Out now! In collaboration with Hiroshi Nishimasu's lab, we uncover how a dual reverse transcriptase immune system builds double-stranded DNA from both RNA and protein templates. www.cell.com/cell/abstrac... Previous thread for the preprint: bsky.app/profile/ster...

Coordinated RNA- and protein-templated synthesis of double-stranded DNA by a dual reverse transcriptase immune system

Bacterial reverse transcriptases defend against viruses, yet how their DNA products stop infection remains unknown. Bacteriophage inhibition of a host recombination enzyme activates the DRT3 defense s...

cell.com

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

1/8 🚨 New preprint from the @sternberglab.bsky.social & @martinjinek.bsky.social labs! CRISPR-associated transposases (CASTs) insert large DNA cargoes at precise genomic locations — no double-strand breaks needed.

1/9 New preprint from the Sternberg Lab in collaboration with the Nishimasu Lab! We uncover how the DRT3 antiphage immune system pairs two reverse transcriptases, one RNA-templated and one protein-templated, to build a double-stranded DNA effector. doi.org/10.64898/202...

New preprint from the Sternberg lab! We used pooled oligonucleotide library mutagenesis + high-throughput sequencing to systematically dissect the molecular determinants of IStron transposition, RNA-guided DNA cleavage, and self-splicing. 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...

1/9 Metagenomics lets us read microbiomes in nature without cultivation, but writing (editing) them in their native context is still a major challenge. Meet MetaEdit: a platform for pathway-scale metagenomic editing inside the gut microbiome. science.org/doi/10.1126/...

Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases

Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce ...

science.org

Please RT. Post-doc opportunity alert! 💥 closing 10th December.. Come join our team (www.thelowlab.org) at Imperial, London, working on the structure and mechanism of bacterial secretion systems. For more details and to apply please see www.imperial.ac.uk/jobs/search-...

1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from? Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria. www.biorxiv.org/content/10.1...

Antiviral reverse transcriptases reveal the evolutionary origin of telomerase

Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...

biorxiv.org

1/16 New pre-print from the Sternberg Lab! We uncover how temperate phages can use RNA-guided transcription factors to remodel the flagellar composition of their bacterial host and enhance their fitness. Find the preprint and full story here: tinyurl.com/mshwjd77

Gene editing pioneer David Liu discusses baby K.J. Muldoon, the first person treated with a customized gene editing therapy, what made K.J.'s treatment possible, and how on-demand treatments for rare genetic diseases could one day become routine. #GeneEditing #Science

Q&A: One scientist’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases

Broad core member and gene editing pioneer David Liu describes a framework that could enable the treatment of 1,000 patients with personalized gene editing therapies by 2030.

broadinstitute.org

🧬🌽 Happy Transposon Day! 🌽🧬 Today we celebrate the birthday of Barbara McClintock - scientist extraordinaire and discoverer of jumping genes. Still the only woman to have an unshared Nobel Prize in the biomedical sciences #TransposonDay2025

Nature invented CRISPRa way before scientists did 🤩 Awesome work by the @sternberglab.bsky.social Looking forward to seeing cool applications coming out of this !

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...

Did you think you needed a promoter for CRISPRa? Think again!

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

6/10 dCas12f-Sigma factors are able to recruit their native RNA polymerase (RNAP) to drive RNA-guided transcription at programmable sites. Remarkably, we were able to generate RNA (see RNA-seq) without relying on promoters in intergenic sequences, even within genes, and on either DNA strand.

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...

Did you see the recent buzz about evoCAST, a new CRISPR-transposon tool that can insert entire genes into human cells? We've got a quick explainer on how CASTs work and how evoCAST improves on them! @isaacwitte.bsky.social @sternberglab.bsky.social blog.addgene.org/cas...

CASTing Off for New Shores in Human Genome Editing

This post describes evoCAST, a new CRISPR-associated transposase tools optimized for genetic editing in human cells.

blog.addgene.org

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...

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

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...

Always grateful to investigators like @sternberglab.bsky.social and David Liu who share their plasmids through @addgene.bsky.social. www.addgene.org/browse/artic...

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

1/10 Today in @science.org in collaboration with the Liu group we report the development of a laboratory-evolved CRISPR-associated transposase (evoCAST) that supports therapeutically relevant levels of RNA-programmable gene insertion in human cells. drive.google.com/file/d/1I-Ub...

"..one of the biggest challenges right now for evoCAST, and other large DNA editing tools under development, is delivery. 'How do we actually get these tools and their payloads into the cells or tissues of interest?'” www.cuimc.columbia.edu/news/sternbe...

www.nature.com/articles/d41... Coverage of our collaboration with the Liu group.. ' “This is crazy directed evolution!” - Makoto Saito'

Powerful CRISPR system inserts whole gene into human DNA

‘Directed’ evolution in the laboratory creates an editing tool that outperforms classic CRISPR systems.

nature.com

Excited to introduce evoCAST: a platform for efficient, programmable gene integration in human cells. This work, a close collab between my PhD lab (Liu group) and @sternberglab.bsky.social, has been such a fun journey to help lead. Huge thanks to all contributors! www.science.org/doi/10.1126/...

Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase

Programmable gene integration in human cells has the potential to enable mutation-agnostic treatments for loss-of-function genetic diseases and facilitate many applications in the life sciences. CRISP...

science.org

1/10 Today in @science.org in collaboration with the Liu group we report the development of a laboratory-evolved CRISPR-associated transposase (evoCAST) that supports therapeutically relevant levels of RNA-programmable gene insertion in human cells. drive.google.com/file/d/1I-Ub...

💥🥳 At long last, our latest paper is out! Gag proteins of endogenous retroviruses are required for zebrafish development www.pnas.org/doi/10.1073/... Led heroically by Sylvia Chang & @jonowells.bsky.social A study which has changed the way I think of #transposons! No less! 🧵 1/n

Gag proteins encoded by endogenous retroviruses are required for zebrafish development | PNAS

Transposable elements (TEs) make up the bulk of eukaryotic genomes and examples abound of TE-derived sequences repurposed for organismal function. ...

pnas.org

Join GEN on June 11 for: "The State of CRISPR & Genome Editing" virtual summit. Guests include: Feng Zhang, @urnov.bsky.social , @juliemakani.bsky.social @nevillesanjana.bsky.social; Alexis Komor & Nicole Gaudelli, and Beth Shapiro Registration is free! webinars.liebertpub.com/e/the-state-...

One of my students pointed me to this great podcast that gives an overview of phage history! #PhageSky open.spotify.com/episode/4XTa...

Bacteriophages

In Our Time · Episode

open.spotify.com

We've been fortunate to celebrate a few wins in the lab recently. Dr. George Lampe received the Columbia Dean’s Award and Henry Le was awarded a Soros Fellowship. Cheers and congratulations to you both!!

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