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FRISC: The Faculty Research Interests Science Comparator |
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Professor of Biochemistry and Internal Medicine
Biological Chemistry
VA Medical Center, Bldg 3, Room 116
(214) 372-7097
Our laboratory studies bacteria that affect human health. We study infectious spread of
antibiotic resistance by R100 (a conjugal plasmid isolated from Shigella flexneri ),
and the molecular epidemiology of infectious bacteria in hospitals. We also study the high
genetic variability of the ulcer-causing Helicobacter pylori .
Infectious spread of R100 is regulated by the product of a single gene traJ . We
have shown that traJ can be transcribed from three different promoters, its own and
the promoters of two genes immediately upstream. Transcription initiates continuously from
the traJ promoter but the transcript reaches full length only if it is translated.
Normally its translation is blocked by an antisense RNA which forms a double-stranded RNA
molecule with the traJ transcript at its ribosome binding site. The upstream
promoters are activated during infectious spread and their activity provides additional traJ
transcripts whose presence overcomes the antisense RNA sufficiently to allow continuous
translation of the traJ transcript to occur. This TraJ protein then acts as a
molecular switch by creating a new promoter that initiates transcription of the 26 genes
needed to transfer the R100 into another bacterium. We are currently studying several
factors that activate these upstream promoters. We are constructing an entirely in
vitro system to define the regulation precisely.
Molecular epidemiology of hospital infections analyzes bacterial DNA with modern
molecular biological techniques to determine the genetic relatedness of bacteria that
infect patients.
Helicobacter pylori is found in most cases of stomach ulcers. Presently data
indicate that it is the causative agent for many ulcers. The technique of using short
arbitrary primers and PCR reveals that the DNA of this strain varies with unusually high
frequency. In a joint study, we are using this method to track infectious strains in
patients and to identify the segments of DNA that are variable. We hope to discover the
reason for the high variability.
Selected Publications:
Lam H-M, Tancula E, Dempsey WB, and Winkler ME (1992) Suppression of insertions in the
complex pdxJ operon of Escherichia coli K-12 by lon mutations. J
Bacteriol 174:1554-1567
Dempsey WB (1993) Key regulatory aspects of transfer of F-related plasmids. pp 53-73.
In: Bacterial Conjugation . Clewell DB (ed) Plenum Press, New York
Dempsey WB (1994) traJ Sense RNA initiates at two different promoters in R100-1
and forms two stable hybrids with antisense finP RNA. Mol Microbiol
13:313-326
Dempsey WB (1994) Regulation of R100 Conjugation Requires traM in cis to traJ
Mol Microbiol 13:987-1000
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Last updated: 17 Nov 2000
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