The Schlierf group has a strong background in single-molecule biophysics, in particular single-molecule FRET and force spectroscopy method development as well as application to dynamic structural biology questions.  Key research topics include DNA replication, DNA recombination and membrane protein structure and dynamics^1-5. In recent years, the group has been involved in defining community standards for data acquisition and analysis^6,7, developed large-throughput single-molecule methods⁸ and discovered increased structural dynamics in polypeptides through chaperone binding⁹ and mechanical regulation of DNA recombination¹⁰. In collaboration with the Alberti and the Jahnel labs, RNA structures and dynamics during protein interactions and in condensates are characterized, elucidating RNA regulatory mechanisms.

References:

1. Cheng et al. Bacterial initiators form dynamic filaments on single-stranded DNA monomer by monomer. Nucleic Acids Res. 2015;43(1):396-405. https://doi.org/10.1093/nar/gku1284
2. Grieb et al. Dynamic stepwise opening of integron attC DNA hairpins by SSB prevents toxicity and ensures functionality. Nucleic Acids Res. 2017;45(18):10555-10563. https://doi.org/10.1093/nar/gkx670
3. Schlierf et al. Hexameric helicase G40P unwinds DNA in single pair steps. Deindl S, Kuriyan J, Spies M, eds. eLife. 2019;8:e42001. https://doi.org/10.7554/eLife.42001
4. Krainer et al. A minimal helical-hairpin motif provides molecular-level insights into misfolding and pharmacological rescue of CFTR. Commun Biol. 2018;1(1):154. https://doi.org/10.1038/s42003-018-0153-0
5. Swoboda et al. Enzymatic Oxygen Scavenging for Photostability without pH Drop in Single-Molecule Experiments. ACS Nano. 2012;6(7):6364-6369. https://doi.org/10.1021/nn301895c
6. Hellenkamp et al. Precision and accuracy of single-molecule FRET measurements—a multi-laboratory benchmark study. Nat Methods. 2018;15(9):669-676. https://doi.org/10.1038/s41592-018-0085-0
7. Agam et al. Reliability and accuracy of single-molecule FRET studies for characterization of structural dynamics and distances in proteins. Nat Methods. 2023;20(4):523-535. https://doi.org/10.1038/s41592-023-01807-0
8. Hartmann et al. An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics. Nat Commun. 2023;14(1):6511. https://doi.org/10.1038/s41467-023-42232-3
9. Chamachi et al. Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates. Proc Natl Acad Sci. 2022;119(9):e2118919119. https://doi.org/10.1073/pnas.2118919119
10. Vorobevskaia et al. The recombination efficiency of the bacterial integron depends on the mechanical stability of the synaptic complex. bioRxiv. Published online January 1, 2024:2024.04.09.588808. https://doi.org/10.1101/2024.04.09.588808