9316625 Zinder Our studies of the bacteriophage f1 are concentrated on two areas of phage biology, its assembly and its interaction with its E. coli host. Both of these areas bring to the fore the two fundamental biological problems for which the study of virus can be especially useful. These involve questions about the assembly of complex structures and interaction of multi-protein and nucleic acid structures, and inquiries into the basic aspects of the higher order elements of cell metabolism. Very little is known about the facilitated assembly of complex structures at the molecular level (as distinct from the self assembly of most bacteriophage and of the ribosome). The assembly and extrusion of this simple phage involves five membrane associated coat proteins, a ssDNA-binding protein complex, and two morphogenetic proteins encoded by the phage and one (thioredoxin) encoded by the host. We are particularly interested in the role of the morphogenetic genes, since we have only fragmentary information on how they carry out their role. One of these morphogenetic gene products induces expression of a host operon containing five genes; a deeper understanding of the mechanism by which this induction takes place, and of the role of these gene products in the normal life of E. coli, should shed light on the mechanism by which f1 pIV, the morphogenetic protein, acts to promote phage assembly and extrusion from the cell. This protein is related to others found in many species of bacteria, where it is part of a general macromolecular transport system required for the export of other protein, including virulence factors. %%% A new method, phage display, of selecting DNA sequence which encode proteins, including immunoglobulins, that bind with high affinity to desired target is increasingly being used. Applications include the generation of what are effectively human monoclonal antibodies, catalytic antibodies, hormones that bind receptors with higher than native a ffinity, and many other proteins of general interest. Filamentous phage are extensively (almost exclusively) used as carriers of both the DNA encoding these proteins and, on the same particle, the protein itself. Since no new method is without its technical problems, there is keen interest in both the academic and industrial sector in the structure, life cycle, and assembly of the filamentous phages. Some of the experiments in this research deal with expanding the utility of phage display. ***
