Research group Junior-Prof. Dr. Alexander Marchanka

Solid-State NMR of biomolecules

In our group we are working on the development of new solid-state NMR methods for structural characterization of RNA. We are investigating disease-related viral and bacterial RNAs by NMR, EPR and complementary biophysical techniques to obtain valuable structural and functional information on the RNA molecule. The availablity of the precise structural information will support development of new effective drugs and contribute to the fast growing field of RNA therapeutics.

Solid-State NMR of biomolecules

In our group we are working on the development of new solid-state NMR methods for structural characterization of RNA. We are investigating disease-related viral and bacterial RNAs by NMR, EPR and complementary biophysical techniques to obtain valuable structural and functional information on the RNA molecule. The availablity of the precise structural information will support development of new effective drugs and contribute to the fast growing field of RNA therapeutics.

RESEARCH: SOLID-STATE NMR SPECTROSCOPY

Ribonucleic acids (RNA) play crucial functional and regulatory roles in cellular processes. While RNA is one of the most significant parts of complexes, such as ribosomes or spliceosomes, it also represents the most important component of riboviruses and retroviruses. The elucidation of RNA activity mechanisms requires knowledge of their structure. This task is difficult for large RNAs due to the limited applicability of most main-stream structural biology methods for large RNAs. Solution-state NMR has an intrinsic molecular weight limit and faces severe difficulties for RNA longer than 100 nucleotides. X-ray crystallography and cryo-EM on RNA is complicated due to the high flexibility of the RNA. Flexible regions of RNA that are most interesting and provide the basis of molecular recognition are almost invisible to X-ray or EM.

Solid-state NMR (ssNMR) represents an emerging structural biology technique s that can be applied to biomolecular complexes of any size and allow selective zoom on the relevant areas of biomolecules. Although ssNMR has been successfully applied to structural studies of membrane proteins, assemblies and fibrils, studies on RNA by solid-state NMR remain limited. We have pioneered solid-state NMR on RNA and are one of the few groups that are actively working on this topic.

Research in our group has two major directions. One direction of research is focussed on developing of ssNMR methodology to address structure and dynamics of RNA in large protein-RNA and RNA-RNA complexes. Second direction of our research includes structural characterization of disease-related viral and bacterial RNAs by solid-state NMR-driven integrative structural biology. Identification of their mechanisms of action will contribute to development of new effective drugs and new methods of treatment of these diseases.