Marc Morais, Ph.D.
Pseudo-atomic structure of bacteriophage f29 determined using a combination of cryo-EM and X-ray crystallography.
Our laboratory uses a combination of cryo-electron microscopy, x-ray crystallography, and bioinformatics to elucidate the structures of complex macromolecular assemblies and machines. Our work focuses on virus structure and the general principles by which viruses self-assemble. In particular, we are interested in how virus self-assembly strategies can be targeted in the design of anti-viral therapeutics, and how these same strategies might be employed in the construction of nanomachines.
We are also interested in the structures of morphologically heterogeneous viruses with low, partial, or no internal symmetry. Many viruses relevant to human health fit this description, yet their structures remain largely unknown (Ebola, Hantaan, SARS corona, influenza, HIV, and Smallpox are but a few examples). We are developing methods to facilitate structure determination for these types of viruses.
Finally, we are interested in virus evolution and the viruses which infect the archea. Because hyperthermophilic archea possess metabolisms well-suited for the hot anaerobic conditions thought to prevail on an early earth, hyperthermophilic viruses likely played an important role in the early stages of evolution. Studies on genome organization, replication and regulation of gene expression indicate an evolutionary relationship between archeal viruses and viruses of mesophilic bacteria and eukaryotes. Verification of this hypothesis by sequence comparison is difficult because the rapid evolution of viral genes precludes detection of relationships over large evolutionary distances. However, structural similarity often persists during evolution in spite of vanishing sequence homology. Thus, the structures of viruses infecting hyperthermophilic archea should provide insights into virus origin and the evolution of viruses and cells.
Structure of a virus DNA packaging motor determined by cryo-EM. Two protein components of the motor are shown in green and blue, and an RNA component is shown in magenta. The atomic structure of DNA, shown as spheres, was modeled into its corresponding cryo-EM density. The motor tranlocates viral DNA into a preformed virus capsid.