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TRR 267:  Non-coding RNA in the cardiovascular system

Subject Area Medicine
Biology
Term since 2019
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 403584255
 
Despite considerable therapeutic progress, diseases of the cardiovascular system are still the leading cause of death in Western societies and worldwide. In the last two decades, drug development based on protein targets has yielded only incremental benefit, thus prompting a paradigm shift towards new classes of targets and drugs. Nucleic acids open enormous possibilities, both as targets or active therapeutic entities. This became evident by the success of mRNA-based COVID-19 vaccines, and also by the approval of several oligonucleotide-based drugs – achievements that became possible through breakthroughs in nucleic acid technologies, including the synthesis of chemically modified and cell type-directed nucleic acids. In parallel, non-coding (nc)RNA molecules were unravelled as a new class of drug targets in various diseases, including cardiovascular disease where the first ncRNA-targeting drugs are now in Phase I/II clinical trials. Nonetheless, the field faces the tremendous task to identify critical ncRNAs among the thousands of unexplored candidates, to define their cardiovascular role, and to develop their therapeutic manipulation. The Collaborative Research Centre TRR 267 was founded in 2019 as the first research consortium in Germany to focus on ncRNAs in a disease context. Our consortium has applied and improved highly innovative methods for ncRNA analysis, including TWAS to identify disease-disposing SNPs in ncRNA genes, quantitative and spatial expression analysis at the single-cell level, and RNA imaging at the subcellular level. TRR 267 has discovered, characterised and validated ncRNAs as targets in cardiovascular disease and provided proof of concept for their therapeutic exploitation. Strong scientific output, a powerful transdisciplinary structure, and efficient career programmes make TRR 267 a highly visible consortium, and our policy of innovation and collaboration will continue to push this nascent field further. A key facet are recruitment and career programmes to increase the proportion of female scientists and scientists in their early career. We will also further strengthen the sharing and analysis of data to optimise the collaborative usage of the immense amount of information generated. Whereas our principle structuring in two research areas for cardiovascular ncRNAs remains (A: Regulation & mechanisms of action, B: Disease relevance), we will adjust the project focus where needed to adapt to new scientific questions. A further emphasis is placed on lncRNAs, where the few of the candidates analysed thus far (>19000 are believed to be functional) have clearly demonstrated therapeutic potential. Three of the four new research projects focus on lncRNAs and each of them is led by an early-career PI. Adaptions to emerging scientific questions, a growing connectivity to translational consortia, and structural measures will continue to strengthen the prominent position of TRR 267 in the evolving field of non-coding RNAs.
DFG Programme CRC/Transregios

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Co-Applicant Institution Goethe-Universität Frankfurt am Main
 
 

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