9306418 Kutter The bacteriophage T4 laboratory at The Evergreen State College (Olympia, WA) is continuing studies on the transition from host to phage metabolism (host takeover). The laboratory has focussed for many years on the function of the phage T4 alc gene, which shifts transcription from cytosine-containing bacterial DNA to T4 DNA containing 5-hydroxymethylcytosine. They have now cloned alc gene, which was possible only in an expression vector designed for very lethal genes. Experiments with purified Alc confirm that it interacts with the host RNA polymerase (RNAP) and stops transcript elongation, and it can cause release at specific, complex sites. They propose further studies on the action of Alc. The Alc protein has an interesting basic domain whose role will be studied by means of mutant analysis, partial proteolytic digestion, and antibodies directed against specific domains. The laboratory has also been completing the T4 genomic map and sequence integration, and they have been studying the process of host takeover more globally, including sequencing a 12-kbp region of the t4 genome that includes many new genes that are probably involved. They will clone and study the effects of some of these new genes, as well as the previously identified genes controlling nuclear disruption and internal proteins, and a region of the genome they have characterized that controls stimulation of, and changes in lipid metabolism. They plan to particularly focus on identifying T4 genes that stop host translation, using the genomic sequence data they have assembled; they will study new T4-encoded ribosome- binding proteins and identify other translation effects upon induction of cloned new genes. They also will also look for T4 factors that modify host factors, inactivate host messenger RNA , or release nascent host protein from the ribosomes. %%% These studies are of general interest in modeling a wide range of mechanisms viruses may use in subverting host cells to virus multiplication and in analyzing lethal genes. A number of undergraduate students will also have the opportunity to take part in a stimulating research problem. ***
