Schanda Group

Biomolecular Mechanisms from Integrated NMR Spectroscopy

Life is in motion. While one immediately realizes the inherently dynamic aspect of living organisms on the macroscopic level, simply by observing it by eye or under a microscope, it is clear that ultimately it is the jiggling and wiggling of the atoms within molecules, and their interactions with each other, that allow life to unfold.

The Schanda group is particularly interested in understanding how biomolecules – primarily proteins – perform their tasks, and how their structural dynamics governs their functions. Their work has several aspects. On the one hand, the group studies a number of puzzling biological questions. For example, how do proteins transport other proteins across the cell, across biological membranes or into membranes? By studying how those proteins – chaperones, receptors, translocases – are structured, how they move and how they interact, they decipher how cells are able to transport large and highly aggregation-prone polypeptides all across the cell and ultimately refold them into their native environment. For example, this work unravels how membrane proteins are getting imported into mitochondria, or how megadalton-large chaperones help other proteins to fold.

On the other hand, the group is interested in somewhat more fundamental physio-chemical aspects of protein dynamics. How do the motions around the active site of an enzyme control its function? And how exactly do the side chains and main chain of proteins move – in solution, in crystals, and in large assemblies? How do protein domains move relative to each other, and does the packing in biological assemblies or crystals impact this motion?

To answer these questions, the Schanda group uses nuclear magnetic resonance (NMR) spectroscopy, which they combine with a host of other biophysical, biochemical, in-silico and in-vivo methods. The integration of these methods, and the further development of NMR methodology is another key interest of the group, as they develop, for example, methodologies that allow solving three-dimensional structures of large proteins or protein complexes from novel NMR experiments, coupled to cryo-EM. Other new NMR methods allow to decipher in great detail how particular parts of proteins move, which then allows linking those motions to function.

The group, thus, spans activities from nuclear spin dynamics and biophysics to challenging biological problems.