Phosphorylation-driven signaling plays a central role in how cells communicate. In this study, together with @saezlab.bsky.social , we revisit the EGF signaling pathway and ask: How well does our traditional understanding hold up in the era of modern phosphoproteomics? www.nature.com/articles/s41...
10 years and still standing strong @EMBL 🍾💪
Huge thanks to all members, alumni, supporters & colleagues who made it possible.
Here’s to the next decade! 🙏
Science is a team sport. Huge thanks to the Savitski & @saezlab.bsky.social (esp. @martingarridorc.bsky.social , @parime.bsky.social , Dimitris, Isabelle, Clement), plus PCF, GeneCore, and the @zimmermannlab.bsky.social @embl.org and others. Study led by @miraburtscher.bsky.social .
The payoff? New kinase drug combination opportunities and a previously unrecognized mechanistic link between ETV3 phosphorylation, glucose metabolism, and metabolic adaptation to BRAF inhibition.
Multi-Omics Network Integration of multimodal phosphoproteomic, transcriptomic and functional proteomics data can then link signaling to protein function and cellular phenotypes
Next, we systematically prioritised functionally relevant phosphosites using biophysical phosphoproteomics to identify phosphorylation events that alter protein solubility or localisation.
We applied this strategy to BRAFV600E-mutant cancer cell lines, starting by profiling their phosphoproteomes across tissue contexts and over time.
Rewiring of oncogenic signaling in #DrugResistance is a moving target. In our new study, we used biophysical phosphoproteomics to investigate #BRAF mutant cancer, linking phosphorylation changes to protein function and #MolecularMechanisms through #Multi-Omics integration.
tinyurl.com/funsignaling
ICYMI during the holidays. I am really proud of Bolor's efforts and the first work coming out of the lab!
Read it here: www.biorxiv.org/content/10.6...
HT-PELSA, a new proteomics tool by EMBL researchers, processes samples 100x faster and works directly with complex crude cell, tissue, and bacterial lysates – developments which could accelerate drug discovery and basic biological research 💊
🔗 www.embl.org/news/science...
Happy to see our HT-PELSA paper now published in @natsmb.nature.com 🎊 Big thanks for the constructive review process! 📖Read the manuscript here (www.nature.com/articles/s41...) & check the thread for additional information ⬇️
So grateful and honored to receive the MCP Lectureship Award at the #ASBMBProteomics meeting at the Broad Institute! Huge thanks to the wonderful organizers and to everyone—past and present—who’s been part of our lab.
The final version of our multi-omics study on kidney fibrosis is out now (tinyurl.com/kidneyfibMSB). Together w/ Pepperkok + Savitski labs @embl.org, we present a time-resolved #multiomics + computational network modeling approach in combination w/ phenotypic assays to study #kidneyfibrosis
integrated temporally resolved transcriptomic, proteomic, and secretomic profiling of human kidney mesenchymal cells from @savitski-lab.bsky.social @saezlab.bsky.social @miraburtscher.bsky.social identify dynamic changes upon TGF-beta stimulation ➡️ www.embopress.org/doi/full/10....
Beautiful work from my friend @kiranrpatil.bsky.social . Gut bacteria can accumulate Forever chemicals and help us get rid of them! Happy we could contribute! www.nature.com/articles/s41...
Some small molecules modulate protein condensation in cells, but how? Our latest work shows a possible mechanism of action of the small molecule lipoamide. This molecule prevents condensation of stress granules whose components are found as protein aggregates in ALS.
www.nature.com/articles/s41...
Hiro's paper is out! @hiro-cg5445.bsky.social
Collaboration and Tour de Force with Richard Wheeler @zephyris-science.bsky.social and many other coauthors.
Big congratulations and thank you to anyone involved!
www.nature.com/articles/s41...
Thank you for this great perspective on our #glycoproteomics study @timveth.bsky.social and @nmriley.bsky.social!
Data can be explored 2u7b8b-nico0h0ttmann.shinyapps.io/PELSAAPP/;
This work was led by Kejia Li @kejiali.bsky.social and Clément Potel with contributions from Isabelle Becher, Nico Hüttmann @nicohuettmann.bsky.social , Martín Garrido-Rodríguez
@martingarridorc.bsky.social, and Jennifer Schwarz.
3/3 We extended its application to crude human cell line, bacteria, and tissue lysates and sensitively identify membrane targets! It works extremely well in tissues which allowed us to identify off-targets for sunitinib in mouse heart tissue and could explain its well-known cardiotoxicity.
2/3 We provide a large collection of ATP-binding proteins in E.coli and give rich information on how they respond to ATP. Our data nicely showed how chaperon protein DnaK binds ATP at ATP-binding region at low ATP concentration and dissociates the substrate protein at high ATP concentration.
1/3 We extended the original PELSA protocol to work with 96-well plates and show a 100-fold higher throughput, excellent reproducibility, accurate determination of drug-binding affinities in dose-response experiments as shown by a strong correlation of 0.88 with kinobeads-based measurements.
Want to know how the ligands interact with proteins beyond model cell lines, e.g., in tissues or bacteria? Interested in membrane targets? Check out our High-Throughput PELSA method which allows you do all these cool screenings for dozens of ligands within two hours! www.biorxiv.org/content/10.1...
Bacteria can influence how sugars modify proteins in the brain – shown for the first time by EMBL researchers.
In their study, the scientists describe a new method to study glycosylation systematically & quantitatively, leading to new biological insights. 🧪🧠📈
www.embl.org/news/science...
All data can be interactively explored 🖥️ apps.embl.de/glycoapp/. This work was led by Clement Potel, @miraburtscher.bsky.social and @martingarridorc.bsky.social. We thank our great collaborators @zimmermannlab.bsky.social and @typaslab.bsky.social.
Finally, we once again uncovered site-specific modulation of glycosylation upon perturbation, meaning that only some glycoforms on some glycosites are modulated, even within the same protein, suggesting complex regulatory mechanisms.
Next, we showed remodeling of the mouse brain glycoproteome upon gut microbiome colonization 🐭 The link b/w gut microbiome & brain physiology is long known, but molecular mechanisms remain elusive. We showed that proteins involved in neurotransmission & axon guidance were particularly affected.
We next used our quantitative approach to measure the dynamics of glycosylation changes in human cells treated with a fucosylation inhibitor 🧫 We discovered pervasive site-specific modulation of glycosylation upon perturbation.
Very little is known about glycoform functionality. We developed a functional glycoproteomics approach enabling the proteome-wide characterization of the solubility of different glycosylated proteoforms in the mouse brain 🐭
To understand structural features governing the level of site microheterogeneity, we leveraged our comprehensive dataset in combination with AlphaFold DB 🖥️
