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Epigenetics / Chromatin Chemical Biology

The regulated expression of genes underlies virtually any biological process ranging from development and cell differentiation to the onset of disease such as cancer. The majority of this regulation takes place at the level of chromatin and transcription.
However, the picture of gene expression regulation has reached a dazzling complexity in the last decade, owing to the discovery of a wealth of regulatory elements that dynamically control the structure, molecular composition and transcriptional activity of chromatin. These include long-range chromatin interactions, noncoding RNA transcripts and the dynamic decoration of DNA, RNA and nuclear proteins with regulatory chemical marks.

While the mere discovery and mapping of regulatory elements becomes increasingly straightforward, the knowledge of their precise biological roles remains however largely incomplete, since detailed studies of the structure, function and dynamics of the involved protein-nucleic acid complexes in an unperturbed, cellular environment are hampered by a lack of suitable methodology.

Our group is focused on generating new insights into the function of regulatory elements in chromatin by approaches of chemical biology. We aim to identify novel strategies to reengineer basic molecular properties of nucleic acid-interacting proteins directly in cells and with high precision. This involves the modulation of molecular recognition (i.e. the selectivity and predictability of DNA- and RNA-binding) and the engineering of (physico)chemical properties (i.e.  reactivity and spectroscopic accessibility). We thereby combine a range of chemical and biological methodologies including organic synthesis, biomolecular chemistry and genetic code expansion, directed molecular evolution and high throughput genomic analyses.

See publication list for previous projects.

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