Opportunity for a Master’s/Bachelor’s student:
- Join us for up to 5 months 🗓️
- Build computational/mathematical models 💻
- Learn about genotype-phenotype maps and evolution 🧬
- Work closely with PhD student Manuela Giraud - full info here:
www.crg.eu/en/content/t...

🚨JOB ALERT🚨

FRIENDS PLEASE SPREAD and RT

We are building a small expert team within the @bokelab.bsky.social at @crg.eu @prbb.org to investigate fundamental questions in oocyte cell biology, focusing on how proteostasis regulation influences dormancy and fertility.

See below 2 calls👇

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

Co-authors when you ask them to go over a draft in August

🎲 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.

As the world warms, plants in natural ecosystems and agricultural settings find ways to respond to the heat.

In a new special issue of Science, researchers examine how heat affects plants at multiple scales, from the molecular level to the biosphere. scim.ag/44cSw3Z

... 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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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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