Mentor: Robert Tycko, Ph.D. | robertty@mail.nih.gov
Lab
Solid State NMR and Biomolecular Physics Section, Laboratory of Chemical Physics, NIDDK
NIDDK

New Technology for Time-Resolved NMR and for High-Resolution MRI at Low Temperatures

Our lab develops and applies new methods and new technology for structural studies of protein assemblies by nuclear magnetic resonance (NMR) spectroscopy and for magnetic resonance imaging (MRI) at the micron scale.  Recent work involves experiments at temperatures in the 5-30 K range, where NMR and MRI signals are stronger than at room temperature by factors of 10-60 and where signals can be further enhanced by a phenomenon called “dynamic nuclear polarization” (DNP).

In our time-resolved NMR experiments, we have developed novel methods for monitoring processes such as protein folding or self-assembly, in which the molecular structures of proteins undergo major changes on the millisecond time scale.  The experiments are based on home-built equipment for rapid mixing of protein solutions, rapid inverse temperature jumps, and rapid freezing.  In our micron-scale MRI experiments, we have obtained the world’s first MRI images with isotropic spatial resolution below 2.0 microns by combining low-temperature DNP with radio-frequency microcoils and other tricks.

Progress in both areas of research depends on further developments in equipment, measurement protocols, and computational methods for data analysis.  Progress also depends on the production of appropriate samples by methods of molecular biology or chemical synthesis.  Thus, this research is highly multidisciplinary, involving the design and fabrication of instrumentation, electronics, chemistry, biology, mathematics, computer programming, numerical simulations, etc.

The BESIP student will participate in aspects of this multidisciplinary research that align most closely with the student’s interests and background, and that will contribute most directly to the evolving needs of our lab’s current projects.