Chemical Biology of Nucleic Acids

Ribonucleic acids (RNAs) are key components of the cellular machinery that facilitates gene expression. In addition to serving as messengers from genes to proteins, RNAs comprise a vast repertoire of other functions. For example, nucleic acids that catalyze reactions in analogy to enzymes (so-called ribozymes) have been characterized. Other types of RNA (so-called aptamers) are able to behave similar to antibodies, binding tightly and specifically to target molecules.

In addition, RNA functions can be combined in a truely modular fashion. By combining different functional RNA motifs in one molecule, we are aiming at rationally designing desired properties of the resulting sequence. Specifically, we are interested in gaining enhanced control over several RNA functions. For example, we are aiming at controlling RNA functions such as catalytic activity (ribozymes), binding affinity (aptamers), as well as participation in the regulation of gene expression (riboswitches and RNA interference).

By following the guidelines of the emerging field of synthetic biology, we are engineering nucleic acids which can be regulated by external stimuli such as the addition of small molecules. In order to render the nucleic acid function "switchable", we attach suited sequences that allow external regulation. Aptamers binding to small molecules are well suited for such purposes. In addition, we are exploring the use of guanine-rich, four-stranded nucleic acids (so-called quadruplexes) as regulatory domains in biological processes.