I am so excited to share our new findings with you! We provide the structural evidence for a direct protein-to-DNA information pathway, showing how a bacterial enzyme 'reads' its own structure to 'write' DNA. www.science.org/doi/10.1126/...

Protein-templated DRT3 expands the textbook definition of reverse transcriptases further! Beautiful paper led by Pujuan Deng, Hyunbin Lee, and Carlo Armijo!

Amazing findings in geometry-based immune activation! Two bacterial defence systems detect phage-encoded ring oligomers, assemble high-order molecular complexes, and trigger abortive infection.

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

A phage protein screen identifies triggers of the bacterial innate immune system - Nature Microbiology A library of 400 phage protein-coding genes is used to find a trove of antiphage systems, revealing systems that target tail fibre and major capsid proteins.

I’m thrilled to share our work on phage triggers of the bacterial immune system in its final form @natmicrobiol.nature.com 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...

The vault associates with membranes in situ The eukaryotic vault particle is a giant ribonucleoprotein complex that assembles into an iconic barrel-like cage. Its cellular function has remained elusive despite extensive characterization. Using ...

Vaults. They are cell biology's greatest puzzle! This preprint from Martin Beck's lab shows them docked on ER membranes with a ribosome inside. What on earth is going on there??

#CellBiology #WTFology

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...

Poly-immunity arrays associated with Rhs toxins confer wide protection against competitors Martinkus et al. show that Photorhabdus and Xenorhabdus species encode arrays of immunity genes whose protein products neutralize toxins secreted by competitors. These arrays, often linked to Xer pass...

We propose immuno-centric view of secreted polymorphic toxin diversification and involvement of novel XPC systems in this process! Fantastic work of @jmartinkus.bsky.social with lab of @cascaleslab.bsky.social !
www.cell.com/current-biol...

De novo origin of numerous microproteins in enterobacteria

Igor Fesenko, Svetlana A Shabalina, Gisela Storz, Eugene V Koonin.
Nucleic Acids Research, Volume 53, Issue 22, 11 December 2025
doi.org/10.1093/nar/...

Phages are full of genes of unknown function that are likely adaptive in specific conditions.
New preprint: Phage TnSeq identifies essential genes rapidly and knocks all non-essentials. We would like to send a pool of phiKZ mutants to anyone wanting it! Reach out
tinyurl.com/bdcfrejh

Intracellular competition shapes plasmid population dynamics From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating g...

Hot off the press! Our latest paper led by @fernpizza.bsky.social, understanding how plasmids evolve inside cells. These small, self-replicating DNA circles live inside bacteria and carry antibiotic resistance genes, but also compete with one another to replicate. 1/
www.science.org/doi/10.1126/...

🚨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

Filament formation and NAD processing by noncanonical human FAM118 sirtuins Nature Structural & Molecular Biology - Baretić and Missoury et al. identify vertebrate proteins FAM118B and FAM118A as sirtuins similar to bacterial antiphage enzymes and show that...

Very happy to share our collaborative project on FAM118 proteins - noncanonical sirtuins that form filaments and process NAD in human and other vertebrate cells.

Wilkinson Lab We discover and study reverse transcriptases

The Wilkinson Lab is open for science! @mskcancercenter.bsky.social

🧬We'll be finding funky new RNA biology, mainly by looking at reverse transcriptases (i.e. the Best Enzymes In The World)🧬

annnd: I'm hiring - come join! Especially postdocs and PhD students - please get in touch (NYC is great)

Thank you! I'd love to swing by your lab and chat sometime.

Thanks, there is so much more to explore!

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...

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

Many thanks to our wonderful collaborators and to the Gao lab to make this work possible!

Our findings reveal an incredible diversity of protease-based regulatory strategies that can respond to diverse phage stimuli.

4. EACC1, another small hypothetical protein, assembles into a toxic membrane pore after proteolytic removal of its N-terminal auto-inhibitory domain. Surprisingly, some EACC1-protease pairs are fused to divergent Dnak-like chaperones.

3. The small hypothetical protein, Pepco, pre-assembles into a β-barrel oligomer that is toxic after cleavage of 2kDa C-terminal fragments. Pepco oligomers are remarkably stable, surviving detergent and heat.

2. A toxic α/β-hydrolase is activated by proteolytic removal at two distinct internal sites and requires two of the three fragments for cellular toxicity.

1. A toxic zinc-dependent nuclease with an MBL fold is activated by proteolytic cleavage of two auto-inhibitory linkers and requires all three fragments for cellular toxicity.

These findings support fantastic work by @owentuck.bsky.social and the @doudna-lab.bsky.social!

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...