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Research in the Dieckmann Lab
RNA Biophysics, Structure and Function
Dr. Thorsten Dieckmann
NMR-spectroscopy, RNA and protein structure, RNA-protein interactions, RNA catalysis, viral infections and cellular defense mechanisms
Nuclear magnetic resonance spectroscopy has developed into a powerful method for the structure determination of small and medium sized proteins (up to ca. 250 aa) and nucleic acids (up to ca. 50 nt) in solution. NMR spectroscopy is in many ways complementary to x-ray crystallography: The structures are obtained in solution, its strength lies in the area of smaller biomolecules, and NMR allows a detailed study of weak intermolecular interactions and dynamic processes.
RNA plays a central role in numerous central processes in all living cells. It fulfills functions ranging from structural roles (in vaults and ribosomes) over that of an information carrier (mRNA, viral genomes) to catalysis (self-splicing introns, plant virus ribozymes). The "RNA-world" hypothesis assumes an even greater importance of RNA with it being the sole information carrier and catalyst for all reactions in pre-biotic times and maybe in primitive life forms. The laboratory will focus on two areas of RNA related research: Small RNAs with interesting ligand binding or catalytic properties and the structure and function of RNA-protein complexes.
Aptamers are RNA or DNA molecules that have been selected in vitro to bind to a ligand of choice. In vitro selection experiments have been used to evolve the ATP-binding aptamer into a 5’-RNA kinase. The determination of the structure of this kinase ribozyme and the study of its reaction mechanism will provide important insights into RNA evolution and its role as a catalyst. Other small RNAs of interest include a phenylalanyl-tRNA synthetase binding aptamer and self-aminoacylating RNA.
The structure determination of RNA and RNA-protein complexes by NMR requires the development and application of heteronuclear, multi-dimensional NMR techniques in combination with complete or specific 13C, 15N, and 2H labeling of the molecules under investigation. In addition in vitro selection can be applied to find RNAs with high affinities for target proteins or modules of these proteins. The study of ion-binding to RNA and the investigation of the molecular dynamics of free RNAs and their complexes will add to a more complete picture of the structure and function of RNA and RNA-protein interactions on a molecular level.