Our research involves the coordinated application of high resolution
cryo-electron microscopy (cryoEM) and three-dimensional (3D) image
reconstruction techniques to answer questions about how viruses infect
a wide range of animal, plant, fungal, and bacterial hosts. We are
also exploring the molecular mechanisms by which hosts with an immune
system recognize virus antigens and by which viruses evade such a
defense system.

 The cryoEM techniques we use involve the preparation of thin,
unstained specimens suitable for transmission electron
microscopy. Vitrified samples are maintained at -160 degrees
Centigrade or below in the microscope while images are recorded under
low-irradiation conditions to minimize electron beam damage to the
specimen.  Micrographs are digitized and analyzed by computer to
combine information from up to hundreds of individual particle images
to reconstruct the 3D structure of each virus. CryoEM techniques are
popular since they provide a direct, objective approach to observe the
"native", hydrated structure of biological specimens (see figure).

 Exciting results have recently been obtained with several viruses in
which information obtained at low resolution (20-25 angstroms) from
cryoEM has been combined with high resolution information (3-4
angstroms) from x-ray crystallography. These studies provide a
detailed view of molecular interactions between viruses, antibodies,
and cellular receptor molecules. The results have provided new
insights about viral recognition by the immune system and the process
by which viruses recognize and attach to cells.