Life is not static and neither are the majority of proteins crucial to the function of our cells. However, our structural understanding of these microscopic machines is often limited to one or at best few static snap-shots.
We focus on the application of electron microscopy to visualize such dynamic entities in a native-like environment in order to deduce the structural pathways at the heart of biological processes. Different from e.g. protein crystallization, EM allows for the rapid trapping of intermediate states by either vitrification (“snap freezing”) or by chemical crosslinking in heavy metal stains. Trapped structures can then be determined to high resolution, visualizing the key structural transitions that are associated with a protein's biological activity.
Our main interest is in those proteins that are associated with or embedded into the lipid membranes of our cells. Membranes are paramount for the identity of a cell, as they shield the interior from the surrounding environment, but must not be static as controlled passage over these biological barriers is necessary for life. The structural basis for how proteins can give diverse functions to membranes is still largely lacking, especially with regard to the dynamic interplay between lipids and proteins. To allow us to visualize such dynamic entities in their native-like environment, we furthermore develop sample preparation strategies that will enable us to investigate membrane proteins in defined functional states.