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Research Focus |
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The focus of my research program is the use of solid-state NMR for structural
and biophysical characterization of locally ordered protein networks. These
solid or semi-solid biomaterials have significant short-range order, but lack
the long-range crystallinity required for X-ray crystallography. Materials of
this type are central to many interesting biophysical questions. For example,
many physiologically important proteins are associated with phospholipid membranes.
The structure and function of these proteins may depend on interactions with
the lipid environment and may not remain intact when the protein is removed
from the membrane. Other locally ordered protein networks are implicated in
disease states, such as amyloid fibrils or the branched filaments found in cataracts
of the eye lens. Because they are typically insoluble and non-crystalline, these
materials are not amenable to structure determination by traditional biophysical
techniques such as solution-state NMR or single-crystal X-ray diffraction. They
may also have complicated intermolecular interactions that are not easily probed
by single-molecule studies. Therefore, locally ordered protein networks represent
a frontier of structural biology.
NMR spectroscopy of biological macromolecules is most effectively performed using high magnetic fields. These molecules have a large number of chemically inequivalent sites, and are usually only available in limited quantities. Therefore the higher sensitivity and resolution afforded by high-field magnets are required. However, working at high magnetic field presents several challenges for solid-state NMR. In the solid state, anisotropic interactions such as dipolar couplings and chemical shift anisotropy, which are averaged out in liquids by molecular tumbling, are typically removed by a combination of magic-angle spinning (MAS) and high power decoupling. High magnetic fields necessitate faster spinning, higher decoupling power, and better sample cooling, all while conforming to the space constraints imposed by the small bore sizes of high-field magnets. Designing and building experimental equipment is necessary in order to pursue challenging biological systems. My research group will further develop and use modern solid-state NMR methods to investigate biologically relevant locally ordered protein networks, using the 800 MHz spectrometer at UC Irvine. |
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