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Kosinski Group

Integrative modelling of infection cycles

The Kosinski group investigates infection cycles and host–pathogen interactions using computational and experimental approaches.

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Previous and current research

The research in our lab follows two major directions:

1) Integrative structural modeling of macromolecular complexes.

We develop and apply computational methods for modeling large macromolecular complexes by integrating electron microscopy and other data. We have built models of one of the largest complexes in the cell – the nuclear pore complex from humans (Nature, 2015; Science, 2016) and other species (Nature Communications, 2018; Nature, 2020; BioRxiv, 2021). Our model of the Elongator complex (EMBO Reports, 2017) has recently been confirmed by a high-resolution structure published (Science Advances, 2019). We also work on complexes involved in infection such as the Type VII Secretion System (Science Advances, 2021) and membrane complexes involved in malaria (Plasmofraction project). Our modeling methods are available in the Assembline package. We also develop a popular crosslinking and model analysis software Xlink Analyzer.  

2) Integrative pathway modeling of viral infection cycles.

During infection, viruses undergo complex life cycles, interact with the molecular systems of their hosts, and disturb and hijack host molecular machines for their own purposes. We aim to create comprehensive multiscale 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 multi-omics data, fluorescence microscopy, and cryo-electron tomography. Currently, we focus on the influenza A virus in our own lab and the Lassa virus in collaboration.

Fluorescence microscopy images of influenza A virus infecting cells. We use fluorescence microscopy, cryo-electron tomography, and proteomics to map the infection cycle of the influenza A virus and to validate bioinformatics predictions. [Photo: Ying Wang]

Our lab is located in the Centre for Structural Systems Biology (CSSB), right next to EMBL Hamburg on the DESY campus. We are an interdisciplinary team of scientists who combine computational biology (structural modeling, systems biology) with wet-lab experimentation (cell biology, proteomics, fluorescence microscopy, electron tomography). Our research is highly collaborative and involves common projects with other EMBL and CSSB groups, CSSB partners, and external groups.

Future projects and goals

  • Integrative structural modelling of macromolecular complexes.
  • Integrative modelling of infection cycles based on multi-omics and structural data.
  • Mechanisms of subversion of the nuclear pore complex by pathogens.
  • Identification and characterisation of host–pathogen interactions most promising for therapeutic intervention.
  • Understanding the evolution of eukaryotes through structural biology.
Gallery of our structural models.
Integrative modeling of infection cycles.
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