Insulin secretory granule (ISG) acts as not only the delivery container of insulin, but also the signaling hub for various regulatory pathways in pancreatic β-cell. Dysregulation of the ISG maturation, transport, docking and fusion step is a hallmark of type-2 diabetes (T2D), which accounts for over 90% patients with diabetes.

Our current research focus is to have a comprehensive description of the molecular architecture of insulin secretory granules and its fusion process with plasma membrane. The future study will involve the structure determination of key molecular components by cryo-EM SPA, cryo-ET of isolated secretory granules and cryo-ET of pancreatic β-cells to elucidate the membrane fusion process.

1. Jasnin, M.; Hervy, J.; Balor, S.; Bouissou, A.; Proag, A.; Voituriez, R.; Schneider, J.; Mangeat, T.; Maridonneau-Parini, I.; Baumeister, W. ; Dmitrieff, S.; Poincloux, R.: Elasticity of podosome actin networks produces nanonewton protrusive forces. Nature Communications 13 (1), 3842 (2022)

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2. Van den Hoek, H.; Klena, N.; Jordan, M. A.; Viar, G. A.; Righetto, R. D.; Schaffer, M.; Erdmann, P. S.; Wan, W.; Geimer, S.; Plitzko, J. M. ; Baumeister, W.; Pigino, G.; Hamel, V.; Guichard, P.; Engel, B. D.: In situ architecture of the ciliary base reveals the stepwise assembly of intraflagellar transport trains. Science 377 (6605), pp. 543 - 548 (2022)

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3. Peters, J. J.; Leitz, J.; Guo, Q.; Beck, F.; Baumeister, W.; Brunger, A. T.: A feature-guided, focused 3D signal permutation method for subtomogram averaging. Journal of Structural Biology 214 (2), 107851 (2022)

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4. Riemenschneider, H.; Guo, Q.; Bader, J.; Frottin, F.; Farny, D.; Kleinberger, G.; Haass, C.; Mann, M.; Hartl, F. U.; Baumeister, W. et al.: Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons. EMBO Reports 23, e53890 (2022)

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5. Martinez Sanchez, A.; Baumeister, W.; Lucic, V.: Statistical spatial analysis for cryo-electron tomography. Computer Methods and Programs in Biomedicine 218, 106693 (2022)

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6. Riera-Tur, I.; Schäfer, T.; Hornburg, D.; Mishra, A.; Padilha, M. D.; Fernandez-Mosquera, L.; Feigenbutz, D.; Auer, P.; Mann, M.; Baumeister, W. et al.: Amyloid-like aggregating proteins cause lysosomal defects in neurons via gain-of-function toxicity. Life science alliance 5 (3), e202101185 (2021)

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7. Moebel, E.; Martinez-Sanchez, A.; Lamm, L.; Righetto, R. D.; Wietrzynski, W.; Albert, S.; Lariviere, D.; Fourmentin, E.; Pfeffer, S.; Ortiz, J. O. et al.: Deep learning improves macromolecule identification in 3D cellular cryo-electron tomograms. Nature Methods 18, pp. 1386 - 1394 (2021)

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8. Bäuerlein, F. J. B.; Baumeister, W.: Towards Visual Proteomics at High Resolution. Journal of Molecular Biology 433 (20), 167187 (2021)

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9. Xu, P.; Mahamid, J.; Dombrowski, M.; Baumeister, W.; Olins, A. L.; Olins, D. E.: Interphase epichromatin: last refuge for the 30-nm chromatin fiber? Chromosoma 130 (2-3), pp. 91 - 102 (2021)

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10. Wilfling, F.; Lee, C.-W.; Erdmann, P. S.; Baumeister, W.: Autophagy ENDing unproductive phase-separated endocytic protein deposits. Autophagy 17 (10), pp. 3264 - 3265 (2021)

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11. Sakata, E.; Eisele, M. R.; Baumeister, W.: Molecular and cellular dynamics of the 26S proteasome. Biochimica et Biophysica Acta-Proteins and Proteomics 1869 (3), 140583 (2021)

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12. Burbaum, L.; Schneider, J.; Scholze, S.; Böttcher, R. T.; Baumeister, W.; Schwille, P.; Plitzko, J. M.; Jasnin, M.: Molecular-scale visualization of sarcomere contraction within native cardiomyocytes. Nature Communications 12 (1), 4086 (2021)

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13. Erdmann, P. S.; Hou, Z.; Klumpe, S.; Khavnekar, S.; Beck, F.; Wilfling, F.; Plitzko, J. M.; Baumeister, W.: In situ cryo-electron tomography reveals gradient organization of ribosome biogenesis in intact nucleoli. Nature Communications 12 (1), 5364 (2021)

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14. Gupta, T. K.; Klumpe, S.; Gries, K.; Heinz, S.; Wietrzynski, W.; Ohnishi, N.; Niemeyer, J.; Spaniol, B.; Schaffer, M.; Rast, A. et al.: Structural basis for VIPP1 oligomerization and maintenance of thylakoid membrane integrity. Cell 184 (14), pp. 3643 - 3659.e23 (2021)

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15. Huang, B.; Guo, Q.; Niedermeier, M. L.; Cheng, J.; Engler, T.; Maurer, M.; Pautsch, A.; Baumeister, W.; Stengel, F.; Kochanek, S. et al.: Pathological polyQ expansion does not alter_the conformation of the Huntingtin-HAP40 complex. Structure 29 (8), pp. 804 - 809 (2021)

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16. Martinez Sanchez, A.; Laugks, U.; Kochovski, Z.; Papantoniou, C.; Zinzula, L.; Baumeister, W.; Lucic, V.: Trans-synaptic assemblies link synaptic vesicles and neuroreceptors. Science Advances 7 (10), eabe6204 (2021)

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17. Pöge, M.; Mahamid, J.; Imanishi, S. S.; Plitzko, J. M.; Palczewski, K.; Baumeister, W.: Determinants shaping the nanoscale architecture of the mouse rod outer segment. eLife 10, e72817 (2021)

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18. Trinkaus, V. A.; Riera-Tur, I.; Martinez Sanchez, A.; Bäuerlein, F. J. B.; Guo, Q.; Arzberger, T.; Baumeister, W.; Dudanova, I.; Hipp, M. S.; Hartl, F. U. et al.: In situ architecture of neuronal alpha-Synuclein inclusions. Nature Communications 12 (1), 2110 (2021)

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19. Zinzula, L.; Basquin, J.; Bohn, S.; Beck, F.; Klumpe, S.; Pfeifer, G.; Nagy, I.; Bracher, A.; Hartl, F. U.; Baumeister, W.: High-resolution structure and biophysical characterization of the nucleocapsid phosphoprotein dimerization domain from the Covid-19 severe acute respiratory syndrome coronavirus 2 acute respiratory syndrome coronavirus 2. Biochemical and Biophysical Research Communications 538, pp. 54 - 62 (2021)

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20. Zinzula, L.; Beck, F.; Klumpe, S.; Bohn, S.; Pfeifer, G.; Bollschweiler, D.; Nagy, I.; Plitzko, J. M.; Baumeister, W.: Cryo-EM structure of the cetacean morbillivirus nucleoprotein-RNA complex. Journal of Structural Biology 213 (3), 107750 (2021)

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21. Bäuerlein, F. J. B.; Fernandez-Busnadiego, R.; Baumeister, W.: Investigating the Structure of Neurotoxic Protein Aggregates Inside Cells. Trends in Cell Biology 30 (12), pp. 951 - 966 (2020)

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22. Salfer, M.; Collado, J. F.; Baumeister, W.; Fernandez-Busnadiego, R.; Martinez-Sanchez, A.: Reliable estimation of membrane curvature for cryo-electron tomography. PLoS Computational Biology 16 (8), e1007962 (2020)

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23. Albert, S.; Wietrzynski, W.; Lee, C.-W.; Schaffer, M.; Beck, F.; Schuller, J. M.; Salome, P. A.; Plitzko, J. M.; Baumeister, W.; Engel, B. D.: Direct visualization of degradation microcompartments at the ER membrane. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 117 (2), pp. 1069 - 1080 (2020)

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24. Chakraborty, S.; Jasnin, M.; Baumeister, W.: Three-dimensional organization of the cytoskeleton: A cryo-electron tomography perspective. Protein Science 29, pp. 1302 - 1320 (2020)

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25. Chakraborty, S.; Mahamid, J.; Baumeister, W.: Cryoelectron Tomography Reveals Nanoscale Organization of the Cytoskeleton and Its Relation to Microtubule Curvature Inside Cells. Structure 28 (9), pp. 991 - 1003.e4 (2020)

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26. Majumder, P.; Baumeister, W.: Proteasomes: unfoldase-assisted protein degradation machines. Biological Chemistry 401 (1), pp. 183 - 199 (2020)

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27. Martinez Sanchez, A.; Kochovski, Z.; Laugks, U.; Meyer Zum Alten Borgloh, J.; Chakraborty, S.; Pfeffer, S.; Baumeister, W.; Lucic, V.: Template-free detection and classification of membrane-bound complexes in cryo-electron tomograms. NATURE METHODS 17, pp. 209 - 216 (2020)

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28. Seefelder, M.; Alva, V.; Huang, B.; Engler, T.; Baumeister, W.; Guo, Q.; Fernandez-Busnadiego, R.; Lupas, A. N.; Kochanek, S.: The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin. BMC Evolutionary Biology 20, 162 (2020)

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29. Turk, M.; Baumeister, W.: The promise and the challenges of cryo-electron tomography. FEBS Letters 594 (20), pp. 3243 - 3261 (2020)

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30. Wietrzynski, W.; Schaffer, M.; Tegunov, D.; Kämmerer, S.; Kanazawa, A.; Plitzko, J. M.; Baumeister, W.; Engel, B. D.: Charting the native architecture of Chlamydomonas thylakoid membranes with single-molecule precision. ELIFE 9, e53740 (2020)

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31. Wilfling, F.; Lee, C.-W.; Erdmann, P. S.; Zheng, Y.; Sherpa, D.; Jentsch, S.; Pfander, B.; Schulman, B. A.; Baumeister, W.: A Selective Autophagy Pathway for Phase-Separated Endocytic Protein Deposits. Molecular Cell 80 (5), pp. 764 - 778.e7 (2020)

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32. Baumeister, W.: The persuasive power of Ernesto Carafoli. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 520 (4), pp. 657 - 658 (2019)

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33. Collado, J.; Kalemanov, M.; Campelo, F.; Bourgoint, C.; Thomas, F.; Loewith, R.; Martinez Sanchez, A.; Baumeister, W.; Stefan, C. J.; Fernandez-Busnadiego, R.: Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity. DEVELOPMENTAL CELL 51 (4), pp. 476 - 487.e7 (2019)

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34. Jasnin, M.; Beck, F.; Ecke, M.; Fukuda, Y.; Martinez Sanchez, A.; Baumeister, W.; Gerisch, G.: The Architecture of Traveling Actin Waves Revealed by Cryo-Electron Tomography. STRUCTURE 27 (8), pp. 1211 - 1223.e5 (2019)

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35. Mahamid, J.; Tegunov, D.; Maiser, A.; Arnold, J.; Leonhardt, H.; Plitzko, J. M.; Baumeister, W.: Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 116 (34), pp. 16866 - 16871 (2019)

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36. Majumder, P.; Rudack, T.; Beck, F.; Danev, R.; Pfeifer, G.; Nagy, I.; Baumeister, W.: Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle. Proceedings of the National Academy of Sciences of the United States of America 116 (2), pp. 534 - 539 (2019)

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37. Mendes, M. L.; Fischer, L.; Chen, Z. A.; Barbon, M.; O'Reilly, F. J.; Giese, S. H.; Bohlke-Schneider, M.; Belsom, A.; Dau, T.; Combe, C. W. et al.: An integrated workflow for crosslinking mass spectrometry. MOLECULAR SYSTEMS BIOLOGY 15 (9), e8994 (2019)

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38. Schaffer, M.; Pfeffer, S.; Mahamid, J.; Kleindiek, S.; Laugks, T.; Albert, S.; Engel, B. D.; Rummel, A.; Smith, A. J.; Baumeister, W. et al.: A cryo-FIB lift-out technique enables molecular-resolution cryo-ET within native Caenorhabditis elegans tissue. Nature Methods 16 (8), pp. 757 - 762 (2019)

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39. Zhao, D. Y.; Pöge, M.; Morizumi, T.; Gulati, S.; Van Eps, N.; Zhang, J.; Miszta, P.; Filipek, S.; Mahamid, J.; Plitzko, J. M. et al.: Cryo-EM structure of the native rhodopsin dimer in nanodiscs. JOURNAL OF BIOLOGICAL CHEMISTRY 294 (39), pp. 14215 - 14230 (2019)

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40. Zinzula, L.; Nagy, I.; Orsini, M.; Weyher-Stingl, E.; Bracher, A.; Baumeister, W.: Structures of Ebola and Reston Virus VP35 Oligomerization Domains and Comparative Biophysical Characterization in All Ebolavirus Species. Structure 27 (1), pp. 39 - 54.e6 (2019)

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