@miraburtscher.bsky.social

Predoc @savitski_lab @EMBL | Computational Biology @saezlab | Interested in functional proteomics and systems biology 🧫🧬

One of the main stories of my postdoc is finally out! It builds on an intuition from my early days in omics data analysis: our signaling pathways are simply too small, underrepresenting cellular complexity after stimulation. Something obvious, yet surprisingly hard to quantify.

Saez-Rodriguez Group@saezlab.bsky.social · 7mo ago

Interested in kinase-driven signaling interactions? Check out our (now peer-reviewed) paper together with @savitski-lab.bsky.social on reconstructing signaling networks from phosphoproteomics data and prior knowledge: ➡️ doi.org/10.1038/s414...

Happy to share new work led by @miraburtscher.bsky.social, together with colleagues from @savitski-lab.bsky.social, @saezlab.bsky.social (shout-out to @martingarridorc.bsky.social), @zimmermannlab.bsky.social and others. Original post + paper below! 👇

Savitski Lab@savitski-lab.bsky.social · 7mo ago

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

When I first learned about omics at university, I confidently stopped caring about single proteins. Fast-forward 4 years of a system’s biology PhD, I now have the most amazing favorite single protein which I can’t stop thinking about. Here is the story of how that happened 👀

Savitski Lab@savitski-lab.bsky.social · 7mo ago

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

New year, new preprint! 🎊 We are excited to share our recent work on #E3 ligase regulation in #metabolism! www.biorxiv.org/content/10.6... #ubiquitin #targetedproteindegradation #chemicalbiology 1/6

A CK2-FBXW11 kinase-E3 ubiquitin ligase cascade is a metabolic sensor regulating Tryptophan 2,3-dioxygenase stability

Small molecules toggling the ubiquitin-proteasome system (UPS) are powerful regulators of protein degradation. Yet, mechanistic knowledge of how endogenous ligands gate UPS decisions remains rudimentary. Here, we define control of UPS access to Tryptophan-2,3-dioxygenase (TDO2), which converts the essential amino acid tryptophan (Trp) to N-formylkynurenine. When Trp concentrations are limiting, TDO2 is degraded to avert tryptophanemia. Using CRISPRi screening and biochemistry, we identify a CK2-FBXW11 kinase-E3 ligase cascade that generates and recognizes tandem TDO2 phosphodegrons when not protected by Trp. Trp binding to an exosite safeguards TDO2 from phosphorylation-dependent ubiquitylation. Effects of Trp analogs on CK2-FBXW11-dependent ubiquitylation indicated that the indole, amino, and carboxylate groups are necessary for substrate shielding. Cryo-EM reveals how these moieties order a region proximal to the phosphodegrons; without Trp, this segment is flexible, enabling phosphorylation-coupled ubiquitylation. Overall, our data uncovered an endogenous small molecule allosterically stabilizing its own metabolizing enzyme through protection from a phosphorylation-ubiquitylation cascade. ### Competing Interest Statement B.A.S. is a member of the scientific advisory boards of Proxygen and Lyterian. The other authors declare no competing interests. Max Planck Society, https://ror.org/01hhn8329 European Union, ERC AdvG, UPSmeetMet, 101098161 to BAS Boehringer Ingelheim Fonds, https://ror.org/00dkye506

biorxiv.org

Want to learn about the theoretical aspects of proteins/peptides analysis by mass spectrometry? Then join the #EMBLProteomics course where you will get hands-on experience in sample preparation and perform tandem mass tag labelling. Apply by 3 March:https://s.embl.org/sdp26-01-bl 🔬💻

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How can we find out what’s really going on inside cells when we’re generating so much complex data? CORNETO is an open-source tool that uses machine learning to turn tangled omics datasets into clear maps of how genes, proteins, and signalling pathways interact. www.ebi.ac.uk/about/news/r... 🧪

CORNETO: machine learning to decode complex omics data

New tool combines biological knowledge with machine learning to help researchers extract meaningful insights from complex omics data.

ebi.ac.uk

Big congrats to everyone involved - it was a blast! 🎊 If you're interested in #multiomics integration or #kidneyfibrosis, check it out! ⬇️

Saez-Rodriguez Group@saezlab.bsky.social · last yr.

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

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...

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