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Developing CRISPR adaptation platforms for basic and applied research

Descrizione del progetto

Una nuova piattaforma per far luce su adattamento del CRISPR e immunità batterica contro i virus invasori

Ad oggi, molte persone hanno sentito almeno parlare del sistema «CRISPR». Nell’ultimo decennio, questa tecnica semplice ed economica per l’editing genetico in vivo ha conquistato il mondo grazie al proprio potenziale per la terapia genica delle malattie. Il progetto CRISPRsition, finanziato dall’UE, ci riporta alle sue umili origini. Le brevi ripetizioni palindrome aggregate regolarmente distanziate (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR) e le proteine associate al CRISPR (CRISPR-associated, Cas) sono parte del sistema immunitario adattativo nei procarioti. I batteri lo utilizzano per preservare una «memoria» dell’invasione da parte di un fago, impiegando lo splicing su un pezzo dell’acido nucleico del fago invasore nel sistema CRISPR in un processo chiamato adattamento. CRISPRsition pianifica di fornire una piattaforma che identifichi le parti pertinenti di genomi batterici e fagici con potenziale per la nuova terapia «antibiotica».

Obiettivo

The CRISPR-Cas system has been extensively studied for its ability to cleave DNA. In contrast, studies of the ability of the system to acquire and integrate new DNA from invaders as a form of prokaryotic adaptive immunity, have lagged behind. This delay reflects the extreme enthusiasm surrounding the potential of using the system’s cleavage capabilities as a genome editing tool. However, the enormous potential of the adaptation process can and should arouse a similar degree of enthusiasm. My lab has pioneered studies on the CRISPR adaptation process by establishing new methodologies, and applying them to demonstrate the essential role of the proteins and DNA elements, as well as the molecular mechanisms, operating in this process. In this project, I will establish novel platforms for studying adaptation and develop them into biotechnological applications and research tools. These tools will allow me to identify the first natural and synthetic inhibitors of the adaptation process. This, in turn, will provide genetic tools to control adaptation, as well as advance the understanding of the arms race between bacteria and their invaders. I will also harness the adaptation process as a platform for diversifying genetic elements for phage display, and for extending phage recognition of a wide range of hosts. Lastly, I will provide the first evidence for an association between the CRISPR adaptation system and gene repression. This linkage will form the basis of a molecular scanner and recorder platform that I will develop and that can be used to identify crucial genetic elements in phage genomes as well as novel regulatory circuits in the bacterial genome. Together, my findings will represent a considerable leap in the understanding of CRISPR adaptation with respect to the process, potential applications, and the intriguing evolutionary significance.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

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Invito a presentare proposte

(si apre in una nuova finestra) ERC-2018-COG

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Istituzione ospitante

TEL AVIV UNIVERSITY
Contributo netto dell'UE
€ 2 000 000,00
Costo totale
€ 2 000 000,00

Beneficiari (1)