The primary objective of this research is to understand the molecular mechanisms underlying F-mediated restriction of T7 and of mutants of the related organism, bacteriophage T3. Genetic and biochemical studies are being employed to investigate the pleiotropic physiological defects associated with the abortive infection. These include perturbations in gene expression, both transcriptional and translational, an inhibition of phage DNA replication and possible membrane dysfunctions. The work will include studies both on the phage genes and those chromosomal or F-plasmid encoded genes which determine F-mediated restriction. Pseudorevertants of mutant T3 strains that have regained the ability to overcome F-restriction will be analyzed by biochemical means to investigate the intracellular role of the major capsid protein in controlling the transcriptionally-mediated entry of DNA into the cell and in early steps in phage DNA metabolism. These studies will also be conducted in parallel with phage T7, using its abortive infection of Shigella sonnei as a primary biological assay system.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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University of Texas Austin
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United States
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Molineux, Ian J; Panja, Debabrata (2013) Popping the cork: mechanisms of phage genome ejection. Nat Rev Microbiol 11:194-204
Casjens, Sherwood R; Molineux, Ian J (2012) Short noncontractile tail machines: adsorption and DNA delivery by podoviruses. Adv Exp Med Biol 726:143-79
Nguyen, Andre H; Molineux, Ian J; Springman, Rachael et al. (2012) Multiple genetic pathways to similar fitness limits during viral adaptation to a new host. Evolution 66:363-74
Lee, Young-Sam; Johnson, Kenneth A; Molineux, Ian J et al. (2010) A single mutation in human mitochondrial DNA polymerase Pol gammaA affects both polymerization and proofreading activities of only the holoenzyme. J Biol Chem 285:28105-16
Savalia, Dhruti; Robins, William; Nechaev, Sergei et al. (2010) The role of the T7 Gp2 inhibitor of host RNA polymerase in phage development. J Mol Biol 402:118-26
Chang, Chung-Yu; Kemp, Priscilla; Molineux, Ian J (2010) Gp15 and gp16 cooperate in translocating bacteriophage T7 DNA into the infected cell. Virology 398:176-86
Bull, J J; Vimr, E R; Molineux, I J (2010) A tale of tails: Sialidase is key to success in a model of phage therapy against K1-capsulated Escherichia coli. Virology 398:79-86
Lee, Young-Sam; Lee, Sujin; Demeler, Borries et al. (2010) Each monomer of the dimeric accessory protein for human mitochondrial DNA polymerase has a distinct role in conferring processivity. J Biol Chem 285:1490-9
Panja, Debabrata; Molineux, Ian J (2010) Dynamics of bacteriophage genome ejection in vitro and in vivo. Phys Biol 7:045006
Keller, Thomas E; Molineux, Ian J; Bull, James J (2009) Viral resistance evolution fully escapes a rationally designed lethal inhibitor. Mol Biol Evol 26:2041-6

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