Owen Tuck
owentuck.bsky.social
Owen Tuck
@owentuck.bsky.social
chem bio PhD student in the Doudna Lab @Berkeley
Pinned
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
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...
www.science.org
Reposted by Owen Tuck
🚨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
November 20, 2025 at 8:40 PM
Reposted by Owen Tuck
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...
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...
www.biorxiv.org
November 15, 2025 at 11:49 PM
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...
www.biorxiv.org
November 15, 2025 at 10:21 PM
Thank you Aude!!
November 15, 2025 at 9:51 PM
Thanks Cress friends!
November 14, 2025 at 6:09 PM
Thanks Jason! We miss you
November 14, 2025 at 5:46 PM
Reposted by Owen Tuck
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.
November 14, 2025 at 7:51 AM
Thanks Luuk!
November 14, 2025 at 5:44 PM
Thanks François - your work was influential in our thinking on this project (and others)
November 14, 2025 at 5:43 PM
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
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...
www.science.org
November 13, 2025 at 10:15 PM
Reposted by Owen Tuck
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.
Isolation, engineering and ecology of temperate phages from the human gut - Nature
Human host-associated cellular products may act as induction agents for bacteriophages.
nature.com
October 15, 2025 at 9:41 PM
Reposted by Owen Tuck
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...
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...
doi.org
October 1, 2025 at 4:44 PM
Reposted by Owen Tuck
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...
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature
Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.
www.nature.com
October 1, 2025 at 5:57 PM
Reposted by Owen Tuck
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...
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 ...
www.biorxiv.org
September 23, 2025 at 8:28 PM
Reposted by Owen Tuck
Some pics of our awesome PhD candidate, @sophswartz.bsky.social, presenting at the Cold Spring Harbor Laboratory conference!
August 25, 2025 at 8:43 PM
Reposted by Owen Tuck
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.
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...
www.biorxiv.org
August 22, 2025 at 7:02 PM
Congrats and best of luck!
August 18, 2025 at 7:54 PM
Reposted by Owen Tuck
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.
Welcome JASON NOMBURG! With great pleasure we announce that Jason Nomburg is one of the Starting Principal Investigators LS who will join AITHYRA in October 2025. Jason wants to understand the function of proteins in the virome.
More information: www.oeaw.ac.at/aithyra/rese... #AITHYRA #StartingPI
August 15, 2025 at 7:54 PM
Reposted by Owen Tuck
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/
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...
www.nature.com
July 30, 2025 at 6:05 AM
Reposted by Owen Tuck
‼️ New pre-print from co-leads @owentuck.bsky.social and Jason Hu! Check out this fascinating example of how coevolution enables defense system innovation.
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
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...
tinyurl.com
July 29, 2025 at 9:18 PM
Thanks Luuk!
July 29, 2025 at 7:06 PM
Absolutely! Caspases seem particularly useful for proenzyme activation… 🧐
July 29, 2025 at 6:44 PM
Congratulations!
July 29, 2025 at 6:43 PM
Thanks Jason!
July 29, 2025 at 4:03 PM
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
July 29, 2025 at 4:02 PM