Objectif DNA replication is a fundamental biological process enabling the transmission of genetic information to progeny. In bacteria, its initiation involves a set of genes whose regulation is critical to ensure genome stability, both under optimal conditions and in response to environmental cues, including changes in nutrient availability. The highly conserved bacterial initiator protein DnaA has been proposed as a primary target for the nutritional control of DNA replication. Nevertheless, surprisingly little is known about the molecular mechanisms modulating its activity in response to nutrient limitation. Previous work showed that the synthesis and degradation of DnaA are both subject to control mechanisms that respond to environmental changes in the model organism Caulobacter crescentus. The 5’-UTR of dnaA mRNA was discovered to be required for the downregulation of the protein and the block of DNA replication initiation in response to nutrient depletions by a so far unknown post-transcriptional mechanism. Based on my preliminary in silico analysis I hypothesize that the 5’-UTR of dnaA can assume distinct conformations with different ribosome binding site accessibilities. Switching between these conformations is likely triggered by a trans-acting factor, either a small RNA, an RNA-binding protein or a metabolite, that is produced in response to nutrient availability. The present project proposal aims to elucidate the precise molecular mechanism underlying the post-transcriptional control of dnaA and to determine its consequences on DNA replication and cellular survival by combining classical biochemistry and genetics with cutting-edge molecular biology techniques. I expect that this work will contribute to the development of new strategies for bacterial growth control in industry and medicine. Importantly, the results of this study will provide key insights for the understanding of one of the most important biological processes: the regulation of DNA replication. Champ scientifique sciences naturellessciences biologiquesmicrobiologiebactériologiesciences naturellessciences biologiquesgénétiqueADNsciences naturellessciences biologiquesbiochimiebiomoléculeprotéinessciences naturellessciences biologiquesgénétiqueARNsciences naturellessciences biologiquesbiologie moléculaire Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2017 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2017 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-ST - Standard EF Coordinateur STOCKHOLMS UNIVERSITET Contribution nette de l'UE € 173 857,20 Adresse Universitetsvagen 10 10691 Stockholm Suède Voir sur la carte Région Östra Sverige Stockholm Stockholms län Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Autres sources de financement € 0,00
