MOLINEUX, IAN J

Ian J Molineux

Professor
Molecular Biosciences


Mechanisms of phage infection and genome ejection in vivo; phage evolutionary genetics and applications of phage
molineux@austin.utexas.edu

Phone: 512-471-3143

Office Location
NMS 1.116

Postal Address
The University of Texas at Austin
Molecular Biosciences, College of Natural Sciences
2506 Speedway
Austin, TX 78712

Research Summary:

The major research interest is understanding how nucleic acids pass through lipid bilayers. Our model system is bacteriophage T7, which uses three different motor proteins to transport its DNA into the cell at the initiation of infection. The phage ejects proteins into the cell that make a channel for DNA transport across the cell envelope and constitute the first molecular motor. We are characterizing this channel and motor with the aim of reconstructing a DNA translocation system in vitro. The second and third motors are RNA polymerases that transport the T7 genome into the cell by transcription. We collaborate with structural biologists who use electron cryo-tomography to obtain extremely high resolution structures of intermediates of different phages during infection. 

Other interests include various host-parasite interactions; currently we are determining the molecular basis for exclusion of T7 by cells containing the F plasmid, evaluating phages for use in phage therapy protocols, using phages as models in evolutionary genetics, and phage genomics. A more specific project underway is to determine the mechanism by which transcription of the T7 genome is switched from catalysis by E. coli to the phage RNAP. Two T7 proteins: gp0.7 and gp2, are involved; in their absence the phage undergoes an abortive infection where the phage genome is degraded. We are analyzing rare mutants that bypass the requirement for these proteins, anticipating that we will uncover a novel regulatory genetic network for phage development.

Publications:

2013. He Q, Shumate CK, White MA, Molineux IJ, Yin YW,  Exonuclease of human DNA polymerase gamma disengages its strand displacement function. Mitochondrion 13:592-601

2013 Bull J, Joyce P, Gladstone E, Molineux IJ,  Empirical Complexities in the Genetic Foundations of Lethal Mutagenesis. Genetics 195:541-552.

2013. Schofield DA, Sharp NJ, Vandamm J, Molineux IJ, Spreng KA, Rajanna C, Westwater C, Stewart GC, Bacillus anthracis diagnostic detection and rapid antibiotic susceptibility determination using 'bioluminescent' reporter phage. J Microbiol Methods. 95:156–161.

2013. Cecchini N, Schmerer M, Molineux IJ, Springman R, Bull JJ. Evolutionarily stable attenuation by genome rearrangement in a virus. G3 3:1389-1397.

2013. Lemay, SG, Panja D, Molineux, IJ, Role of osmotic and hydrostatic pressures in bacteriophage genome ejection. Physical Rev. E 87:022714

2013. Molineux IJ, Panja, D.  Popping the cork: mechanisms of phage genome ejection. Nature Rev. Micro. 11:194-204.

2013. Hu B, Margolin W, Molineux IJ, Liu J, The bacteriophage T7 virion undergoes extensive structural remodeling during infection. Science. 339:576-579.

2012 Casjens, SR Molineux IJ. Short noncontractile tail machines: adsorption and DNA delivery by podoviruses. Adv Exp Med Biol. 726:143-179. PMID: 22297513

2012 Häuser,R., S. Blasche, T. Dokland, E. Haggård-Ljungquist, A. von Brunn, M. Salas, S. Casjens, I. Molineux, & P. Uetz, Bacteriophage Protein–Protein Interactions, Adv. Virus Res. 83: 219-298

2012 Schofield, D. A., C. T. Bull, I. Rubio, W. P. Wechter, C. Westwater, C., & I. J. Molineux, Development of an engineered 'bioluminescent' reporter phage for the detection of bacterial blight of crucifers, Appl Environ Microbiol 78: 3592–3598

2012 Bull, J. J., I. J. Molineux, & C. O. Wilke, Slow fitness recovery in a codon-modified viral genome., Mol. Biol Evol. PMID: 22532576

2012 Bull, J. J., G. Otto & I. J. Molineux, In vivo growth rates are poorly correlated with phage therapy success in a mouse infection model., Antimicrob Agents Chemother. 56: 949-954

2011 Nguyen, A. H., I. J. Molineux, R. Springman, & J. J. Bull, Multiple genetic pathways to similar fitness limits during viral adaptation to a new host, Evolution 66: 363–374

2011 Bhardwaj, A., I. J. Molineux, S. R. Casjens, & C. Cingolani, Atomic structure of bacteriophage Sf6 tail needle knob, J. Biol. Chem 286: 30867-30877

2010 Panja, D., & I. J. Molineux, Dynamics of bacteriophage genome ejection in vitro and in vivo., Phys. Biol. PMID: 21149974 7: 045006

2010 Savalia, D., W. P. Robins, S. Nechaev, I. J. Molineux, & K. Severinov., The role of the T7 gp2 inhibitor of host RNA polymerase in phage development., J. Mol. Biol. 402: 118-126

2010 Chang, C-Y., P. Kemp, & I. J. Molineux, Gp15 and gp16 cooperate in translocating bacteriophage T7 DNA into the infected cell, Virology 398: 176-186.

2010 Bull, J. J., E. R. Vimr & I. J. Molineux, A tale of tails: sialidase is key to success in a model of phage therapy against K1-capsulated Escherichia coli, Virology 398: 79-86

2010 Springman, R., T. Keller, I. J. Molineux, & J. J. Bull, Evolution at a high imposed mutation rate: adaptation obscures the load in phage T7, Genetics 184: 221-232

2009 Schofield, D. A., I. J. Molineux, & C. Westwater., Diagnostic bioluminescent phage for the detection of Yersinia pestis, J. Clin. Micro. 47: 3887-3894

2009 Keller, T.E., I. J. Molineux, & J. J. Bull, Viral resistance evolution fully escapes a rationally designed inhibitor, Mol Biol Evol 26: 2041-2046

2009 Heineman, R. H., J. J. Bull, & I. J. Molineux, Multiple layers of evolvability in a bacteriophage life history trait., Mol. Biol. Evol. 26: 1289–1298

2008 Bull, J. J. & I. J. Molineux, Predicting evolution from genomics: experimental evolution of bacteriophage T7, Heredity 100: 453-463

2008 Savalia, D., L. F., Westblade, M. Goel, L. Florens, P. Kemp, N. Akulenko, O. Pavlova, J. C. Padovan, B. T.Chait, M. P. Washburn, H-W. Ackermann, A. Mushegian, T. Gabisonia, I. Molineux, & K. Severinov, Genomic and proteomic analysis of phiEco32, a novel Escherichia coli phage, J. Mol. Biol. 377: 774-789