We then moved this into more real-world complexity: clinical bacterial strains. We found phage genes that are conditionally essential only in specific hosts. Some of those genes with previously unknown function we could match to bacterial immunity systems of the respective hosts. 🛡️⚔️

For example, some T4 genes become essential only when the host expresses specific defense systems like rIIA/B for the RexAB, dmd for RnlAB etc.

First test: can HIDEN-SEQ reproduce knowledge that we have for classical phage models like T4 🤔? YES and with remarkably high resolution. It recapitulates an essentiality map that took decades of work to assemble.

In bacteria, TnSeq revolutionized genetics by linking genes to phenotypes at scale. But for phages nothing equivalent exists. So we built HIDEN-SEQ, the first TnSeq approach for phages, enabled by a hide-and-seek interplay between the host CRISPR-Cas13a and a phage anti-CRISPR protein.

🚀New preprint from our lab!
I am very excited to finally share what has been the main focus of my PhD for the past almost 3 years! It is about viral dark matter and a powerful tool we built to shed light on it. 🧬💡
Continue reading (🧵)