Timothée Lionnet

Missed #FluorescenceFriday, but let's go for #GlowingSaturday!
freshly out of the prep JF549 derivative for a colleague

it's been one of those years

📣 I hereby make my Bluesky debut to announce that our work linking DNA binding affinities and kinetics 𝘪𝘯 𝘷𝘪𝘵𝘳𝘰 and 𝘪𝘯 𝘷𝘪𝘷𝘰 for the human transcription factor KLF1 just got published in Cell! @cp-cell.bsky.social

www.cell.com/cell/fulltex...

Key findings in a thread (1/6):

We developed a 'smart STED microscope' to detect rare objects/events in cells, and unraveled the 3D morphology of a nuclear membraneless organelle (paraspeckle). Amazing collaboration with Sjoerd Stallinga, Bernd Rieger (TU Delft) and @mixmue.bsky.social 🙏 (1/3) www.nature.com/articles/s41...

Here is a copy of last year's Twitter thread explaining our preprint - jump to (21) for the new stuff 👀

Synergy between cis-regulatory elements can render cohesin dispensable for distal enhancer function

now revised and journal accepted at www.science.org/doi/10.1126/...

🧵👇

Fig. 1: Real-time observation of mammalian transcription elongation. a, Composite structural model of the human transcription EC with a set of elongation factors, as supplied in our system, decorating the Pol II surface. The model incorporates published structures for the mammalian EC (PDB 6TED), TFIIS (PDB 8A40), ELOF1 (PDB 8B3F) and a fitted AlphaFold prediction of IWS1 based on the position of Spn1 in the yeast EC (PDB 7XN7). b, Schematic of the single-molecule experimental setup. The starting location of the EC is marked by the ATTO647N-labeled RNA, while Cy3-labeled DNA probes that hybridize to the nascent RNA indicate active elongation. c, An example of transcription elongation by a single mammalian EC observed in real time. Top: kymograph showing the EC position on the DNA template, indicated by RNA (magenta) and probe (green) signals, as a function of time. Bottom: elongation trajectory extracted from the kymograph. Raw data (gray dots) were fitted to discrete linear segments (black line). Change points are marked as filled circles. The slopes for each segment are indicated, differentiating active elongation (blue) from pausing or stalling events (red). d, Eight additional examples of fitted elongation trajectories by individual mammalian ECs aligned by their starting positions. NTP, nucleoside triphosphate.

Fig. 7: Summary of the distinct roles that each elongation factor serves in mammalian Pol II transcription on DNA. The relative EC activity for each factor omission condition is color coded as indicated on the right. Clockwise from the top left: ΔTFIIS increases pausing but has a minimal effect on the elongation speed; ΔP-TEFb abrogates the phosphorylation of Pol II CTD and DSIF, which in turn destabilizes the binding of PAF1C, SPT6 and RTF1, thereby severely reducing the elongation speed; ΔPAF1C exerts the most direct negative impact on EC speed and also completely abolishes RTF1 recruitment; ΔRTF1 shifts the EC from high speed to medium speed; ΔSPT6 reduces EC speed by destabilizing PAF1C binding even though SPT6 itself does not directly activate EC; ΔDSIF exerts a dual effect on EC kinetics by reducing its pausing and also lowering its speed partially via the destabilization of RTF1 binding.

Transcribing Pol2
With elongation factors
Kinetic control

#ChromatinHaiku #SingleMolecule
www.nature.com/articles/s41...

International Day for the Elimination of Violence against Women | United Nations The International Day for the Elimination of Violence against Women aims to create awareness of the fact that violence against women is a human rights violation that impedes progress in many areas, in...

Today is the International day for the elimination of violence against women. In 2024, an estimated 50,000 women and girls were killed by intimate partners or family members worldwide. That is 137 women and girls every day. One every ten minutes. www.un.org/en/observanc...

NY folks, please support this initiative!

differential contribution of H3K9 methyltransferases to boundaries at satellites

A new and fascinating story from @bencarty.bsky.social and the group, with crucial help from the teams of @naltemose.bsky.social, Simona Giunta, and @dfachinetti.bsky.social. Many thanks to all for a fantastic collaboration.
www.nature.com/articles/s41...

I'm guest-editing a collection on "Enhancer-promoter interactions" at Genome Biology. Please send us your exciting stories!

link.springer.com/collections/...

AIC at HHMI Janelia Introduction to the AIC at HHMI Janelia blog on FocalPlane

We are kicking off a blog series with @focalplane.bsky.social to provide insight into life at the AIC, microscopy careers, image analysis, and more! Read our intro post here: focalplane.biologists.com/2025/11/20/a...

Proteins are dynamic structures, but structural biology often shows them as static snapshots. Inspired by long-exposure photography and generative art, I built ProteinCHAOS, an artistic tool inspired by molecular dynamics to capture protein flexibility over time, much like long-exposure images.

This is an amazing sentence: "The Peekskill Meteorite Car ("PMC"), a 1980 red Chevy Malibu, is one of the two most famous objects struck by a meteorite (the other, Ms. Ann Hodges, died in 1972). "

meteoritecar.com

A schematic picture of a cell, showing condensates, a nucleus and the cytoskeleton.

We wrote a review on the "Physics of droplet regulation in biological cells": arxiv.org/abs/2501.13639 Beside the basic #physics of phase separation, we discuss three aspects that separate cellular from traditional droplets:

the plot thickens...

race for the igNobel keeps starting earlier and earlier

Hypothesis-based research: not dead yet

Check out our paper on transcriptional control of an artificial condensate, including engineering a feedback loop that includes phase separation. Led by the amazing @samwilken.bsky.social

BigVolumeBrowser: a new 3D multi volume/mesh/point clould (SMLM) data viewer Hello everyone, I’d like to share with you another 3D viewer for FIJI, BigVolumeBrowser (full documentation link). It‘s a first initial public release, so there is still space for improvements. Le...

Finally, the first public release of #BigVolumeBrowser, so after teasers, you can try it yourself. For details, please check the announcement post (1/2)
forum.image.sc/t/bigvolumeb...

Gene-scale in vitro reconstitution reveals histone acetylation directly controls chromatin architecture Reconstituting 20-kb chromatin shows that tuning acetylation alone reshapes its folding, dynamics, and contact domain formation.

To probe gene-scale chromatin physics, we built 96-mer (20 kb) arrays with defined histone marks. Combining single-molecule tracking, AFM imaging, and developing in vitro Hi-C, we saw how specific modifications dictate chromatin structure and dynamics. www.science.org/doi/10.1126/...

four radiolaria sculptures sitting on a black surface

Radiolaria are microscopic unicellular sea creatures that create skeletons from silica. Their skeletons are among the most beautiful and complex natural microstructures, resembling elaborate filigree. blog post: n-e-r-v-o-u-s.com/blog/?p=9861

We just released a new major version of TrackMate (v8), the cell and organelle tracking plugin of Fiji.

It ships many new features, detailed below, but that are articulated around the following:

Very excited to present OpenCGChromatin🔥🔥🔥

A new coarse-grained model that probes full chromatin condensates at near-atomistic resolution to reveal the molecular regulation of chromatin structure and phase separation

Brilliantly led by @kieran-russell.bsky.social, with the Rosen and Orozco groups

Wonderful to see the beautiful preprint from Sabate et al now published - TADs are also dynamic structures in human cells, with remarkably similar parameters between mESCs and HCT116 cells
www.nature.com/articles/s41...

Re-upping this with a Bluetorial in a shameless act of self-promotion. 1/n

Possibly made pewter

Part 10 of 200 in historically interesting things to inspire your ttrpg

Guillotine Earrings From France’s Reign of Terror

U.S. Congress considers sweeping ban on Chinese collaborations Researchers speak out against proposal that would bar funding for U.S. scientists working with Chinese partners or training Chinese students

This is lunacy. The Chinese scholars I know are among the hardest working, most selfless people I've ever encountered. They want to contribute to our intellectual endeavors, and they make our research teams better.

I'd guess that 85-90% of American scientists would be ineligible for future funding under this law, maybe close to 100% in the R1 universities. So much for funding proposals based on scientific merit.

Apart from being sinophobes, the people pushing this have no clue how science or higher ed works.

New preprint 🥳! We made photoclickable HaloTag ligands to precisely control protein labeling on living cells. With it, we can do some cool multicolor stuff. Huge congrats to Franzi and all co-authors! Check it out 👇

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