How cells defend their cytosol against invading bacteria
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The cytosol of mammalian cells appears an attractive niche for bacterial pathogens since it is rich in nutrients whereas, in fact, most intracellular bacteria avoid the cytosol and rather reside inside vesicles. We think this paradox is caused by autophagy and other powerful, but poorly characterized, cell-autonomous immune mechanisms that protect the cytosol (reviewed in Randow et al., Science 2013).
Our lab has identified several genes that defend the cytosol against bacterial invasion, for example NDP52, a receptor that targets cytosolic bacteria for autophagy (Thurston et al., Nature Immunol 2009), and Galectin-8, a danger receptor that catches bacteria by sensing the membrane damage bacteria cause when entering the host cytosol (Thurston et al., Nature 2012).
A position for an enthusiastic PhD student interested in cell-autonomous defence against bacteria or viruses is available. Projects could focus either on novel E3 ligases that ubiquitylate cytosol-invading bacteria, on a novel danger receptor distinct from galectins, or on the control of anti-bacterial autophagy. Projects will focus on the mechanisms of cell-autonomous immunity and will employ a wide variety of molecular and immunological methods.
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., Ryzhakov, G., Bloor, S., Muhlinen, von, N., and Randow, F. (2009).
The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria.
Nat Immunol 10, 1215–1221.
Thurston, T.L.M., Wandel, M.P., Muhlinen, von, N., Foeglein, A., and Randow, F. (2012).
Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion.
Nature 482, 414–418.