Timothée Lionnet

Sharing ZATELLITE 🛰️ - a tool to visualize and manipulate repetitive loci in living cells using designer zinc fingers tinyurl.com/ZATELLITE led by Nestor Saiz, collab with Marcus Noyes, @teresadavoli.bsky.social, @glennislogsdon.bsky.social, @liamholt.bsky.social & @jefboeke.bsky.social (1/n)

AI in Microscopy: A BioImaging Guide (bioimagingai.janelia.org) is available now! This free, online textbook bridges the gap between tool developers & microscopists + biologists. Whether you’re new to AI or already using it, we hope this book gives you the confidence to apply AI in your research.

Not all nuclei are the same. We went to some of biology’s most exceptional nuclei 👉 dinoflagellates with genomes 80× ours 👉 Giardia’s twin nuclei 👉 ciliates carrying two nuclei in one cytoplasm & asked a simple question: what sets nuclear density? 🧵 Preprint: www.biorxiv.org/content/10.6...

Today it’s magic mushrooms! But not THAT kind. Together with @janetahlberg.bsky.social I have started experimenting with the strange alchemical art of mushroom dyeing and we are beginning to get exciting results. Have a look at this little fellow! This is Cortinarius semisanguineus.

fascinating work on how the unit of 3D structure in our genomes (TADs) have evolved

This is fascinating and chemistry is at the heart of it #chemchat

the investment in AI so far ($1T) would have funded bell labs for... a millenium!?!?! 🤯

Thrilled to share my freshly "baked" Baker lab paper. We took a bottom-up approach to designing transcriptional regulators. Instead of relying on natural activation domains, we designed compact proteins that recruit specific cofactors. Activators for now, repressors to come!

Design of synthetic activators for programmable gene expression doi.org/10.64898/202...

There seems to be a bigger mystery- MYF appears to have dropped for FY2026 overall at NIH but number of new/competitive renewal have not come back to pre 2025 levels- is there an explanation? The MYF reduction is spotty at institute level @maxkozlov.bsky.social @grantwitness.org

We are looking for a postdoc. Candidates should have a PhD, at least one first-author paper, hands-on cryo-EM experience, and strong protein biochemistry skills. Please send your CV, research statement, and contact information for three references.

🎉 Our paper is out today in @science.org! How does the intestine maintain the right balance of cell types? We find that signalling rhythms matter! So proud of our three shared first authors, Sonja Weterings, @hiromuneeto.bsky.social & @jddeleede.bsky.social! 🔗 www.science.org/doi/10.1126/...

🐟 Transactions of the American Fisheries Society New York: [American Fisheries Society], 1885-1896. [Source]

1/ Our paper, “Enhancer binding kinetics explain transcription factor hub formation,” is now published! Here we set out to understand why transcription factors form bright clusters or “hubs” in the nucleus, and whether those hubs actually control gene activity. tinyurl.com/38uf8348

Been a while since I worked on the evolution of regulatory DNA. >12 years ago we described a phenomenon we coined "repurposing" where elements change cell activity patterns over time. ML has now enabled us to see the complex and subtle sequence changes underlying this.

Happy #FluorescenceFriday. Single immune cell migration is fascinating. But these cells can also behave like a coordinated collective, like 🐝 from a hive. I captured some embryonic myeloid cells (🔴) displaying swarming behaviour in a migrating ectoderm cell sheet (🔵), like neutrophils in our body!

Two extremely cool new papers on how AID gets targeted to appropriate genes for somatic hypermutation: paper 1 from Schatz lab at Yale shows that NELF and elongation components of the SEC are required- and suggests NELF can travel into genes /1 www.nature.com/articles/s41...

In 1954, Albert Einstein was so upset by the Oppenheimer hearing and the McCarthy era attacks on the loyalty of scientists, that he said that if he were just starting out he'd become a plumber or peddler, instead of a physicist. He soon got an invitation to join a plumbing firm! #Einstein #science

#FluorescenceFriday: Given the recently grown interest in ciliary beating, here is a movie of beating cilia in a human airway model that I captured last week with lattice light-sheet microscopy. No AI „processing“, this is the raw data! Frame rate is ca. 170fps, displayed here at 25fps.

In 2022 we published an open-source hardware, software, and protocols ecosystem for repurposing sequencers as automated fluidics coupled imaging instruments. On Oct 13 @yougotkunal.bsky.social & @nygenome.org will host a workshop on current applications. Register here: regenseq.github.io/meeting/

This is worth reading - a real world pilot of a lottery based grant funding system in Canada. TL;DR Pass/Fail with pass going to lottery and each reviewer (of 3 per grant) has a “unmissable” vote to give to a grant. If 2/3 of reviewers give an unmissable the grant gets funded with committee review.

great piece, along with giorgio.gilest.ro/the-weimar-o... I'm feeling somewhat protected because I evolve in an experimental data-driven field, but definitely feeling the flood coming, and the need for new incentives

#FluorescenceFriday #STED pure and real 8-color STED microscopy & happy TxIF to everyone 🌴

Hey! You can have a look at our new preprint on #CellCycle regulation and #Pluripotency! A little thread 100% human 0% AI slop is coming (bear with me the mistakes). Let's thank first @maulik_nariya, the fantastic postdoc that led this project: www.biorxiv.org/content/10.6...

🧵 4/8: Here, we performed 3D-targeted FIB milling to capture the inactive X chromosome in ~130 nm thick lamella, then used cryo-electron tomography to directly visualise its native chromatin structure with contextual information at sub-single nucleosome resolution.

love to start the week with some gorgeous in situ chromatin structures!

Fold Spacer lets you fly through protein structures (Weekend project #2). It’s my first game: I originally set out to build a racer with structures as the tracks, but was a little too crazy. So it became this instead. You can upload your own structures. 🌐 martin-steinegger.github.io/Fold-Spacer/

wow, that's a huge loss. biomart is so useful and has been the perfect entry into data mining for so many projects, especially with trainees

🧬🔬 Why are enhancers transcribed and how does that impact gene regulation? I’m really excited to share our new paper in @science.org showing that noncoding RNAs control the timing of gene activation in embryos. With Mike Levine #ScienceResearch @columbiamed.bsky.social A few highlights below... 🧵👇

Incredibly happy to share the first publication from our lab, now published in Nature Cell Biology! 🎉 How do cells coordinate RNA processing with nuclear organization and the cell cycle? www.nature.com/articles/s41...

Did you know that the cells of old animals contain much less mRNA than the cells of young ones? Let me share with you some results from an ongoing project in the lab, where we are finding that a progressive depletion of total mRNA abundance is a crucial part of aging 1/22

1/20 In 1990, Sean Connery took a Soviet submarine across the Atlantic in total silence. No propeller. A "caterpillar drive" that made Red October invisible to sonar. Two years later, Japan launched a real ship with no propeller at all. A small 🧵https://youtu.be/NSiAsQMBSRA

We would like to add one or two postdocs to our lab in the next couple of years. If you are close to finishing your PhD and interested in the science we do, feel free to reach out to discuss opportunities.

How do nuclear compartments form inside cell nuclei? We show RNA glues certain loci together to form a nuclear compartment. This involves special GC-rich regions of highly expressed genes that also associate with nuclear speckles, but interactions between these loci are independent of speckles!

Formation of an RNA-mediated nuclear compartment https://www.biorxiv.org/content/10.64898/2026.08.20.746005v1

Remember this? bsky.app/profile/did:... Rigorous visualization of the structure in your high-dimensional data. Fantastic work by @dhdegroot.bsky.social With help of the reviewers of Nat Biotech it is now updated, extended an officially published here: www.nature.com/articles/s41... 1/n

In 2023, @nature.com published 'Papers and patents are becoming less disruptive over time', receiving world-wide media attention. Our Matters Arising, published after a 32 month delay (more on that soon), shows that the reported decline can largely be attributed to dataset artefacts. 🧵

Excited to share our newest work! We asked whether RNA molecules need to be in a specific place in the cell to do their job. We found that a single RNA must reach the midbody, the structure that pinches two dividing cells apart, for cell division to finish efficiently. 🧵⬇️

(1/4) We are very excited to share our latest preprint from @sauer-lab.bsky.social: Mega Expansion Microscopy (Mega-ExM)! We combine iterative hydrogel expansion with whole-proteome NHS labeling and post-expansion immunostaining, reaching tunable expansion factors up to ~1500× in whole cells 🤯

🔬🧫 Biology friends. Who do you outsource cell line CRISPR editing to? We could do in my lab, but given people and time constraints I want to explore commercial $ to edit standard hES cell line - KO/cKO. Bonus if work is done in USA and not shipped to international facility.

One thing strikes me : while LLMs now seem to excel in maths, they have yet to produce any great book (despite having been trained on virtually everything available that was ever written, and having been used to produce text for several years now).

New preprint from Shendure Lab on Locus-Scale aka Long-@$$ MPRAs led by the amazing Abby McGee & @carinabiar.bsky.social Most MPRAs test ~300 bp fragments next to a promoter. But real enhancers are bigger, act combinatorially and from a distance. 1/n www.biorxiv.org/content/10.6...

RNA-seq tells us how much RNA is present in the cell. But to understand gene regulation, we need to easily measure the synthesis and decay rates driving this abundance. We introduce AIR-seq: analog intrinsic recoding sequencing. (1/6) www.biorxiv.org/content/10.6...