CSSB Centre for Structural Systems Biology
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Kosinski Group

Integrative Modeling of Infection Cycles

Dr. Jan Kosinski

Group Leader

+49 40 8998 87573

Home Institute

European Molecular Biology Laboratory

We investigate the structure of macromolecular complexes using integrative structural modeling based on data from techniques such as electron microscopy and crosslinking. We also study viral infection cycles to identify new infection pathways and virus-host interactions by pathway modeling and wet-lab experiments.

Research Projects

Integrative structural modeling

Integrative structural modeling allows determining the structure of large macromolecular complexes by combining experimental data from electron microscopy, crosslinking, SAXS, and other techniques. It involves representing the data as restraints, generating structural conformations that satisfy these restraints using optimization procedures, and analysing the resulting ensembles of models. We develop methods for all these stages as well as work on automated modeling pipelines (Kosinski, 2016) and graphical interfaces such as XlinkAnalyzer software. We then apply our methods to collaborative projects.

Integrative pathway modeling of viral infection cycles

During infection, pathogens undergo complex life cycles, interact with molecular systems of their hosts, and disturb and hijack host molecular machines for their own purposes. We aim at creating comprehensive multi-scale models of entire infection cycles to discover host-pathogen interactions and identify which of them are the most crucial for infection. To this end, we integrate systems biology data with structural information using novel pathway modeling methods. We then characterize the most promising interactions using bioinformatics and wet-lab experiments.

We currently focus on the infection cycle of the influenza virus. In addition to computational pathway modeling of the influenza infection cycle, we study this virus both experimentally in our own lab (Biosafety Level 2) to collect additional data and validate our computational hypotheses.

Nuclear pore complex

The nuclear pore complex (NPC) is responsible for the transport between the cytoplasm and the nucleus. It is one of the largest complexes in the cell. Recently, together with Martin Beck’s group at EMBL Heidelberg, we applied our integrative methods to build a near-atomic model of the human NPC, based on data from cryo-electron tomography and crosslinking mass spectrometry (von Appen, 2015; Kosinski, 2016). In collaboration with the Beck group, we continue working on the NPC to extend the model, understand its structure in more detail, and characterize its evolution.

Bacterial secretion systems

Many bacterial pathogens use multi-subunit secretion systems to translocate effector proteins across the cell wall into the host cell. Understanding their structure could reveal how these molecular machines work and help in development of antimicrobial therapeutics. We collaborate on two types of these systems, Type VII of Mycobacteria (T7SS, collaboration with Matthias Wilmanns) and Type III of Shigella flexner (T3SS, CSSB Seed Project with Michael Kolbe from CSSB), contributing our integrative modeling expertise.



  • Integrative structural modeling of macromolecular complexes and cellular landscapes
  • Development and application of methods for integrative modeling of infection cycles
  • Accelerating discovery of host-pathogen interactions most promising for therapeutic intervention through pathway modeling
  • Mechanisms of subversion of the nuclear pore complex by pathogens

Research Team


Group Leader

Dr. Jan Kosinski
Phone:+49 40 8998 87573


Postdoctoral Scientist

Dr. Lenka Cernikova
Phone:+49 40 8998 87578


PhD Student

Iuliia Kotova
Phone:+49 40 8998 87578


Postdoctoral Scientist

Dr. Marc Siggel
Phone:+49 40 8998 87574


Laboratory Officer

Dr. Ying Wang
Phone:+49 40 8998 87578


PhD Student

Dingquan Yu
Phone:+49 040 8998 87580


Postdoctoral Scientist

Dr. Daniel Ziemianowicz
Phone:+49 040 8998 87578




Mosalaganti S, Obarska-Kosinska A, Siggel M, Taniguchi R, Turoňová B, Zimmerli CE, Buczak K, Schmidt FH, Margiotta E, Mackmull MT, Hagen WJH, Hummer G, Kosinski J, Beck M (2022) AI-based structure prediction empowers integrative structural analysis of human nuclear pores. Science. 376(6598):eabm9506. doi: 10.1126/science.abm9506.


Rantos V, Karius K, Kosinski J (2021) Integrative structural modeling of macromolecular complexes using Assembline. Nat Protoc. doi: 10.1038/s41596-021-00640-z

Zimmerli CE, Allegretti M, Rantos V, Goetz SK, Obarska-Kosinska A, Zagoriy I, Halavatyi A, Hummer G, Mahamid J, Kosinski J, Beck M (2021) Nuclear pores dilate and constrict in cellulo. Science. 10.1126/science.abd9776. doi: 10.1126/science.abd9776

Masarati G, Landau M, Ben-Tal N, Lupas A, Kosloff M, Kosinski J (2021) Integrative structural biology in the era of accurate structure prediction. J Mol Biol.167127. doi: 10.1016/j.jmb.2021.167127

Beckham KSH, Ritter C, Chojnowski G, Ziemianowicz DS, Mullapudi E, Rettel M, Savitski MM, Mortensen SA, Kosinski J, Wilmanns M. (2021) Structure of the mycobacterial ESX-5 type VII secretion system pore complex. Sci Adv. 7(26):eabg9923. doi: 10.1126/sciadv.abg9923.


Pazicky S, Dhamotharan K, Kaszuba K, Mertens HDT, Gilberger T, Svergun D, Kosinski J, Weininger U, Löw C (2020) Structural role of essential light chains in the apicomplexan glideosome. Commun Biol.3(1):568. doi: 10.1038/s42003-020-01283-8.

Vorländer MK, Jungblut A, Karius K, Baudin F, Grötsch H, Kosinski J, Müller CW (2020) Structure of the TFIIIC subcomplex τA provides insights into RNA polymerase III pre-initiation complex formation. Nat Commun.11(1):4905. doi: 10.1038/s41467-020-18707-y

Allegretti M, Zimmerli CE, Rantos V, Wilfling F, Ronchi P, Fung HKH, Lee CW, Hagen W, Turoňová B, Karius K, Börmel M, Zhang X, Müller CW, Schwab Y, Mahamid J, Pfander B, Kosinski J, Beck M (2020) In-cell architecture of the nuclear pore and snapshots of its turnover. Nature. doi.org/10.1038/s41586-020-2670-5


Dauden MI, Jaciuk M, Weis F, Lin TY, Kleindienst C, Abbassi NEH, Khatter H, Krutyhołowa R, Breunig KD, Kosinski J, Müller CW, Glatt S (2019) Molecular basis of tRNA recognition by the Elongator complex. Sci Adv 5: eaaw2326 doi: 10.1126/sciadv.aaw2326

Ural-Blimke Y, Flayhan A, Strauss J, Rantos V, Bartels K, Nielsen R, Pardon E, Steyaert J, Kosinski J, Quistgaard EM, Löw C (2019) Structure of Prototypic Peptide Transporter DtpA from E. coli in Complex with Valganciclovir Provides Insights into Drug Binding of Human PepT1. J Am Chem Soc 141: 2404-2412 doi: 10.1021/jacs.8b11343


Mosalaganti S, Kosinski J, Albert S, Schaffer M, Strenkert D, Salomé PA, Merchant SS, Plitzko JM, Baumeister W, Engel BD, Beck M (2018) In situ architecture of the algal nuclear pore complex. Nat Commun 9: 2361 doi: 10.1038/s41467-018-04739-y

Mathieson T, Franken H, Kosinski J, Kurzawa N, Zinn N, Sweetman G, Poeckel D, Ratnu VS, Schramm M, Becher I, Steidel M, Noh KM, Bergamini G, Beck M, Bantscheff M, Savitski MM (2018) Systematic analysis of protein turnover in primary cells. Nat Commun 9: 689 doi: 10.1038/s41467-018-03106-1

Beck M, Mosalaganti S, Kosinski J (2018) From the resolution revolution to evolution: structural insights into the evolutionary relationships between vesicle coats and the nuclear pore. Curr Opin Struct Biol 52: 32-40 doi: 10.1016/j.sbi.2018.07.012


Teimer R, Kosinski J, von Appen A, Beck M, Hurt E (2017) A short linear motif in scaffold Nup145C connects Y-complex with pre-assembled outer ring Nup82 complex. Nat Commun 8: 1107 doi: 10.1038/s41467-017-01160-9

Sadian Y, Tafur L, Kosinski J, Jakobi AJ, Wetzel R, Buczak K, Hagen WJ, Beck M, Sachse C, Müller CW (2017) Structural insights into transcription initiation by yeast RNA polymerase I. EMBO J 36: 2698-2709 doi: 10.15252/embj.201796958

Dauden MI, Kosinski J, Kolaj-Robin O, Desfosses A, Ori A, Faux C, Hoffmann NA, Onuma OF, Breunig KD, Beck M, Sachse C, Séraphin B, Glatt S, Müller CW (2017) Architecture of the yeast Elongator complex. EMBO Rep 18: 264-279 doi: 10.15252/embr.201643353


Thierry E, Guilligay D, Kosinski J, Bock T, Gaudon S, Round A, Pflug A, Hengrung N, El Omari K, Baudin F, Hart DJ, Beck M, Cusack S (2016) Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains. Mol Cell 61: 125-137 doi: 10.1016/j.molcel.2015.11.016

Kosinski J, Mosalaganti S, von Appen A, Teimer R, DiGuilio AL, Wan W, Bui KH, Hagen WJ, Briggs JA, Glavy JS, Hurt E, Beck M (2016) Molecular architecture of the inner ring scaffold of the human nuclear pore complex. Science 352: 363-365 doi: 10.1126/science.aaf0643

Hoffmann NA, Sadian Y, Tafur L, Kosinski J, Müller CW (2016) Specialization versus conservation: How Pol I and Pol III use the conserved architecture of the pre-initiation complex for specialized transcription. Transcription 7: 127-132 doi: 10.1080/21541264.2016.1203628

Ferber M, Kosinski J, Ori A, Rashid UJ, Moreno-Morcillo M, Simon B, Bouvier G, Batista PR, Müller CW, Beck M, Nilges M (2016) Automated structure modeling of large protein assemblies using crosslinks as distance restraints. Nat Methods 13: 515-520 doi: 10.1038/nmeth.3838

Bertipaglia C, Schneider S, Jakobi AJ, Tarafder AK, Bykov YS, Picco A, Kukulski W, Kosinski J, Hagen WJ, Ravichandran AC, Wilmanns M, Kaksonen M, Briggs JA, Sachse C (2016) Higher-order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle. EMBO Rep 17: 1044-1060 doi: 10.15252/embr.201541960


von Appen A, Kosinski J, Sparks L, Ori A, DiGuilio AL, Vollmer B, Mackmull MT, Banterle N, Parca L, Kastritis P, Buczak K, Mosalaganti S, Hagen W, Andres-Pons A, Lemke EA, Bork P, Antonin W, Glavy JS, Bui KH, Beck M (2015) In situ structural analysis of the human nuclear pore complex. Nature 526: 140-143 doi: 10.1038/nature15381

Kosinski J, von Appen A, Ori A, Karius K, Müller CW, Beck M (2015) Xlink Analyzer: software for analysis and visualization of cross-linking data in the context of three-dimensional structures. J Struct Biol 189: 177-183 doi: 10.1016/j.jsb.2015.01.014

Hoffmann NA, Jakobi AJ, Moreno-Morcillo M, Glatt S, Kosinski J, Hagen WJ, Sachse C, Müller CW (2015) Molecular structures of unbound and transcribing RNA polymerase III. Nature 528: 231-236 doi: 10.1038/nature16143


Kosinski J*, Barbato A*, Tramontano A (2013) MODexplorer: an integrated tool for exploring protein sequence, structure and function relationships. Bioinformatics 29: 953–4.


Barbato A, Benkert P, Schwede T, Tramontano A, Kosinski J, (2012) Improving your target-template alignment with MODalign. Bioinformatics 28: 1038–9.


Milanowska K, Krwawicz J, Papaj G, Kosinski J, Poleszak K, Lesiak J, Osinska E, Rother K, Bujnicki JM (2011) REPAIRtoire--a database of DNA repair pathways. Nucleic Acids Res. 39: D788–92.


Kosinski J, Hinrichsen I, Bujnicki JM, Friedhoff P, Plotz G (2010) Identification of Lynch syndrome mutations in the MLH1-PMS2 interface that disturb dimerization and mismatch repair. Hum. Mutat. 31: 975–82.

Pukáncsik M, Békési A, Klement E, Hunyadi-Gulyás E, Medzihradszky KF, Kosinski J, Bujnicki JM, Alfonso C, Rivas G, Vértessy BG (2010) Physiological truncation and domain organization of a novel uracil-DNA-degrading factor. FEBS J. 277: 1245–59.


Kosinski J*, Plotz G*, Guarné A, Bujnicki JM, Friedhoff P (2008) The PMS2 subunit of human MutLalpha contains a metal ion binding domain of the iron-dependent repressor protein family. J. Mol. Biol. 382: 610–27.


Chovancová E, Kosinski J, Bujnicki JM, Damborský J (2007) Phylogenetic analysis of haloalkane dehalogenases. Proteins 67: 305–16.

Kosinski J, Kubareva E, Bujnicki JM (2007) A model of restriction endonuclease MvaI in complex with DNA: a template for interpretation of experimental data and a guide for specificity engineering. Proteins 68: 324–36.

Liu Y, Li Z, Lin Q, Kosinski J, Seetharaman J, Bujnicki JM, Sivaraman J, Hew C-L (2007) Structure and evolutionary origin of Ca(2+)-dependent herring type II antifreeze protein. PLoS One 2: e548.

Miyazono K, Watanabe M, Kosinski J, Ishikawa K, Kamo M, Sawasaki T, Nagata K, Bujnicki JM, Endo Y, Tanokura M, Kobayashi I (2007) Novel protein fold discovered in the PabI family of restriction enzymes. Nucleic Acids Res. 35: 1908–18.


Ahrends R, Kosinski J, Kirsch D, Manelyte L, Giron-Monzon L, Hummerich L, Schulz O, Spengler B, Friedhoff P (2006) Identifying an interaction site between MutH and the C-terminal domain of MutL by crosslinking, affinity purification, chemical coding and mass spectrometry. Nucleic Acids Res. 34: 3169–80.

Skowronek KJ, Kosinski J, Bujnicki JM (2006) Theoretical model of restriction endonuclease HpaI in complex with DNA, predicted by fold recognition and validated by site-directed mutagenesis. Proteins 63: 1059–68.

Zegers I, Gigot D, van Vliet F, Tricot C, Aymerich S, Bujnicki JM, Kosinski J, Droogmans L (2006) Crystal structure of Bacillus subtilis TrmB, the tRNA (m7G46) methyltransferase. Nucleic Acids Res. 34: 1925–34.


Armalyte E, Bujnicki JM, Giedriene J, Gasiunas G, Kosiński J, Lubys A (2005) Mva1269I: a monomeric type IIS restriction endonuclease from Micrococcus varians with two EcoRI- and FokI-like catalytic domains. J. Biol. Chem. 280: 41584–94.

Kosinski J, Feder M, Bujnicki JM (2005) The PD-(D/E)XK superfamily revisited: identification of new members among proteins involved in DNA metabolism and functional predictions for domains of (hitherto) unknown function. BMC Bioinformatics 6: 172.

Kosinski J, Gajda MJ, Cymerman IA, Kurowski MA, Pawlowski M, Boniecki M, Obarska A, Papaj G, Sroczynska-Obuchowicz P, Tkaczuk KL, Sniezynska P, Sasin JM, Augustyn A, Bujnicki JM, Feder M (2005) Frankenstein becomes a cyborg: the automatic recombination and realignment of fold recognition models in CASP6. Proteins 61 Suppl 7: 106–13.

Kosinski J, Steindorf I, Bujnicki JM, Giron-Monzon L, Friedhoff P (2005) Analysis of the quaternary structure of the MutL C-terminal domain. J. Mol. Biol. 351: 895–909.


Ye X, O’Neil PK, Foster AN, Gajda MJ, Kosinski J, Kurowski MA, Bujnicki JM, Friedman AM, Bailey-Kellogg C (2004) Probabilistic cross-link analysis and experiment planning for high-throughput elucidation of protein structure. Protein Sci. 13: 3298–313.


Kosinski J, Cymerman IA, Feder M, Kurowski MA, Sasin JM, Bujnicki JM (2003) A “Frankenstein’s monster” approach to comparative modeling: merging the finest fragments of Fold-Recognition models and iterative model refinement aided by 3D structure evaluation. Proteins 53 Suppl 6: 369–79.