Ben Adler

Chemical inhibition of a bacterial immune system Bacteriophages are promising alternatives to antibiotics for treating bacterial infections. However, bacteria possess immune systems that neutralize bacteriophages. Zang et al. discover small molecule...

Really phenomenal work from the Gerdt lab at Indiana University... I hope this becomes a major boon for phage therapy:
"Chemical inhibition of a bacterial immune system"
www.cell.com/cell-host-mi...

Life science research is plagued with repetitive rote work. This system is designed to support, organize and execute tasks across the research stack. procurement, inventory management, equipment telemetry, safety, and regulatory can be managed with and by the system.

I’ve jumped completely off the deep end and I’m building a stateful agentic environment for computational and experimental life science research. Inspired by some of the systems I’ve seen here, but different. It’s goal oriented and research focused

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...

All you want for christmas is.... transposon mutagenesis!

Our new work at @cultivarium.bsky.social screening lots of transposon vectors in lots of bacteria, from @charliegilbert.bsky.social and team.

Transposon and promoter modular parts available on Addgene (pooled library will be there soon too)

On this episode of the "What's in the vault?!?!" saga...

Protein domains have no single definition, so why stick to one segmentation? 🧩

Instead of forcing structures into rigid classifications, we built AFragmenter. It uses AlphaFold PAE networks for a tuneable approach to domain parsing.

You control the granularity. 👇
🔗 doi.org/10.1093/bioi...

🚀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 (🧵)

Ah, this is amazing work! 🤩🤩

Big congratulations to the team!

🚨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

We built GenoPHI: a machine learning workflow that predicts phage-host interactions at strain level. This could help rapidly select phages to treat drug-resistant bacterial infections or for microbiome engineering without exhaustive lab testing.

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

📣 New preprint from us at phagefoundry.org 📣
A solid machine learning framework & to predict strain-level phage-host interactions across diverse bacterial genera from genome sequences alone. Avery Noonan from the Arkin Lab led this massive effort
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...

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...

I’m excited to share my recent postdoc work. Here, we interrogate how different phage infection outcomes (productive vs. restrictive) affect the expression of phage defense systems. We find that a restricted infection not only inhibits the phage but also induces increased immune protein abundance.

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...

Amazing piece of work from @rtoshiro.bsky.social
& Kim Seed at UC Berkeley. 🙌
Played a tiny role in this work.

Surviving phage attack dynamically regulates bacterial immunity to defeat counterdefenses

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

Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...

Very excited to share our latest work in Science on metagenomic editing (MetaEdit) of the gut microbiome in vivo & directly modifying unculturable immune-modulatory SFB bug in the small intestine. 🦠🧬🛠️
www.science.org/doi/10.1126/...

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...

#microsky #phagesky #phage defence

Thanks, @crypticprophage.bsky.social for pointing it out on “the other side”

www.science.org/doi/10.1126/...

A mysterious lactamase-nuclease module found in multiple defense systems finally solved ! Congrats @owentuck.bsky.social et al. !

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.

Huge congrats to Owen, Jason, and team! Such a fun story

Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...

1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge.

Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...

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

Scalable and systematic hierarchical virus taxonomy with vConTACT3 Viruses are key players in diverse ecosystems, but studying their impacts is technically and taxonomically challenging. Taxonomic complexities derive from undersampling, diverse DNA and RNA genomes wi...

🚨vConTACT3 preprint live!🚨(Peer Review soon...!)

vConTACT3 delivers a unified, scalable, and transparent framework for genome-based virus taxonomy — helping translate big viral data into systematic classification.

🔗 Read the preprint: doi.org/10.1101/2025...

Improvements details below 👇

Preprint: Bacteria sense virus-induced genome degradation via methylated mononucleotides

tinyurl.com/ch3damp

We show how molecular byproducts released during virus-induced cell exploitation are used as signals to trigger host immunity

Revealed by the amazing Ilya Osterman. See his thread below👇

Bacteria can sense when a virus starts shredding their genome — by detecting methylated mononucleotides.
Here’s the story of how we discovered the Metis defense system 👇
www.biorxiv.org/content/10.1...

An updated evolutionary classification of CRISPR–Cas systems including rare variants - Nature Microbiology An exploration of previously undescribed variants from the long tail of the CRISPR–Cas distribution.

After 5 years of waiting, the new #CRISPR classification by Makarova et al. is out @natmicrobiol.nature.com www.nature.com/articles/s41...

Big experiments are only big if they can fail Some reflections on Arena Bioworks' unexpected wind down as a fellow institutional experimentalist

"We need more institutional experiments for science" makes sense to me @seemaychou.bsky.social. We might not like some of 'em and some'll fail, but given academic science often looks like a feudal system needing an industrial revolution trying things can't hurt.. seemay.substack.com/p/big-experi...

🚨New preprint out!
We present a foundational genomic resource of human gut microbiome viruses. It delivers high-quality, deeply curated data spanning taxonomy, predicted hosts, structures, and functions, providing a reference for gut virome research. (1/8)
www.biorxiv.org/content/10.1...

An updated evolutionary classification of CRISPR–Cas systems including rare variants - Nature Microbiology An exploration of previously undescribed variants from the long tail of the CRISPR–Cas distribution.

#microsky #phagesky CRISPR-cas galore

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