Samuel Zambrano

As always, a pleasure working with @davidemazza.bsky.social and his fantastic lab and learn from them about the dynamic mysteries of p53. Great effort from @emabiong.bsky.social with @sarapozzi.bsky.social and @alessialoffreda.bsky.social ... thank you all!
There is more to come- stay tuned!

And voilà.
The simple model matches exactly what we observe:
• Enhanced p53 accumulation when NF-κB and p53 are co-activated (vs p53 alone)
• No discernible p53 activation when NF-κB is activated alone
Once you consider the whole system, the apparent mystery disappears. (6/n)

This is where even a simple model becomes useful.
Activating NF-κB perturbs a specific portion of the signaling network. The model embeds that perturbation in the full system and lets us simulate three scenarios: what if we activate NF-κB alone, p53 alone, or both together? (5/n)

Naively, you might expect that activating NF-κB alone would also lead to a big increase p53.
But, "mysteriously", experimentally that’s not what happens. (4/n)

NF-κB is activated by cytokines like TNF-α, while p53 is activated by γ-irradiation.
Here’s our key observation: We show that NF-κB induces TP53 gene expression. So when you co-activate NF-κB and p53, you get higher p53 levels. (3/n)

This work is also a nice example of how even simple mathematical models are incredibly useful in biological systems.
They provide a rigorous description of what a perturbation actually does — within the context of the full network, not in isolation. (2/n)

So grateful to my buddy the great @davidemazza.bsky.social and all the contributors from our teams to this joint effort to unravel NF-κB–p53 crosstalk. Davide’s thread nicely explains the main findings — here’s a short side note from me 🧵👇 (1/n)

What we found surprised us: these two transcription factors cooperate at the molecular level, yet this cooperation produces functional antagonism.
Even more intriguingly, inflammatory signals can impair DNA repair by reshaping the temporal dynamics of p53.
If you’re curious, here’s the story 👇

🧵 I’m very happy to share a new preprint from the @samuzambrano.bsky.social group and ours — a project driven by @emabiong.bsky.social, a PhD student bold enough to tackle a question at the interface of our two expertises: how the biological oscillators p53 and NF-κB talk to each other.

Antigen affinity modulates ERK pulsing frequency during T cell activation Real-time, single-cell imaging reveals ERK signaling dynamics in response to T cell receptor stimulation.

New preclinical work in #ScienceSignaling reveals how #Tcells respond in real time to signaling inputs of varying intensities and could shed further light on how these cells become activated in the context of immunity and inflammation. https://scim.ag/4qN2h1d

#FluorescenceFriday

Proud of our the last paper @cellcommlab.bsky.social & 1st one of @jboixcampos.bsky.social

We continue to study #CellMigration & how cells decide where to go: ↖️↗️⬇️?

(movie of the actin #cytoskeleton)

Full www.science.org/doi/10.1126/...
@focalplane.bsky.social @science.org 🧪🔬

Un fantástico tónico intelectual como dice Savater, que por lo demás está en las antípodas de bigotes.

Chance favors the (theoretically) prepared mind In defense of the role of theory in innovation

Blog post: Chance favors the (theoretically) prepared mind
Data is big, machines are learning, so what good is theory anyway? Isn't most discovery driven by serendipity anyway, with theory mostly a "post-mortem"? I argue that this view discounts the value of theory.
open.substack.com/pub/arjunraj...

Extremely funny to call the pope “holier-than-thou”

Fig. 6: Mathematical model

Network Medicine is entering a new phase: one that demands we rethink how we study, model and ultimately treat complex diseases.

www.sciencedirect.com/science/arti...

#ComplexSystems #NetworkScience #Medicine #MedSky 🧪🧬🌐

🧵 1/

Hay un poco de batiburrillo entre sanciones y aranceles en el artículo. Lo último es algo más novedoso. No tengo muy claro que obedezca a una tendencia histórica irreversible, pero con Trump erro todos mis pronósticos :-)

Interesante pero un poco impreciso, no? Las sanciones y las vallas europeas anteceden con mucho a Trump.

Dynamical Systems (in) Biology We are a team interested in (nonlinear) dynamical systems, in cell biology, in systems biology and in combinations of these elements. Here you can learn about us, who we are, what we publish, how to c...

Halloween is a nice day to share our new site, where you can find more info on what our team does. It can briefly be summarized as Dynamical Systems (in) Biology: sites.google.com/view/dynamic...

How do dynamics of signalling molecules skew cell fate decisions? With this review we try to move our first steps in the signalling dynamics field, together with the expert lead of @samuzambrano.bsky.social! Kudos to Fulvio, Sara and Erika for their excellent work!

As usual it was a pleasure and lots of fun to collaborate with @davidemazza.bsky.social and his lab in this effort led by Fulvio Bonsignore, Sara Pozzi and Erika Aloi.

We discuss the evidence from the main areas where this connection is being established (immunity, response to DNA damage, growth factors and developmental cues) outlining the common methodologies used and potential future directions of this emerging dynamic point of view on how cells make decisions.

Frontiers | Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges Our ever-growing capacity to observe dynamic processes at the single-cell level has highlighted how cells use complex signaling dynamics to provide adequate ...

Cells respond to stimuli by activating signaling pathways with a surprising variety of dynamics. Why? As we review here, there is growing evidence connecting dynamics with specific cell fate decisions www.frontiersin.org/journals/cel...

DB-OTO Gene Therapy for Inherited Deafness | NEJM Genetic deficiency of otoferlin, a protein critical to synaptic transmission by the sensory hair cells of the ear, causes congenital deafness. Medicines to treat the condition are lacking; children...

New @nejm.org
One-shot gene therapy for a type of congenital deafness enabled some children to hear for the first time, and 3 of 12 kids achieved normal hearing
www.nejm.org/doi/full/10.1056/NEJMoa2400521

Philosophical Transactions of the Royal Society B: Biological Sciences: Vol 380, No 1936

How dit life originate in our planet? How can we create it in the lab?Our @royalsocietypublishing.org Theme Issue "Origins of Life: the possible and the actual", coedited with @sfiscience.bsky.social C Kempes and Susan Stepney is out! royalsocietypublishing.org/toc/rstb/202... @manlius.bsky.social

Pasta Physics Scoops Up an Ig Nobel Prize A group of Italian physicists was awarded the Ig Nobel Prize in Physics for their study of the phase diagram of a cheesy sauce renowned in Italy.

How do you prevent cacio e pepe sauce from congealing? A thoroughly researched answer earned its authors a prize!

I wrote a response to Thomas Friedman's "magical thinking" on AI here: aiguide.substack.com/p/magical-th...

David Baltimore passed away this weekend. A pioneer of molecular virology who won the Nobel prize in medicine & physiology for his discovery of viral reverse transcriptase. This essay he wrote in 2018 reflecting of his 60yr career in science is a great read.
www.annualreviews.org/content/jour...

Our @ourworldindata.org we visualise weekly updates of wildfire data from the Global Wildfire Information System.

Spain was having a pretty low/average year until the past few weeks when it went roaring past previous years.

You can track this data here:
ourworldindata.org/wildfires

Myocastor coypus - Wikipedia

Creo haber visto hace poco a un pariente cercano de la chungunga en un acuario de Lisboa. Nombre mucho mejor que el de nutria, que además evita problemas con los italianos, que a las nutrias las llamen 'lontre' y llaman 'nutrie' a otros bichos menos guapos. Un lío it.wikipedia.org/wiki/Myocast...