Electron cryo Microscopy of Biological assemblies and Macromolecular complexes
The organization of proteins and/or RNA into assemblies can be regarded as the first layer of integration that converts bulk chemical reactions into temporarily and spatially co-ordinated processes. This temporal and spatial patterning is a decisive factor of living systems.
At the low level this co-ordination is realized by larger complexes that combine different functionalities and act as scaffolds that co-ordinate down-stream and up-stream factors. We want to understand the building principles that enable such integration. In particular we want to elucidate how different components and modules of complexes can generate interdependent functionalities.
We use a multidisciplinary experimental approach that combines structural, biochemical and biophysical information. At the heart of our methodological portfolio is structure determination by electron cryo microscopy and image processing. This is a powerful method for elucidating the structure and conformational plasticity of biological assemblies. The method allows imaging of complexes “in solution” under a wide range of conditions in different functional states.
Combining many thousands of images of a certain complex often results in three-dimensional structures with almost atomic resolution. Statistical methods give further information on the probable conformational and compositional sub-state of each individual complex in a population of complexes.
Electron cryo microscopy is widely applicable. We are interested in many different complexes. Some are molecular machines in RNA-processing, such as the Ccr4Not complex, RNA-polymerases or RNAse P/MRP. Other complexes are involved in sensing pressure in bacteria (mechanosensitive channels), organizing the active zone of synapses or are viral capsids that segregate and protect the viral genome.