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GRK 1384:  Enzymes and Multienzyme Complexes Acting on Nucleic Acids

Subject Area Basic Research in Biology and Medicine
Term from 2006 to 2015
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 19985993
 
Final Report Year 2016

Final Report Abstract

The International Research Training Group (IRTG) was formed by scientists from the Justus‐Liebig‐Universität Giessen, the Philipps‐Universität Marburg, the Lomonosov Moscow State University and the Russian Academy of Sciences. In addition, scientists from the Institute of Biotechnology (Vilnius) and the International Institute of Molecular and Cell Biology (Warsaw) were associated. All participants were selected based on the strength of their expertise in enzymology, molecular and cellular biology, bioinformatics, structural biology, bioorganic and biophysical chemistry. The IRTG focussed on the training of doctoral researchers in the biochemistry of enzymes and multienzyme complexes acting on nucleic acids. These enzymes are crucial for copying, maintenance, repair, and expression of genetic information. Malfunction of several of these enzymes is causally related to human diseases, and understanding their mechanism of action may eventually lead to new therapeutic concepts. Our study and research programme did not only consider proteins as individual structures, but also as components of macromolecular machines or larger networks. Using an array of interdisciplinary expertise present among the partners, we made substantial progress in understanding the structure and function of these enzymes and enzyme complexes, as well as in uncovering functional implications of the cooperation of subunits in multienzyme complexes. Our network based on three main pillars: classical and cutting‐edge methodologies to investigate chromatin/DNA‐ and RNA‐associated processes, modern global genome/transcriptome‐wide experimental approaches, and bioinformatic expertise and capacities. The doctoral researchers analysed in detail the molecular mechanisms of how enzymes acting on nucleic acids function at the single‐molecule level and used this knowledge to develop cutting‐edge tools e.g. for precision genome surgery. Moreover, we used novel chemical and biochemical approaches to investigate large, complex and dynamic complexes both in vitro for high‐resolution structural analysis as well in vivo on a global scale. During the course of the IRTG the emerging role of small non‐coding RNA in cellular function was investigated, and tools for high‐precision genome engineering were developed. High‐throughput approaches, including RNA (RNA‐Seq) deep sequencing, or ChIP‐based techniques, such as ChIP‐Chip or ChIP‐Seq combined with bioinformatic analyses opened up global and integrated views of the dynamics of expression and the processing of genetic information. We attracted dedicated doctoral researchers who learnt and applied contemporary interdisciplinary approaches to address important and timely questions about a subject of central importance in biochemistry and molecular biology, namely the enzymology of enzymes acting on nucleic acids. Our network offered unique opportunities to pursue research projects in an environment of research excellence provided by partners who have similar interests and complementary expertise.

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