Max Wilkinson

Proteolytic activation of diverse antiviral defense modules in prokaryotes Linked protease–effector modules are widespread in prokaryotic antiviral defense, yet the mechanisms of most remain poorly understood. Here we show that four of the most prevalent modules—metallo-β-la...

I am so excited to share our project with you! We find prokaryotic proteases activate toxic enzymes and pores as a modular strategy in phage defense. We studied four fascinating protease-toxin pairs that are abundant across bacterial genomes:

www.biorxiv.org/content/10.1...

Image showing 4 tRNAs being produced from only 2 loci, the tRNA genes completely overlap

Oh, your favorite genetic locus only encodes one gene? That's boring.

Amazing work from Jess Warren (www.hhmi.org/scientists/j...) to figure this out and prove it was real, given the wacky and challenging insect system we've got here.

www.biorxiv.org/content/10.1...

93229-Postdoctoral Researcher – Laboratory of Max Wilkinson | Memorial Sloan Kettering Cancer Center

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

Wilkinson Lab We discover and study reverse transcriptases

The Wilkinson Lab is open for science! @mskcancercenter.bsky.social

🧬We'll be finding funky new RNA biology, mainly by looking at reverse transcriptases (i.e. the Best Enzymes In The World)🧬

annnd: I'm hiring - come join! Especially postdocs and PhD students - please get in touch (NYC is great)

a highly attractive hypothesis for the origin of telomerase, but imo more evidence is needed to rule out convergent evolution
1- other RT phylogenies place TERT within eukaryotic retroelement clades
2- template jumping could plausibly evolve into repeat synthesis activity multiple independent times

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?? 👀

Public access to the first fly connectome that spans the whole CNS - BANC!: codex.flywire.ai?dataset=banc

Different from prior connectomes - it is brain + cord (think spinal cord)

We use it to ‘embody’ the system and find it resembles ‘subsumption architecture’ doi.org/10.1101/2025...

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.

Structure and biochemistry-guided engineering of an all-RNA system for DNA insertion with R2 retrotransposons - Nature Communications R2 retrotransposons are natural RNA guided gene insertion systems. Here, Edmonds et al. characterize the structure and biochemistry of an avian R2 and engineer a compact, all-RNA system to integrate D...

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)

If you like transposons...
If you you love genome editing...
Or if you just like random bird animations,

we have the paper for you!

We (@kedmonds.bsky.social et al) are happy to share our work turning a songbird retrotransposon into a genome editing tool. 🐣 (1/n)

Nice visit to the lovely Princeton campus. Could not be prouder of @automnenine.bsky.social. For those who are looking for a postdoc, there are exciting opportunities to join his lab!

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

Ridiculously good work by George on LINE-1 retrotransposition! Also the paper is an inspiring read - there's some really super biochem in it

TIGR-Tas: A family of modular RNA-guided DNA-targeting systems in prokaryotes and their viruses RNA-guided systems provide remarkable versatility, enabling diverse biological functions. Through iterative structural and sequence homology-based mining starting with a guide RNA-interaction domain o...

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.

we recently found some really neat RNA-guided DNA-cutting systems in phages. Despite remarkable similarities to CRISPR systems, including encoding guide RNAs in arrays, they appear entirely evolutionarily distinct (but definitely related to snoRNAs 🤓)
We decided to call them TIGR-Tas systems 🐯

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.

please go check out this glowing pink blob and what it does to the shiny gold blob

(it's a spliceosome! Truly it was a nostalgic pleasure to help out with this paper, a super fun collaboration with @uwmadisonrna.bsky.social & Kathy and Karli)

me plz me plz (recent video on my page, more to come)

for less wiggly proteins and more actual science, please go here www.science.org/doi/full/10....

gonna start shamelessly crossposting some of my molecular movies from the Other Place. Starting with my favourite: showing how wacky reverse transcription can defeat viruses. Bonus: some noises 🎹🎻

Our fly brain connectome papers are now live (www.nature.com/immersive/d4...), and is getting traction (www.bbc.co.uk/news/article...). With ~139k neurons, >8k cell types, synapses annotated, transmitters predicted, ~134 evo-devo units denoted, so much is now possible in the fly.