William A. Rosche
 
-B.A., DePauw University
-Ph.D., Texas A&M University

Office: 330C Oliphant Hall
Phone: (918) 631-2759
Email: william-rosche@utulsa.edu

Research Interests:

  • Spontaneous Mutagenesis
  • DNA Structure
  • DNA Supercoiling
  • Bioremediation

The research in my laboratory focuses around my favorite molecule, DNA. Faithful transmission of genetic material from parent to offspring is essential to retaining cellular function, but mistakes do occur. These spontaneous mutations can lead to inherited genetic disorders and cancer.

In my laboratory we use bacteria to study the mechanisms of chromosomal organization and spontaneous mutagenesis. The projects in the lab are as follows:
 
Leading/Lagging Strand Mutagenesis
DNA is a double helix, with the strands held together by complimentary base pairing. The double stranded nature of the molecule is important to it's function, but the two strands are not equivalent. One important parameter in which the strands are non-equivalent is the polymerase subunits that synthesizes each strand. In Escherichia coli, the major replicative DNA polymerase is an asymmetric dimer called DNA polymerase III holoenzyme. This dimer molecule is asymmetric in relationship to the strand being polymerized, the leading or lagging strand. Because of this asymmetry, the mutation rates or mutation spectrum could be different between the strands.
Previous work has shown that deletions stimulated by DNA secondary structures can be increased when the DNA secondary structures are present in the lagging strand. To date, little work has been done to determine the genetic requirements controlling these asymmetric mutation events. We are currently examining the genetic requirements that control this asymmetry.

Stationary Phase Mutagenesis 
The phase of the bacterial life cycle in which the population of cells has a balance of growth and death, producing a static population, is called stationary phase. Spontaneous mutations that arise in stationary phase can be different from those mutations that arise in logarithmically growing cells. For one model system, the types of mutations that are produced and the genetic requirements are fairly well established. However, only preliminary studies have been done to examine the role of different chromosomal context in relationship to stationary phase mutagenesis. We are currently placing multiple mutation targets into multiple chromosomal context and examining the effects on the rate and nature of the mutation events. 

Microbiology of Acid Mine Drainage
In collaboration with Dr. Tom Harris (TU Chemistry department) we are identifying and quantifying the number of sulfate-reducing bacteria in a novelly designed bioreactor. It is well known that a number of bacteria are important to the bioremediation process, but much work needs to be done on determining the optimal conditions for the bacteria.
 
Teaching Fields:

  • Biol3084-Fundamentals of Microbiology
  • Biol4023-Environmental Microbiology
  • Biol4123/6823-Selected Topics in Microbiology: Adv. Microbial Genetics
  • Biol1053-Plagues and Pestilence (Block III) 

Selected Publications:

  • Jonathan M. Budzik, William A. Rosche, Arne Rietsch, George A. O'Toole "Isolation and Characterization of a Generalized Transducing Phage for Pseudomonas aeruginosa Strains PAO1 and PA14". Journal of Bacteriology, 2004 186(10):3270-3
  • Vera I. Hashem, William A. Rosche, Richard R. Sinden." Genetic Recombination Destabilizes (CTG)n·(CAG)n repeats in E. coli" Mutation Research, 2004 Oct 4;554(1-2):95-109
  • van Noort V, Worning P, Ussery DW, Rosche WA, Sinden RR. " Strand misalignments lead to quasipalindrome correction." Trends Genet. 2003 Jul;19(7):365-9.
  • Vera I. Hashem, Ella A. Klysik, William A. Rosche, Richard R. Sinden. Instability of repeated DNAs during transformation in Escherichia coli. Mutation Research 502 (1-2):25-37, 2002
  • Vera I. Hashem, William A. Rosche, and Richard R. Sinden. Genetic assays for measuring rates of (CAG)o(CTG) repeat instability in Escherichia coli. Mutation Research 502(1-2):39-46, 2002
  • Anthony Papinsick (TURC): Antimicrobial Resistance to Essential Oils
    Erika Johnson (UMEB): Spectrum of Mutations to Rifampicin Resistance
    Andrew Bussman (UMEB): Microbiology of Acid Mine Drainage
    Tad Schoedel (UMEB): Stationary Phase Specific Mutators
  • Rosche, W. A. and P. L. Foster, 1999. The role of transient hypermutators in adaptive mutation in Escherichia coli. Proc Natl Acad Sci U S A 96(12): 6862-7.
  • Sinden, R. R., Hashem, V. I. & Rosche, W. A., 1999. DNA-directed mutations. Leading and lagging strand specificity. Ann N Y Acad Sci 870, 173-89.
  • Foster, P. L. and W. A. Rosche, 1999. Mechanisms of mutation in nondividing cells. Insights from the study of adaptive mutation in Escherichia coli. Ann N Y Acad Sci 870: 133-45.
  • Rosche, W. A., L. S. Ripley, R.R. Sinden, 1998. Primer-template misalignments during leading strand DNA synthesis account for the most frequent spontaneous mutations in a quasipalindromic region in Escherichia coli. J Mol Biol 284(3): 633-46.
  • Rosche, W. A., T. Q. Trinh, R.R. Sinden, 1997. Leading strand specific spontaneous mutation corrects a quasipalindrome by an intermolecular strand switch mechanism. J Mol Biol 269(2): 176-87.
  • Rosche, W. A., A. Jaworski, et al., 1996. Single-stranded DNA-binding protein enhances the stability of CTG triplet repeats in Escherichia coli. J Bacteriol 178(16): 5042-4.
  • Bowater, R. P., W. A. Rosche, et al., 1996. Relationship between Escherichia coli growth and deletions of CTG.CAG triplet repeats in plasmids. J Mol Biol 264(1): 82-96.
  • Rosche, W. A., T. Q. Trinh, R.R. Sinden, 1995. Differential DNA secondary structure-mediated deletion mutation in the leading and lagging strands. J Bacteriol 177(15): 4385-91. 

Research Students and Projects:

  • Anthony Papinsick (TURC): Antimicrobial Resistance to Essential Oils
  • Erika Johnson (UMEB): Spectrum of Mutations to Rifampicin Resistance
  • Andrew Bussman (UMEB): Microbiology of Acid Mine Drainage
  • Tad Schoedel (UMEB): Stationary Phase Specific Mutators

Other Responsibilities:

  • Computer Committee, Chair
  • Pre-Med Advisor