Projektbeschreibung
Molekulare Einblicke in mikrobielle Abwehrmechanismen
Von Restriktionsenzymen bis hin zu CRISPR-Cas-Nuklease-basierten Editiersystemen haben Prokaryoten eine ganze Reihe von Immunreaktionen zur Bekämpfung von Parasiten entwickelt. Gleichzeitig haben sich diese Abwehrsysteme in den Händen der Wissenschaft als wertvolle Werkzeuge für die Gentechnik und die Genomchirurgie erwiesen. In den vergangenen Jahren wurden die Vor- und Nachteile der CRISPR-Geneditierungstechnologie deutlich, was die Notwendigkeit einer weiteren Entwicklung unterstreicht. Vor diesem Hintergrund wird das EU-finanzierte Projekt CRISPR2.0 die molekularen Strukturen und Mechanismen alternativer CRISPR-basierter Systeme untersuchen. Letztlich geht es darum, die Evolution der Abwehrmechanismen des Genoms zu verstehen und neuartige Genomchirurgie-Werkzeuge zu erstellen.
Ziel
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.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesgeneticsgenomesprokaryotic genomes
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
8006 Zurich
Schweiz