please look here for more information about a postdoc position careers.mskcc.org/vacancies/93...

there are a few solved phage tail structures, do any of them fit the density ok? I think most tailed phages have the same fold for the major tail protein. The pitch and twist also seem similar

Is that a phage tail in Fig 4?? 👀

Really interesting q! It depends if insect rDNA::R2 inactivation is targeted, e.g. by piRNAs. If so, then maybe there's no problem because mammalian lineages lost R2 and so might have also lost specific defences. But if rDNA has inherent quality control / self-silencing, then this could happen.

Full story here!
We hope this expands the toolkit of retrotransposon-based gene editors. Also, check out related work from Kathy Collins lab, who also illuminated how R2 can be used for mammalian genome engineering, and @akankshathawani.bsky.social who also recently solved an R2Tg structure! (fin)

This project was a huge team effort.
The hugest shoutout to @kedmonds.bsky.social for her HEROIC engineering and optimisation (+ birb drawing 🐦🥚)
Also to Hongyu Chen and Dangliang Liu for RNA chemistry, Feng Zhang for fearless leadership, and all the amazing authors who made this possible. (6/n)

RNA stability may limit efficiency. With help from Xiao Wang and her lab, we added chemical modifications to protect donor RNA from exonucleases.
Combined with LNP delivery, this boosted integration efficiency to >80% in multiple human cell lines, all with an RNA system. Which is kinda nuts. (5/n)

The fabulous Grace then took over. She replaced parts of R2Tg RNA with custom sequences — “tricking” the retrotransposon into integrating cargo instead of itself.
She then defined the minimal R2 elements required for integration, leading to a compact, efficient “mini donor”. (4/n)

We found that the R2 retrotransposon from zebra finch (Taeniopygia guttata, “R2Tg”) looked really promising! I had fun playing around with its biochemistry, and solved the cryo-EM structure of it copying its own RNA. We found key features that differ from the more well-studied insect R2. (3/n)

R2 retrotransposons are neat! They're pretty widespread across the animal kingdom, and they propagate by copying themselves into ribosomal DNA, a highly repetitive region of the genome.
This natural system inspired our design: we thought the rDNA could be a good 'safe harbour' for transgenes. (2/n)

big fan of southern blots!! Do you have any ideas why the 3'UTR is not required?

absolute pleasure working on this with @guilhemfaure.bsky.social, Makoto Saito, other great colleagues, and our fearless leader Feng Zhang.

Lots more details here: www.science.org/doi/10.1126/...

(I'll try to make a fancier movie in time for the press version 🤞🤞)

(hashtag #TIGR #Tas)

TIGR might have some advantages over CRISPR in genome editing (absolutely tiny, no PAM), but more importantly it's just some really neat, mysterious biology. Maybe TIGR is used by phages to fight other viruses? We don't know yet! Many many many questions left.

exactly!

it does, which is the main inaccuracy of the video! As it happens, the RT does actually make dsDNA, but only after synthesising some repeats and then changing direction to perform second-strand synthesis. This would be fun to animate, but I thought it would make the movie too confusing.