Owen Tuck

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

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‼️ 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!

Thanks Jason!

This work was co-led by Jason Hu and would not have been possible without wonderful colleagues/coauthors in the @doudna-lab.bsky.social including @benadler.bsky.social, Claire, Santi, Kendall, Charlotte, @erinedoherty.bsky.social and @arushi-lahiri.bsky.social

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...

Excited to finally share this work!
We noticed a pair of genes - a nuclease and a protease - shuffles between antiviral systems. We show how proteolysis activates the nuclease, triggering defense in known and unknown immune contexts.
tinyurl.com/2uwwy4ty

Recurrent acquisition of nuclease-protease pairs in antiviral immunity https://www.biorxiv.org/content/10.1101/2025.07.28.667249v1

Beautiful study - congratulations!

CRISPRi-ART enables functional genomics of diverse bacteriophages using RNA-binding dCas13d - Nature Microbiology Leveraging RNA-targeting dCas13d enables selective interference with phage protein translation and facilitates measurement of phage gene fitness at a transcriptome-wide scale.

It is finally out!

Muntathar Al-Shimary, @doudna-lab.bsky.social , @cresslab.bsky.social and I present a gene knockdown tool that works in diverse bacteriophages: CRISPRi through antisense RNA Targeting (CRISPRi-ART)!

Check it out @naturemicrobiol.bsky.social
www.nature.com/articles/s41...

Our paper out @Nature: CARD domains mediate anti-phage defense in bacterial gasdermin systems

CARDs are essential for caspase recruitment during human inflammasome activation. We now find them in bacterial immune systems

Congrats Tana Wein! Thank you Kranzusch lab!
www.nature.com/articles/s41...

👋 Hi antiphage defense community, we are soon releasing an update of DefenseFinder.

We are doing our best to include all the great discoveries from the community, but with so much going on we might miss things.

Please answer wt preprints/papers with new systems or mail/git them to us. 🙏

My friend @benadler.bsky.social and I co-led this work. Huge thanks to collaborators Emily Armbruster & Joe Pogliano, as well as talented Berkeley MCB students Arushi Lahiri, Jason Hu (a star roton), and Julia Zhou (since graduated!). Lastly, we're indebted to Jennifer for her support. 14/14

Beyond mechanistic insights into a fascinating immune system, we hope to highlight the diverse and integral functions of helicases in immunity. 13/14

There are functional symmetries and phylogenetic relationships between HamB and the Ski2-like recombination helicase Hel308. Hel308 is only present in archaea and metazoans. Could the two be evolutionarily linked? 12/14

We propose Hachiman activates in response to abberant DNA states. DNA ends load into the helicase, triggering ATP hydrolysis and release of HamA. HamA chews up DNA, potentially amplifying the immune response by creating more sites for HamAB loading. 11/14

In another cryo-EM structure, we visualized nuclease-dead HamAB binding intact DNA in an orthogonal mode. We imagine this 'sliding' or binding state enables the helicase to thread ssDNA lesions into the active site. 10/14

But why is Hachiman so effective against diverse phages? The trigger must be central to phage infection. We show that direct DNA damage induced by a drug activates Hachiman in the absence of phage! This key insight implies HamAB recognizes DNA damage as a viral signature. 9/14

Our collaborators Emily Armbruster and Joe Pogliano @ucsd showed Hachiman in action. When infected with phage, HamB completely shreds both phage and host DNA, leaving behind "phantom cells" devoid of genomes. Infected cells sacrifice themselves in service of the colony. 8/14

In another surprise, we discovered HamB is a DNA helicase! A set of structures shows DNA entering the HamB active site. We resolved 'ratcheting' states that lead to large domain movements upon activation. This motion may release the HamA nuclease. 7/14

The structure led us to identify an active site for the HamA DUF! HamA is a nuclease homologous to nucleases in Type IIS restriction modification systems. HamA insertions mediate binding to HamB. The HamAB complex cuts DNA in vitro. 6/14

To get at the mechanism, we turned to cryo-EM. HamA and HamB form a heterodimeric complex, with HamA contacting an N-terminal helical bundle in HamB. 5/14