Excited to share my last major PhD work from the @SternbergLab. We discovered a mechanism that initiates transcription at programmable sites, without requiring promoter sequences - a novel mode of transcription regulation in bacteria.
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
Our 2 papers on RNA-guided transcription are now out @Nature. This mechanism re-writes the traditional concept of bacterial transcription and allows RNA transcripts to be generated de novo from potentially any cellular DNA sequence. 🧬 See below for links and thread 🧵
Out now! In collaboration with @LeifuChangLab, we uncover the molecular and structural underpinnings of CRISPR-Cas12f-like RNA-guided transcription systems!
Links to the articles in the following tweet:
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.
doi.org/10.1101/2025.10.16.6…
In parallel to our RNA-guided transcription biology story, we collaborated with @LeifuChangLab and determined how Cas12f interacts with a Sigma factor to recruit RNA polymerase. See their thread on the magnificent dCas12f-Sigma-RNAP structure below:
Our new preprint is live! doi.org/10.1101/2025.06.10.6…
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.
Know the feeling when two things look similar, and yet turn out to be quite different? Seems like defense-associated reverse transcriptases will continue to surprise us...
Another thrilling story uncovered in collaboration with @WiedenheftLab! Check it out:
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/10.1101/…
Thrilled, and also in a bit of disbelief, to see our paper featured on the cover of @ScienceMagazine! "Finding Neo" wasn't easy, but we just kept swimming (read: stared at a sequence of DNA) until the Eureka moment hit.
The central dogma of molecular biology states that genetic information flows from DNA and RNA to protein, with reverse transcription converting RNA to DNA.
In the pursuit of understanding how bacteria defend themselves from viral infection, two groups have found alternative pathways to making genes from RNA that did not previously encode proteins. Learn more this week in Science: bit.ly/3ZO7tI1
Huge congratulations to the most brilliant scientist I‘ve met so far - @shsternberg. Hard to come across a more dedicated PI and mentor - I can‘t even imagine the amazing discoveries this will enable you and the whole @SternbergLab to make in the future! 🧬 🎉
Preprint alert 🚨 from the @SternbergLab ‘De novo gene synthesis by an antiviral reverse transcriptase’: new central-dogma-expanding work led by @stephentang23 is now online! You won’t want to miss this thread:
biorxiv.org/content/10.1101/…
I am delighted to share the newest work from the @SternbergLab, in which we discover RNA-templated gene creation as a mechanism of antiviral immunity. This is a story for anyone who loves molecular biology, and one that repeatedly left us in disbelief. doi.org/10.1101/2024.05.08.5…
Not a single week without a new paper from the @SternbergLab: led by bioinformatics star @TannerWiegand
Bacteria use ancestral CRISPR-Cas genes as transcription factors!#crispr
Emergence of RNA-guided transcription factors via domestication of transposon-encoded TnpB nucleases
New pre-print from the Sternberg Lab! Transposon-encoded nucleases (TnpB/IscB) gave rise to the CRISPR-associated proteins (Cas9 and Cas12), but were TnpB-like proteins domesticated for other functions? 𝙔𝙀𝙎!! doi.org/10.1101/2023.11.30.5…
We’re beyond excited to share the newest pre-print from the Sternberg Lab! You thought all bacterial transposons (aka IS elements) were simple? Think again…🤓1/6
Thrilled to share our work on how type V-K CRISPR-associated transposases (CASTs) select their target sites, now published in @ScienceMagazine!
science.org/doi/full/10.1126…
In this study, we've enhanced the accuracy of type V-K CASTs up to 99%.🧵 on the bioRxiv version below: #CRISPR
In a major milestone for science, for medicine, and for patients, the world’s first CRISPR drug has been approved in the UK.
“A new treatment for sickle-cell disease and transfusion-dependent β-thalassemia has been authorised by the Medicines and Healthcare products Regulatory Agency (MHRA) for patients aged 12 and over after a rigorous assessment of its safety, quality and effectiveness.”
Congratulations to the many scientists, doctors, patients, and industry leaders who made this development possible.🍻
gov.uk/government/news/mhra-…
We're hiring! Join the Biochemistry and Molecular Biophysics department here at Columbia, in wonderful NYC, and pursue your best scientific ideas amidst fantastic colleagues and a growing community.
Happy to answer any questions about the department or application process.
Who would not want to start the independent career working with this amazing group of junior faculty? Having peers that get you, share your problems, and can have a drink with you at the end of the week is key for success! BMB is hiring- please apply:apply.interfolio.com/131823
Thrilled to see our latest work published this week, on the essential roles of IscB/TnpB -- ancestral homologs of Cas9/Cas12 -- in transposon maintenance & spread. A wonderful team effort led by the talented Chance Meers! Thread on bioRxiv version below...
nature.com/articles/s41586-0…
Great news - our lab's latest manuscript is out on bioRxiv!
Led by postdoc Chance Meers, we discovered that RNA-guided DNA cleavage by transposon-encoded nucleases arose to facilitate the pervasive spread and inheritance of transposons. 🧵: (1/6) biorxiv.org/content/10.1101/…
New paper from our lab @shsternberg, led by Chance Meers Ph.D., is now online @Nature! We explored the ancestors of the genome editors Cas9 and Cas12 (IscB & TnpB) and their importance for transposon spread. Fortunate to be part of this team!
What a blast we had at @ColumbiaCMBS’s first off-site retreat post C.! Great science presented by the PhD students, community building & fun activities in an unforgettable Gatsby setting. Thank you for making this possible @Columbia! What a start for the new first year PhDs.
We had a wonderful time at our 2023 CMBS retreat! Fantastic talks and posters presented by our students made for fun scientific conversations. Thanks to the student and faculty organizers for putting together a great event! @ColumbiaMed@ColumbiaGSAS
🎥 credits to @fthoffmann
What a day! We had such a blast sharing our science with middle-schoolers in Long Island, at the inaugural Cutting-Edge Science Camp! Big shout-out to all the volunteers from @Columbia, and to @SawickiScience@jameshmccabe@dharls1@WenWanso and all the teachers from East Meadow!