The Karam laboratory is using methods of genomic and protein analysis to study the genetic processes that control DNA replication of bacteriophage T4. This bacterial virus produces all the proteins (about 30) that it requires for replication. Most recent studies have focused on an analysis of DNA polymerase genes from a large number of T4-like phages that are evolutionarily diverged from another. The polymerase genes of these phages are being cloned and expressed in E. coli and their protein products are being analyzed for the ability to function with proteins of the T4 DNA replisome. Both in vivo and in vitro approaches are being used to analyze the protein-protein, protein-DNA and protein-RNA interactions that determine specificity of mutual recognition between the polymerase and other components of the phage DNA replication complex.