Owen Tuck

A prophage-encoded abortive infection protein preserves host and prophage spread - Nature A Gifsy-1 prophage–encoded higher eukaryotes and prokaryotes nucleotide-binding protein, HepS, senses Siphoviridae infection, activates abortive defence by cleaving host transfer RNAs, blocks rival ph...

A prophage-encoded abortive infection protein preserves host and prophage spread www.nature.com/articles/s41...

Diverse bacterial pattern recognition receptors sense the conserved phage proteome Recognition of foreign molecules inside cells is critical for immunity in all domains of life. Proteins of the STAND NTPase superfamily, including eukaryotic nucleotide-binding oligomerization domain ...

NLR-like immunity in bacteria

A new study from the Alex Gao lab. The scope of this work is incredible!!!

www.biorxiv.org/content/10.6...

Environment and physiology shape antiphage system expression Bacteria and archaea encode on average ten antiphage systems. Quorum sensing, cellular, or transcription factors can regulate specific systems (CRISPR-Cas, CBASS). Yet, a systematic assessment of anti...

Bacterial genomes encode a rich repertoire of antiphage systems, but we still know surprisingly little about when these systems are actually expressed.

In this preprint, Lucas Paoli et al, ask what shapes antiphage systems expression in native contexts.
www.biorxiv.org/content/10.6...

Leveraging defense system modularity to discover anti-phage systems Bacterial exposure to constant phage attack drives rapid diversification of anti-phage defense systems, often through the exchange of modular defensive domains. Here, we leverage this modularity signa...

#microsky #phagesky

More anti #phage systems in E. coli

www.biorxiv.org/content/10.6...

Viral enzymes degrade to evade Across all domains of life, immune systems rely on nucleotide-based signaling molecules to activate defense responses. In a recent Cell Host & Microbe study, Doherty, Nomburg, and colleagues identify ...

A very nice Preview of our work in
@cp-cellhostmicrobe.bsky.social
this morning from Chrishan Fernando & Nicole D. Marino! www.cell.com/cell-host-mi...

✨New preprint!

🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al!
Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬

🔗👇

Systematic discovery of TIR-based immune signaling systems in bacteria Toll/interleukin-1 receptor (TIR) domains are important for immune signaling across humans, plants and bacteria. These domains were recently found to produce immune signaling molecules in plant immuni...

I’m happy to share our new preprint! We uncovered the full diversity of bacterial TIR-based antiviral immune signaling, massively expanded the known diversity of Thoeris systems, and revealed conservation of TIR-derived immune signals across the tree of life.

www.biorxiv.org/content/10.6...

🚨Preprint alert - this is a big one! We transfer the revolutionary power of TnSeq to bacteriophages.

Our HIDEN-SEQ links the "dark matter" genes of your favorite phage to any selectable phenotype, guiding the path from fun observations to molecular mechanisms.

A thread 1/8

Proteolytic activation of diverse antiviral defense modules in prokaryotes Linked protease–effector modules are widespread in prokaryotic antiviral defense, yet the mechanisms of most remain poorly understood. Here we show that four of the most prevalent modules—metallo-β-la...

I am so excited to share our project with you! We find prokaryotic proteases activate toxic enzymes and pores as a modular strategy in phage defense. We studied four fascinating protease-toxin pairs that are abundant across bacterial genomes:

www.biorxiv.org/content/10.1...

Beautiful preprint from Simone Evans et al. in Alex Gao's group looking at MBL/nuclease and other cool zymogens (pepco, EACC1) in antiphage defense systems. Great to see this paradigm extended - probably many more proteolytically activated effectors out there...
www.biorxiv.org/content/10.1...

Thank you Aude!!

Thanks Cress friends!

Thanks Jason! We miss you

Fascinating discovery - anti-phage defense protein is a proenzyme that is cleaved by partner protease after phage infection and all three! products of cleavage form active nuclease.

Thanks Luuk!

Thanks François - your work was influential in our thinking on this project (and others)

Recurrent acquisition of nuclease-protease pairs in antiviral immunity Antiviral immune systems diversify by integrating new genes into existing pathways, creating new mechanisms of viral resistance. We identified genes encoding a predicted nuclease paired with a trypsin...

Our nuclease-protease story is out! We explored a fascinating case of coevolution and modularity in prokaryotic immune systems: www.science.org/doi/10.1126/...

Thanks to wonderful coauthors/collaborators/friends, the whole @doudna-lab.bsky.social and everyone at @innovativegenomics.bsky.social

Isolation, engineering and ecology of temperate phages from the human gut - Nature Human host-associated cellular products may act as induction agents for bacteriophages.

Very excited to share the latest work from our lab, which was published today in Nature!
nature.com/articles/s41...

PhD graduate and now post-doc Sofia Dahlman, along with co-senior author Sam Forster from The Hudson and other researchers from our lab and others.

Megaplasmids associate with Escherichia coli and other Enterobacteriaceae Humans and animals are ubiquitously colonized by Enterobacteriaceae , a bacterial family that contains both commensals and clinically significant pathogens. Here, we report Enterobacteriaceae megaplas...

New pre-print from the Banfield lab, highlighting an interesting case of 1.5Mb megaplasmids found in human gut.

Plasmid genomes were resolved using #PacBio HiFi sequencing with hifiasm-meta for #metagenome assembly. Host association was detected using epigenetic signals.

doi.org/10.1101/2025...

A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

Today in @nature.com , we highlight how a cousin of CRISPR-Cas10, mCpol, establishes an evolutionary trap in anti-phage immune systems.

Check out @erinedoherty.bsky.social and my work from @doudna-lab.bsky.social lab here:
www.nature.com/articles/s41...

Proteolytically activated antibacterial toxins inhibit the growth of diverse Gram-positive bacteria Many species of bacteria produce small-molecule antibiotics that enter and kill a wide range of competitor microbes. However, diffusible antibacterial proteins that share this broad-spectrum activity ...

A recent cool preprint by John Whitney's lab on a new family of antibacterial proteins secreted by Gram-positive bacteria that enter and kill a broad spectrum of bacteria. Cell entry is receptor-independent and relies on cleavage by a co-secreted protease and the PMF.
www.biorxiv.org/content/10.1...

Some pics of our awesome PhD candidate, @sophswartz.bsky.social, presenting at the Cold Spring Harbor Laboratory conference!

Divergent viral phosphodiesterases for immune signaling evasion Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase...

Excited to share our new preprint co-led by @jnoms.bsky.social!

Here we reveal an exceptional diversity of viral 2H phosphodiesterases (PDEs) that enable immune evasion by selectively degrading oligonucleotide-based messengers. This 2H PDE fold has evolved striking substrate breath & specificity.

Congrats and best of luck!

Very happy to share that I will be starting my lab at AITHYRA in October! My lab will use structural bioinformatics and functional genomics to understand the function of viral proteins, with a special emphasis on understanding how viruses subvert innate immunity.

Manipulation of the nucleotide pool in human, bacterial and plant immunity - Nature Reviews Immunology Modification of the nucleotide pool is emerging as key to innate immunity in animals, plants and bacteria. This Review explains how immune pathways conserved from bacteria to humans manipulate the nuc...

We wrote a review on the free nucleotide pool as a central playground in human, bacterial, and plant immunity – now out in Nature Reviews in Immunology

www.nature.com/articles/s41...

Was fun to write this piece with Dina Hochhauser!

Here is a thread to explain the premises

1/

‼️ New pre-print from co-leads @owentuck.bsky.social and Jason Hu! Check out this fascinating example of how coevolution enables defense system innovation.

Thanks Luuk!

Absolutely! Caspases seem particularly useful for proenzyme activation… 🧐

Congratulations!