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Inserting large, scarless DNA sequences is a major hurdle for gene therapy. We explored if site-specific retrotransposons, natural genome editors found across the tree of life, could be engineered for this task. Excited to share STITCHR in nature with Jonathan Gootenberg!

In @nature we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR-Cas9 enzymes, offering safer & more genome editing tools. 🧬🖥️ Rachel Silverstein CGM at MGH @MGH_RI MassGeneral News Harvard Medical School nature.com/articles/s4158…

Been eagerly awaiting this one—never expected 30% efficiency! 🤯 Incredible work, and huge congrats to all the authors from Sternberg Lab and David R. Liu Labs!

Coverage of our collaboration with the Liu group.. ' “This is crazy directed evolution!” - Makoto Saito' nature.com/articles/d4158…

Excited to share our newest paper, online today nature! We report the discovery of a highly unusual mechanism of antiviral immunity through the synthesis of long, homopolymeric DNA. nature.com/articles/s4158…

Our latest story is now online nature! We discovered a phage defense system that deploys kilobase-long DNA homopolymers to protect against viral infection. Congratulations to all authors, and to the Wiedenheft Lab for a fun and fruitful collaboration! nature.com/articles/s4158…

Despite the chaos and turmoil, our lab is blessed to have 3 new postdoctoral fellow openings and we would welcome scientists interested in: - combining single-molecule studies with cryo-EM - developing new protein design tools using bioinformatics and structure-based tools -

Excited to share my last major PhD work from the Sternberg Lab. We discovered a mechanism that initiates transcription at programmable sites, without requiring promoter sequences - a novel mode of transcription regulation in bacteria.

The lightning (Cas12f-Sigma) does strike twice today.⚡️See below for a thread by our collaborators Leifu Chang describing the massive cryo-EM structure of the RNA-guided transcription initiation complex, featuring Cas12f, Sigma and RNA polymerase:

"If my career has taught me anything, it’s that resilience alone doesn’t guarantee survival. But sometimes, it gives you just enough time to catch the next opportunity before the door closes." #ScienceWorkingLife scim.ag/43DGNLM

Excited to share our work on the structure of a natural RNA nanocage formed by the ROOL noncoding RNA, originally discovered by Zasha Weinberg and Ronald Breaker many years ago. Great collaboration with Xiaobin Ling, Jinbiao Ma, and Korostelev Lab! rdcu.be/erdqY

New cryo-EM structures shine light on key steps in CRISPR-based adaptive immunity! Viral DNA induces a structural change in the Cas1-2/3 integrase needed for recruitment to the CRISPR. We capture how CRISPR repeat is unwound to allow complete integration! biorxiv.org/content/10.110…

Introducing Arc Institute’s first virtual cell model: STATE

What determines who a phage can infect? We tackled this question for temperate phages of Klebsiella — a bacterial pathogen — using a genome-wide association study (GWAS) and a massive protein testing effort. 👇 A thread!

Can we use RNA to insert kilobases of DNA into the human genome, opening up a new way to engineer cells or treat disease? Excited to share our latest work turning a retrotransposon (a “jumping gene” with an RNA intermediate) from songbirds into a genome editing tool. 🧵 (1/7)

Identifying phage proteins that activate the bacterial innate immune system biorxiv.org/content/10.110… #biorxiv_micrbio

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

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⬇️ biorxiv.org/content/10.110…

My second PhD project is out in NAR! We investigate a remarkable transposase involved in genome rearrangement in the ciliate Oxytricha trifallax. Endless gratitude to Laura (Laura Landweber), Sam (Sternberg Lab) and our brilliant collaborators. ⬇️ academic.oup.com/nar/article/do…

Thrilled to see our Kiwa story out today! A membrane-associated supercomplex that senses infection and blocks replication and transcription. Huge congratulations to ugobananas @Zhangzhiyi58692 and Thomas Todeschini, and to all our collaborators. shorturl.at/l0ayB