Jack Bravo

Phage-encoded CasPRs transcriptionally silence diverse CRISPR-Cas systems Anti-CRISPRs (Acrs) are diverse proteins or RNAs that protect invading phages and plasmids from host CRISPR-Cas immunity. Most Acrs neutralize their cognate Cas proteins via direct physical interaction. Here we describe CasPRs, a particularly widespread family of DNA-binding Acrs that recognize specific sequence motifs within cas gene coding regions, thereby blocking RNA polymerase and silencing transcription. We demonstrate that eight diverse CasPRs bind to the cas8b gene to repress the type I-B CRISPR-Cas system in its native host, Listeria seeligeri . Meanwhile, a CasPR from Streptococcus dysgalactiae silences type II-A CRISPR-Cas immunity by binding to the cas9 coding sequence. We found that one CasPR is required to inhibit CRISPR immunity during lysogeny by its host prophage. Taken together, our results indicate that members of the CasPR family have diverged to silence completely unrelated CRISPR types, and suggest transcriptional repression is a common mode of phage-mediated immune antagonism. ### Competing Interest Statement AJM is a co-founder and advisor of Profluent Bio. The other author declares no competing interests. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM142460, GM136534 U.S. National Science Foundation, FAIN2235762 Defense Advanced Research Projects Agency, https://ror.org/02caytj08, HR00112590142 Rita Allen Foundation, https://ror.org/0515k5w36

Phage-encoded CasPRs transcriptionally silence diverse CRISPR-Cas systems | bioRxiv https://www.biorxiv.org/content/10.64898/2026.02.23.707548v1?rss=1

Congrats Patrick! Great to see this published

Structure and mechanism of antiphage retron Eco2 - Nature Structural & Molecular Biology This study shows how the bacterial retron Eco2 defends against viruses. Phage nucleases trigger activation of Eco2, which cuts RNAs, shuts down protein production and stops phage replication.

Structure and mechanism of antiphage retron Eco2 | Nature Structural & Molecular Biology https://www.nature.com/articles/s41594-026-01754-2?utm_source=twitter&utm_medium=social&utm_campaign=nsmb

Two independent super-elegant studies from Maxwell & Laub labs find immune proteins that sense infection by binding to oligomeric phage protein rings (i.e phage portal), using them as a scaffold to assemble into their active immune effector form 🤯

Highly recommend read! 🤓📖l

A dynamic displacement mechanism drives protein import into mitochondria Most mitochondrial proteins are produced in the cytosol and imported through the translocase of the outer mitochondrial membrane (TOM) to reach their final destination. Although this protein entry gat...

📢 New preprint alert!
How do proteins enter mitochondria? We uncovered a surprising mechanism at the mitochondrial entry gate—using #NMR, in vivo single-particle tracking, yeast experiments, and MD simulations to crack the code.
www.biorxiv.org/content/10.6...
#StructuralBiology #Mitochondria
🧵 1/8

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

Structure of cytoplasmic RNA polymerase II www.biorxiv.org/content/10.64898/2025.12.10.692585v1 #cryoEM

📢 We have multiple open PhD positions to study bacterial immune systems using cutting-edge cryo-EM, microbiology, and biochemistry in our group! Join us and uncover how bacterial defenses eliminate predators and engineer next-gen biotech tools.

🔥 Apply by Jan 8, 2026

Details: phd.pages.ista.ac.at

So happy to see this work out! Was such a pleasure to co-lead this effort with Erin. Do you like viral immune evasion, and using protein structure to study immune antagonists? Give it a read!

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/...

What a fantastic Austrian Cryo-EM Symposium!
Huge thanks to my fellow organizers, our amazing admin team, ISTA for hosting, all invited speakers, sponsors, and every participant who made the day so inspiring.

Great science, great people, great energy.
Already looking forward to the next one!

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

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...

🚨 Abstract submission extended to Oct 21!
Join us for the Austrian Cryo-EM Symposium (Nov 11–12) at @istaresearch.bsky.social / ISTA 🇦🇹

Explore cutting-edge cryo-EM, meet top speakers, and visit beautiful Vienna.
👉 cryoem-symposium.pages.ist.ac.at

The Institute of Science and Technology Austria (ISTA) @istaresearch.bsky.social is hiring a tenure-track staff scientist in Computational Structural Biology (cryo-EM, cryo-ET, structural prediction methods, image analysis)!

More info here: apply.ista.ac.at/comp_structu...

Join us for the Austrian Cryo-EM Symposium from Nov 11–12 at ISTA! Top speakers, cutting-edge cryo-EM, and a chance to explore Vienna & the ISTA campus. Register now 👉 cryoem-symposium.pages.ist.ac.at/registration/

#cryoEM

How do SMC complexes load onto DNA to get ready for loop extrusion?

@roisnehamelinf.bsky.social & co discovered that Wadjet, an SMC complex involved in bacterial DNA immunity, performs some impressive molecular gymnastics 🤸‍♂️🤸‍♂️🤸‍♂️.

Check out the new paper: www.cell.com/molecular-ce...

Phages with a broad host range are common across ecosystems - Nature Microbiology Proximity-ligation-based sequencing from 111 samples and 5 environments reveals that a substantial proportion of phages infect multiple species.

A fresh view on phage specificity, which challenges the traditional view of a narrow host spectrum of phages by unveiling that multihost associations are common across ecosystems kudos at @mmarbout.bsky.social &
@rkoszul.bsky.social www.nature.com/articles/s41...

Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons Transposon-encoded TnpB nucleases gave rise to type V CRISPR-Cas12 effectors through multiple independent domestication events. These systems use diff…

Functional RNA splitting drove the evolutionary emergence of type V CRISPR-Cas systems from transposons - ScienceDirect https://www.sciencedirect.com/science/article/pii/S0092867425010359?dgcid=rss_sd_all

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 megaplasmids of up to 1.58 Mbp in length in infant and adult guts, and other microbiomes. Of the 19 complete plasmid genomes, one was reconstructed from an Escherichia coli isolate; others were linked to species of Citrobacter and Enterobacter via analysis of genome modification patterns. The detection of related plasmids in different Enterobacteriaceae , conjugation machinery, and more diverse modified motifs in certain plasmids compared to hosts suggests that these elements are self-transmissible, with a broad host range. The plasmids encode multi-drug efflux systems and potential secreted effectors. Up to 208 tRNAs are encoded, and include sequence variants that may counter tRNA-centric defense mechanisms. Overall, the vast megaplasmid coding capacity may broaden host range, increase competitiveness, control invasion by other elements, and counter programmed cell death. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, 5R01AI092531 Swiss National Science Foundation, IZJFZ3-177614 Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/X011011/1, BBS/E/QU/230002A, BB/T008717/1 Chan Zuckerberg Initiative (United States), https://ror.org/02qenvm24 Finnish Multidisciplinary Centre of Excellence in Antimicrobial Resistance Research, 346127

Megaplasmids associate with Escherichia coli and other Enterobacteriaceae | bioRxiv https://www.biorxiv.org/content/10.1101/2025.09.30.679422v1?rss=1

How the twin-arginine translocase (Tat) system manages to transport folded proteins across membranes without any leaks? To answer this fundamental question we solved the first structure of TatB3C3 complex with bound cargo. Please check out new preprint!
t.co/962Kj9pt6F

Heading to the Austrian Cryo-EM Symposium in November? Let's catch up! We'll be on hand to share how freely diffusing smFRET can complement this already exquisitely detailed technique #cryoEM #smfret #singlemolecule

Join us for the Austrian Cryo-EM Symposium Nov 11–12 at @istaresearch.bsky.social!

Top speakers, cutting-edge cryo-EM, and a chance to explore Vienna & the ISTA campus.

Register now 👉 cryoem-symposium.pages.ist.ac.at #cryoEM #teamtomo

Looking for a new approach to studying or eliminating phages? Check out our study introducing anti-phage ASOs (antisense oligos) out in @Nature today. nature.com/articles/s4158…

A conserved PIWI silencing complex detects piRNA-target engagement pubmed.ncbi.nlm.nih.gov/40912244/ #cryoEM

They are inaccurate/disagree with those in the pdb report. Might have used a different model iteration for the stats vs the deposited one. There are also a couple of massive typos (0.143 FSC used for map-to-model instead of 0.5, favoured and disallowed both 89.67%)

The stats in the SI are much better than those on the PDB (<1% disallowed rotamers, clashscore ~20 etc) i.e. false. The map also has awful anisotropy, but there is sadly a precedent for this particular complex dating back to a 2018 ms from others. Total failures of peer review and a sad day for EM

Registration is now open! Please share & repost!

...Beata Turonova, Maya Topf, Florian Wilfling, & Manuela Hospenthal, organized by myself, @aliciakmichael.bsky.social @haselbachlab.bsky.social @schurlab.bsky.social Clemens Plaschka & Thomas Heuser, between @impvienna.bsky.social @istaresearch.bsky.social and @vbcscitraining.bsky.social

Thrilled to announce the nexy Austrian Cryo-EM Symposium, taking place 11th-12th November at @istaresearch.bsky.social, with speakers inc. @grigoriefflab.bsky.social, @oliveiramann.bsky.social, @bjgreber.bsky.social @svenklumpe.bsky.social @sebastianglatt.bsky.social ‪‬https://tinyurl.com/cryo2025