The main goal of our work is to understand how the
fungal pathogen Histoplasma capsulatum senses and manipulates its
environment to cause disease. Histoplasma is found mainly in two
locations: the soil, where it grows as long chains of cells (mycelia),
and in a mammalian host, where it switches its morphology and grows
in a round, budding yeast form. The former cell type infects the
host because it aerosolizes easily and enters the host via a respiratory
route. Conversion from this mycelial form to the yeast form is required
to estabalish disease in the host. These yeast-form cells are engulfed
by macrophages. Normally, macrophages kill the microbes that they
phagocytose, but Histoplasma is able to survive and multiply within
the macrophage phagosome. Although the host eventually gains control
of the infection, Histoplasma is not completely eradicated and instead
persists in the host for many years. The molecular players required
for Histoplasma to regulate its morphology and pathogenesis are unknown.
We have used functional genomics to identify genes that are regulated
under specific conditions (in the infectious form, the pathogenic
form, inside macrophages, and under various stresses). We are now
able to generate and test a variety of hypotheses about the function
of these genes in the regulation of morphology, infectivity, pathogenesis,
and persistence. |
Gebhart, D., Bahrami, A., and Sil, A. (2006) Identification of a Copper-Inducible Promoter for Use in Ectopic Expression in the Fungal Pathogen Histoplasma capsulatum. Eukaryotic Cell, 5(6): 935-44.
Nittler, M.P., Murray, D.H., Foo, C., and Sil, A. (2005) Identification of Histoplasma capsulatum Transcripts Induced in Response to Reactive Nitrogen Species. Molecular Biology of the Cell. 16(10): 4792-813.
Hwang, L., Hocking-Murray, D., Bahrami, A., Andersson, M., Rine, J., and Sil, A. (2003) Identifying Phase-Specific Genes in the Fungal Pathogen Histoplasma capsulatum Using a Genomic Shotgun Microarray. Molecular Biology of the Cell, 14: 2314-2326.
McBride, H.J.*, Sil, A.*, Measday, V., Yu, Y., Moffat. J., Maxon,
M.E., Herskowitz, I., Andrews, B., and Stillman, D.J. (2001) The
protein kinase Pho85 is required for asymmetric accumulation of
the Ash1 Protein inSaccharomyces cerevisiae. Molecular Microbiology,
42(2), 345-53.
*These two authors contributed equally to this work.
Takizawa, P.A., Sil, A., Swedlow, J.R., Herskowitz, I., Vale,
R.D. (1997) Actin-dependent localization of an RNA encoding a cell-fate
determinant in yeast. Nature, 389(6646):90-93.
Sil, A. and Herskowitz, I. (1996) Identification
of an Asymmetrically Localized Determinant Required for Lineage-Specific
Transcription
of the Yeast HO Gene. Cell, 84: 711-722.
information last updated June 2006 |
Biomedical Sciences (BMS) Graduate Program
