Research
We are interested in cell autonomous innate immunity, i.e. in the ability of individual cells to defend themselves against infection.
Cytosolic defence against bacterial invasion
The cytosol is rich in nutrients but very few bacteria can colonize it. We wish to understand how cells deploy the ubiquitin system and autophagy to defend their cytosol.
Regulation of NF-kB and IRF signalling
The defence against pathogens requires profound changes in gene expression, which are coordinated by latent transcription factors of the NF-kB and IRF families. We aim to understand how infection activates NF-kB and IRF signalling.
Somatic cell genetics
The genetic analysis of somatic cell lines holds significant potential to our understanding of signal transduction (and other cell autonomous traits). Through homologous recombination and chemical mutagenesis we have obtained a large collection of gene deficient human and murine cells, with which we address problems of cell autonomous innate immunity.
Publications
- Noad, J., Malsburg, von der, A., Pathe, C., Michel, M.A., Komander, D., and Randow, F. (2017)
LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading bacteria by activating autophagy and NF-κB.
Nat. Microbiol 2: 17063. - Thurston TL, Boyle KB, Allen M, Ravenhill BJ, Karpiyevich M, Bloor S, Kaul A, Noad J, Foeglein A, Matthews SA, Komander D, Bycroft M, Randow F. (2016)
Recruitment of TBK1 to cytosol-invading Salmonella induces WIPI2-dependent antibacterial autophagy.
EMBO J. 35: (16):1779-92. - Beale, R., Wise, H., Stuart, A., Ravenhill, B.J., Digard, P., and Randow, F. (2014)
A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.
Cell Host and Microbe 15: 239–247. - Randow, F., MacMicking, J.D., and James, L.C. (2013)
Cellular self-defense: How cell-autonomous immunity protects against pathogens.
Science 340: 701–706. - Thurston, T.L.M., Wandel, M.P., Muhlinen, Von, N., Foeglein, Á., and Randow, F. (2012)
Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion.
Nature 482: 414–418. - Muhlinen, von, N., Akutsu, M., Ravenhill, B.J., Foeglein, A., Bloor, S., Rutherford, T.J., Freund, S.M.V., Komander, D., and Randow, F. (2012)
LC3C, Bound Selectively by a Noncanonical LIR Motif in NDP52, Is Required for Antibacterial Autophagy
Molecular Cell 48: 329–342. - Bloor, S., Maelfait, J., Krumbach, R., Beyaert, R. and Randow, F. (2010)
Endoplasmic reticulum chaperone gp96 is essential for infection with vesicular stomatitis virus.
Proc Natl Acad Sci U S A 107: 6970-6975. - Thurston, T.L., Ryzhakov, G., Bloor, S., von Muhlinen, N. and Randow, F. (2009)
The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria.
Nat Immunol 10: 1215-1221. - Bloor, S., Ryzhakov, G., Wagner, S., Butler, P. J., Smith, D. L., Krumbach, R., Dikic, I., and Randow, F. (2008)
Signal processing by its coil zipper domain activates IKK gamma
Proc Natl Acad Sci U S A 105: 1279-1284