DESCRIPTION: (Adapted from the Investigator?s abstract): Viral infection is a significant cause of human illness, ranging from relatively minor ailments such as the common cold to life threatening diseases such as cancer and AIDS. Thus, understanding the viral life cycle is an important component of any research program aimed improving human health. Despite considerable efforts, the details of virus assembly are not entirely clear. In particular, the mechanism by which the viral genome is packaged into the virus capsid remains obscure. Many of the tailed, double-stranded DNA (dsDNA) bactenophages use a molecular motor to tranlocate their genomes into a preformed viral capsid. dsDNA animal viruses such as herpes virus and adenovirus are believed to package their DNA in a similar fashion. The goal of this proposal is to model the assembly process and genome packaging machinery of the model virus bacteriophage cp29 using the complementary techniques of cryo-electron microscopy and X-ray crystallography. The synthesis of these two methods allows a depth of knowledge not possible using approach alone. This work is expected to provide a deeper understanding of the principles underlying macromolecular assembly, extend our knowledge of the use and design of molecular motors in nature, and to suggest novel strategies for the development of anti-viral therapeutics.