Our laboratory explores unknown roles of RNA modifications, in particular RNA-linked coenzymes, in biology. Furthermore, we develop methods for imaging and microscopy of RNA in living cells, with a focus on super-resolution techniques. In another research area we develop, characterize and apply photoswitchable biomolecules. We also have a long-standing interest in the origin of life. Our work combines organic synthesis with molecular and cellular biology, biochemistry, bioinformatics and modern bioanalytical methods.
A list of our equipment can be found here!
NEW RNA MODIFICATIONS IN BIOLOGY
At first glance, RNA appears to be a very simple biomolecule, composed of only four monomers. However, it is becoming increasingly clear that the more than 200 known natural chemical modifications affect the functions of RNAs. We have discovered RNAs in bacteria that are linked at their 5' end – in a cap-like manner – to the central redox coenzyme NAD+. This work has established the new field of non-canonical capping, and the NAD captureSeq method developed by us has been adapted in numerous laboratories world-wide. We study how the NAD is incorporated into RNA, how it is removed, and what functional changes it causes in RNA. We are also looking for RNAs that are linked to other coenzymes, such as coenzyme A, FAD, and thiamine, and aim to establish their biological relevance. This work is funded by an ERC Advanced Grant and by the German Research Foundation.
Fluorescent proteins such as GFP have revolutionized molecular cell biology because - after attaching to a target protein - they allow its fate to be determined from biosynthesis to interactions and degradation in living cells. Unfortunately, there are no naturally fluorescent RNAs that could play a similar role in the further development of RNA biology. We are developing new imaging systems based on aptamers. We have developed dye-binding aptamers in combination with contact-quenched fluorescent dyes, which we have successfully used for SIM super-resolution microscopy. Another high performance system based on silicon rhodamines allows for the first time the observation of RNAs in living cells using STED microscopy.
Our newest spyrocyclic dye is comercially available at https://spirochrome.com/product/spyrho/
Light is a convenient and powerful trigger to control the reactivity of biomolecules. Complex and compartimentalized environments, such as cells, not only benefit from the non-invasive and non-interfering nature of light, but also from its high spatial and temporal resolution. We have invented entirely new classes of diarylethene photoswitches in which one of the aryl residues is a purine or pyrimidine nucleoside, a nucleotide, or even an oligonucleotide. We have been improving these photochromic compounds over the years, and our current photoswitches offer full reversibility over up to 200 switching cycles, near-quantitative switching and high thermal and photophysical stability. These compounds enable new applications in bionanotechnology, information storage and processing, and synthetic biology.
ORIGIN OF LIFE
The Jäschke lab has a long-standing interest in the origin of life. Currently, we study – in collaboration with Dieter Braun’s lab in Munich – the evolutionary origin of the genetic code. The genetic code links a three-letter nucleobase code to the corresponding amino acid. It encodes proteins from genetic information and is a fundamental and essential mechanism of life. Theories, speculations, and correlations are abundant regarding the evolutionary origin of this code, but there are very little experimental data. We try to answer – by combining ultrahigh-throughput kinetics, next-generation sequencing, and microscale thermophoresis – whether there are intrinsic differences in binding affinity or reactivity between different RNA sequences that may have given rise to the original assignment of a certain triplet to a specific amino acid.
PAST RESEARCH AREAS
RIBOZYMES AND SELEX
We have isolated RNA molecules from combinatorial libraries that catalyze C-C bond formation by Diels-Alder reaction. These catalysts show remarkable stereo-, regio- and chemoselectivities. We could demonstrate true catalysis of bimolecular reactions, enantioselective bond formation, and catalytically active L-nucleic acids. The mechanism and kinetics of the reaction have been investigated using spectroscopic, crystallographic, and computational methods in combination with mutation analysis and various substrate and product analogs, chemical and enzymatic probing, fast kinetic methods, and nucleotide analog interference mapping. This research has turned the Diels-Alderase ribozyme into the most-studied artificial ribozyme known.
If you are intrested in using our equipment please get in touch with us.
300 and 500 MHz
HR-ESI, MALDI, APCI and LC-MS
Typhoon FLA 7000
32P and 35S
Leica DM IL LED