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Principal Investigator: William W Brey
Organization: FLORIDA STATE UNIVERSITY
Fiscal Year: 2024
Award: $1,052,841
Funding agency: National Institute of General Medical Sciences
Nuclear magnetic resonance (NMR) spectroscopy is a unique set of experimental tools for understanding
the intricacies of biology, from macromolecular complexes to complex mixtures, from atomic resolution structure
to dynamics on timescales of picoseconds to seconds, from chemistry to functional mechanisms and kinetic
processes. No other technology has such breadth and potential for basic and applied research and for interfacing
with other technologies, such as X-ray crystallography, small angle X-ray scattering, Cryo-EM, mass
spectrometry, and many other spectroscopic and analytical tools. Structural characterization serves as the
framework for using NMR to understand biological activities, protein-protein and protein interface interactions,
functional mechanisms, and kinetic models. Dynamics can be exceptionally well characterized by NMR, which
can lead to detailed understanding about how proteins and other macromolecules function, how complexes are
formed, and how certain kinetic processes and rates are achieved. The solution NMR spectroscopy of complex
mixtures is particularly useful in combination with mass spectrometry for metabolomics and other complex
mixtures, whereas solid-state NMR (ssNMR) is uniquely capable of measuring chemical shift and quadrupolar
tensors to provide insights into chemical biology. Here, we focus on the frontiers of NMR technology made
possible by recent breakthroughs in materials research and instrumentation, and their implementation for a broad
user community pursuing fundamental questions at atomic resolution at the forefront of biomedical research.
Three Technology Development Projects (TDP) advance the sensitivity of NMR, each featuring novel
technologies. TDP1 features the use of high temperature superconductors (HTS) for RF coils, leading to high
sensitivity for solution NMR spectroscopy. TDP2 takes advantage of our 600 MHz MAS-DNP NMR instrument,
which will provide enhanced sensitivity through the transfer of magnetization from electrons to protons. New and
much more robust DNP probes with expanded temperature ranges will be developed. TDP3 uses the 36 T Series
Connected Hybrid (36T-SCH) and all-HTS 32 T superconducting (32T-SCM) magnets for ssNMR and solution
NMR spectroscopy – the 36T-SCH is the highest-field NMR spectrometer in the world, and the 32T-SCM will be
the highest-field spectrometer with low-temperature (4-30 K) capabilities for NMR explorations of biosolids.
These platforms will lead to dramatic enhancements in sensitivity and spectacular reductions in signal averaging
times. The science will be driven by a select team of ten scientists with Driving Biomedical Projects (DBP), and
over 30 Collaborative and Service Projects (CSP) and Technology Partnership Projects (TPP) that span a very
broad range of biomedical and biochemical research areas. A major team effort will be placed on training a new
generation of NMR users through annual workshops, as well as dissemination through publications and
presentations at meetings, a wide variety of scientific organizations, news media, a dedicated website for this
Resource, training and educational activities, and posting of training lectures and videos of demonstrations.
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