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 |
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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
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