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Adaptive immunity in prokaryotes how Bacteria do not forgive and do not forget...

Adaptive immunity in prokaryotes how Bacteria do not forgive and do not forget their enemies Microbes in natural ecosystems are under constant evolutionary pressure from viruses. To survive in this hostile environment microbes have evolved an adaptive immune system called CRISPR-Cas. The immune system is based on incorpor... ver más

31/05/2020

TU Delft

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

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

TRL 4-5

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-05-31

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-StG-2014: ERC Starting Grant

I+D

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3 Participantes

TU Delft

1.37M€ | Lider

SERVICIO INDUSTRIAL DE ELECT...

424.93K€ | Participante

125.89K€ | Participante

Últimas noticias

30-11-2024: Cataluña Gestión For... Se ha cerrado la línea de ayuda pública: Gestión Forestal Sostenible para Inversiones Forestales Productivas para el organismo:

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

Duración del proyecto: 63 meses Fecha Inicio: 2015-02-11
Fecha Fin: 2020-05-31

Líder del proyecto

TECHNISCHE UNIVERSITEIT DELFT

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto Microbes in natural ecosystems are under constant evolutionary pressure from viruses. To survive in this hostile environment microbes have evolved an adaptive immune system called CRISPR-Cas. The immune system is based on incorporation of invader DNA sequences in a memory locus (CRISPR), the formation of guide RNAs from this locus, and the degradation of invading target DNA using CRISPR RNA-guided protein complexes. Invaders escape immunity by making point mutations in the targeted region of their DNA, but hosts quickly restore immunity by integrating new memory sequences against the same invader in a process called priming. Recently, I have made the remarkable discovery that hosts mount a primed immune response even when facing heavily mutated invaders. This implies that the memory of the CRISPR-Cas system not only functions in the short term against relatively recent threats, but also remembers a range of revisiting old foes in the long term, providing a huge evolutionary benefit for the host in the arms race with their invaders. This proposal sets out to determine the mechanism of the enigmatic process of primed memory formation against heavily mutated invaders. Using a combination of genetic, biochemical and structural approaches, including state-of-the-art single molecule imaging of CRISPR immunity in living Escherichia coli cells, I will investigate the driving hypothesis that perfectly matching and degenerate targets are differentially recognized, and trigger either target DNA degradation or priming. Moreover, I will test the supposition that degenerate priming is a universal phenomenon among different CRISPR-Cas types. If this is the case, degenerate priming will impair the use of viruses as therapeutic agents to treat antibiotic resistant bacterial infections. To prevent CRISPR resistance I propose to screen for organic molecules that inhibit the formation of CRISPR resistance. These molecules can be co-administered with viruses to potentiate treatments.

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