Mapping and inferring CRISPR nuclease specificity trajectories across evolutionary space and timecore
Seq2cut · Horizon Europe grant · 2026-09-01–2028-08-31
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call HORIZON-MSCA-2025-PF · scheme HORIZON-TMA-MSCA-PF-EF · topic HORIZON-MSCA-2025-PF-01-01. CORDIS record →
Objective
Programmable nucleases such as CRISPR-Cas12 open an important window for understanding microbial defense. Nucleases like Cas12 rely on an RNA guide’s (gRNA) sequence to direct it towards specific DNAs – typically those derived from previously-encountered mobile genetic elements (MGEs), like phages. Features – such as how fast they operate on DNA targets, or how well they distinguish gRNA-matched DNA from partially matched DNA (specificity) – can tell us a lot about the environments they operate in, the MGEs they face, and even how well we can expect them to operate in new genomes. We lack complete understanding of these features, these complex phenotypes, like specificity. How does gRNA programming distinguish each nuclease’s potential targets? Current methods, both genome-wide assays and computational predictions, are context-dependent, often obscuring nuclease-intrinsic features. As a result, specificity remains too complex to predict from nuclease sequence alone. This could be possible with an appropriate high-throughput strategy, especially one that leverages nucleases’ natural diversity to indicate how their features change across evolution. The Seq2Cut project seeks to uncover the evolutionary basis of the key nuclease features such as specificity and establish a comparative framework for understanding how nuclease function evolves. Seq2Cut will overcome current limitations with high-throughput methods that integrate biochemistry, computation, bioinformatics, and engineering to generate standardized, comparable datasets across a diverse set of Cas12 proteins. By combining experimental measurements with computational modeling, I aim to uncover how critical nuclease features have evolved, mapping these functions to their protein sequence and structure. Under the supervision of Dr. Stephen Jones who has vast experience in employing these technologies, I anticipate making fundamental advances in our understanding and biotechnology uses for CRISPR in genome editing
Beneficiaries (1)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| VILNIAUS UNIVERSITETAS | LT | coordinator | €181,136 |
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