Max Stammnitz

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...

Are you looking for a PhD? Join us in Barcelona! You'll dive into a community of >100 PhD students from 30 countries exploring the frontiers of biology. You can also join an online workshop on 6 November (15:00 CET) to learn how to find the right lab for you.

More info: www.crg.eu/en/content/t...

Congrats @ferriol.bsky.social and co!!

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.

🎲 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...

[7/7]

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 …



[6/7]

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 … 🔎🕵️💚

[5/7]

Now what does one get out of this??



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

[4/7]

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.

[3/7]

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).



[2/7]

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

[1/7]