Interferons (IFNs) trigger anti-viral activities in the host cell by inducing a concerted program of IFN-stimulated genes (ISGs). We use fluorescent ISG reporter systems to analyze gene induction at the single cell level. Recent studies in intestinal epithelial cells and mini-gut organoids revealed that ISG induction and acquisition of the antiviral status in a clonal cell populations is bimodal, meaning that only a fraction of cells is protected from infection (Rand et al., MolSysBiol 2012; Bhushal et al., Front Immunol 2017). Ongoing work identified gap junction-mediated communication as a novel strategy that diminish this cell-to-cell heterogeneity in ISG induction. However, the nature of the exchanged signal is still unknown.
The aim of this project is to elucidate the molecular basis of this cell-to-cell interaction. We hypothesize that molecules are exchanged between cells via gap-junctions and that this exchange overcomes negative feed-back loops of IFN signaling. Within this project is planned to down-regulate selected negative regulators (at the mRNA level) and miRNAs by siRNAs and antagomirs in cell culture and examine the effect on ISG induction and IFN signal transduction.
Proposed work plan includes mammalian cell culture, cultivation of organoids, Western Blot, Immunofluorescence staining, FACS analysis and confocal laser-scanning microscopy. The project includes infection of mammalian cell lines with virus and analysis of gene induction by qRT-PCR.
- Model Systems for Infection and Immunity- Prof. Dr. Dagmar Wirth
Prof. Dr. Dagmar Wirth
Tel. +49 531-6181-5040,
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The HZI International Graduate School for Infection Research (GS-FIRE) provides an innovative structured PhD programme within the field of Infection Research.