Past Research

Developing Instrumentation for Dynamic Nuclear Polarization (DNP) NMR to Address Biologically Relevant Questions

Current treatment of HIV/AIDS entails a highly active antiretroviral therapy (HAART) which keeps the HIV replication process suppressed to a point where the virus in the plasma is undetectable. However, HAART is not a complete cure due to remaining latent reservoirs of HIV. Recent studies have shown that prostatin and the more potent bryostatin are activators of protein kinase C (PKC) and have the ability to activate latent HIV. However, these PKC activators have potent side-effects because they not only activate the latent HIV, but they also activate many other pathways in the body. Thus, a better understanding of the structure and dynamics of PKC activators, such as bryostatin, is needed.  

Dynamic nuclear polarization (DNP) is an excellent tool for enhancing the sensitivity of NMR experiments to examine the atomic level structures of medically relevant molecules such as proteins and drugs. This gain in sensitivity is due to the polarization in the electron paramagnetic resonance spins (EPR) being transferred to nuclear spins. The transfer from electron spins to nuclear spins only happens efficiently in temperature conditions below 100 Kelvin (-173.2 °C/-279.7 °F). Not only do these temperatures help the transfer of polarization from electron spins to nuclear spins, they also increase magnetic resonance sensitivity since lower thermal temperature means lower energy and so, more spins will occupy the lower energy level. However, current NMR techniques have not fully taken advantage of these cryogenic temperatures to design new drugs. 

In order to run NMR experiments with better efficiency, our group implements a gyrotron that can be easily tuned and is capable of emitting a wide range of electromagnetic waves to have a better control over the EPR spins. In addition, we build transmission line style NMR probe capable of handling multiple nuclei and high power (1 kilowatt). Our current workhorse probe is capable of handling four nuclei (1H, 31P, 13C, 15N)  simultaneously. This probe can generate a γB1 of 312 kHz and is capable of experiments from 8 Kelvin to room temperature.