Our research group is interested in understanding how RNAs change structures in order to perform their function. Until recently, only snapshots of molecules could be observed, hiding their modus operandi. We employ Nuclear Magnetic Resonance (NMR), and other biophysical techniques, to investigate the molecular mechanism of RNA function. When function of these molecular machines becomes apparent, it also provides a variety of unique new drug targets. The lab develops methods in NMR and RNA biochemistry to address these questions. Current projects include viral, bacterial and eukaryotic regulatory RNAs, e.g. microRNAs, ribosomal RNAs or RNA from HBV.
The human genome encodes more than 1500 microRNAs regulating at least 30% of all proteins expressed. Dysregulated miRNAs have been found in cancer and play a central role in cellular and organism development. Understanding miRNA structure and motion will allow to comprehend and manipulate miRNA function. We study miR-34a that activates the cancer suppression protein p53 by interacting with the mRNA of the Sirt1 protein. miR-34a also targets other mRNAs important to all type of cellular function (e.g. CD44, Jagged, Notch…), but until now it is not known why which specific mRNA is selected and when.
The ribosome is the largest known RNA machine and its motions correlated to function have been characterized on a global structural level with snapshots produced by X-ray Crystallography and Cryo-Electron Microscopy. Unfortunately, no dynamic measurements have yet been accomplished to understand and characterize these motions at atomic level. The interface spanning helix 44 is a central part of these motions and we investigate alternative states in this helix leading to the ratchet motion the ribosome executes to transport the tRNA–mRNA complex from A- to P- to E-site, when producing now proteins.
Measuring motions in RNA is size limited; we intend to push those limits with new and modified pulse sequences as well as with clever sample production. Furthermore, current measurements are time consuming and give limited information, we work on increasing the probes we can test. Our lab is also working to combine NMR with other methods to elucidate RNA motion in more detail and overcome current limitations.