Research

• Signaling via membrane micro-domains formed by small membrane proteins
• The importance of small molecules for short- and long-term signaling memory

Metabolite sensing is a fundamental biological process, and the perception of dynamic changes in the extracellular environment is of paramount importance for the survival of organisms. This applies in particular to single cell organisms such as bacteria, which execute sophisticated and rapid signaling strategies in response to intracellular and extracellular cues. In our group, we are exploring the impact of these signaling strategies on the entire proteostasis network that controls protein production, folding, trafficking and degradation. We are particularly interested in the role of membrane micro-domains and small signaling molecules in bacterial adaptation.

Keywords

Bacterial adaptation, translational control, antimicrobial peptides, alarmones, stress response.

“Our goal is to explore universally conserved strategies of signal perception and integration.”

Ten most important publications

• Ribosome inactivation by a class of widely distributed C-tail anchored membrane proteins. Njenga et al., (2024), Structure 32, 1-17, doi: 10.1016/j.str.2024.09.019
• Central role of Tim17 in mitochondrial presequence protein translocation. Fielden, L. et al., (2023), Nature 621, 627-634, doi: 10.1038/s41586-023-06477-8
• mRNA targeting eliminates the need for the signal recognition particle during membrane protein insertion in bacteria. Sarmah, P. et al., (2023), Cell reports 42, 112140, do: 10.1016/j.celrep.2023.112140
• Shutdown of secretory pathway by the bacterial alarmones (p)ppGpp. Czech L. et al., (2022)Nature Comm.  13:1069. doi: 10.1038/s41467-022-28675-0.
• Post-translational insertion of small membrane proteins by the bacterial signal recognition particle. Steinberg R.  (2020) PloS Biology 18(9), e30000874, doi: 10.1371/journal.pbio.3000874.
• The cbb₃-type cytochrome oxidase assembly factor CcoG is a widely distributed cupric reductase. Marckmann D. et al.  (2019), Proc. Natl. Acad. Sci. USA 116, 21166-21175 doi: 10.1073/pnas.1913803116.
• The signal recognition particle contacts uL23 and scans substrate translation inside the ribosomal tunnel. Denks K. et al. (2017). Nature Microbiol. 2, 16215 doi: 10.1038/nmicrobiol.2016.265.
• FtsY, the bacterial SRP receptor functionally and physically interacts with the SecYEG translocon. Angelini S. et al. (2005), EMBO Rep. 6, 476-481 doi: 10.1038/sj.embor.7400385.
• Differential interactions between a twin-arginine signal peptide and its translocase in Escherichia coli. Alami M. et al. (2003). Mol. Cell 12, 937-946 doi: 10.1016/s1097-2765(03)00398-8.
• SRP-dependent cotranslational targeting and SecA-dependent translocation analyzed as individual step in the export of a bacterial protein. Neumann-Haefelin C. et al., (2000). EMBO J. 19, 6419-6426 doi: 10.1093/emboj/19.23.6419.