Our main focus is to reveal the macromolecular organization of living cells by means of cryo-electron tomography. Cryo-electron tomography is the only technique that allows to obtain molecular resolution images of intact cells in a quasi-native environment. The tomograms contain an imposing amount of information; they are essentially a three-dimensional map of the cellular proteome and depict the whole network of macromolecular interactions. Information mining algorithms exploit structural data from various techniques, identify distinct macromolecules and computationally fit atomic resolution structures in the cellular tomograms, thereby bridging the resolution gap.
A multitude of biological questions can be answered by electron tomography; visualization of the cellular structure at molecular resolution is largely uncharted territory. The team works with a wide spectrum of specimens, including prokaryotic and eukaryotic cells, but also model systems. Prokaryotic cells are smaller and can therefore be easily penetrated by the electrons. Eukaryotic cells have compartments in which the protein density is lower, facilitating pattern recognition techniques. Model systems, on the other hand, are particularly helpful in improving computational algorithms and in providing solutions for cell systems that are too complex to be investigated by electron tomography. Hence we visualize macromolecules in an unperturbed cellular environment and chart the network of interactions underlying cellular functions.
Fig. 01: The 3D reconstruction of a human endothelial cell: The image was generated by cryo electron tomography. The organelles are depict in different colours: Cell-cell contact sites (light brown), nucleus and nucleus membrane (blue), nuclear pore (red), microtubule (green), mitochondria (pink) and endoplasmic reticulum (grey blue).