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Courses:
Cell and Molecular Biology (BIO 214)
Research Interests: Bacteriophage Genomics
Bacteriophages (phages) are viruses that infect
bacteria. Because they kill bacterial cells, phages and the genes found
in their genomes are of great interest as potential clinical and
diagnostic tools. Their fascinating structure, usefulness as genetic
tools, and important role in the world's microbial ecosystems, coupled
with their safe, inexpensive, and simple cultivation in the laboratory
have made them ideal subjects for biologists for decades. Phages are
thought to be the most numerous organisms on the earth, and analysis of
the relatively small number of completely sequenced phage genomes
suggests that the global population of phages is rich in genetic
diversity. A small number of phages have been studied genetically and
biochemically in great detail, but these represent a vanishingly small
proportion of the global population. Furthermore, it is unclear
whether much of what is known about the few well characterized phages
is generally applicable to the much larger number of uncharacterized
phages. However, recent advances in DNA sequencing technology have made
it possible for several labs to determine the complete genomic
sequences of about 400 phages. Thus, the stage is set for a new era of
phage biology--one in which genomics plays a central role.
My lab studies phages that infect Mycobacterium smegmatis, a
fast-growing, non-pathogenic soil bacterium related to the human
pathogen Mycobacterium tuberculosis.
We are developing and using bioinformatics tools that help us to
understand the unusual way that bacteriophage genomes are organized.
This software also aids in identifying phage genes that are peculiar
for various reasons, allowing us to hypothesize about their particular
function or role within the infectious cycle of the phage. Such genes
are then subjected to experimental approaches to test and refine our
hypotheses. For example, recent bioinformatics work has identified
several phage genes that may be members of a novel type of mobile
genetic element, and experiments are being designed to test this
prediction.
There are opportunities available in my lab for
student collaborators to pursue either microbiology- or
bioinformatics-based projects. The microbiology projects utilize
standard techniques from the fields of genetics, biochemistry and
molecular biology to test predictions about gene function.
Alternatively, the bioinformatics projects involve computer programming
in the Python programming language in a Linux environment.
Selected
Publications:
Turner PC, Dilling BP, Prins C, Cresawn SG, Moyer
RW, Condit RC. Vaccinia virus temperature-sensitive mutants in the A28
gene produce non-infectious virions that bind to cells but are
defective in entry. Virology. 2007 May 10.
Cresawn SG, Condit RC. A targeted approach to
identification of vaccinia virus postreplicative transcription
elongation factors: genetic evidence for a role of the H5R gene in
vaccinia transcription. Virology. 2007 Jul 5;363(2):333-41.
Cresawn SG, Prins C, Latner DR, Condit RC. Mapping
and phenotypic analysis of spontaneous isatin-beta-thiosemicarbazone
resistant mutants of vaccinia virus. Virology. 2007 Jul 5;363(2):319-32.
Hanauer DI, Jacobs-Sera D, Pedulla ML, Cresawn SG,
Hendrix RW, Hatfull GF. Inquiry learning. Teaching scientific inquiry.
Science. 2006 Dec 22;314(5807):1880-1.
Pitcher RS, Tonkin LM, Daley JM, Palmbos PL, Green
AJ, Velting TL, Brzostek A, Korycka-Machala M, Cresawn S, Dziadek J,
Hatfull GF, Wilson TE, Doherty AJ. Mycobacteriophage exploit NHEJ to
facilitate genome circularization. Mol Cell. 2006 Sep 1;23(5):743-8.
Prins C, Cresawn SG, Condit RC. An
isatin-beta-thiosemicarbazone-resistant vaccinia virus containing a
mutation in the second largest subunit of the viral RNA polymerase is
defective in transcription elongation. J Biol Chem. 2004 Oct
22;279(43):44858-71.
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