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Gene network rewiring by an engineered CRIPSR-Cas12a variant

Project description

Large-scale gene editing

Recent years have witnessed the use of omics technologies to produce an unparalleled amount of information on cellular function, which, however, awaits experimental validation. The EU-funded GNRECC project builds on a previously developed CRISPR/12-based genome engineering tool capable of performing multiplex editing in dozens of endogenous genes simultaneously. In GNRECC, scientists plan to increase the efficiency of this molecular tool to rewire signalling pathways involved in cellular proliferation. For this purpose, they will design novel Cas12a protein variants, and using statistical physics alongside protein and genome engineering, they will build the foundation towards the large-scale engineering of gene networks.

Objective

In the last 10 years, an increasing number of studies employed -omics technologies to describe the molecular changes underpinning cellular functions. However, a large part of these findings is awaiting an experimental validation. This is due to the lack of efficient molecular tools able to control both multiple and distinct genetic interactions. Recently, I described a new CRISPR/12-based genome engineering tool that, for the first time, it provides the constitutive, conditional, inducible, orthogonal and multiplexed engineering of dozens of endogenous genes, simultaneously. In this research proposal, I aim to increase the efficiency of this platform in the context of multiplexed genome engineering applications, such as gene network rewiring. To this aim, I will use techniques inspired by the statistical physics of complex disordered systems, to design a more potent version of my CRISPR/Cas12-based genome engineering tool and, I will use this novel platform to rewire signaling pathways involved in cellular proliferation. This research proposal is structured into the following tasks: rational design of novel Cas12a variants, validation of novel Cas12a variants, gene network rewiring by a novel Cas12a variant. By coupling statistical physics to both protein and genome engineering this project will pave the way for efficient and large-scale engineering of gene networks.

Keywords

Coordinator

POLITECNICO DI TORINO
Net EU contribution
€ 171 473,28
Address
CORSO DUCA DEGLI ABRUZZI 24
10129 Torino
Italy

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Region
Nord-Ovest Piemonte Torino
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 171 473,28