Biology subjects

Kaser, S.

Publications and source records attributed to Kaser, S..

4 recordsLinked to original sources

bioRxiv2025

Unified down-stream analysis of crosslinking mass spectrometry results with pyXLMS

Crosslinking mass spectrometry has become the method of choice for the identification of protein-protein interactions and for gaining insight into the structures of proteins in vivo. However, connecting crosslink search engine results with down-stream analysis tools, and therefore gaining biological insight from crosslink identifications, has remained a manual and cumbersome step in the analysis that often requires expert bioinformatics knowledge. Here we introduce pyXLMS, a python package and public web application which aims to simplify and streamline this intermediate step, enabling researchers even without bioinformatics knowledge to conduct in-depth crosslink analyses. In its current state pyXLMS supports input from seven different crosslink search engines, as well as the mzI-dentML format of the HUPO Proteomics Standards Initiative. Down-stream analysis is facilitated by functionality that is directly available within pyXLMS such as aggregation, validation, annotation, filtering, and visualization. In addition, the data can easily be exported to more than ten supported down-stream analysis tools and formats. We demonstrate the applicability and benefits of pyXLMS by re-analyzing a publicly available crosslink dataset with a variety of different search engines and show how the same data analysis workflow can be applied using pyXLMS. pyXLMs is available via https://github.com/hgb-bin-proteomics/pyXLMS.

bioinformatics↗

bioRxiv2025

Escherichia-Shigella expansion and metabolite dysregulation in type 3c diabetes

Emerging evidence supports a bidirectional gut-pancreas axis in which microbial dysbiosis, barrier dysfunction, and altered metabolite fluxes contribute to pancreatogenic diabetes (T3cDM). Whether gut microbial changes reflect systemic metabolic disturbances or primarily arise from exocrine pancreatic insufficiency (EPI) remains unclear. We profiled the gut microbiome of 48 outpatients with T3cDM, type 1 diabetes (T1DM), and healthy controls. Genus-level 16S rRNA data were analysed using cross-validated LASSO logistic regression and patient-specific community metabolic models. T3cDM showed reduced -diversity and distinct {beta}-diversity compared with T1DM and controls. Key compositional shifts included enrichment of Enterobacteriaceae (notably Escherichia-Shigella) and Streptococcaceae in T3cDM. LASSO models discriminated T3cDM from T1DM (AUC 0.867; accuracy 0.818), highlighting Blautia, Escherichia-Shigella, Streptococcus, Clostridium, and Faecalibacterium as predictors. Metabolic modelling indicated elevated Escherichia-Shigella growth in T3cDM and disease-specific metabolite fluxes. Gut microbial shifts in T3cDM predominantly reflect EPI rather than systemic metabolic disturbances characteristic of T1DM, underscoring the central role of exocrine pancreatic dysfunction in shaping the gut microbiome and its metabolic activity.

microbiology↗

bioRxiv2024

TXNIP mediates LAT1/SLC7A5 endocytosis to reduce amino acid uptake in cells entering quiescence

Entry and exit from cellular quiescence require dynamic adjustments in nutrient acquisition, yet the mechanisms by which quiescent cells downregulate amino acid (AA) transport remain poorly understood. Here, we demonstrate that cells entering quiescence select plasma membrane-resident AA transporters for endocytosis and lysosomal degradation, to match AA uptake with reduced translation. We identify the -arrestin TXNIP as a key regulator of AA uptake during quiescence, since it mediates the endocytosis of the SLC7A5-SLC3A2 (LAT1-4F2hc) transporter complex in response to reduced AKT signaling. Mechanistically, TXNIP interacts with HECT-type ubiquitin ligases to facilitate transporter ubiquitination. Loss of TXNIP disrupts this regulation, resulting in dysregulated AA uptake, sustained mTORC1 signaling, and accelerated quiescence exit. A novel TXNIP loss-of-function mutation in a patient with severe metabolic disease further supports its role in nutrient homeostasis and human health. These findings highlight TXNIPs role in controlling SLC7A5-SLC3A2 mediated AA acquisition with implications for quiescence biology and disease.

cell biology↗

bioRxiv2023

A Msp1-containing complex removes orphaned proteins in the mitochondrial outer membrane of trypanosomes

The AAA-ATPase Msp1 extracts mislocalized outer membrane proteins and thus contributes to mitochondrial proteostasis. Using pull down experiments we show that trypanosomal Msp1 localizes to both glycosomes and the mitochondrial outer membrane, where it forms a stable complex with four outer membrane proteins. The trypanosome-specific pATOM36 mediates complex assembly of a-helically anchored mitochondrial outer membrane proteins such as protein translocase subunits. Inhibition of their assembly triggers a pathway that results in the proteasomal digestion of unassembled substrates. Using inducible single, double and triple RNAi cell lines combined with proteomic analyses we demonstrate that not only Msp1 but also the trypanosomal homolog of the AAA-ATPase VCP are implicated in this quality control pathway. Moreover, in the absence of VCP three out of the four Msp1-interacting mitochondrial proteins are required for efficient proteasomal digestion of pATOM36 substrates suggesting they act in concert with Msp1. pATOM36 is a functional analogue of the yeast MIM complex and possibly of human MTCH2 suggesting that similar mitochondrial quality control pathways linked to Msp1 might also exist in yeast and humans.

biochemistry↗