All viruses select useful bits of the host macromolecular machinery and subvert them to viral purposes. Bacteriophage, which are viruses that prey on bacteria, resemble other viruses in this respect, but we understand so much more of the genetics and biochemistry of bacteria than we do of most plant and animal cells that the always artificial boundary between study of a virus and study of its host is only an academic inconvenience here. Bacteriophage offer us a window through which we can see and study important pieces of the bacterial macromolecular machinery, pieces that may be less accessible from other viewpoints and, indeed, whose existence may have become apparent only when it was discovered that they were needed by a virus. However, bacteriophage also have a semi-autonomous existence: they express, replicate, and recombine their genes at a different tempo than do their hosts, they follow their own developmental pathways, and they evolve in response to different selective pressures. In addition they are a major force in bacterial evolution, able to confer on their hosts the ability to occupy new environmental niches. Thus, bacteriophage provide a useful springboard for jumping into the world of cellular organisms and are fascinating life forms in their own right. The home page of the bacteriophage division of the American Society for Microbiology is a useful site to begin a more detailed exploration.
The Section on Microbial Genetics, headed by Robert Weisberg, is an independent
research lab within the Laboratory of Molecular Genetics of the National Institute
of Child Health and Human Development. This laboratory is a group of
ten independent investigators and their collaborators that is comparable in
many respects to a university department of developmental and molecular biology.
The principal research goal of the Microbial Genetics Section is to understand
molecular mechanisms that underlie the control of gene expression.
The ability of organisms to adjust to environmental stress and to choose between alternative pathways of development requires that they control their patterns of gene expression. The first step in gene expression is the transcription of information from DNA into RNA. The polymerization of ribonucleotides into RNA using the information encoded in a DNA template is catalyzed by RNA polymerase, a large, multisubunit enzyme whose core is structurally and functionally conserved in all kingdoms of life and which is a target of numerous genetic regulatory pathways. Transcription can be divided into three stages: initiation, elongation, and termination. We concentrate our efforts on understanding the mechanisms of elongation and termination in the bacterium E. coli. These two steps, like initiation, are the targets of various regulatory pathways but are less well understood than is initiation. The conservation of structure and enzymatic properties among multisubunit RNA polymerases argues that information obtained from studies of the bacterial enzyme will be useful for understanding the mechanisms and control of elongation and termination in many other organisms. For the reasons explained in the following sections, we are intensively studying an elongation control mechanism found in a virus that parasitizes E. coli.
