Research

The central theme of our research are the structural dynamics of biopolymers, in particular RNA and protein folding in all its flavors - folding into three-dimensional structures, refolding between multi-stable conformations and unfolding of structures during metabolic processes. 

RNA is the central biomolecule in regulatory processes among all living cells, and its structural dynamics are essential for its functionality. In particular bacterial mRNAs feature a plethora of structural elements such as riboswitches, ribozymes and RNA thermometers that modulate essential processes such as transcription, translation and degradation through their structural dynamics. These dynamics are however dependent on intrinsic molecular features of the RNA and also on its interaction partners in the involved macromolecular complexes e.g. RNA polymerase and the ribosome in the expressosome.

 

To describe refolding reactions of RNAs in isolation as well as its functional macromolecular complexes in terms of kinetic, thermodynamics and structure at atomic resolution, we use NMR spectroscopy as the major experimental tool.

 

NMR- experiments are supplemented with other biophysical techniques such as fluorescence and CD-spectroscopy.

Specifically, we are interested how proteins also as part of large macromolecular complexes modulate the folding landscape of RNAs and regulatory RNA elements. Proteins with such functionality are RNA chaperones and RNA helicases. Whereas the latter class of proteins requires external energy sources, chaperones shield repulsive interactions in the RNA solely by means of transient interactions. However, for both -helicases and chaperones- an exact atomistic description on how RNAs are un- or re-folded upon interaction with the proteins is largely missing. Particular, the interplay of mutual dynamic changes during the interaction of the chaperone/helicase and the target RNA is poorly understood. Richard Feynman taught that “everything that living things do can be understood in terms of the jiggling and wiggling of atoms”, therefore we hypothesize that RNA based regulation of cellular processes can only be fully comprehended once the modulation of RNA folding by proteins is deciphered.