The viruses of bacteria and archaea, phage, are touted to be the most abundant organisms on Earth, and a great deal is known about their molecular biology, structure, and mechanisms of replication. Nevertheless there remain fundamental unanswered or incompletely answered questions about the population biology, ecological role, and evolution of these viruses. In this investigation we will address and provide answers to three of these fundamental questions: 1- What are the ecological, genetic and evolutionary conditions for lytic (virulent) phage to be maintained in and regulate the densities of bacterial populations? 2- Under what conditions will selection favor a temperate rather than a purely lytic mode of phage replication and transmission? 3- Under what conditions will selection by lytic and temperate phage favor the evolution and maintenance of CRISPR-Cas mediated adaptive immunity, rather than envelope or other constitutive resistance mechanisms? To address these questions, we will use mathematical and computer simulation models, the properties of which will be analyzed numerically with parameters estimated in the experimental systems that will be employed for population dynamic and evolutionary experiments. We will test the predictions (hypotheses) generated from our analysis of these models in populations of bacteria and phage maintained in liquid, surface, and semisolid culture. Based on the results of these experiments, we will modify our models to make them more realistic. The experiments will be done with Escherichia coli, Pseudomonas aeruginosa, Pseudomonas syringae, and Staphylococcus aureus and their lytic and/or temperate phage. In addition to their importance to academic ecology, population and evolutionary biology, the results of this basic science study may well have practical utility. This investigation will provide an empirically supported theory that could be used to facilitate the design and evaluation of programs to use phage for the treatment of bacterial infections in humans and domestic animals, and to control outbreaks of pathogenic bacteria in crops. !

Public Health Relevance

Although the viruses of bacteria and archaea (phage) are touted to be the most abundant organisms on Earth and research with bacteriophage has played and continues to play a central role in the development of molecular biology and biotechnology, there remain fundamental unanswered questions about the evolution of these viruses and their contribution to the ecology and evolution of their hosts. The proposed jointly theoretical and experimental study of the population biology and evolution of bacteriophage will address and answer three classes of questions: 1- Existence conditions; under what conditions will phage be maintained and regulate the densities of these host populations? 2- Horizontal versus vertical transmission: under what conditions will natural selection favor the evolution and maintenance of a lysogenic rather than a purely lytic mode of phage replication? 3- The evolution and maintenance of adaptive immunity: under what conditions will selection mediated by virulent and temperate phage lead to the evolution of and maintenance of CRISPR-Cas - mediated adaptive immunity? !

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Unknown (R35)
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Special Emphasis Panel (ZRG1)
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Janes, Daniel E
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Emory University
Schools of Arts and Sciences
United States
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