Group Goldeck/Holzer/Mikula
Research Focus
Our research focuses on the chemistry and biology of nucleic acids, with an emphasis on these biomolecules’ capability to provide highly versatile messenger molecules. The most prominent way of encoding information is their base sequence, that is translated by the ribosome machinery to produce proteins. Additionally, a great variety of nucleic acid modifications at the bases or internucleotide linkages as well as the nucleic acid structure and conformation can encode different information that is read out by a large set of nucleic acid sensors and processing enzymes. Given these key functions and the enormous regulatory potential, nucleic acids have become an important target for diagnostics and drug design. However, current tools to manipulate and measure nucleic acids are still limited due to several reasons.
Main Objectives
Within the Young Investigator Research Group bioSTAR we aim for the design and development of programmable chemical probes capable of selectively binding to a specific RNA sequence followed by a bioorthogonal reaction. This approach will improve the binding to target RNA and furthermore enable the regulation of gene expression, which – for example – can be used to design new antibiotics based on the genetic code of bacteria. Hence, such probes can rapidly be redesigned if bacterial resistance arises due to mutation of the target, and thus may enable the development of therapies against antibiotic-multiresistant bacteria. Furthermore, the bioorthogonal reaction can be designed in such a way that an active molecule is released right upon and induced by the binding to the target sequence. We aim to use this cleavage mechanism to achieve selective release of fluorescent reporters or highly potent drugs inside cells.
Content of Research
For the design and development of such novel antisense oligonucleotide we are applying an interdisciplinary approach combining chemical, biological and biophysical tools. We are applying click-chemistry based approaches for the synthesis of programmable oligonucleotides that we then characterize in different biological systems including mammalian cell lines as well as bacterial cells. Additionally, biophysical approaches including surface plasmon resonance experiments allow for an in-depth analysis of the binding kinetics and selectivity of our probes.
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