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Faculty
Peter Setlow
Professor of Molecular, Microbial and Structural Biology
2006 Osborn Biomedical Science Graduate Teaching Award Recipient
setlow@nso2.uchc.edu
Areas of Interest:
The conversion of a dormant bacterial (Bacillus) spore into a
vegetative bacterium by the process of spore germination is a relatively
simple differentiating system which is readily amenable to both
biochemical and genetic analysis. A major feature of this
differentiation process is extensive and rapid hydrolysis of spore
protein. Previous work from Dr. Setlow's laboratory has shown that the
proteins degraded in this process are a group of small, acid-soluble,
spore proteins (SASP), the products of an extensive divergent,
multi-gene family, which are synthesized only during sporulation under
transcriptional control. Recent work has shown that SASP are general DNA
binding proteins, which change DNA conformation from the B form to A
form, with striking effects on DNA properties including photochemistry,
transcription and nuclease sensitivity. Current specific aims are to: 1)
continue structural studies on individual purified SASP in solution; 2)
determine the structure of a SASP-DNA complex; 3) determine the effects
of SASP binding on DNA properties, and the effect of DNA binding on SASP
properties; and 4) elucidate the details of the structure, mechanism,
regulation and structure of a spore specific protease responsible for
degrading SASP during spore germination.
Dr. Setlow's laboratory also has ongoing research projects attempting
to determine: 1) the mechanisms involved in the extraordinary resistance
of spores to heat and oxidizing agents; 2) the role of specialized
peptidoglycan in spore properties; 3) the function of individual enzymes
involved in peptidoglycan synthesis; and 4) the mechanisms of spore
germination.
Lab Rotation Projects:
1) Analysis of the mechanism of the uptake of a major spore small
molecule during spore formation;
2) isolation and characterization of a mutation that increases
the rate of spontaneous spore germination;
3) overexpression in spores of an enzyme that degrades the
spore’s peptidoglycan cortex in the first min of spore germination, and
analysis of the effect of this overexpression on spore stability and
germination;
4) analysis of the effects of temperature and fatty acid
composition on the permeability of the spore’s inner membrane, the
barrier to entry of most small molecules into the spore’s protoplast or
core;
and
5) overexpression and purification of the B. subtilis
transglutaminase that appears to be involved in crosslinking of specific
proteins in the spore’s coats.
Selected Publications:
Perkins, D.L., C.R. Lovell, B.V. Bronk, B. Setlow, P. Setlow and M.L.
Myrick, The effects of autoclaving on bacterial endospores studied by
Fourier transform infrared spectroscopy, Appl. Spectrosc. In
press (2004).
Ren, D., L. Bedzyk, P. Setlow, S. Thomas, R.W. Ye and T.K. Wood, Gene
expression in Bacillus subtilis surface biofilms with and without
sporulation and the importance of yucR for biofilm maintenance,
Biotechnol. Bioengineer. In press (2004).
Igarashi, T., B. Setlow, M. Paidhungat and P. Setlow, Analysis of the
effects of a gerF (lgt) mutation on the germination of spores of
Bacillus subtilis, J. Bacteriol. In press (2004).
Cowan, A.E., E.M. Olivastro, D.E. Koppel, C.A. Loshon, B. Setlow and
P. Setlow, Lipids in the inner membrane of dormant spores of Bacillus
species are immobile, Proc. Natl. Acad. Sci. U.S.A. In press
(2004).
Frenkiel-Krispin, D., J. Englander, E. Shimoni, M. Eisenstein, E.
Bullitt, R. Horowitz-Scherer, C.S. Hayes, P. Setlow, A. Minsky and S.G.
Wolf, Structure of DNA-SspC complex implications for DNA packaging,
protection and repair in bacterial spores, J. Bacteriol. In press
(2004).
Setlow, B., R.-M. Cabrera-Martinez and P. Setlow, Mechanism of the
hydrolysis of 4-methylumbelliferyl--D-glucoside by germinating and
outgrowing spores of Bacillus species, J. Appl. Microbiol.
In press (2004).
Young, S.B. and P. Setlow, Mechanisms of Bacillus subtilis
spore resistance to and killing by aqueous ozone, J. Appl. Microbiol.
In press (2004).
Ren, D., L.A. Bedzyk, P. Setlow, D.F. England, S. Kjelleberg, S.M.
Thomas, R.W. Ye and T.K. Wood, Differential gene expression to
investigate the effect of
(5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone on Bacillus
subtilis. Appl. Environ. Microbiol. In press (2004).
Perkins, D.L., C.R. Lovell, B.V. Bronk, B. Setlow, P. Setlow and M.L.
Myrick, Classification of endospores of Bacillus and
Clostridium species by FT-IR reflectance microspectroscopy and
autoclaving. Appl. Spectrosc. In press (2004).
Young, S.B. and P. Setlow, Mechanisms of killing of Bacillus
subtilis spores by Decon and Oxone™, two general decontaminants for
biological agents, J. Appl. Microbiol. 96, 289-301 (2004).
Cortezzo, D.E., B. Setlow and P. Setlow, Analysis of the action of
compounds that inhibit the germination of spores of Bacillus
species, J. Appl. Microbiol. 96, 725-741 (2004).
Shapiro, M., B. Setlow and P. Setlow, Studies on the killing of
spores of Bacillus subtilis by a modified Fenton reagent
containing CuCl2 and ascorbic acid, Appl. Environ. Microbiol. 70,
2535-2539 (2004).
Nicholson, W.L., B. Setlow and P. Setlow, UV photochemistry of DNA
in vitro and in Bacillus subtilis spores at earth-ambient and
low atmospheric pressure: implications for spore survival on other
planets or moons in the solar system, Astrobiology 2, 417-425
(2003).
Ragkousi, K., P. Eichenberger, C. Van Ooij and P. Setlow,
Identification of a new gene essential for germination of Bacillus
subtilis spores with Ca2+-dipicolinate, J. Bacteriol.
185, 2315-2329 (2003).
Cowan, A.E., D.E. Koppel, B. Setlow and P. Setlow, A cytoplasmic
protein is immobile in the cytoplasm of the dormant spores of
Bacillus subtilis; but exhibits rapid mobility in the germinated
spore cytoplasm: implications for spore dormancy, Proc. Natl. Acad.
Sci. U.S.A. 100, 4209-4214 (2003).
Cabrera-Martinez, R.-M., F. Tovar-Rojo, V. Ramana Vepachedu and P.
Setlow, Effects of overexpression of nutrient receptors on germination
of spores of Bacillus subtilis, J. Bacteriol. 185,
2457-2464 (2003).
Young, S.B. and P. Setlow, Mechanisms of killing of Bacillus
subtilis spores by hypochlorite and chlorine dioxide, J. Appl.
Microbiol. 95, 54-67 (2003).
Tovar-Rojo, F., R.-M. Cabrera-Martinez, B. Setlow and P. Setlow,
Studies on the mechanism of the osmoresistance of spores of Bacillus
subtilis, J. Appl. Microbiol. 95, 167-179 (2003).
Setlow, B., A.E. Cowan and P. Setlow, Germination of spores of
Bacillus subtilis with dodecylamine, J. Appl. Microbiol. 95,
637-648 (2003).
Setlow, P., Spore germination, Curr. Opinion Microbiol. 6,
550-556 (2003).
Kosman, J. and P. Setlow, Effects of carboxyl-terminal modifications
and pH on the binding of a Bacillus subtilis small, acid-soluble
spore protein to DNA, J. Bacteriol. 185, 6095-6103 (2003).
Setlow, B., A. Cabrera-Hernandez, R.M. Cabrera-Martinez and P. Setlow,
Identification of aryl-phospho--D-glucosidases in Bacillus subtilis,
Arch Microbiol. 181, 60-67 (2003). |
