Our research focuses on establishing structure-function relationships in large viruses and macromolecular complexes using electron cryomicroscopy (cryoEM) and three-dimensional (3D) reconstruction as the primary tools. The first area of our research involves plant and insect reoviruses, including rice dwarf virus and cytoplasmic polyhedrosis virus. These median-sized viruses of high stability share many features in viral assembly to their human counterparts and thus are ideal model systems for developing method for 3D reconstruction, as well as for establishing the structural basis of reovirus assembly and infection. The cryoEM images of these viruses have been recorded to 4-Å resolution using a 400kV electron cryomicroscope. Our research aims at developing novel computational procedures to reconstruct the 3D structures of these viruses to an unprecedented detail. The second area of our research is human herpesvirus (HHV), a family of dsDNA viruses of extraordinarily large size and high complexity. The eight types of HHV are causative agents of cold sores, blindness, cancers and life-threatening conditions in immuno-suppressed individuals. Our previous 3D structure studies of the HHV-1 capsids have elucidated the structural and functional roles of capsid proteins in viral assembly. Current effort focuses on the more clinically important or newly emerging herpesviruses including cytomegolovirus (HHV-5), HHV-6 and HHV-8. Comparative 3D structural analyses provide a unified picture of the molecular mechanisms underlying the morphogenesis and infectivity of all herpesviruses.