Savitski Lab

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....

Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances - Nature Microbiology Human gut bacteria bioaccumulate per- and polyfluoroalkyl substances (PFAS), commonly known as forever chemicals, in intracellular aggregates. Colonization of gnotobiotic mice with bioaccumulating bac...

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...

Small-molecule dissolution of stress granules by redox modulation benefits ALS models - Nature Chemical Biology Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic...

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...

Small-molecule dissolution of stress granules by redox modulation benefits ALS models - Nature Chemical Biology Uechi et al. found that a small-molecule lipoamide dissolves stress granules (SGs) by targeting SFPQ, a redox-sensitive disordered SG protein, alleviating pathological phenotypes caused by amyotrophic...

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.

High-throughput peptide-centric local stability assay extends protein-ligand identification to membrane proteins, tissues, and bacteria Systematic mapping of protein-ligand interactions is essential for understanding biological processes and drug mechanisms. Peptide-centric local stability assay (PELSA) is a powerful tool for detectin...

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 🖥️

It is essential to differentiate surface-exposed glycoforms from intermediate species. To address this, we treated intact living human cells with two enzymes, enabling proteome-wide characterization of mature glycoforms 🧫

Using our quant approach, we discovered that many sites have similar glycosylation patterns across tissues 🐭However, we identified a subset of sites driving tissue-specificity, enriched in domains involved in cell adhesion, signaling & immunity. E.g., only N445 exhibits tissue specificity on INSR.

We are very happy to present our work on N-glycoproteomics!🍬 Our method enables the selective enrichment and precise quantification of intact N-glycopeptides to explore the dynamics of glycosylation microheterogeneity.
www.nature.com/articles/s41...