Project description DEENESFRITPL 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. Show the project objective Hide the project objective 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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsgenomes Keywords CRISPR-Cas12 Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator POLITECNICO DI TORINO Net EU contribution € 171 473,28 Address CORSO DUCA DEGLI ABRUZZI 24 10129 Torino Italy See on map Region Nord-Ovest Piemonte Torino Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 171 473,28