Research

Past and current research

Cells form the smallest autonomous units of life. Supramolecular complexes perform all essential cellular functions and processes and are also the basic structural elements of cells. The strictly regulated structural and functional organization of a cell at this level is currently only rudimentarily understood. A comprehensive analysis of this organization and its dynamic changes requires methodological approaches that allow to study these complexes in their natural environment. We use cryo electron tomography (KryoET) in combination with other techniques to study selected aspects of this highly ordered network and to analyze protein complexes in situ. Sample preparation by rapid freezing, under formation of amorphous ice, ensures excellent structure preservation down to atomic detail.

The research group has significantly advanced the application of cryo-electron tomography for the structural analysis of pleomorphic viruses. Examples are the elucidation of the three-dimensional supramolecular organization for herpes, retro- and bunya viruses. Next, we concentrated on the cell biology of viral infection. Understanding the entirety of a viral "life cycle" requires understanding its various transient structures and states at the molecular level. The goal is to obtain a comprehensive picture of the functional interactions between viral protein complexes and cell structures during the course of infection. Viruses also serve as dedicated tools to decipher molecular details of cellular processes. Viruses are e.g. able to enter the cell physiologically and are also well distinguishable among the numerous other structures within the cytoplasm of the host cell. This gives us the possibility to better understand dynamic cellular processes.

Cryoelectron microscopy offers an excellent platform for the combination with other approaches, such as biochemical and X-ray crystallographic investigations and the integration of this information with native subcellular structural information. Driven by our biological questions we are involved in various method developments. These include e.g. the combination of cellular and molecular cryoET with single particle approaches, or advanced fluorescence (cryo)microscopy or X-ray cryo-microscopy / tomography, typically in a correlative approach. We also work on better integration with protein-protein interaction data (e.g. from mass spectrometry) and molecular dynamics simulations.