Our ability to fight infections relies not only on the capacity of our professional immune system but also on the skills of individual cells to defend themselves. While the contributions of professional immune cells to innate and acquired immunity have been extensively studied, much less is known about how regular body cells defend themselves against pathogens, a process known as cell-autonomous immunity. Inspired by the ability of unicellular organisms to rely exclusively on cell-autonomous defences, we investigate how mammalian cells protect their interior against bacterial invasion.
Our recent work has revealed that mammalian cells deposit host proteins onto cytosol-invading bacteria, forming polyvalent arrays that convert bacterial surfaces into anti-bacterial signalling platforms. Notable examples include the ubiquitylation of bacterial lipopolysaccharide (LPS), the first known instance of ubiquitylation targeting a non-proteinaceous substrate (Otten Nature 2021), and the recruitment of guanylate-binding proteins (GBPs), a family of interferon-induced GTPases (Wandel Nat Immunol 2020). LPS ubiquitylation and GBP recruitment are essential for anti-bacterial autophagy and caspase-4—dependent pyroptotic cell death, respectively.
We are currently seeking an enthusiastic PhD student interested in host-pathogen interactions. Work will focus on the transformation of bacterial surfaces into signalling platforms. Potential areas of investigation include:
- functional and structural characterization of LPS ubiquitylation by RNF213
- mechanisms by which GBPs detect bacteria
- discovery of novel anti-bacterial effector mechanisms triggered by polyvalent protein coats on bacterial surfaces.
References
Shigella flexneri evades LPS ubiquitylation through IpaH1.4-mediated degradation of RNF213
Nature Structural & Molecular Biology: (2025)
Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection
Nature 594(7861): 111-116 (2021)
Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.
Nat Immunol 21(8): 880-891 (2020)