Out now in @natcomms.nature.com: We found a plasmid in a preterm infant’s gut microbiome that’s 1.58 million base pairs long, about 30X the size of a typical E. coli plasmid. Then we found its relatives in hundreds of microbiomes worldwide. Read on to learn more about the elusive pMEGAs! 🧵
Excited to share this one, led by Theo and my postdoc Bel! We uncover how RNase E generates pAgo guide RNAs and how SPARMA turns that recognition into defense. We solved the cryo-EM structures in the Bravo lab. Great collaboration with Swarts & Zaremba! 🧬
www.researchsquare.com/article/rs-1...
New preprint from my Post-Doc in the Swarts lab
How are the guide RNAs generated that direct prokaryotic Argonautes to invading DNA?
This has been an open question for >10 years.
Our new study reveals that the host housekeeping enzyme RNase E is responsible!
A 🧵:
1/14
Heads up! The Symposium on the Immune System of Bacteria 2027 is now open for registrations!
20-22nd July 2027, Churchill College, University of Cambridge, UK
Places are limited, so register soon. Visit the website to see our fantastic line-up of speakers: sisb2027.info#phage
Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11
Our results identify host tRNA as a source of immune messages. We also found other predicted sensor–effector proteins encoded beside Cas13. Their roles remain to be tested, raising questions about how broadly RNA cleavage feeds immune signaling. 10/11
Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11
We then asked how the candidate messengers affect 2TMβ assembly. Mass photometry showed that synthetic 2′,3′-cUMP and GpU(2′,3′-cp) promoted larger assemblies of the purified, soluble β-barrel. Pocket mutations altered this response. 8/11
In cells, activating the complete system arrested growth, reduced ATP and increased membrane permeability. These effects depended on 2TMβ. Together with the phage assays, the results support a model in which infected-cell shutdown protects the population. 9/11
Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11
Targeted mass spectrometry directly identified GpU(2′,3′-cp), a two-nucleotide product released by Cas13b6 from tRNA in vitro. This gave us a chemically defined candidate for the signal connecting Cas13 to 2TMβ. 6/11
In cells, removing either the membrane-spanning region or β-barrel of 2TMβ strongly reduced toxicity. The predicted ligand-pocket mutations Y157A and Y197A each also restored viability, linking this pocket to the cellular response. 7/11
Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11
We established a phage-free activation assay by targeting GFP RNA in E. coli. Mutating Cas13b6’s extra histidine in HEPEN1 rescued cell viability. Yet the mutant still cleaved tRNAs in vitro, with an altered pattern. This gave us a clue: could specific cuts generate the signal for 2TMβ? 4/11
We then used RNA-seq to map the cuts. Activated Cas13b6 preferentially cleaved a subset of host tRNAs at their anticodon loops. The pattern suggested release of 2′,3′-cUMP and GpU(2′,3′-cp)—candidate signals for its membrane partner, 2TMβ. 5/11
Excited to share our work on bacterial immune signaling! Our preprint reveals how RNA-guided Cas13 cleaves host tRNAs to generate small-molecule messengers that activate 2TMβ, linking RNA recognition to membrane damage and phage defense. 1/11
Many bacterial immune pathways synthesize signals from nucleotides and cofactors. Genome mining revealed Cas13 paired with 2TMβ, a membrane effector usually reported alongside cyclases in CBASS and Panoptes. Could RNA cleavage supply the signal? 2/11
We reconstituted the Cas13–2TMβ system in E. coli and challenged the cells with phages. Both genes were required for full defense. One question remained: what molecule carries the signal from Cas13 to its membrane partner? 3/11
I’m happy to share our study out in Microbiome! link.springer.com/article/10.1... Knowing that coculture interactions often disappear in larger communities, we used cocktails of phages to study vitamin exchange interactions within enrichment cultures.
My final postdoc project is out today in Nature! We show microbes co-migrated with humans out of Africa; three independent methods agree, and timing matches archaeological / genetic evidence (Fig. 4c). Seeing Fig. 4c for 1st time was one of my most memorable "eureka" moments! doi.org/10.1038/s415...
None of this year's science Nobel Prizes have gone to women.
The number of these prizes to go to women remains at 27 out of more than 600.
See how many you can name in our quiz: www.nature.com/immersive/d4...
BREAKING NEWS
The Royal Swedish Academy of Sciences has decided to award the 2026 #NobelPrize in Chemistry to Henri B. Kagan and Kenso Soai “for the discovery of non-linear effects and autocatalysis in asymmetric organic synthesis.”
Exciting news: @uwgenome.bsky.social will be hiring for two tenure-track faculty positions this year, one open rank and one assistant professor. Both are “Genome Sciences” interpreted broadly so we welcome applicants working in a variety of fields and methods. Ad will be out shortly.
Huge congratulations to all three Nobel Laureates, and especially Peter Hegemann! 👏
His seminal work on the green alga Chlamydomonas 🦠 laid the foundation for optogenetics. Thank you for putting Chlamy in the spotlight! ✨
Proof that groundbreaking discoveries don't always come from animal models! 🔬
BREAKING NEWS
The 2026 Nobel Prize in Physiology or Medicine has been awarded to Karl Deisseroth, Peter Hegemann and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.”
Our story with @hobbslabutah.bsky.social discovering CBASS sensing of phage proteases out now in @science.org
New data include CBASS recognition of diverse proteases beyond T4, and verifying CD-NTase activation loop cleavage as the trigger for defense in vivo
www.science.org/doi/10.1126/...
After >10 years of our lab studying bacterial cGAS-like enzymes, @hobbslabutah.bsky.social finally reconstitutes viral sensing in vitro and discovers how these ancient receptors sense phage protease enzymes to detect virion assembly and activate antiviral immunity
www.biorxiv.org/content/10.6...
Before #CRISPR, there was VIPR — a tool viruses used to battle each other with a never-before-seen genetic coding system, uncovered by researchers in the Doudna Lab. Read more here: https://ow.ly/KblS50ZOxwQ#AI#LanguageModel#RNA
Discover all the wonderful ways you can join the @hhmi-science.bsky.social, with opportunities ranging from undergraduate students to senior investigators. There will be no upper limit on career-stage eligibility for the Investigator program!
The shared principles of human and bacterial antiviral immunity
An honor to highlight remarkable discoveries from many labs over the past 12 years that unite previously disparate fields of how animal cells and prokaryotes defend against viruses.
www.nature.com/articles/s41...rdcu.be/fzwyB
Tim Blower and I are guest editing a Biochemical Journal @biochemsoc.bsky.social themed collection on:
The Prokaryotic Immune System
It's now open for research submissions and we'd welcome submission of research and review articles.
More info: portlandpress.com/biochemj/pag...
🚨 Registration for VEGA26 is 👏 officially open 👏 🚨
The 5th edition of our Viral EcoGenomics and Applications symposium will be held November 18-19, 2026, on the UC Berkeley campus 🧬 🦠 🔬 🧫
Event website ➡️ jgi.doe.gov/work-with-us...
Registration link ➡️ cvent.me/e0RnA0
my first 'data descriptor'! hoping this one will be useful for folks interested in tracing the distribution of genomes/genes/proteins over physicochemical gradients in the (deep) marine water column.
Deeply-sequenced metagenomes and over 1000 draft genomes from the epipelagic to bathypelagic Northeast Pacific Ocean https://www.biorxiv.org/content/10.64898/2026.07.18.739368v1
Thrilled to share our collab led by Grace Hibshman with the Shipman lab! Type IX retron-Kva2 structure reveals phage detection via an HTH fold, not a primary sequence. We computationally designed triggers that program bacteria cell death, pointing toward designer antimicrobials.
Humans and bacteria share strategies to defend against viruses.
We wondered: could they use each other's genes? Yes, both can!
Bacteria can use human immune genes to defend against phages AND
Human cells can use bacterial genes for viral defense.
www.biorxiv.org/content/10.6...
Our paper "Gene ancestries reveal diverse microbial associations during eukaryogenesis.” is finally out in Nature.
Eukaryogenesis was likely a gradual process shaped by multiple microbial partners and virus-mediated gene transfer, rather than a single binary symbiosis.
doi.org/10.1038/s415...
Big congrats to Susan Mullen and coauthors on this new preprint. 🎉
We're excited to share this work exploring microbial dispersal and establishment across river water, groundwater, soil, and hyporheic zone environments in the East River watershed.
Read the preprint: www.biorxiv.org/content/10.6...
(1/6) Thrilled to share this story! In our preprint from my PhD in the @kranzuschlab.bsky.social, with help from the Hatfull lab and @soreklab.bsky.social, we discover RyDEP, a phage-encoded RyR-domain glycosidase that allows phages to evade Thoeris defense. Highlights below! doi.org/10.64898/202...
We told you it wouldn’t be a long wait. 👀 Even more predicted protein structures have been added to the #AlphaFold Database.
This time, the database has expanded to include heterodimers – protein complexes made up of two different proteins.
alphafold.ebi.ac.uk
Now live! Submit a 100 word proposal to win free #PacBio HiFi sequencing for #metagenomics. Long-read metagenomics is rapidly gaining traction and this is a great time to apply it to your research.
programs.pacb.com/l/1652/2026-...
1/ Our new paper in Systematic Biology "Modeling Site-and-Branch-Heterogeneity with GFmix" led by @cgpmcc.bsky.social describes improved ways to model compositional heterogeneity across both sites and branches—an important source of error in deep phylogenomics.
doi.org/10.1093/sysb...
As an editor at the Biochemical Journal, I'd love to see more papers submitted in the areas of bacterial immune systems / CRISPR / archaeal molecular biology / nucleic acid processing enzymes
Researchers at our Read & Publish institutions can benefit from fee-free OA publishing and access to read content in our journals. Not sure if your institution has signed up? Check out the full list on our website: https://ow.ly/yeH150Z0THn 🧪
Our lab is proud to present our latest work harnessing Bridge Recombinase for genome-scale editing in diverse bacteria, microbiome editing, and programmable horizontal gene transfer.