Levayer Lab

Levayer Lab

@levayerr.bsky.social

Epithelial cell death, cell extrusion, self-organisation, mechanotransduction and many other things

3.5K followers503 following253 posts

Levayer Lab reposted

Not sure how the community will be consulted, but if so this will be really critical and time to be vocal...delegating our peer judgement (admittedly imperfect) to LLM feels like removing the cornerstone of how science works. If this is the way it goes, I'd rather become a teacher or bake bread🤷‍♂️

As the discussion turns to potential actions, research communities must be consulted and engaged. As a first step, we will explore a joint community survey.

Here it is...by delegating decision to non transparent AI models we generate an incentive for grant applicants to use AI writing to tweak system and the vicious/absurd feedback loop is set (which all started by an overload of grant application driven by AI writing). www.science.org/content/arti...

science.orgU.K. funder uses ‘AI triage’ to reject grant proposals—leaving researchers dismayedThe AI-based assessment, which wasn’t explicitly described in the funding call, has raised privacy and fairness concerns

To be honnest, I would almost find it more acceptable to have a real random decision process as it was partially implemented in the SNF. At least, the "random" triage does not generate wrong incentive impacting the way you write a grant proposal and does not trigger such loop...

Levayer Lab reposted

Had a UKRI funded grant proposal rejected at the "AI triage stage". "This AI-based triage was used only to identify approximately 50% of the strongest proposals to take forward to full human review." 🧪 #academicsky

Levayer Lab reposted

A funded postdoctoral position is available at the IBPS, Sorbonne University/CNRS/INSERM in Paris, to investigate the formation of the olfactory organ in zebrafish. We are looking for an postdoctoral researcher with expertise in transcriptomics and bioinformatics, (scRNAseq analysis).

Only one week left to apply ! Check below for more details but the course will be great. Please spread the word 🙏

Levayer Lab@levayerr.bsky.social

📢master or PhD student interested in cell biology ? There are spots left for the Molecular Biology of the Cell course @pasteur.fr. Check the amazing list of lecturers + 1 week practical pocking choano cytokeleton with @thibautbrunet.bsky.social team. Registration 👇 www.pasteur.fr/fr/nous-conn...

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You may wonder how this "memory" is molecularly encoded ? Well...we do as well and despite trying many candidates (that you will find in the big supp fig. Supp 5 and 6) we could not find anything obvious.

Most likely this could be based on partial cleavage of numerous substrates affecting the susceptibility to extrusion and where timescale is defined by protein turnover (but this still remains to be proven).

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Can we now use it to "bias" apoptosis ? We performed a very mild activation of optocaspase in clones and let them develop. Cells in the clones were 3x more likely to die compared to neighbouring cells, suggesting that this previous priming sensitise them to "later" developmental caspase activation.

Overall, this revealed complex business taking place downstream of terminal caspase activation. There is a lot of heterogeneity between cells that encompass temporal information and relative information between neighbours.

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Can we now also better predict the physiological death ? We previously found a negative feedback where the first extruding cell blocks apoptosis in the direct neighbours through ERK activation. This implies that cell death decision is not fully autonomous and is about who is the "fastest" to die.

So can we predict who among neighbours will be the first ? Using time serie forest (machine learning adapted to use temporal features) we could predict in close to 80% of the case who will the first using relative present and past caspase activity among neighbours

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Can we go back to the previous experiment and explain the heterogeneity we observed ? Actually the domain of high sensitivity revealed by the global pulse of caspase are mostly explained by the history of cells. Doing the same expt. after "erasing" past caspase removed most of the spatial bias.

This also explains a good deal of cell to cell heterogeneity. Accordingly, the cells that are more likely to die upon a pulse of optogenetic caspases are the one that were already exposed in the past.

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So what explains then this heterogeneity ? We looked systematically at geometrical/signaling/spatial features that may correlate with the caspase activity at which cells engage in apoptosis. The correlation matrix you see below outlines a clear neg. correlation with past caspase activation.

In other words, cells already exposed to caspase in the last 3-5 hours die at lower caspase activity. We used again the optogenetic caspase to validate this prediction using pulses of activation separated in time comparing contralateral regions exposed 1 or 2 times and confirming the "priming"

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We checked this in the Drosophila pupal notum segmenting ~20,000 cells and checking systematically at which caspase activity cells engage in cell extrusion and cell death. Using the "derivative" of the GC3Ai caspase sensor was quite predictive but revealed a large heterogeneity of thresholds

Not only we found cell to cell differences, but also global spatial pattern of caspase sensitivity. Using an optogenetic caspase that we previously developed (optoDronc) and doing mild global activation revealed zones much more sensitive to caspases.

Works over the past decades outlined numerous non-apoptotic functions of caspases, and the large proportion of cells surviving to effector caspase activation during development. But what makes the difference between a surviving and dying cell ? Maybe a simple threshold ?

The last version of our EpiCure tool is now out in @dev-journal.bsky.social, a user friendly Napari plugin for epithelial segmentation curation. A bit thanks to @gaellel.bsky.social for carrying all along this joint department effort (check the details below). Feel free to use it and expand it !

Levayer Lab reposted

Levayer Lab reposted

A very intriguing story by Joao F. Botelho et al shows that in bird, the digit formation (their ✋) is not only governed by apoptosis but also due to changes in the rate of growth extension and cell division between the interdigital zone and the digital zone. So cool! #devbio doi.org/10.1016/j.cd...

Levayer Lab reposted

We’re recruiting postdocs to join our @wellcometrust.bsky.social , Decoding Competition in the Brain. How does the brain resolve competing needs and prioritise behaviour? 📅 New deadline: 15 September 🔗 Apply: rezavallab.org Please share!

rezavallab.orgHome​ ​Animals must make crucial behavioural choices on a minute by minute basis to survive in a changing environment. A long-standing enigma is, how are alternative options evaluated in the brain...
Carolina Rezaval@crezaval.bsky.social

We’re recruiting postdocs! Join our @wellcometrust.bsky.social funded programme 'Decoding competition in the brain'. How does the brain resolve competing needs and prioritise behaviour? 📅 Deadline: 1 September Apply: rezavallab.org Please share! www.jobs.ac.uk/job/DSM781/r...

Levayer Lab reposted

🧵 What if one reason fertility declines with age isn’t just genetic-but mechanical? Thrilled to share our new paper in @NatureCellBio : Elevated contractility drives implantation failure in mouse embryos from aged females… here’s what we found 👇 www.nature.com/articles/s41... 1/11

nature.comElevated contractility drives implantation failure in mouse embryos from aged females - Nature Cell BiologyCavanaugh et al. show that embryos from aged mice have increased contractility and tissue viscosity on embryonic day 4.5, which leads to poor spreading and attachment. Similar age-associated mechanica...

Levayer Lab reposted

Please save the date: The Microphysio Conference is back and will be held in Cargèse from April 25th to April 30th! With a great lineup of speakers, it’s an excellent opportunity to exchange ideas in fields related to organ-on-chip, organoids, bioprinting, mechanobiology, and much more! Stay tuned.

Levayer Lab reposted

Sign up now for the EMBO meeting 'quantitative biology to molecular mechanisms'. Fantastic speaker lineup and plenty of speakers slots selected from abstracts. Submit your abstract before Sept 11!

EMBL Events@events.embl.org

You only have until 11 Sep to submit your abstract for #EMBOomics! ➡️ s.embl.org/omx26-01-bl Join us to discuss the latest developments in the field with leaders in genomics, dynamic proteomics, quantitative imaging, and synthetic biology.

Levayer Lab reposted

Levayer Lab reposted