DNP-NMR technology development
Solid-state NMR (ssNMR) is unique in its ability to measure interatomic distances and characterize molecular dynamics within materials, biomolecules, and complex heterogeneous environments, such as membranes and even intactcells. The drawback of ssNMR is inherently weak sensitivity, which can be increased by transferring signal intensity from electron spins to nuclear spins in a process known as dynamic nuclear polarization (DNP). However, the existing technology only provides a fixed microwave frequency during EPR/NMR, and the inability to tune the microwave frequency results in inefficient DNP transfers at higher temperatures and higher fields. We are improving high-frequency DNP instrumentation and making this instrumentation more available to the scientific community by:
- Implementing frequency-agile gyrotrons (microwave sources) to generate microwave-chirped pulses.
- Explore new designs and implementation of novel spherical rotors to access higher spinning frequencies.
- Designing dielectric lenses to focus the microwave beam to enhance our ability to coherently control electrons.
- Development of new DNP methods: Electron decoupling, frequency-chirped DNP using pulsed microwaves. We are currently also developing technology for the implementation of pulsed DNP.
- Development of high field magnet technology.
Applications of DNP-NMR technology
Improved ssNMR sensitivity will particularly benefit the structural characterization of membrane proteins. We are especially interested in understanding how the structure and interactions between the membraneprotein PKC (protein kinase C) and PKC modulatory drugs influences the reactivation potential of these drugs as HIV cures. We are also interested in understanding HIV reactivation and PKC modulation in intact human cells. We develop unique fluorescent DNP reagents and explore their use in intact cells towards gaining a better understanding of the HIV reactivation process in the cellular context, at the atomic level.