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kabalak.bsky.social
@kabalak.bsky.social
58 followers 68 following 15 posts
A proteomics adventurer on the multiple social media road(s). Interested in proteolysis research, likes human plasma
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And one final comment - this work would not be possible without belief & funds for the idea to perform large-scale N-terminomics in patients (@mrinschen.bsky.social) and dozens of methods developed by/with colleagues: (S)HUNTER, MOFA, TPP-PISA and Human Kidney Organoids. Thanks for all this.
To summarize: we identified the C3-LHF1 cleavage in a large-scale N-terminomics screen of a cross-sectional cohort which is increasingly present in SLE patients, inhibiting the CP & MBL pathways of the complement system while at the same time being a trigger for a IL6 response. Thanks for reading.
For further testing this interaction, we performed C3-LHF1 application to HEK-Blue IL6 reporter cell lines. We could observe a triggered IL6 response, albeit lower than IL6 agonist levels. The C3-LHF1 IL6 response can't be blocked by tocilizumab. There is even a little competition for IL6 & C3-LHF1.
Next, we screened putative interacting proteins for our rec. C3-LHF1 in human kidneys by classical pull-down assays and Thermal Proteome Profiling, PISA style): One of the top candidates is the IL6ST (aka gp130), a very important (co-)receptor for IL6 signalling.
We produced C3-LHF1 as a rec. protein & performed complement assays, revealing an inhibitory effect of C3-LHF1 on the classical and MBL pathway of the complement system. These assays were done with the SVAR Complement ELISA kits. Inhibiting complement can come in handy, but do we see other effects?
Combining all of this data into a fabulous circle plot clearly pointed towards an important role of the cleavage at pos. 1514, generating C3-LHF1. This became the focus of our future efforts. #LHF1 #CirclePlot
Knowing this, we wanted to know, if these cleavages could be generated by four proteases of the complement system: MASP-1/-3, C1r/s. We generated substrate profiles for these proteases & identified common substrates as well as intriguingly present cleavages at the C-terminus of C3, alike C3-LHF1
Generating mass spec data is trivial, but deriving conclusions is difficult, thus we applied the MOFA2 framework for analysis of our data. It yields significant correlations between some MOFA factors and clinical parameters and interestingly the presence of our C3-LHF1 cleavage in one of the factors
Looking at proteolytis in human plasma, we observed a lot of cleavages in complement C3, with known cleavages for C3a, C3b, and C3(d)g - but also a cleavage at pos. 1514, which represented a quite intriguing lupus-enriched cleavage, thus we named it C3-LHF1 for complement "C3 Lupus Human Fragment 1"
Starting with an unbiased screening in human plasma, we needed to optimize our already published HUNTER method (doi.org/10.1074/mcp....) for high-throughput and the demands of handling a larger cohort with > 100 patients, optimizing efficiency. Stream-lined "label-free-like" N-terminomics. #SHUNTER
After a looong journey, here the results of a deep investigation of human plasma proteolysis by MS: SLE N-terminomics paper with a complement C3 fragment at the core, EMBOJ: www.embopress.org/doi/full/10.... - highlights: a resource on proteolytically processed N-termini in human plasma #LHF1 #SLE🧪
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See you at Palazzo dei Normanni in Palermo for the 2026 Protein Termini Conference | Co- and post-translational modifications | Proteolytic processing and degradation pathways | Microbes, plants, animals #ProteinTermini2026 #Proteostasis #ProteinModifications #PalazzoDeiNormanni #Palermo2026
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Wer hat ihn, den berühmten Dessertmagen? 🙋🏼‍♀️

Ich fand diese Studie von vor ein paar Monaten super interessant, denn sie zeigt: Dieselben Nervenzellen, die uns nach dem Essen satt machen, setzen bei Zucker gezielt β‑Endorphin frei (= körpereigenes Opioid) das uns dazu treibt, weiter zu naschen (🐁)
Thalamic opioids from POMC satiety neurons switch on sugar appetite
High sugar–containing foods are readily consumed, even after meals and beyond fullness sensation (e.g., as desserts). Although reward-driven processing of palatable foods can promote overeating, the n...
www.science.org
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Weather’s going wild, and now your mass spec data’s a mess too?

Coindidence? Nope!

We reveal how weather-driven air pressure fluctuations impact diaPASEF-based high troughput proteomics - and how to fix it!

Check out our new paper! #diaPASEF #Weatheromics

pubs.acs.org/doi/10.1021/...
Impact of Local Air Pressure on Ion Mobilities and Data Consistency in diaPASEF-Based High Throughput Proteomics
Data-independent acquisition (DIA) on ion mobility mass spectrometers enables deep proteome coverage and high data completeness in large-scale proteomics studies. For advanced acquisition schemes such as parallel accumulation serial fragmentation-based DIA (diaPASEF) stability of ion mobility (1/K0) over time is crucial for consistent data quality. We found that minor changes in environmental air pressure systematically affect the vacuum pressure in the TIMS analyzer, causing ion mobility shifts. By comparing experimental ion mobilities with historical weather data, we attributed observed drifts to fluctuations in the ground air pressure. Moderate air pressure changes of e.g. fifteen mbar induce ion mobility shifts of 0.025 Vs/cm2. These drifts negatively impact peptide quantification across consecutively acquired samples due to drift-dependent abundance changes and increased missing values for ions located at the boundaries of diaPASEF isolation windows, which cannot be corrected by postprocessing. To address this, we applied an in-batch mobility autocalibration feature on a run-wise basis, leading to full elimination of ion mobility drifts.
pubs.acs.org
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Danish defense of Greenland sorted!
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I try super hard to be positive, but I seriously think we're at almost 9 out of 10 papers with "single cell proteomics" in the title don't feature the analysis of one actual cell in them anywhere. Case in point - super nice study. Obfuscating terminology. proteomicsnews.blogspot.com/2024/12/scpr...
SCPro - Not single cell proteomics, at all, in any way, but still pretty cool!
Here, I fixed it for ya! Even though I can clearly see why I also wouldn't have recommended Ben Orsburn as a reviewer for this one, I do a...
proteomicsnews.blogspot.com
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I thought this poster of my facility turned out nice so I tight I’d share :)
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If you are interested to learn about our research towards new targets for the antibiotics of the future, check out my eye-opener video. Thanks to the Leiden Institute of Chemistry, the Faculty of Science and the KNCV for making this possible.
www.eye-openers.nl/en/seethecas...
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Aufgefüllt und aufgeräumt!
Die #kirppudk 707 in #Tilst hat jetzt jede Menge Playmobil und Barbie, Schleichpferde, Mia&me, ...
Had there even been a real reason to use TEAB?
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Wer einen McDonald's im Ort hat, weiß, wie viel Müll dadurch überall herumliegt. Das wäre wirklich eine Verbesserung. Wären da nicht die Leute, die auch Pfandflaschen wegwerfen, weil zu viel Mühe ...
Single-use fast-food packaging hangs in the balance
France has already banned it — now industry is lobbying hard to ensure the EU doesn’t do the same.
www.politico.eu
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Happy to share the phenomenal PhD work of Dr. Amanda Lorentzian now out in its peer-reviewed from in @NatureComms. Amanda shows that targetable genome variants and proteome features are mostly stable from diagnosis to relapse in pediatric leukemia. 1/ www.nature.com/articles/s41...