Chemical Biology of Transcription Regulation
The regulated expression of genes is key for the correct execution of virtually any biological process and consequently, its deregulation
leads to the development of various diseases including cancer. The majority of this regulation takes place at the level of transcription.
However, the current picture of transcription regulation has reached a dazzling complexity in recent years, owing to a wealth of
new regulatory elements that have been identified in genomics projects, such as novel genomic protein binding sites and RNA transcripts
with potential regulatory functions. This is further complicated by a previously unknown complexity of the epigenetic modification
repertoire of genomic DNA. However, while the mere discovery and mapping of such regulatory elements becomes increasingly
straightforward, the knowledge of their actual biological roles remains largely incomplete, since detailed structural and functional studies
of the involved protein-nucleic acid complexes in an unperturbed, natural environment are hampered by a lack of suitable methodology.
Our group is focused on getting new insights into the functions of transcriptional regulatory elements that are enabled by approaches of
chemical biology. We aim to identify novel strategies to manipulate 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 of (physico)chemical properties (i.e. nucleic acid-directed reactivities and spectroscopic accessibility).
Selected Recent Publications
G. Kubik, M. J. Schmidt, J. E. Penner and D. Summerer*, Programmable and highly resolved detection of 5-methylcytosine by TALE-controlled DNA replication, Angew. Chem. Int. Ed., 2014, in press.
M. J. Schmidt, A. Weber, M. Pott, W. Welte and D. Summerer*, Structural basis of furan-amino acid recognition by a polyspecific aminoacyl-tRNA-synthetase for its genetic encoding in human cells, ChemBioChem, 2014, in press.
M. J. Schmidt and D. Summerer*, Genetic code expansion as a tool to study regulatory processes of transcription, Front. Chem., 2014, 2 (7), 1-11.
M. J. Schmidt, J. Borbas, M. Drescher* and D. Summerer*, A genetically encoded spin label for electron paramagnetic resonance distance measurements, J. Am. Chem. Soc., 2014, 136, 1238-41.
M. J. Schmidt, D. Summerer*, Red-light-controlled protein-RNA crosslinking with a genetically encoded furan, Angew. Chem. Int. Ed., 2013, 52, 4690-93.
D. Summerer*, High-throughput DNA sequencing beyond the four-letter code: epigenetic modifications revealed by single molecule bypass kinetics, ChemBioChem, 2010, 11, 2499-501
D. Summerer*, Enabling technologies of genomic-scale sequence enrichment for high throughput sequencing, Genomics, 2009, 94, 363-8