Master Theses

2019-03-08

MSYS

Modulation of Interferon-dependent gene induction by cell-to-cell communication

Tasks

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.

Aim:

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.

Methods:

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.

Location

Headquarter Braunschweig

Research Group

Published on

2019-03-08

Prof. Dr. Dagmar Wirth 
Tel. +49 531-6181-5040, 
dagmar.wirth@helmholtz-hzi.de 

Die Arbeiten sollen zeitnah beginnen. Weitere Information erhalten Sie bei Dr. Mario Köster Tel. 0531-6181-5091, mario.koester@helmholtz-hzi.de oder Prof. Dr. Dagmar Wirth Tel. 0531-6181-5040, dagmar.wirth@helmholtz-hzi.de und, an die auch die Bewerbungsunterlagen geschickt werden sollen.

Did you now?

HZI International Graduate School

The HZI International Graduate School for Infection Research (GS-FIRE) provides an innovative structured PhD programme within the field of Infection Research.

PhD programme “Epidemiology”

The PhD programme “Epidemiology” is a three-year doctoral programme in the area of epidemiological research and is coordinated by the Department of Epidemiology of the HZI.

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