Description du projet
Un aperçu moléculaire des outils de défense microbienne
Des endonucléases de restriction aux systèmes d’édition basés sur la nucléase CRISPR-Cas, les procaryotes ont développé toute une batterie de réponses immunitaires pour combattre les parasites. Dans le même temps, ces systèmes de défense ont servi de précieux outils de génie génétique et d’édition du génome entre les mains des scientifiques. Ces dernières années, les avantages et les inconvénients de la technologie d’édition de gènes CRISPR ont été mis en évidence, soulignant la nécessité de poursuivre son développement. Dans ce contexte, le projet CRISPR2.0 financé par l’UE, étudiera les architectures et mécanismes moléculaires des systèmes alternatifs basés sur CRISPR. L’objectif final est de comprendre l’évolution des mécanismes de défense du génome et de générer de nouveaux outils d’édition de gènes.
Objectif
The constant arms race between prokaryotic microbes and their molecular parasites such as viruses, plasmids and transposons has driven the evolution of complex genome defence mechanisms. The CRISPR-Cas defence systems provide adaptive RNA-guided immunity against invasive nucleic acid elements. CRISPR-associated effector nucleases such as Cas9, Cas12a and Cas13 have emerged as powerful tools for precision genome editing, gene expression control and nucleic acid detection. However, these technologies suffer from drawbacks that limit their efficacy and versatility, necessitating the search for additional exploitable molecular activities. Building on our recent structural and biochemical studies, the goal of this project is to investigate the molecular architectures and mechanisms of CRISPR-associated systems and other genome defence mechanisms, aiming not only to shed light on their biological roles but also inform their technological development. Specifically, the proposed studies will examine (i) the molecular basis of cyclic oligoadenylate signalling in type III CRISPR-Cas systems, (ii) the mechanism of transposon-associated type I CRISPR-Cas systems and their putative function in RNA-guided DNA transposition, and (iii) molecular activities associated with recently described non-CRISPR defence systems. Collectively, the proposed studies will advance our understanding of the molecular functions of genome defence mechanisms in shaping the evolution of prokaryotic genomes and make critical contributions to their development as novel genetic engineering tools.
Champ scientifique
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesgeneticsgenomesprokaryotic genomes
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
8006 Zurich
Suisse