Cell & Molecular Biology Program Event
Dr. Adam Sateriale
Cellular and Molecular Biology
University of Vermont
Gene regulation in phagocytic Entamoeba histolytica
Tuesday October 30th, 2012
The protozoan parasite Entamoeba histolytica causes colitis and acute and chronic dysentery by invading the colonic wall. In rare cases, this parasite disseminates through the host circulation, most commonly to the liver causing abscess formation. Invasive cases, however, only make up approximately 10% of E. histolytica infections. Whether an amebic infection becomes invasive depends on the complex interactions between amebic virulence, and host genetic and environmental factors.
Our lab focuses on understanding E. histolytica phagocytosis better, as phagocytic ability correlates with amebic virulence. Using ligand coated paramagnetic beads as ?bait?, HM-1:IMSS strain trophozoites were separated based on phagocytic ability. Microarray analysis of the sorted ?phagocytic? and ?non-phagocytic? populations identified 121 genes upregulated in the phagocytic trophozoites, amongst which genes involved in actin binding and cytoskeleton organization were significantly over-represented based on functional annotation and gene cluster analysis. We hypothesized that the act of phagocytosis may alter gene expression and that this may lead to a heightened phagocytic ability, in essence a feed forward regulation of E.
histolytica phagocytic ability. Follow-up work demonstrated increased expression of a subset of the genes after interaction with ligand-coated beads, and increased phagocytic ability after interaction with lymphocytes. Furthermore, phenotypic analyses following gene silencing confirmed a role in phagocytosis for 5 of 14 genes analyzed. Our lab is currently pursuing the underlying transcriptional regulation of the genes identified from our microarray analysis using in silico DNA motif identification.