Research Areas
The research department Structural Cell Biology of Viruses has pioneered the application of electron cryo tomography (cryoET) to pleomorphic viruses revealing their three-dimensional supramolecular organization. Examples are structures of Herpes simplex virus, HIV-1 and Bunyaviruses. They have expanded these analyses to study crucial steps in the cell biology of virus infection. Understanding the entirety of a virus ‘life cycle’ requires an understanding of its transient structures at the molecular level. The aim is a comprehensive picture of the dynamic functional interaction between viral protein complexes and cellular structures. Viruses also serve as dedicated tools to mine the molecular detail of cellular tomograms. Being able to enter cells via physiological pathways and being recognizable among the multitude of other structural features inside the host’s cytoplasm, viruses allow following dynamic cellular processes.
Membrane Modulations
The structural design of viruses provides a remarkable example of simplicity and functionality in biological systems. Viral particles and machineries work as highly effective molecular devices to mediate membrane traversal to transfer viral genomes and accessory proteins into and out of cells and their sub-compartments. We analyze dynamic interactions of viral and cellular protein complexes leading to perturbations of the curvature of membranes. This includes aspects in membrane fusion (entry of enveloped viruses), membrane rupture (entry of non-enveloped viruses) and membrane curvature modulation (viral transport across membranes and viral assembly). To this end we address various levels of detail and complexity with dedicated experimental subsystems.
Integrative and Correlative Microscopy
Electron cryo microscopy (cryoEM) provides an excellent platform for combinations with other approaches, like biochemical, proteomics and X-ray crystallographic studies by integration of their results with native sub-cellular structural information. Driven by our biological questions, we are involved in various efforts of methods development. This includes the combination of cryoET with ‘single particle’ approaches, super-resolution fluorescence cryo microscopy modalities and soft X-ray cryo-microscopy/tomography in a correlative fashion, as well as micromachining of samples to make them amenable for cryoEM analyses.
Image Analysis/Processing and Computational Biology
Image analysis (e.g. sub-volume averaging) is an integral part of cryoEM data processing. We are part of the community efforts to constantly advance the respective processing, visualization and validation tools required for the different levels of resolution and complexity. This is done in the collaboration with specialists. Integrative structural biology requires moreover dedicated means to combine data from different modalities e.g. fitting of higher resolution into lower resolution structures. We contribute to new approaches to establish intraviral and viral-cellular protein-protein interaction networks.