Böttcher Group

We use and develop high-resolution electron cryo microscopy and image processing to understand how biological complexes work. In particular we are interested in the modular organization, which enables complex functionalities by combining various modules with different properties into a single entity.  

Structural dynamics of Biological Complexes

To learn more about the unifying structural principles of complex functionality we study many different types of complexes in different functional states. Among these complexes are mechanosensitive channels of small conductance. Here we want to elucidate how the interplay between proteins and lipids enables gating and mechanosensation.  Other complexes include viral capsids, for which we want to clarify the structural mechanisms of signalling and viral maturation.

Website Chair of Biochemistry

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.

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.

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

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.

Current position

Professor for Biochemistry with Focus on Electron Cryo Microscopy at the Julius-Maximilians University Würzburg (since 2016).

Research Experience

Education

Editorial Work

Honors and Awards

Lecture/ seminar in imaging techniques in the life sciences

Literature seminar `Electron Microscopy in Structural Biology`

Methods in Life Sciences (Focus Lecture)

Lecture /Seminar Electron microscopy and image processing in structural biology

Internship Electron microscopy und imaging techniques