Johannes Gutenberg Univ. Mainz, DE
Synthesis and detection of RNA modifications
Mark Helm is an Associate Professor at the University of Mainz and a Professor for Pharmaceutical Chemistry. He holds a Personal Chair in RNA and Gene Expression. He did his Diploma at the Univesity of Würzburg in Chemistry and Ph.D. at the IBMC du CNRS, Strasbourg, France. In 1999, he moved to the USA to carry out postdoctoral research in the laboratory of G. Attardi (California Institute of Technology).In 2001, he joined the Institute for Chemistry at the Free University of Berlin.
The Helm group integrates disciplines from chemistry, biology, physics, bioinformatics, and pharmacy to advance research on nucleic acids, in particular on RNA. The central focus is on RNA modifications of natural or synthetic origin. Insight into how and why nature chemically modifies ribonucleosides guides the design and synthesis of man-made nucleic acids, with applications in fundamental science, biotech, and therapy alike. The Helm group has made significant contributions to two major areas of interest which are RNA modification and delivery of modified RNA. We have been able to do so mainly because we maintain a balanced spectrum of in-house competences and cooperations that includes synthetic organic chemistry, single-molecule biophysics, sophisticated RNA biochemistry, cutting edge RNA analytics, and cell culture. The methods applied in the Helm group are acquired or adapted according to scientific demands, but in the basic repertoire is a strong emphasis on nucleic acid bioconjugate chemistry. This concerns in particular the so-called ”clickâ chemistry, for example by Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC), which is most frequently applied to label with fluorophores. Analytics of RNA bioconjugates, as well as of naturally occurring modifications are typically analyzed by HPLC-MS. Fluorescence labeling enables tracing of RNA molecules in extremely small quantities, and the combination of two communicating fluorophores allows sophisticated investigations by Förster Resonance Energy Transfer (FRET) of parameters such as structural dynamics and RNA integrity.