Ziel
CRISPR-Cas immune system represents one of the most effective weapons against mobile genetic elements in the host defense arsenal. Bacteriophages (phages) armed with anti-CRISPR proteins can, however, inhibit CRISPR immunity by sabotaging components of the immune system with evolutionary advantages. This proposal sets out to discover novel phage-encoded anti-CRISPR proteins and understand the molecular mechanisms of the inhibitory processes.
I will focus on novel anti-CRISPR proteins for Cas9-containing type II CRISPR-Cas systems in lactic acid bacteria (LAB). I expect anti-CRISPR proteins to be present in phages for LAB, for which the CRISPR system is an important line of defense. It is highly plausible that LAB-infecting phages have evolved to possess anti-CRISPR proteins. However, none of anti-CRISPR proteins against type II CRISPR have been described so far. To identify novel type II anti-CRISPR proteins encoded by phage genomes and explore novel features of the anti-CRISPR proteins, I will establish high-throughput screening methods using an integrated approach consisting of metagenomics, bioinformatics and mass spectrometry. After identifying candidate anti-CRISPR proteins, I will uncover the underlying molecular mechanisms of these viral anti-CRISPR proteins utilizing state-of-the-art single-molecule fluorescence methodologies.
The fierce virus–host arms race has resulted in high diversity of distinct prokaryotic CRISPR-Cas systems. Therefore, I anticipate that my high-throughput screening will lead to discovery of remarkably diverse anti-CRISPR proteins, specifically anti-CRISPR variants targeting Cas9. The proposed combination of viral diversity screening and single-molecule approaches will reveal novel mechanisms of anti-CRISPR activity that are difficult to obtain by traditional biochemistry, will impact potential applications of Cas9, and will provide unique insights into the host-virus arms race.
Wissenschaftliches Gebiet
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
- natural scienceschemical sciencesorganic chemistryorganic acids
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
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MSCA-IF-EF-ST - Standard EFKoordinator
2628 CN Delft
Niederlande