disciplines and institutions of higher education in SC. MUSC, the College of Charleston (CofC), the University of South Carolina Columbia (USC), and Clemson University (CU) have a long history of cooperation and this inter-institutional project strengthens the collaborative research and education programs of all four universities. The requested instrumentation becomes part of MUSC's shared NMR facility and more effectively meets the growing scientific needs of as many as eleven academic and governmental research groups working in basic science programs at USC, CU, and three Charleston institutional locations (MUSC, CofC and the Hollings Marine Laboratory (HML)). Projects that benefit from the acquisition of the QCI include structure, function and dynamics studies of RNA and proteins as well as structure determination and macromolecular interactions of bioactive lipids and metabolites. The diverse and interdisciplinary research enabled by a spectrometer equipped with a QCI provides a rich learning environment for graduate students, undergraduates at CofC and a fertile training ground for undergraduates participating in MUSC's Summer Undergraduate Research Program (SURP). Students are exposed to ongoing, cutting-edge NMR research, integrated within the Center for Structural Biology at MUSC. Faster NMR data acquisition generally facilitates teaching efforts utilizing classroom projections from the remotely operated NMR console. A key outreach effort, the bi-annual Charleston NMR Summer Camp, involving the PI and researchers at the HML also benefits from the QCI. The Camp's long-term goal is to attract and develop the next generation of scientists with a passion for cutting-edge NMR in SC, with special emphasis on SC's four-year colleges and minority-serving institutions. It complements MUSC's College of Graduate Studies commitment to recruiting and retaining underrepresented minorities.

Project Report

The Nuclear Magnetic Resonance (NMR) facility at the Medical University of South Carolina (MUSC) in Charleston, SC, supports researchers in their efforts to investigate specific arrangements of atoms within molecules and to study interactions between molecules in solution. Access to state-of-the-art NMR equipment is essential to scientists who are carrying out research at the cutting edge. MUSC’s NMR facility serves as a research resource and shared instrument facility for researchers at MUSC and in the region. It strives to help the local and regional community to realize the potential of NMR spectroscopy. This award supported the acquisition of supercooled probe technology for a 600 MHz NMR spectrometer that offers a large increase in sensitivity in NMR spectroscopy. The cryoprobe-equipped instrument rapidly became an integral part of scientifically diverse projects that were previously limited by small amounts of sample and prohibitively long experiment times. Disciplines that already benefited from the transformative power of the cryoprobe technology range from organic chemistry, microbiology, virology and drug discovery to structural biology. Collaborations facilitated through the shared equipment expose trainees and faculty across institutions of higher education in South Carolina (Clemson University, College of Charleston, MUSC and University of South Carolina) to the scientific capabilities of this outstanding and versatile probe technology. Together with federal partners from the National Institute of Standards and Technology at the local Hollings Marine Laboratory (Charleston, SC), MUSC researchers established the bi-annual Charleston NMR Summer Camp that will benefit from data collected with the instrumentation financed under the auspices of this project. Our NMR facility staff recently initiated another outreach activity and started touring classes from local High Schools to expose them to the purpose-built NMR facility. Collectively, the long-term goal is to attract and develop the next generation of scientists with a passion for cutting-edge NMR in SC, with special emphasis on SC’s four-year colleges and minority-serving institutions.

National Science Foundation (NSF)
Division of Biological Infrastructure (DBI)
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Robert Fleischmann
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Medical University of South Carolina
United States
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