Role of interferon inducible GTPases in immune defence

Bio21 Molecular Science and Biotechnology Institute
Primary Supervisor Email Number Webpage
Prof Ian van Driel

Summary THE VAN DRIEL GROUP investigates innate immune responses in infected tissues are essential for controlling invading pathogens in the early phases of infection preventing the rapid replication and widespread dissemination of pathogens. The van Driel laboratory is seeking to define the main cells and factors that control innate immune responses in tissues and particularly the lung and the gut.

Project Details

Legionella pneumophila is a major cause of Legionnaire's Disease, an acute form of pneumonia. As part of its pathogenesis, L. pneumophila infects alveolar macrophages and replicates in an intracellular vacuole that avoids fusion with lysosomes. Whereas macrophages propagate bacterial replication, other immune cell types are required for bacterial killing. In particular, we have discovered that monocyte derived cells (MDC) play an important role in controlling L. pneumophila infection in the lung. moDC are recruited to the lung in large numbers early during L. pneumophila infection and we believe that MDC internalize and kill the bacteria in an interferon gamma (IFNg) dependent manner. Our RNAseq analysis of lung moDC from wild type and IFNg-deficient mice showed that IFNg induced the expression of multiple interferon inducible GTPases (GBPs/IRGs). While most GBPs and IRGs are not yet characterized, some localize to intracellular pathogen vacuoles and may induce killing through novel mechanisms. We hypothesize that moDC utilize GBPs and IRGs to kill intracellular L. pneumophila.
The aims of this project is to:
A Investigate the intracellular localization of selected GBPs and IRGs during L. pneumophila infection
B Identify GBPs and IRGs that restrict L. pneumophila intracellular replication
C Test selected GBP- and IRG-deficient mice for susceptibility to L. pneumophila infection
Techniques commonly used in this laboratory:
Bacterial culture, in vitro bacterial infection of cultured cells, enumeration of bacterial replication, RNAi knockdown, confocal laser scanning fluorescence microscopy, construction of stable inducible cell lines, molecular biology including primer design, mutagenesis and PCR, western blotting, immunoprecipitation, mouse infection.

School Research Themes

Cell Signalling

Key Contact

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Research Node

Bio21 Molecular Science and Biotechnology Institute

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