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Anti-CRISPR

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Uncovering viral sabotage of host CRISPR Cas immune systems

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 sa... ver más

14/01/2020

TU Delft

178K€

Presupuesto del proyecto: 178K€

Líder del proyecto

TECHNISCHE UNIVERSITEIT DELFT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-01-14

MSCA-IF-2016: Individual Fellowships

I+D

Cerrada hace 8 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

TU Delft

177.60K€ | Lider

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Duración del proyecto: 33 meses Fecha Inicio: 2017-03-17
Fecha Fin: 2020-01-14

Líder del proyecto

TECHNISCHE UNIVERSITEIT DELFT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 178K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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