BÖTTCHER Gruppe
Unsere Gruppe verwendet und entwickelt hochauflösende Elektronenkryomikroskopie und Bildverarbeitung, um die strukturellen Mechanismen mit denen biologische Komplexe arbeiten, zu verstehen. Insbesondere interessiert uns die modulare Organisation von Komplexen. Modularität kombiniert viele Module mit unterschiedlichen Primärfunktionen in einer einzigen Einheit und erzeugt so komplexe Funktionalität.
Strukturelle Dynamik biologischer Komplexe
Um die generellen strukturellen Prinzipien komplexer Funktionalität zu erfassen, untersuchen wir eine Vielzahl verschiedener Komplexe in unterschiedlichen Funktionszuständen. Zu diesen Komplexen gehören mechanosensitive Kanäle kleiner Leitfähigkeit. Hier erforschen wir das Wechselspiel von Protein und Lipid, um den Mechanismus der mechanosensitiven Wahrnehmung und des Kanal-öffnens zu verstehen. Ein anderes Beispiel sind Virenkapside, deren Struktur wir in verschiedenen Konformationszuständen und zusammen mit unterschiedlichen Bindepartnern bestimmen, um Signalgebung und Virenreifung strukturell abzubilden.
Website Lehrstuhl für Biochemie
Burmeister, W.P., Boutin, S., Balestra, A. C., Groger, H., Ballandras-Colas, A., Hutin, S., Kraft, C., Grimm, C., Böttcher, B., Fischer, U. et al (2024) "Structure and flexibility of the DNA polymerase holoenzyme of vaccinia virus." PLoS Pathog 20: e1011652. 10.1371/journal.ppat.1011652
Gerovac, M., Chihara, K., Wicke,L., Böttcher, B., Lavigne, R., Vogel, J. (2024) "Phage proteins target and co-opt host ribosomes immediately upon infection." Nat Microbiol 9: 787-800. 10.1038/s41564-024-01616-x
Khayenko, V., Makbul, C., Schulte, C., Hemmelmann, N., Kachler, S., Böttcher, B., Maric, H. M.(2024) "Induction of Hepatitis B Core Protein Aggregation Targeting an Unconventional Binding Site." elife 13: RP98827. 10.7554/eLife.98827.1
Endres, S., E. Karaev, S. Hanio, J. Schlauersbach, C. Kraft, T. Rasmussen, R. Luxenhofer, B. Bottcher, L. Meinel and A. C. Poppler (2022). "Concentration and composition dependent aggregation of Pluronic- and Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media." J Colloid Interface Sci 606: 1179-1192. 10.1016/j.jcis.2021.08.040
Haider, M. S., A. K. Mahato, A. Kotliarova, S. Forster, B. Bottcher, P. Stahlhut, Y. Sidorova and R. Luxenhofer (2022). "Biological Activity In Vitro, Absorption, BBB Penetration, and Tolerability of Nanoformulation of BT44:RET Agonist with Disease-Modifying Potential for the Treatment of Neurodegeneration." Biomacromolecules. 10.1021/acs.biomac.2c00761
Seifert, A., T. Tylek, C. Blum, N. Hemmelmann, B. Bottcher, U. Gbureck and J. Groll (2022). "Calcium phosphate-based biomaterials trigger human macrophages to release extracellular traps." Biomaterials 285: 121521. 10.1016/j.biomaterials.2022.121521
Alexander, L. T., R. Lepore, A. Kryshtafovych, A. Adamopoulos, M. Alahuhta, A. M. Arvin, Y. J. Bomble, B. Bottcher, C. Breyton, V. Chiarini, N. B. Chinnam, W. Chiu, K. Fidelis, R. Grinter, G. D. Gupta, M. D. Hartmann, C. S. Hayes, T. Heidebrecht, A. Ilari, A. Joachimiak, Y. Kim, R. Linares, A. L. Lovering, V. V. Lunin, A. N. Lupas, C. Makbul, K. Michalska, J. Moult, P. K. Mukherjee, W. S. Nutt, S. L. Oliver, A. Perrakis, L. Stols, J. A. Tainer, M. Topf, S. E. Tsutakawa, M. Valdivia-Delgado and T. Schwede (2021). "Target highlights in CASP14: Analysis of models by structure providers." Proteins 89: 1647-1672. 10.1002/prot.26247
Böttcher, B. (2021). Hepatitis B Core Protein Capsids. Macromolecular Protein Complexes III: Structure and Function. J. R. Harris and J. Marles-Wright. Cham, Springer International Publishing: 451-470.
Flegler, V. J., A. Rasmussen, K. Borbil, L. Boten, H. A. Chen, H. Deinlein, J. Halang, K. Hellmanzik, J. Loffler, V. Schmidt, C. Makbul, C. Kraft, R. Hedrich, T. Rasmussen and B. Bottcher (2021). "Mechanosensitive channel gating by delipidation." Proc Natl Acad Sci U S A 118. 10.1073/pnas.2107095118
Flegler, V. J., T. Rasmussen and B. Bottcher (2021). "More Than Just Closed and Open: Unraveling a Mechanosensor." Trends Biochem Sci. 10.1016/j.tibs.2021.04.002
Grauel, A., J. Kagi, T. Rasmussen, I. Makarchuk, S. Oppermann, A. F. A. Moumbock, D. Wohlwend, R. Muller, F. Melin, S. Gunther, P. Hellwig, B. Bottcher and T. Friedrich (2021). "Structure of Escherichia coli cytochrome bd-II type oxidase with bound aurachin D." Nat Commun 12: 6498. 10.1038/s41467-021-26835-2
Makbul, C., V. Khayenko, H. M. Maric and B. Bottcher (2021). "Conformational Plasticity of Hepatitis B Core Protein Spikes Promotes Peptide Binding Independent of the Secretion Phenotype." Microorganisms 9: 956. 10.3390/microorganisms9050956
Makbul, C., C. Kraft, M. Griessmann, T. Rasmussen, K. Katzenberger, M. Lappe, P. Pfarr, C. Stoffer, M. Stohr, A. M. Wandinger and B. Bottcher (2021). "Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97." Viruses 13. 10.3390/v13112115
Flegler, V. J., A. Rasmussen, S. Rao, N. Wu, R. Zenobi, M. S. P. Sansom, R. Hedrich, T. Rasmussen and B. Bottcher (2020). "The MscS-like channel YnaI has a gating mechanism based on flexible pore helices." Proc Natl Acad Sci U S A 117: 28754-28762. 10.1073/pnas.2005641117
Hahn, L., M. Maier, P. Stahlhut, M. Beudert, V. Flegler, S. Förster, A. Altmann, F. Toppke, K. Fischer, S. Seiffert, B. Böttcher, T. Luhmann and R. Luxenhofer (2020). "Inverse Thermogelation of Aqueous Triblock Copolymer Solutions into Macroporous Shear-Thinning 3D Printable Inks." ACS Appl Mater Interfaces 12: 12445-12456. 10.1021/acsami.9b21282
Haider, M. S., M. M. Lubtow, S. Endres, S. Förster, V. J. Flegler, B. Böttcher, V. O. Aseyev, A. C. Pöppler and R. Luxenhofer (2020). "Think beyond the core: The impact of the hydrophilic corona on the drug solubilization using polymer micelles." ACS Appl Mater Interfaces 12: 24531-24543. 10.1021/acsami.9b22495
Makbul, C., M. Nassal and B. Bottcher (2020). "Slowly folding surface extension in the prototypic avian hepatitis B virus capsid governs stability." Elife 9. 10.7554/eLife.57277
Wiest, J., J. Kehrein, M. Saedtler, K. Schilling, E. Cataldi, C. A. Sotriffer, U. Holzgrabe, T. Rasmussen, B. Bottcher, M. Cronin-Golomb, M. Lehmann, N. Jung, M. Windbergs and L. Meinel (2020). "Controlling Supramolecular Structures of Drugs by Light." Mol Pharm 17: 4704-4708. 10.1021/acs.molpharmaceut.0c00720
Architecture of the mycobacterial type VII secretion system. Famelis N., Rivera-Calzada A., Degliesposti G., Wingender M., Mietrach N., Skehel J. M., Fernandez-Leiro R., Böttcher B., Schlosser A., Llorca O. and Geibel S. (2019). Nature Oct 9; doi: 10.1038/s41586-019-1633-1.
Structural Basis of Poxvirus Transcription: Vaccinia RNA Polymerase Complexes. Grimm C., Hillen H. S., Bedenk K., Bartuli J., Neyer S., Zhang Q., Huttenhofer A., Erlacher M., Dienemann C., Schlosser A., Urlaub H., Böttcher B., Szalay A. A., Cramer P. and Fischer U. (2019). Cell Dec 12; 179 (7): 1537-50 e19. doi: 10.1016/j.cell.2019.11.024.
Homologous bd oxidases share the same architecture but differ in mechanism. Thesseling# A., Rasmussen# T., Burschel S., Wohlwend D., Kagi J., Müller R., Böttcher* B. and Friedrich* T. (2019). Nat Commun Nov 13; 10 (1): 5138. doi: 10.1038/s41467-019-13122-4.
Structure of the Mechanosensitive Channel MscS Embedded in the Membrane Bilayer. Rasmussen T., Flegler V. J., Rasmussen A. and Böttcher B. (2019). J Mol Biol Aug 9; 431 (17): 3081-90. doi: 10.1016/j.jmb.2019.07.006.
Capabilities of the Falcon III detector for single-particle structure determination. Song, B., J. Lenhart, V. J. Flegler, C. Makbul, T. Rasmussen and B. Böttcher (2019). Ultramicroscopy 203: 145-154. https://www.ncbi.nlm.nih.gov/pubmed/30738626
Hepatitis B virus core protein phosphorylation: Identification of the SRPK1 target sites and impact of their occupancy on RNA binding and capsid structure. Heger-Stevic J., Zimmermann P., Lecoq L., Böttcher B. and Nassal M. (2018). PLoS Pathog Dec 19; 14 (12): e1007488. doi: 10.1371/journal.ppat.1007488.
Structure of Mutant Hepatitis B Core Protein Capsids with Premature Secretion Phenotype. Böttcher B. and Nassal M. (2018). J Mol Biol 430 4941–54. doi: 10.1016/j.jmb.2018.10.018.
Geometrical and Structural Dynamics of Imatinib within Biorelevant Colloids. Wiest J., Saedtler M., Böttcher B., Grune M., Reggane M., Galli B., Holzgrabe U. and Meinel L. (2018). Mol Pharm Aug 28; 15 4470-80. doi: 10.1021/acs.molpharmaceut.8b00469.
Near-Atomic Resolution Structure of a Plant Geminivirus Determined by Electron Cryomicroscopy. Hipp K., Grimm C., Jeske H. and Böttcher B. (2017). Structure Aug 01; 25 (8): 1303-9 e3. doi: 10.1016/j.str.2017.06.013.
Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes. Sundaramoorthy R., Hughes A. L., Singh V., Wiechens N., Ryan D. P., El-Mkami H., Petoukhov M., Svergun D. I., Treutlein B., Quack S., Fischer M., Michaelis J., Böttcher B., Norman D. G. and Owen-Hughes T. (2017). Elife Mar 23; 6 doi: 10.7554/eLife.22510.
Biophysical characterization and activity of lymphostatin, a multifunctional virulence factor of attaching & effacing Escherichia coli. Cassady-Cain R. L., Blackburn E. A., Alsarraf H., Dedic E., Bease A. G., Böttcher B., Jorgensen R., Wear M. and Stevens M. P. (2016). J Biol Chem Jan 19; 291 5803-16. doi: 10.1074/jbc.M115.709600.
Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans. Currie S. M., Gwyer Findlay E., McFarlane A. J., Fitch P. M., Böttcher B., Colegrave N., Paras A., Jozwik A., Chiu C., Schwarze J. and Davidson D. J. (2016). J Immunol Mar 15; 196 (6): 2699-710. doi: 10.4049/jimmunol.1502478.
Prof. Dr. Bettina Böttcher
Josef-Schneider-Str. 2
Dr. Vanessa Flegler
Josef-Schneider-Str. 2
Naomi Hemmelmann
Josef-Schneider-Str. 2
97080 Würzburg
Tamsanqa Tafara Hove
Josef-Schneider-Str. 2
Christian Kraft
Josef-Schneider-Str. 2
97080 Würzburg
Dr. Akiko Rasmussen
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Dr. Tim Rasmussen
Josef-Schneider-Str. 2
Current position
Professor for Biochemistry with Focus on Electron Cryo Microscopy at the Julius-Maximilians University Würzburg (since 2016).
Research Experience
since 2016 | Professor for Biochemistry with Focus on Electron Cryo Microscopy at the Julius-Maximilians University Würzburg |
2013-2016 | Personal Chair in Electron Microscopy and Image Processing at the University of Edinburgh, School of Biological Sciences |
2010-2016 | Head of the Cryo-EM facility in Edinburgh |
2008-2013 | Reader at the University of Edinburgh, School of Biological Sciences |
1999-2008 | Group leader at the EMBL-Heidelberg |
1996-1999 | C1-position in Physical Chemistry at the Albert-Ludwigs University Freiburg |
1992-1996 | PostDoc at the Laboratory of Molecular Biology, Medical Research council, Cambridge UK |
Education
2002 | Habilitation; Venia Legendi in Physical Chemistry; Albert-Ludwigs-Universität Freiburg |
1991 | Dr. rer. nat.: University Stuttgart |
Editorial Work
Since 2017 | Member of the Faculty of 1000 |
since 2014 since 2012 | Member of the editorial board of PeerJ Member of the Editorial Board of Scientifica |
Honors and Awards
2008-2013 | Darwin-Trust Senior Research Fellow |
2000 1998 | Ernst Ruska Prize for Electron Microscopy Boris-Rajewsky Prize for Biophysics |
1995-1996 | Human Capital and Mobility fellowship (EU) |
1994 | EMBO-Fellowship |
1992-1993 | DFG-Research Fellowship |
Vorlesung /Seminar Bildgebende Verfahren in den Lebenswissenschaften
Literaturseminar `Electron Microscopy in Structural Biology`
Methods in Life Sciences (Focus Lecture)
Vorlesung /Seminar Elektronenmikroskopie und Bildverarbeitung in der Strukturbiologie
Praktikum Elektronenmikroskopie und Bildverarbeitung