Very few things in academia are as rewarding as witnessing the progress and growth of your students, their research and discoveries over the years.

Such a nice weekend read by @robjohnnoble.bsky.social 🫶 (also: great title!)

What a piece of art on L1! Big congrats to you all

Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis LINE-1 (L1) retrotransposition generates somatic genomic variation in human cancer, but short-read sequencing has limited our understanding of its structural consequences and dynamics. Using long-read...

Today in
@science.org:
We are pleased to present our last work entitled:
"Concurrent L1 retrotransposition events promote reciprocal translocations in human tumorigenesis"
by Zumalave et al.
www.science.org/doi/10.1126/...

Wonderful to have David Duffy with us last week! Lots of new biodiversity genomics and eDNA approaches in the making ... 🧬🐢🌦️ @crg.eu @prbb.org @ufresearch.bsky.social

Two survival curves. One ('late') goes all the way down, the other ('early') stays well above it all the way and bottoms out at like 30%

This is just nuts.
In a well-powered randomised trial, giving immunotherapy in the morning rather than afternoon/evening produced ludicrously big improvements in progression-free survival
www.nature.com/articles/s41...
via
www.science.org/content/blog...

🌱 Join us tomorrow for the seminar "Deep mutational scanning of plant hormone receptors" by Maximilian R. Stammnitz (@maxstammnitz.bsky.social) from the Center for Genomic Regulation (@crg.eu)

👀 Don't miss it!

👉 https://f.mtr.cool/pgnowtoakf

Isomorphic Labs Drug Design Engine (IsoDDE), a unified computational drug-design system

Announcement:
www.isomorphiclabs.com/articles/the...

Report:
storage.googleapis.com/isomorphicla...

Recent discoveries on the acquisition of the highest levels of human performance Scientists have long debated the origins of exceptional human achievements. This literature review summarizes recent evidence from multiple domains on the acquisition of world-class performance. We re...

Multidisciplinary training, over time, produces the highest impact people

www.science.org/doi/10.1126/...

The power of plant hormones! 🌱+🪱

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

TF-MAPS: fast high-resolution functional and allosteric mapping of DNA-binding proteins by @XianghuaLi2

Are Transcription Factors really 'undruggable'?

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

Why fundamental research is fundamental to progress, seeding major breakthroughs
Editorial @nature.com this week
And 7 basic science discoveries that changed the world
nature.com/articles/d41...
nature.com/articles/d41...

Congrats @ferriol.bsky.social and co!!

O maior fotógrafo do Brasil e um dos maiores do mundo descansa hoje. Vá em paz, Sebastião Salgado.

🎲 Our paper on the genetics, energetics, and allostery in proteins with randomized cores and surfaces is out today @science.org!
🧬 By charting a protein’s sequence universe, we could rationalize which versions were kept through evolution – and why many stable ones were not.

The genetic architecture of G-protein coupled receptor signaling G-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specif...

... so please have a look at our preprint and get in touch if you’d like to learn more, explore and use the data, etc 🙂

AND: definitely also check out @taylor-mighell.bsky.social's fascinating story on GPCRs – with even more receptor dose-response curves!

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

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Deep mutational scanning is developing really fast. One of the new directions lies in the exploration of larger, more dynamic proteins. Another in the study of small-molecule interactions.

Chemically inducible receptors and other glueable dimerisation systems offer us one way forward …



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These rich data allow us to fit thousands of dose-response curves.

With these we can systematically compare mutants’ key signalling parameters including basal phosphatase binding, hormone sensitivity and maximum response.

And there are lots of cool examples & correlations, surprises … 🔎🕵️💚

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Now what does one get out of this??



A massive map of position-, amino acid-, and small-molecule concentration-dependent variant effects!

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To better understand this ABA receptor’s genetic encoding, we mutated every position to all 20 amino acids.

A glueable protein complementation assay (GluePCA) then allowed us to measure the relative binding strength of each receptor variant vs. phosphatase – at 12 different dosages of ABA.

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PYR/PYL receptors (grey) are key to plant water homeostasis and stress signalling. 💦🌱🌞

Abscisic acid ('ABA', green), is bound through a deep hydrophobic pocket. This triggers the allosteric closure of two loops which generate a new binding interface with response phosphatases (white).



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The genetic architecture of an allosteric hormone receptor Many proteins function as switches, detecting chemicals and transducing their concentrations into cellular responses. Receptor switches are key to the integration of environmental signals, yet it is n...

1 plant hormone receptor ☘️
3,500 mutants, to single-site saturation 🧬
>45,000 binding and abundance measurements 📶

Very happy to present our latest work – where deep mutational scanning meets the world of small molecules.



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



With @benlehner.bsky.social

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