How diverse is bacterial immunity ?
We report in @science.org how language models allowed us to predict 2.4M antiphage proteins spanning >23K novel potential systems.
👏 @emordret.bsky.social, @alexhv.bsky.social & al doi.org/10.1126/scie...
Explore them here defensefinder.mdmlab.fr/wiki/refseq_...
Bacterial Schlafen proteins mediate phage defence
(new work from @anemudraia.bsky.social and @artemnemudryi.bsky.social labs)
www.nature.com/articles/s41...
Schlafens are an ancient, mechanistically conserved family of tRNA-targeting immune effectors.
Excited to share our latest work on dissecting the mechanism of processive telomeric DNA synthesis by telomerase. Led by amazing PhD student Sebastian Balch in collaboration with lab members,@automnenine.bsky.social @rachael-kretsch.bsky.social,@rdaslab.bsky.social.
www.nature.com/articles/s41...
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...
Structural basis of antiphage defence by an ATPase-associated reverse transcriptase
@jerrintgeorge.bsky.social
I am happy to share our work on the mechanism of prokaryotic immunity by a reverse transcriptase associated with an SMC-family ATPase, now published in @natcomms.nature.com
🔗 nature.com/articles/s4146…
(🧵 on the bioRxiv version ⬇️)
Ever wondered why some bacteria have multiple CRISPR-Cas systems? Our new study led by Leah Smith shows how type I CRISPR systems can promote the acquisition and retention of new spacers into a co-occuring type III system. www.sciencedirect.com/science/arti...
New from our lab in @narjournal.bsky.social:
We dissect the folding dynamics of a fundamental element of RNA secondary structure—a stem-loop—at single-molecule and microsecond resolution.
doi.org/10.1093/nar/... 1/5
Words cannot describe how excited I am to share the findings from the second half of my postdoc in @aaronwhiteley.bsky.social's lab where we discover that bacteria use functional amyloids to defend themselves from predatory bacteria. rdcu.be/euu5Y. See thread for details on this epic adventure 1/.
We wrote a review on Transposable Elements (TEs) and almost all aspects of TE silencing and their roles in biological processes & disease.
www.nature.com/articles/s41...
New Preprint!! Alejandro González-Delgado accomplished a major feat on this one: ported retron recombineering, which we love so much in E. coli, into 14 new bacterial species via a massive collaborative effort involving 9 labs!
www.biorxiv.org/content/10.1...
Exciting work from the Guarné lab indicating how the elusive TnsE pathway of prototypic Tn7 recognizes DNA replication features using an asymmetric dimer to integrate multiple signals at DNA replication forks linking target recognition to transposase recruitment doi.org/10.1093/nar/...
1/10 New pre-print(s) from the Sternberg Lab in collaboration with Leifu Chang's Lab! We uncover the unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs.
Full story here:
www.biorxiv.org/content/10.1...
We're thrilled to share the published version of our DRT9 story, online today @nature.com! Congratulations to all authors!
www.nature.com/articles/s41...
@science.org 🧫🧬❄️🔬 Molecular basis of influenza ribonucleoprotein complex assembly and processive RNA synthesis | Science www.science.org/doi/10.1126/...
@yiweichang.bsky.social www.yiweichanglab.org @jiwasa.bsky.social #virology #Influenza #Cryo-EM #StructuralBiology #RNA #polymerase
A beautiful discovery by Joel Tan and Philip Kranzusch, out today in Nature:
A DNA-gated molecular guard controls bacterial Hailong anti-phage defence
Congrats Joel and Philip! Was a pleasure to contribute to this discovery together with Sarah Melamed
www.nature.com/articles/s41...
I am thrilled to share the first manuscript from the Wiles lab! We present "Phollow", an in vivo phage-tagging approach that enables direct observation of phage outbreaks with single-virion resolution by live imaging. Here some highlights 👇 www.nature.com/articles/s41...
Check out our new story led by @aesully98.bsky.social describing how bacteria turn immune evasion against phage! In collaboration with @benmorehouse.bsky.social lab, we discover that bacteria guard their nucleotide second messenger pool using a nucleotidyltransferase related to Cas10/CRISPR enzymes
Interested in phage defenses that natively block lytic phage used in therapies?
Or do you want to figure out if a phage has a modified genome?
Meet the END-nucleases, an enzyme family that can broadly restrict phages with many diverse modifications. From talented post-doc Wearn-Xin Yee!
Huge thanks to the Wiedenheft Lab—especially Senuri, Murat, Quynh, Royce, Adelaide, Hannah, Adelaide, Ava and our newest faculty Steve—this work wouldn’t have been possible without your support, insight, and suggestions! 🙏
I'm incredibly grateful to Blake Wiedenheft for being an amazing mentor throughout my time in his lab.
Huge thanks to my co-first author and colleague Nate Burman, who helped me learn cryo-EM. Here’s a fantastic movie he made that captures the key mechanistic steps of this unusual immune system in action!👇
Altogether, our findings reveal how an RT-ATPase immune system assembles a viral surveillance complex using a cDNA ‘harpoon’. Phage flap nucleases trigger its activation, leading to tRNA depletion and translation arrest—while phages fight back by encoding their own tRNAs.
Interestingly phages evade this ATPase-associated RT immune system by encoding their own tRNA-Ser genes! Comparison between phage encoded tRNA-Ser and E.coli tRNA-Ser revealed major differences clustered in the D-loop, which is key for recognition by aminoacyl tRNA synthetase.
Upon co-expressing the retron with phage flap nuclease, we observed nucleoid compaction in E. coli—a hallmark of translation arrest—driven by HNH-mediated depletion of tRNA-Ser. Recently Azam et al. (Nov 24) showed that expression of ATPase+HNH from Eco7 retron depletes tRNA-Tyr.
We then asked: what triggers this system? By sequencing phages that survive retron defense and expressing candidate genes, we found that phage-encoded flap nucleases (yes! the ones that remove Okazaki fragments) are baited to cleave the cDNA scaffold, activating the complex.
We find that HNH is recruited asymmetrically, either in an up or down orientation relative to the RT, and is anchored by a specialized C-terminal claw formed by the ATPase homodimer. Mutations at the ATPase–HNH interface or in claw-stabilizing residues abolished defense.
The long coiled-coil domains of SMC-family ATPases—which typically wrap DNA in repair complexes like Rad50—facilitate interdimer contacts in the retron complex, forming 'bear hug' and 'dorsal fin'-like structures that flank either end of the cDNA scaffold.
Using cryo-EM, we determined that this immune system forms a 364 kDa phage surveillance complex where the extrachromosomal cDNA—made by the RT using the ncRNA—acts as a molecular scaffold to recruit two ATPase homodimers and the nuclease.
Prokaryotic RTs have recently been shown to be key players in antiviral defense. Our story began with a simple question—how does a molecularly odd association of an RT, SMC-ATPase, structured ncRNA, and HNH nuclease (also called retron I-A) orchestrate phage defense?
