My major interests are in three-dimensional organization of large
macromolecular complexes and cell organelles by cryo-electron microscopy
(cryoEM) and cryo-electron tomography (cryoET). CryoEM allows to study symmetric
particles, e.g. spherical viruses, ordered assemblies (2D crystals, helical
arrays, etc.) and asymmetrical complexes in their native state. Unique
structures are studied using cryoET. I am interested in structural studies of
symmetrical as well as of asymmetrical particles by these techniques. Spherical
viruses are highly symmetrical, they infect variety of animal and plant cells.
The structure opens way to understand their mechanism of action and allows to
target specific epitopes to neutralize them. We have constructed
first-of-its-kind BSL-3 cryo-EM containment facility at UTMB where I have
collected images of Western equine encephalitis virus (WEEV), a biological
safety level 3 (BSL-3) agent. This is the first case of safe imaging of a BSL-3
agent in cryoEM. These images were used to determine the three-dimensional
structure of this important human pathogen at 1.3 nm resolution. Asymmetrical
assemblies are the most challenging case for structural studies. An example is
LDL, one of the major lipid carriers in blood. They have only one protein
component, apolipoprotein B-100, whereas the rest of the particle (78%) is
composed of various lipids. Amazingly, despite their high lipid content, they
are rigid enough to maintain their overall shape and characteristic lamellar
organization of the core. We found that the lamellae most likely consist of
cholesteryl esters; therefore with low or no cholesterol in LDL they do not have
striated cores and are less rigid. The findings provide an important hypothesis
that LDL depending on cholesterol content would interact with LDL receptors
differently causing lipid metabolic disorders.
Search PubMed for Dr. Sherman's publications.