Bacteriophage T4 has been studied as a model system to study the effects of environmental stress on the structure of proteins. T4-infected cells develop a host-mediated defense mechanism to block phage reproduction that in principle can also be induced in uninfected cells. This research has been aimed at the identification of both host and phage genes whose expression leads to induction of the host defense mechanism. We have identified some T4 genes required for induction. More recently, we have identified and characterized other genes whose synthesis is repressed in infected cells by a T4 late gene product. We will extend our research to investigate the regulatory circuits that control host and phage gene expression, and also to establish in more detail the nature of the host defense. We will use mutagenesis to identify regulatory genes and to isolate conditional lethal mutants. In particular we will characterize mutants of the rho gene family which we have shown is induced at low temperature and required for induction. Further analysis of these mutants should provide insight into the physiological response and the physiological significance of the rho gene family. BIBLIOGRAPHIC REFERENCES: B.L. Snyder, J.E. Vos and R.E. Lenski. A T4-induced host mutation that is required for rho- induction and for efficient repression of some foreign genes in E. coli. Proc. Natl. Acad. Sci. 74, 1512 (1976). E.V. Barrow and R.E. Lenski. A mutant of bacteriophage T4 that is a conditional host range mutant. J. Mol. Biol. 99, 31 (1976).