Systems Biology studies complex biological systems in a holistic approach. Rather than characterizing one single protein or pathway, systems biology studies the biological network as a whole, trying to fish for correlations or alterations of biological equilibria, which can then be analyzed more in detail by conventional approaches.
In this Structural Systems Biology approach, we aim at studying the entirety of a biological system, by characterizing multicellular tissues or also the entire proteome of one single cell. Here, the individuality of biological cells needs to be taken into account, as stochastic processes often govern cellular behavior, leading to significant differences between one cell and another.
Electron microscopy (EM) is a versatile tool for structural studies of biological samples at various resolution scales, ranging from cellular tissue to macromolecular complexes and down to the single molecule. In this presentation, several approaches of EM to systems biology will be presented. These include multi-cellular tissue characterization by Serial Block-Face Scanning Electron Microscopy, Electron Tomography, or a newly developed single cell structural proteomics approach, termed “Visual Proteomics”1 2 3 . In the latter, we have developed methods to extract the entire proteome from one single, hand-picked cell, which is then analyzed by transmission electron microscopy for establishing a structural inventory of the protein complexes present in that cell. An application to model cells for Parkinson’s disease is discussed.