Connor Tou
@connorjtou
PhD from @MITdeptofBE, Kleinstiver Lab || Editing Genes 🧬 & Running Mountains ⛰
Today in @NatureBiotech, we describe first-gen click editors (CEs), which couple the advantageous properties of DNA-dependent DNA polymerases and HUH endonucleases with RNA-programmable nickases for precise and versatile human genome editing. 🧬 nature.com/articles/s4158…
Excited to share my third and final PhD project! We explored the biological consequences of RNA-guided flagellin regulation in bacteria. This was a real labor of love - spanning microbiology, microscopy, mouse gut colonization, and more. Co-led with the brilliant @EgillRichard.
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
Our new preprint is live! doi.org/10.1101/2025.0… In collaboration with @SternbergLab, we determined the cryo-EM structure of a dCas12f-σE-RNAP complex from F. taeanensis, revealing an RNA-guided transcription mechanism that bypasses canonical promoter motifs.
New pre-print(s) from the Sternberg Lab in collaboration with @LeifuChangLab! We uncover an unprecedented molecular mechanism of CRISPR-Cas12f-like proteins, which drive RNA-guided transcription independently of canonical promoter motifs. Full story here: tinyurl.com/mr3fd493
Today in @ScienceMagazine 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, a collaboration with @SternbergLab. 1/13 drive.google.com/file/d/1I-UbCR…
"Does it work in human cells?" is a question I've gotten a lot this past year. Excited to share our latest work on bridge recombinases! It's been a lot of fun to lead this team effort. If you are excited to hear more, join for my thesis defense tomorrow at 3pm PT. Links below:
Genomes encode biological complexity, which is determined by combinations of DNA mutations across millions of bases In new @arcinstitute work, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement
Genomes encode biological complexity, which is determined by combinations of DNA mutations across millions of bases In new @arcinstitute work, we report the discovery and engineering of the first programmable DNA recombinases capable of megabase-scale human genome rearrangement
What if we could universally recombine, insert, delete, or invert any two pieces of DNA? In back-to-back @Nature papers, we report the discovery of bridge RNAs and 3 atomic structures of the first natural RNA-guided recombinase - a new mechanism for programmable genome design
Excited to share my PhD work… and more CRISPR-Cas9 PAM variants than anybody asked for
In @nature we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR-Cas9 enzymes, offering safer & more genome editing tools. 🧬🖥️ @RachelSilvers11 @CGM_MGH @MGH_RI @MassGeneralNews @harvardmed nature.com/articles/s4158…
So excited to share our new paper out today in @Nature. We repurposed R2 retrotransposons to create STITCHR, a tool that can make diverse edits in mammalian genomes including scarless multi-kilobase scale insertions nature.com/articles/s4158…
The sequel to our DRT2 story is here, and this one is once again full of surprises! This time around, the @SternbergLab teamed up with the @WiedenheftLab to study how DRT9 reverse transcriptases provide antiviral immunity. Here’s what we found: biorxiv.org/content/10.110…
Interested in learning more about genome editing tool dev & their application to treat human diseases? 🧬 🏥 We're hiring graduating seniors who are seeking ~2 years of post-bac research experience. If you're interested in gaining experience in next gen medicines, please reach…
We are excited to report the discovery of TIGRs, a widely-occurring RNA-guided system found in bacteria and their viruses. TIGRs consist of a peculiar repeat region which is transcribed into RNA and processed into multiple guide RNAs to direct TIGR-associated proteins to their…
Thrilled to share that EVOLVEpro is now published @ScienceMagazine Since our preprint, we now demonstrate low-N eningeering of both antibody and enzymes. We hope this model will broadly useful to the protein engineering field. science.org/doi/10.1126/sc…
🧵In new work, we report a systematic engineering roadmap to optimize large serine recombinases (LSRs) for direct, site-specific insertion into the human genome 🧬. We achieved over 50% insertion efficiency and 97% genome-wide specificity, a 10X improvement over our previous work
Our new paper on epigenome editing is out! We mapped which effector domains regulate transcription across genomic, cell type and DNA-binding domain contexts. Then we built new gene repressor and activator tools with improved efficiency & deliverability nature.com/articles/s4158…
Researchers from @CGM_MGH and colleagues published the paper, click editing enables programmable genome writing using DNA polymerases and HUH endonucleases, in @NatureBiotech this past month. Read more: doi.org/10.1038/s41587…
Published today in @Nature, we describe an approach for single-molecule protein reading on @nanopore arrays. By utilizing ClpX unfoldase to ratchet proteins through a CsgG nanopore, we achieved single-amino-acid sensitivity. nature.com/articles/s4158…
Was fun to tune in online with a mini watch party yesterday to catch @FerreiraSilvaJ's presentation on updated & engineered #clickeditors at the @CSHL #CRISPR talk (on behalf of a large collaborative effort in the lab). Excellent talk, Jo! 🧬👏 @CGM_MGH @MGH_RI @MassGeneralNews…
My favourite discovery ever has just come online. Can I please tell you about some seriously wacky molecular biology? The story starts with a reverse transcriptase that SOMEHOW defends bacteria from viruses. (👇 I recommend sound ON for the video 🎹) 1/
Genome editing with DNA-dependent polymerases #NBTNV go.nature.com/3WUmCod
In a new @NatureBiotech study, researchers from @CGM_MGH and colleagues investigated programmable genome writing via click editing with DNA polymerases and HUH endonucleases. Read more: massgeneral.org/news/research-… @BKleinstiver @FerreiraSilvaJ @connorjtou