We are investigating the mechanisms for the assembly of virus particles. The studies focus on genetically well characterized bacteriophages T4 and lambda of E. coli, and P22 Salmonella and involve identifying the genes controlling the assembly process, the proteins which participate in virus assembly, and the structural intermediates in the assembly pathways. In the ds DNA phages a closed shell is first constructed, and then filled with DNA. We are studying the interactions of the coat and scaffolding proteins in forming the precursor double shell. During DNA packaging the scaffolding proteins exit from the structure and recycle, and the coat protein precursor shell is transformed into the mature capsid. We are studying the regulation of these protein interactions within organized structures, and their relation to the packaging of DNA. The DNA packaging steps are inhibited by acridines. We are trying to identify the exact mechanism of the inhibition, both as a means of dissecting the process, and as a model for the development of specific anti-viral drugs. We are also investigating the very early steps in structural protein maturation, protein folding and subunit assembly. These experiments focus on the tail spike protein of P22, and utilize temperature-sensitive mutants which interfere with protein maturation at high temperature. Our goal is to identify intermediates in the pathways of protein folding and maturation, and to better understand the defective phenotypes of temperature-sensitive mutations. The assembly of the tails of bacterial viruses, attachment and DNA injection organelles, involves multiple sequential protein-protein interactions. We are studying the regulation of these interactions, and the genetic mechanisms for the control of morphogenetic variables, such as the lengths of structures composed of repeating subunits.