Stefan Raunser

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Stefan Raunser
Born (1976-06-23) 23 June 1976 (age 48)
Germany, Landau-Palatinate
NationalityGerman
Alma materMax Planck Institute of Biophysics, Goethe University Frankfurt
Known forCryoEM, CryoET, Membrane protein, Toxin, Cytoskeleton, Sarcomere
AwardsGerman Academy of Sciences Leopoldina
EMBO Member
Einstein Foundation Berlin Professorship
Jugend forscht
Scientific career
FieldsBiochemistry
InstitutionsMax Planck Institute of Molecular Physiology, Harvard Medical School, Freie Universität Berlin, Technical University Dortmund, University of Duisburg-Essen
Doctoral advisorProf. Dr. Werner Kühlbrandt
Other academic advisorsProf. Dr. Roger S. Goody, Prof. Dr. Thomas Walz
Websitehttps://www.mpi-dortmund.mpg.de/research/departments/structural-biochemistry

Stefan Raunser.[1][2] (born 23 June 1976 in Landau in der Pfalz, Germany) is a German scientist and structural biologist known for his contributions to the fields of membrane protein, cytoskeleton, toxin, and sarcomere structural biochemistry in which he has advanced our understanding of fundamental biological mechanisms. Since 2014, he has been a director at the Max Planck Institute of Molecular Physiology [1] in Dortmund.

Research and selected publications

Since its inception, the Raunser lab has contributed to various fields of structural biochemistry, employing and developing methods in CryoEM and CryoET to conduct cutting-edge research and uncover the molecular mechanisms in different aspects of cell biology.

Tc Toxin Complexes: Release, Assembly, Membrane Permeation, Protein Translocation, and Intoxication

In the field of Tc toxins, tripartite ABC-type toxins from Photorhabdus luminescens and other bacteria that are used by the bacteria as virulence factors[3], his research has provided a comprehensive understanding of the molecular mechanisms involved in toxin activation[4], toxin release[5], receptor binding[6][7], membrane permeation[8][9], protein translocation[10][11][12], and intoxication[13]. This allowed his group to publish a movie of the intoxication process[14]. His work on Tc toxins has revealed their potential as customisable molecular syringes for delivering proteins across membranes, opening up possibilities for biotechnological and biomedical applications[6].

Software and Hardware Development in cryoEM/cryoET

The Raunser lab has contributed to developments in cryoEM image processing and cryoET hardware development[15]. After the development of SPHIRE[16] (together with Pawel Penczek), which evolved later into TranSPHIRE[17]. The program offers an easy-to-use and versatile image processing suite for the single particle analysis of protein complexes in CryoEM. The group has also developed other software tools, such as SPHIRE-crYOLO[18] and TomoTwin[19][20], for automatic particle picking in cryoEM and cryoET. On the CryoET front, the group has developed a streamlined workflow for automated cryo-focused ion beam milling for the analysis of vitrified samples by electron cryo tomography[21].

Structural Biochemistry of the Cytoskeleton and Muscle Contraction

Single Particle Approach

Raunser's group has pushed the resolution limits of single particle cryoEM reconstructions of essential muscle and cytoskeletal proteins over the years, including actin filaments (F-actin)[22][23], actin filaments in complex with actin-binding proteins[24], toxins[25][13] and ligands[26][27], the actin-tropomyosin complex[28], and the actomyosin complex[29][30][31][32]. The lab has determined the cryoEM structures of F-actin at ~2.2 Å resolution, allowing for the first time the direct visualisation of water molecules in the structure and giving atomic insight into ATP hydrolysis in F-actin[23][33]

Tomography approach

Raunser's group has revealed the three-dimensional organization of the sarcomere in situ[34], resolving the molecular organization of myosin, alpha-actinin-1, and additional sarcomeric components. The group also determined the first structure of native nebulin bound to thin filaments within intact sarcomeres at 4.5 Å resolution[35].

Structural Biochemistry of Membrane Proteins

Rzunser's group has made significant contributions to understanding the structures of key proteins involved in cell signaling, such as the rabbit ryanodine receptor 1[36] and the TRPC4 channel[37], as well as the Drosophila's Slowpoke (Slo) potassium channel[38]. This research has provided insights into the regulatory mechanisms and revealed potential target sites for drug development.

Fellowships and awards (selection)

  • Member of the North Rhine-Westphalian Academy of Sciences and Arts (2022)[39]
  • ERC Synergy Grant (together with D. Görlich, F. Schnorrer, M. Gautel) (2020)[40]
  • German National Academy of Sciences Leopoldina Member (2019)[41]
  • EMBO Member (2018)[42]
  • ERC Consolidator Grant (2014)[43]
  • Einstein Professorship of the Einstein Foundation Berlin (2013)
  • Member of the “Junges Kolleg” (Academy of Sciences and Arts of Northrhine-Westfalia) (2011-2014)[44]
  • Member of the Global Young Faculty; Speaker of the Health group (2009-2011)[45]
  • Emmy-Noether Fellowship German Research Foundation (DFG) (2008-2013)
  • Fellow of the German Academy of Sciences “Leopoldina” (2007 – 2008)
  • Fellow of Harvard Medical School (2005-2006)

Personal Life

Growing up in Germany, Stefan Raunser has always been passionate about nature[46]. As a kid, he dreamt of becoming a chemist and biology teacher and he was the first in his family to earn a high school degree[47].

He is passionate about opera, concert and classical music[46]. He plays the violin and during his postdoctoral studies at Harvard Medical School he played in the Cambridge Symphony Orchestra[46].

Full List of Publications

The full list of Stefan Raunser's publications can be read on his ResearchGate Profile.

References

  1. "Stefan Raunser Orcid".}
  2. "Stefan Raunser Max Planck Institute".
  3. Roderer, Daniel; Raunser, Stefan (2019-09-08). "Tc Toxin Complexes: Assembly, Membrane Permeation, and Protein Translocation". Annual Review of Microbiology. 73 (1): 247–265. doi:10.1146/annurev-micro-102215-095531. ISSN 0066-4227. PMID 31140906.
  4. Gatsogiannis, Christos; Merino, Felipe; Roderer, Daniel; Balchin, David; Schubert, Evelyn; Kuhlee, Anne; Hayer-Hartl, Manajit; Raunser, Stefan (19 Sep 2018). "Tc toxin activation requires unfolding and refolding of a β-propeller". Nature. Springer Science and Business Media LLC. 563 (7730): 209–213. doi:10.1038/s41586-018-0556-6. ISSN 0028-0836. PMID 30232455.
  5. Sitsel, Oleg; Wang, Zhexin; Janning, Petra; Kroczek, Lara; Wagner, Thorsten; Raunser, Stefan (2023). "preprint article on bioRxiv". doi:10.1101/2023.02.22.529496. {{cite journal}}: Cite journal requires |journal= (help)
  6. 6.0 6.1 Roderer, Daniel; Bröcker, Felix; Sitsel, Oleg; Kaplonek, Paulina; Leidreiter, Franziska; Seeberger, Peter H.; Raunser, Stefan (2020). "Glycan-dependent cell adhesion mechanism of Tc toxins". Nature Communications. Springer Science and Business Media LLC. 11 (1): 2694. doi:10.1038/s41467-020-16536-7. ISSN 2041-1723. PMC 7264150. PMID 32483155.
  7. Xu, Ying; Viswanatha, Raghuvir; Sitsel, Oleg; Roderer, Daniel; Zhao, Haifang; Ashwood, Christopher; Voelcker, Cecilia; Tian, Songhai; Raunser, Stefan; Perrimon, Norbert; Dong, Min (October 2022). "CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor". Nature. 610 (7931): 349–355. doi:10.1038/s41586-022-05250-7. ISSN 1476-4687. PMC 9631961. PMID 36171290.
  8. Gatsogiannis, Christos; Merino, Felipe; Prumbaum, Daniel; Roderer, Daniel; Leidreiter, Franziska; Meusch, Dominic; Raunser, Stefan (October 2016). "Membrane insertion of a Tc toxin in near-atomic detail". Nature Structural & Molecular Biology. 23 (10): 884–890. doi:10.1038/nsmb.3281. ISSN 1545-9985. PMID 27571177.
  9. Roderer, Daniel; Hofnagel, Oliver; Benz, Roland; Raunser, Stefan (2019-11-12). "Structure of a Tc holotoxin pore provides insights into the translocation mechanism". Proceedings of the National Academy of Sciences. 116 (46): 23083–23090. doi:10.1073/pnas.1909821116. ISSN 0027-8424. PMC 6859359. PMID 31666324.
  10. Meusch, Dominic; Gatsogiannis, Christos; Efremov, Rouslan G.; Lang, Alexander E.; Hofnagel, Oliver; Vetter, Ingrid R.; Aktories, Klaus; Raunser, Stefan (23 Feb 2014). "Mechanism of Tc toxin action revealed in molecular detail". Nature. Springer Science and Business Media LLC. 508 (7494): 61–65. doi:10.1038/nature13015. ISSN 0028-0836. PMID 24572368.
  11. Gatsogiannis, Christos; Lang, Alexander E.; Meusch, Dominic; Pfaumann, Vanda; Hofnagel, Oliver; Benz, Roland; Aktories, Klaus; Raunser, Stefan (2013). "A syringe-like injection mechanism in Photorhabdus luminescens toxins". Nature. Springer Science and Business Media LLC. 495 (7442): 520–523. doi:10.1038/nature11987. ISSN 0028-0836. PMID 23515159.
  12. Leidreiter, F.; Roderer, D.; Meusch, D.; Gatsogiannis, C.; Benz, R.; Raunser, S. (2019-10-04). "Common architecture of Tc toxins from human and insect pathogenic bacteria". Science Advances. 5 (10): eaax6497. doi:10.1126/sciadv.aax6497. ISSN 2375-2548. PMC 6795518. PMID 31663026.
  13. 13.0 13.1 Belyy, Alexander; Lindemann, Florian; Roderer, Daniel; Funk, Johanna; Bardiaux, Benjamin; Protze, Jonas; Bieling, Peter; Oschkinat, Hartmut; Raunser, Stefan (2022-07-20). "Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin". Nature Communications. 13 (1): 4202. doi:10.1038/s41467-022-31836-w. ISSN 2041-1723. PMC 9300711. PMID 35858890.
  14. Tc toxin mechanism of action, retrieved 2023-08-11
  15. "ThermoFisher - lab portrait".
  16. "SPHIRE".
  17. Stabrin, Markus; Schoenfeld, Fabian; Wagner, Thorsten; Pospich, Sabrina; Gatsogiannis, Christos; Raunser, Stefan (11 Nov 2020). "TranSPHIRE: automated and feedback-optimized on-the-fly processing for cryo-EM". Nature Communications. Springer Science and Business Media LLC. 11 (1): 5716. doi:10.1038/s41467-020-19513-2. ISSN 2041-1723. PMID 33177513.
  18. "crYOLO".
  19. "Phys.org".
  20. "TomoTwin".
  21. Tacke, Sebastian; Erdmann, Philipp; Wang, Zhexin; Klumpe, Sven; Grange, Michael; Plitzko, Jürgen; Raunser, Stefan (2021). "A streamlined workflow for automated cryo focused ion beam milling". Journal of Structural Biology. Elsevier BV. 213 (3): 107743. doi:10.1016/j.jsb.2021.107743. ISSN 1047-8477. PMID 33971286.
  22. Merino, Felipe; Pospich, Sabrina; Funk, Johanna; Wagner, Thorsten; Küllmer, Florian; Arndt, Hans-Dieter; Bieling, Peter; Raunser, Stefan (June 2018). "Structural transitions of F-actin upon ATP hydrolysis at near-atomic resolution revealed by cryo-EM". Nature Structural & Molecular Biology. 25 (6): 528–537. doi:10.1038/s41594-018-0074-0. ISSN 1545-9985. PMID 29867215.
  23. Funk, Johanna; Merino, Felipe; Schaks, Matthias; Rottner, Klemens; Raunser, Stefan; Bieling, Peter (2021-09-09). "A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks". Nature Communications. 12 (1): 5329. doi:10.1038/s41467-021-25682-5. ISSN 2041-1723. PMC 8429771. PMID 34504078.
  24. Belyy, Alexander; Merino, Felipe; Mechold, Undine; Raunser, Stefan (2021-11-16). "Mechanism of actin-dependent activation of nucleotidyl cyclase toxins from bacterial human pathogens". Nature Communications. 12 (1): 6628. doi:10.1038/s41467-021-26889-2. ISSN 2041-1723. PMC 8595890. PMID 34785651.
  25. Pospich, Sabrina; Küllmer, Florian; Nasufović, Veselin; Funk, Johanna; Belyy, Alexander; Bieling, Peter; Arndt, Hans‐Dieter; Raunser, Stefan (4 Mar 2021). "Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States". Angewandte Chemie International Edition. Wiley. 60 (16): 8678–8682. doi:10.1002/anie.202013193. ISSN 1433-7851. PMC 8048601. PMID 33449370.
  26. Belyy, Alexander; Merino, Felipe; Sitsel, Oleg; Raunser, Stefan (2020-11-20). "Structure of the Lifeact–F-actin complex". PLOS Biology. 18 (11): e3000925. doi:10.1371/journal.pbio.3000925. ISSN 1545-7885. PMC 7717565. PMID 33216759.
  27. von der Ecken, Julian; Müller, Mirco; Lehman, William; Manstein, Dietmar J.; Penczek, Pawel A.; Raunser, Stefan (1 Dec 2014). "Structure of the F-actin–tropomyosin complex". Nature. Springer Science and Business Media LLC. 519 (7541): 114–117. doi:10.1038/nature14033. ISSN 0028-0836. PMC 4477711. PMID 25470062.
  28. Behrmann, Elmar; Müller, Mirco; Penczek, Pawel A.; Mannherz, Hans Georg; Manstein, Dietmar J.; Raunser, Stefan (2012). "Structure of the Rigor Actin-Tropomyosin-Myosin Complex". Cell. Elsevier BV. 150 (2): 327–338. doi:10.1016/j.cell.2012.05.037. ISSN 0092-8674. PMC 4163373. PMID 22817895.
  29. Ecken, Julian von der; Heissler, Sarah M.; Pathan-Chhatbar, Salma; Manstein, Dietmar J.; Raunser, Stefan (20 Jun 2016). "Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution". Nature. Springer Science and Business Media LLC. 534 (7609): 724–728. doi:10.1038/nature18295. ISSN 0028-0836. PMID 27324845.
  30. Pospich, Sabrina; Sweeney, H Lee; Houdusse, Anne; Raunser, Stefan (23 Nov 2021). "High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism". eLife. eLife Sciences Publications, Ltd. 10. doi:10.7554/elife.73724. ISSN 2050-084X. PMC 8735999. PMID 34812732.
  31. Import, M. V. S. (2016-07-24). "Was macht Spitzensportler schneller als andere?". scinexx | Das Wissensmagazin (in Deutsch). Retrieved 2023-08-11.
  32. "A pocket full of water molecules". www.mpg.de. Retrieved 2023-08-11.
  33. Wang, Zhexin; Grange, Michael; Wagner, Thorsten; Kho, Ay Lin; Gautel, Mathias; Raunser, Stefan (2021). "The molecular basis for sarcomere organization in vertebrate skeletal muscle". Cell. Elsevier BV. 184 (8): 2135–2150.e13. doi:10.1016/j.cell.2021.02.047. ISSN 0092-8674. PMC 8054911. PMID 33765442.
  34. Wang, Zhexin; Grange, Michael; Pospich, Sabrina; Wagner, Thorsten; Kho, Ay Lin; Gautel, Mathias; Raunser, Stefan (18 Feb 2022). "Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin". Science. American Association for the Advancement of Science (AAAS). 375 (6582). doi:10.1126/science.abn1934. ISSN 0036-8075. PMID 35175800.
  35. Efremov, Rouslan G.; Leitner, Alexander; Aebersold, Ruedi; Raunser, Stefan (1 Dec 2014). "Architecture and conformational switch mechanism of the ryanodine receptor". Nature. Springer Science and Business Media LLC. 517 (7532): 39–43. doi:10.1038/nature13916. ISSN 0028-0836. PMID 25470059.
  36. Vinayagam, Deivanayagabarathy; Quentin, Dennis; Yu-Strzelczyk, Jing; Sitsel, Oleg; Merino, Felipe; Stabrin, Markus; Hofnagel, Oliver; Yu, Maolin; Ledeboer, Mark W; Nagel, Georg; Malojcic, Goran; Raunser, Stefan (25 Nov 2020). "Structural basis of TRPC4 regulation by calmodulin and pharmacological agents". eLife. eLife Sciences Publications, Ltd. 9. doi:10.7554/elife.60603. ISSN 2050-084X. PMC 7735759. PMID 33236980.
  37. Raisch, Tobias; Brockmann, Andreas; Ebbinghaus-Kintscher, Ulrich; Freigang, Jörg; Gutbrod, Oliver; Kubicek, Jan; Maertens, Barbara; Hofnagel, Oliver; Raunser, Stefan (9 Dec 2021). "Small molecule modulation of the Drosophila Slo channel elucidated by cryo-EM". Nature Communications. Springer Science and Business Media LLC. 12 (1): 7164. doi:10.1038/s41467-021-27435-w. ISSN 2041-1723. PMC 8660915. PMID 34887422.
  38. Jansen, Marc (2022-12-15). "Neue Mitglieder 2022: Stefan Raunser (Klasse für Naturwissenschaften und Medizin)". Nordrhein-Westfälische Akademie der Wissenschaften und der Künste (in Deutsch). Retrieved 2023-08-11.
  39. "StuDySarcomere homepage".
  40. "German National Academy of Sciences Leopoldina Member Stefan Raunser".
  41. "Find people in the EMBO Communities". people.embo.org. Retrieved 2023-08-11.
  42. "ERC Consolidator List 2013" (PDF).
  43. "Neue Mitglieder für das Junge Kolleg". Stiftung Mercator (in Deutsch). Retrieved 2023-08-11.
  44. "GYF I: Mitglieder – Global Young Faculty" (in Deutsch). Retrieved 2023-08-11.
  45. 46.0 46.1 46.2 "SBGrid Consortium - Developer Tale - Stefan Raunser - Max Planck Institute of Molecular Physiology in Dortmund, Germany". sbgrid.org. Retrieved 2023-08-11.
  46. "Raunser - Interview".

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