Figure 1: Integrative modelling of infection cycles.
Figure 2: The structure of the nuclear pore complex obtained by integrative modelling (Kosinski et al., Science 2016).
The Kosinski group investigates infection cycles and host–pathogen interactions using computational and experimental approaches.
Previous and current research
The research in our lab follows two major directions:
1) integrative structural modelling of macromolecular complexes.
Recently, we have made significant contributions to developing and applying methods for integrative structural modelling. For example, we built a near-atomic model of one of the largest complexes in the cell – the human nuclear pore complex – based on data from electron tomography and cross-linking mass spectrometry. Our integrative model of the Elongator complex, published in 2017, has recently been confirmed by a high-resolution structure published in 2019. We now develop our methods further and apply them to nuclear pore complexes from humans and other species, and to other complexes.
2) Integrative pathway modelling of viral infection cycles.
We now try to apply our experience and methods for modelling molecular structures to modelling entire molecular processes and systems, such as viral infection cycles. During infection, viruses undergo complex life cycles, interact with 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 with structural information using novel systems biology and structural modelling methods. We then characterise the most promising interactions using bioinformatics and wet-lab experiments
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 bioinformatics with wet-lab experimentation. 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.