Cryo-electron microscopy (cryo-EM) has established itself as a key technique for studying the structure of large and flexible macromolecular complexes at subnanometer resolution. However, the overall challenge today is to bring the molecular resolution enabled by cryo-EM (‘singleparticle’ analysis) to cellular studies (e.g. by cryo-electron tomography, cryo-ET or CET), bridging the divide between molecular and cellular structural studies. The application of cryo-electron tomography (cryo-ET) to complex cellular systems like large cells or tissues is commonly referred to as ‘cellular tomography’. It allows the three dimensional (3D) visualization of the supramolecular architecture of cells in a ‘close-to-life’ state.
To enable the study of biological systems in situ and at different scales (e.g. from ‘cells to molecules’), methods are needed which are capable of navigating, targeting, imaging and analysing complex biological samples in their native environment. Thus major activities of the cryo-EM group aim at developing instrumentation and methodology for in situ structural biology on frozen hydrated biological specimens, namely correlative cryo-fluorescence microscopy, cryo-focused ion beam milling and cryo-electron tomography. With this approach cryo-ET will provide highly resolved 3D maps of the cellular ultrastructure. The cryo-EM group moreover utilizes cryo-electron microscopy/tomography together with novel preparation and advanced computational methods and pair them to other techniques for structural analysis(e.g. NMR, X-Ray and Mass spectrometry), biological imaging and biochemical analysis.
Complexes that are associated to lipid membranes and transient macromolecular complexes carry out many important cellular functions, but their structures are largely elusive to date because these types of macromolecules are extremely difficult to assess by established reductionist approaches. The group of prof. dr. Friedrich Förster studies such complexes in situ using cryo-electron microscopy techniques, protein-protein interactions, and computational modeling. Using this approach, they elucidate the molecular machinery that is associated to the endoplasmic reticulum (ER) and mitochondrial membranes. Specifically, we are interested in the structural basis of ER- and mitochondria-associated protein biogenesis and degradation..