Dr. Scidmore is an Associate Professor in the Department of Microbiology
and Immunology and has been associated with the department since 2001.
She received a bachelor degree in Molecular Biology from the University
of California at San Diego in 1987 and a Ph. D. degree in Molecular Biology
from Princeton University in 1993. Before joining the department of Microbiology
and Immunology, she obtained post-doctoral training at Rocky Mountain
Laboratories, studying the intracellular development of Chlamydia.
Research Interests
| Graduate Fields | Lab
Members | Related Links | Selected
References
Research Interests
The major focus of my laboratory is the identification of the pathogenic
mechanisms utilized by Chlamydia species to promote and maintain their
intracellular survival. Chlamydiae are obligate intracellular bacteria
that are the leading cause of both sexually transmitted disease and preventable
blindness worldwide as well as a leading cause of disease in veterinary
animals. Chlamydiae replicate within a non-acidified vacuole termed an
inclusion, which is actively modified by the bacteria to prevent lysosomal
fusion and promote intracellular survival. A large family of chlamydial
proteins termed inclusion membrane proteins (Inc) that are specifically
localized to the inclusion membrane has recently been identified. Based
upon their intracellular localization, we propose that this unique family
of Inc proteins facilitates multiple aspects of chlamydial pathogenesis
including regulation of the vesicular trafficking properties of the inclusion,
prevention of lysosomal fusion, nutrient acquisition, modulation of host
signal transduction pathways, and the induction and modulation of host
inflammatory responses through recruitment of host proteins to the inclusion.
We are probing the function of each Inc through the identification and
characterization of their specific cellular targets. Toward this goal,
the lab has recently identified a specific interaction between C. trachomatis
IncG and mammalian 14-3-3?, a phosphoserine binding protein that regulates
diverse signal transduction pathways through directed subcellular localization
of signaling complexes. Experiments are ongoing to define the biologic
function of 14-3-3's recruitment to the inclusion and to determine whether
chlamydiae recruit 14-3-3 proteins to exploit and alter 14-3-3 dependent
signaling pathways in infected cells.
Another related facet of the lab's research is directed at identifying
both the host and chlamydial factors that specifically regulate the intracellular
trafficking and the fusogenic properties of the chlamydial inclusion.
The inclusion is trafficked to the peri-Golgi region of the host cell
by processes that are dependent on early chlamydial gene expression. Recently,
the lab has demonstrated the specific recruitment of several Rab GTPases
(Rab1, 4, 6, 10, and 11) to chlamydial inclusions. Current research is
directed toward deciphering the role of each inclusion associated Rab
GTPase through the use of dominant interfering mutants and siRNA technology
as well as in identifying the proteins that recruit each Rab GTPase to
the inclusion.
Graduate Fields
Dr. Scidmore is a member of the following Graduate Fields:
Comparative Biomedical Sciences
Microbiology
Lab Members
Andrew Moorehead, Graduate Student
Asya Smirnov, Postdoctoral Associate
Fae Tompkins, Technical Support
Related Links
Program in Infection and Pathobiology
Chlamydia Basic Research Society
The comprehensive reference and education site to Chlamydia and the chlamydiae:
http://www.chlamydiae.com/chlamydiae/
Selected References
Scidmore, M.A., Fischer, E.R., and Hackstadt, T. 1996. Sphingolipids and
glycoproteins are differentially trafficked to the Chlamydia trachomatis
inclusion. J.
Cell Biol. 134:363-374.
Scidmore-Carlson, M.A., Shaw, E.I., Dooley, C.A., Fischer, E.R., and
Hackstadt, T. 1999. Identification and characterization of an early Chlamydia
trachomatis operon containing four novel inclusion membrane proteins.
Mol.
Microbiol. 33:753-765.
Scidmore, M.A. and Hackstadt, T. 2001. Mammalian 14-3-3b is localized
to the Chlamydia trachomatis inclusion via its interaction with the C.
trachomatis inclusion membrane protein IncG. Mol.
Microbiol. 39:1638-1650.
Rzomp, K. A., Scholtes, L. D., Briggs, B. J., Whittaker, G. R. and Scidmore,
M.A. 2003. Rab GTPases are recruited to chlamydial Inclusions in a species-dependent
and species-independent manner. Infect.
Immun. 71: 5855-5870.
Rzomp, K. A., Moorhead, A. R., and M.A. Scidmore. (2006.) The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229. Infect. Immun. 74:5362-5373.
Moorhead, A. R., Rzomp, K. A., and M. A. Scidmore. (2007). The Rab6 effector, BICD1, is recruited to C. trachomatis inclusions in a biovar-specific manner. Infect. Immun. 75: 781-791.
