Descrizione del progetto
Approfondimento molecolare sugli strumenti di difesa microbica
Dalle endonucleasi di restrizione ai sistemi di editing basati sulle nucleasi CRISPR-Cas, i procarioti hanno sviluppato una serie di risposte immunitarie per combattere i parassiti. Allo stesso tempo, gli scienziati si sono avvalsi di questi sistemi di difesa come preziosi strumenti di ingegneria genetica e di editing del genoma. Negli ultimi anni sono emersi i pro e i contro della tecnologia di editing genetico CRISPR, il che sottolinea la necessità di ulteriori sviluppi. Alla luce di ciò, il progetto CRISPR2.0 finanziato dall’UE, approfondirà le architetture molecolari e i meccanismi dei sistemi alternativi basati su CRISPR al fine di comprendere l’evoluzione dei meccanismi di difesa del genoma e generare nuovi strumenti di editing genico.
Obiettivo
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.
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsDNA
- natural sciencesbiological sciencesgeneticsgenomesprokaryotic genomes
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
8006 Zurich
Svizzera