Because our lab was shut down by the NIAID administration at the end of march this year, we focused on two projects that had some possibility of completion. We did not manage to finish either project, but will continue them through collaborations with other scientists on and off campus. 1) 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 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. 2) 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 siRNA.

Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2013
Total Cost
$348,358
Indirect Cost
City
State
Country
Zip Code
Möhle, Luisa; Mattei, Daniele; Heimesaat, Markus M et al. (2016) Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis. Cell Rep 15:1945-56
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Skinner, Jeff; Kotliarov, Yuri; Varma, Sudhir et al. (2011) Construct and Compare Gene Coexpression Networks with DAPfinder and DAPview. BMC Bioinformatics 12:286

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