Structural basis of supercoiling-induced CRISPR–Cas9 off-target activity - Nature Cas9 structures explain topology sensing and off-target activation.

1/11 In our story out today in @nature.com , we showcase the molecular mechanisms that enable Cas9 to bind and cleave negatively supercoiled ((-)SC) off-targets! 🧬🧵

🔗 www.nature.com/articles/s41...

#CRISPR #Cas9 #DNATopology #AFM #CryoEM #SingleMolecule #Biophysics

Check out our the structure of a DNA-guided Cas12a. It uses the DNA hairpin to mimic structural cues to recognize a target RNA. Gnarly. www.biorxiv.org/content/10.6...

We usually get the results the morning after we ship the samples,so it's very fast!

Amplicon Sequencing - Plasmidsaurus Simple setup and fast results for amplicons of any size.

Plasmidsaurus offers nanopore amplicon sequencing (the Premium PCR option here: plasmidsaurus.com/amplicon) that works well and is very cost effective. They also do the PCR cleanup for you for $5, so you just ship the PCR products directly to them

Out now! In collaboration with Leifu Chang, we uncover the molecular and structural underpinnings of CRISPR-Cas12f-like RNA-guided transcription systems!

Links to the published articles:
tinyurl.com/55kpavet
tinyurl.com/sk6djwx3

Previous thread for the preprint:
bsky.app/profile/did:...

Early registration for the CRISPR 2026 meeting is extended until March 15, 2026. The Abstract deadline is March 31, 2026. Registration is required before submitting an abstract.

web.cvent.com/event/ac20b6...

Save the date! The CRISPR 2026 meeting will be held June 10 - 12 at Yale University, New Haven, Connecticut, USA. Abstract submissions will be opened on February 1st. Spread the word.

For ~century, we’ve asked: why do proliferating cells ferment glucose even when O2 is around? I’m thrilled to share our latest work @natmetabolism.nature.com, led by @thebiokimist.bsky.social. By leveraging conditional essentiality in HPLM, we propose a provocative new answer to this classic Q. 🧵

New preprint! We found that the flavin-dependent halogenase RebH catalyzes sequence-tolerant Trp bromination in peptides 🧪www.biorxiv.org/content/10.64898/2025.12...

Big news! Our team developed Neuro-PERC, a non-viral CRISPR delivery platform for genome editing of the brain. In our new preprint - bit.ly/NeuroPERC_pre - we report efficient editing in multiple models & species, including field-first results in large animals (pigs) 🧵👇

How do cells adapt morphology to function? In a 🔥 preprint by @zjmaggiexu.bsky.social , with @dudinlab.bsky.social and @amyweeks.bsky.social , we identify a self-organizing single-cell morphology circuit that optimizes the feeding trap structure of the suctorian P. collini. 🧵 tinyurl.com/4k8nv926

Type I CRISPR-Cas immunity primes type III spacer acquisition CRISPR-Cas systems are diverse, with microbes harboring multiple classes and subtypes. Type I DNA-targeting and type III RNA-targeting systems often c…

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...

Position-specific frequency matrices can be used to calculate z-scores comparing enzyme-treated and control samples. The z-scores are plotted as heatmaps that represent an enzyme specificity profile.

New preprint: we developed a method that uses phosphoproteome-derived peptide libraries (PhosPropels) for deep specificity profiling of phosphatases and phospholyases www.biorxiv.org/content/10.1...

Bacterial Schlafens mediate anti-phage defense Human Schlafen proteins restrict viral replication by cleaving tRNA, thereby suppressing protein synthesis. Although the ribonuclease domain of Schlafen proteins is conserved across all domains of lif...

First preprint from the Nemudryi Lab! 🍾

In this work, we link antiviral immunity in bacteria and humans by showing that homologs of human Schlafen nucleases protect bacteria from phages.

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

Was my pleasure to chair the #crispr2025 meeting earlier this year in my hometown in NZ @crisprmeeting.bsky.social

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!

Structural basis of antiphage defense by an ATPase-associated reverse transcriptase Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses and retrotransposons. However, recent evidence suggests that RTs have been conscripted by cells f...

I am super excited to share our work uncovering the structure and mechanism of an ATPase-associated reverse transcriptase (RT) involved in prokaryotic antiviral defense, now available as a preprint on bioRxiv!🧬🦠🔬
www.biorxiv.org/content/10.1...
🧵👇

Protein-primed DNA homopolymer synthesis by an antiviral reverse transcriptase Bacteria defend themselves from viral predation using diverse immune systems, many of which sense and target foreign DNA for degradation. Defense-associated reverse transcriptase (DRT) systems provide...

Hello BlueSky! Inaugural post here from the Sternberg Lab. We're excited to share our latest work, in which we teamed up with the @WiedenheftLab to study how DRT9 reverse transcriptases provide antiviral immunity. Here’s what we found: www.biorxiv.org/content/10.1...

My contribution to the Science Homecoming project--I wrote to The Item in Clinton, MA about the impacts that cuts to science funding will have on our health, our economy, and the opportunities available to young people in Clinton www.clintonitem.com/writes-cuts-...

@sciencehomecoming.bsky.social

Finally, in these tough times for science I want to emphasize how this work was supported at every level by NIH: through grants to my lab (DP2); to my students (BTP T32; CBI T32); and from Rohith’s experience as an NIH Postbac in the Tjandra lab. Grateful for the support that made this possible.

Excited to share a new preprint! Wireless devices use FM modulation to transmit multiplexed noise-resistant data. Led by @born2raisecell.bsky.social, we create a biochemical analogue of this paradigm using genetically encoded oscillators (GEOs) for single-cell FM streaming tinyurl.com/nbs8rw42 🧵

CRISPR-Cas supervises diverse anti-phage defense systems www.biorxiv.org/content/10.1101/2024.12....

Systematic functional assessment of antiphage systems in their native host Bacterial resistance to bacteriophages (phages) relies on two primary strategies: preventing phage attachment and blocking post-attachment steps. These latter mechanisms are mediated by defence system...

Finishing the year with a paper submission always feels good! 🛡 🦠 (1/5)
www.biorxiv.org/content/10.1...

Happy holidays everyone! ⭐️🎄

Diverse phage communities are maintained stably on a clonal bacterial host Bacteriophages are the most abundant and phylogenetically diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. In this study, w...

Is it “winner-takes all” when the simplest living things compete? Check out my fresh publication on phage coexistence in Science and a thread below🧵 www.science.org/doi/10.1126/...

If you were on the fence about coming to CRISPR 2025 let us add that Christchurch airport is well connected internationally and from there you can explore many grand sights in the South Island, NZ. Register now and book a conference trip to NZ hashtag#CRISPR2025 lnkd.in/gaSkt-Ng

I hope you won!

Happy Holidays from the Weeks lab! This year's ornament is a working ferris wheel 🎡☃️

Meet one of our speakers: Elizabeth Kellogg is an assistant professor in the department of Molecular Biology and Genetics at Cornell. There's still time to register and get to hear Elizabeth speak at CRISPR 2025 in Ōtautahi, Christchurch, NZ. lnkd.in/gds9sURN