Objective Riboswitches are mRNA-based gene-regulatory elements triggered by direct interactions with small molecular ligands. They are exciting targets for novel antibiotic strategies. Many putative riboswitches have been identified using bioinformatics. However, ligand identification is getting more complicated since many motifs are not expected to be involved in simple feedback regulation mechanisms. For such “classical” riboswitches ligands have been assigned in the past based on testing metabolites selected by educated guesses guided by the associated gene contexts. We are convinced that this approach limits the identification of riboswitches that play regulatory roles in more complex bacterial processes such as virulence, detoxification, communication, and life style adaptations. Within this project, new riboswitch classes will be identified and characterized, paving the way for the development of antibiotics with novel modes of action.We will establish a systematic, robust and unbiased approach for identifying intracellular RNA ligands by fishing small molecules from lysates as well as screening fractionated cellular extracts. The methodology shows great potential for assigning novel riboswitch classes since in preliminary experiments we have successfully isolated a small molecular activity that specifically triggers the ykkC orphan riboswitch motif. A range of analytical and preparative methods will be applied in order to identify the nature of this and further activities. By synthesizing ligands and derivatives thereof we will scout the antibiotic potential of novel riboswitch ligands. The proposed research is highly relevant for one of the major biomedical challenges of the coming decades: Since riboswitches are effective antibacterial targets, the identification of novel riboswitch / ligand interactions has immediate implications for establishing future antibiotic strategies necessary to keep in check the progressing problem of bacterial drug resistance. Fields of science natural sciencesbiological sciencesbiochemistrynatural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibioticsnatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2015 - ERC Consolidator Grant Call for proposal ERC-2015-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator UNIVERSITAT KONSTANZ Net EU contribution € 1 918 600,00 Address Universitatsstrasse 10 78464 Konstanz Germany See on map Region Baden-Württemberg Freiburg Konstanz Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAT KONSTANZ Germany Net EU contribution € 1 918 600,00 Address Universitatsstrasse 10 78464 Konstanz See on map Region Baden-Württemberg Freiburg Konstanz Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
