Because our lab was shut down by the NIAID administration on April 1st, 2013, we focused on three projects that had some possibility of completion. We managed to finish one of these projects, but will continue the others through collaborations with other scientists on and off campus. We also started a new project on the immuno-inhibitory effect of P falciparum. Ongoing projects from the Ghost Lab 1) (completed) analysis of the effect of antibiotics on gene expression in intestinal epithelial cells, and changes in microbiota. 2) (not completed) analysis of the stimulatory effect of P gingivalis (PG) on dendritic cells: we compared the stimulatory capacity of PG with that of E coli and F nucleatum, and found that PG are almost entirely non-stimulatory. For example, it takes 1000 times more PG LPS than E coli LPS to stimulate dendritic cells. Further, PG has the capacity to degrade several key immune cyctokines made by dendritic cells and/or T cells. 3) (not completed) analysis of the effect of GATA4: GATA 4 is a transcription factor highly expressed by the epithelial cells of the jejunum. In mice carrying a targeted deletion in jejunal GATA4, the jejunal epithelial cells upregulate a network of immune genes. To determine whether the immune upregulation is a direct effect of the loss of GATA4, or an indirect effect because of GATA4-induced changes in the intestinal flora, we took two approaches. First we generated germ-free GATA4KO mice. Second we used siRNA to downregulate GATA4 in the intestinal cell line, MODE-K. The germ free mice are now sitting, waiting for a collaborator to collect their tissues, as we are not being allowed to spend our budget to do this. The cell line revealed that at least three immune genes are upregulated, in the absence of bacteria, when GATA4 is downregulated by siena. A new project at LIG 4) we are analyzing the effects of Facliparum that have, or have not been treated with artemesinin on the activation of bone-marrow-derived Dendritic cells. we found that artemesinin treatment did not abrogate the inhibitory effect of live parasites, as measured by surface staining. however, we also found that the parasite has strong effects on the secretion of certain cytokines.
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