1/11 New preprint from the Sternberg lab in collaboration with the Fernández lab! We are excited to share our structure-function study of DRT10, a bacterial defense-associated reverse transcriptase that synthesizes long tandem-repeat DNA.🧵 Read the full story here: www.biorxiv.org/content/10.6...

Mechanism of tandem-repeat DNA synthesis by an antiviral reverse transcriptase

Defense-associated reverse transcriptases (DRTs) employ DNA synthesis to protect bacteria against phage infection[1][1],[2][2]. We previously showed that DRT10, a tripartite system comprising an RT, a...

biorxiv.org

Beautiful work (and beautiful figures!) from Sashital lab alum @yuktidhingra.bsky.social! Congrats, and looking forward to seeing more exciting RNAP work in the future!

Yukti Dhingra@yuktidhingra.bsky.social · last mo.

Happy to share the first paper from my postdoc in the Darst and Campbell labs! 🧵 www.pnas.org/doi/full/10.... We used cryo-EM and allosteric inhibitors as mechanistic probes to visualize conformational landscapes of E. coli and M. tuberculosis RNA polymerases during nucleotide addition. 1/4

Happy to share the first paper from my postdoc in the Darst and Campbell labs! 🧵 www.pnas.org/doi/full/10.... We used cryo-EM and allosteric inhibitors as mechanistic probes to visualize conformational landscapes of E. coli and M. tuberculosis RNA polymerases during nucleotide addition. 1/4

RNA polymerase inhibitors reveal active-site motions essential for the nucleotide addition cycle | PNAS

The nucleotide addition cycle (NAC) of multisubunit DNA-dependent RNA polymerases (RNAPs) involves coordinated conformational changes in conserved ...

pnas.org

Now online @pnas.org: We developed a simple, scalable, and accessible platform for deep profiling of phosphoeraser specificity using human phosphoproteome-derived peptide libraries (PhosPropels!) 🧪👩‍🔬https://www.pnas.org/doi/10.1073/pnas.2523183123

Phosphoproteome-derived peptide libraries for deep specificity profiling of phosphatases and phospholyases | PNAS

Protein phosphorylation is dynamically regulated by the opposing activities of phosphowriter enzymes (kinases) and phosphoeraser enzymes (phosphata...

pnas.org

Le Tour de RNA was an awesome success! Thanks to everyone who helped us celebrate Sam, RNA, and NMR!

Thanks for visiting and sharing your amazing science with us! I'll always have a place in my heart for U2-U6, even if we mostly talked about DNA

Hiten Madhani@hitenmadhani.bsky.social · 3mo ago

Thanks to Sudhir Kumar for hosting me at Iowa State today. I had a lovely visit to the Biomedical Sciences Dept. at their amazing vet school. Great to also catch up with Dipa Shashital, one of my RNA world friends. Once a splicing person, always a splicing person.

Site-specific, multi-kilobase insertions and over-writes in mammalian cells, without DSBs, HDR, recombinases, integrases, transposases, or active cell cycling? Using fully or predominantly single-stranded DNA donors? 1/15

Excited that our paper on enzymatic bromination of peptides is now online at ACS Chemical Biology! Led by Haley Bridge, we showed that the flavin-dependent halogenase RebH and its variants can be used for late-stage chemoenzymatic diversification of bioactive peptides: pubs.acs.org/doi/10.1021/...

Enzymatic Bromination of Native Peptides for Late-Stage Structural Diversification via Suzuki–Miyaura Coupling

Flavin-dependent halogenases (FDHs) provide a biocatalytic approach for the site-selective halogenation of aromatic compounds, but their use in late-stage functionalization of peptides has remained li...

pubs.acs.org

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

Structural basis of supercoiling-induced CRISPR–Cas9 off-target activity - Nature

Cas9 structures explain topology sensing and off-target activation.

nature.com

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...

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:...

Sternberg Lab@sternberglab.bsky.social · last yr.

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...

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 🧪https://www.biorxiv.org/content/10.64898/2025.12.17.694899v1

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

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...

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…

sciencedirect.com

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...

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...

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...

biorxiv.org

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!

Wearn Xin (Edeline)@wearnxin.bsky.social · last yr.

We've identified a group of nucleases that can target multiple phages with hypermodified DNA, using a sensor domain present across many domains of life. We’ve even used this as a tool to find phages with hypermodified DNA! Really thankful to all the co-authors who have been such great help!

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... 🧵👇

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...

biorxiv.org

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...

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...

biorxiv.org

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 https://www.biorxiv.org/content/10.1101/2024.12.27.630466v1

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

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...

biorxiv.org