CAREER: Structural Biology in a Cellular Context with High Sensitivity NMR

Washington University, Saint Louis MO

Investigators

Abstract

An award is made to Washington University in St. Louis to develop new instrumentation for the structural determination of proteins and biomolecules within cells. This technology platform will impact a diverse set of fields including biology and materials science, enabling the study of molecular structures in contexts that have hereto been inaccessible. Understanding biomolecular structures within cells is essential to designing new chemical processes for energy and raw material production from sustainable environmental sources. Unraveling the structures of molecules in cells will also be key to designing the next generation of drugs to combat infectious diseases, cancer, heart disease, etc. Graduate and undergraduate students implementing this powerful instrumentation will gain diverse skill sets ranging from electromagnetic instrumentation design and magnetic resonance spectroscopy to structural biology and biochemistry. The instrument design and biological applications of this research will be taught to graduate and undergraduate students in a magnetic resonance course. Dissemination of this technology will be achieved through a collaboration with industrial partner Bride12 Technologies. In order to achieve and understanding of biomolecular structure at the atomic level within cells, it is necessary to achieve a gain in NMR signal strength of >10,000 fold. Novel magic angle spinning (MAS) NMR instrumentation will allow cooling of NMR samples to extremely cold temperatures of <10 degrees Kelvin using a combination of helium and nitrogen cryogens. New fast-frequency tuning high-power microwave sources will enable pulsed electron paramagnetic resonance in the 200 GHz band in combination with high-resolution NMR. Together, these new cryogenic and microwave technologies will yield a boost in the voltage of NMR signals by a factor of >10,000, compared to the random fluctuation of voltage that results in noise. Such a gain in NMR signal strength will significantly expand the scope of molecular structures that can be studied with NMR, and also drastically shorten the duration of NMR experiments.