A5023294747- Cellular transport and secretion
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Lysosomal Storage Disorders Research
- Advanced Proteomics Techniques and Applications
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Erythrocyte Function and Pathophysiology
- Metabolomics and Mass Spectrometry Studies
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- RNA Interference and Gene Delivery
- Mosquito-borne diseases and control
- interferon and immune responses
- RNA regulation and disease
University of Bonn
2021-2025
Utrecht University
2024-2025
Lysosomes are key degradative compartments of the cell. Transport to lysosomes relies on GlcNAc-1-phosphotransferase-mediated tagging soluble enzymes with mannose 6-phosphate (M6P). GlcNAc-1-phosphotransferase deficiency leads severe lysosomal storage disorder mucolipidosis II (MLII). Several viruses require cathepsins cleave structural proteins and thus depend functional GlcNAc-1-phosphotransferase. We used genome-scale CRISPR screens identify enzyme trafficking factor (LYSET, also named...
ABSTRACT Lysosomes are membrane-enclosed organelles that play a crucial role in the degradation of intra- and extracellular substrates regulation metabolic signaling. These functions carried out by variety proteins, which > 150 currently known to be located lysosomal lumen or embedded its membrane. proteins typically low abundant, necessitating organelle enrichment experiments enable their investigation unbiased mass spectrometry-based proteomics analyses. Enrichment strategies have been...
In eukaryotic cells, lysosomes play a crucial role in the breakdown of variety components ranging from small molecules to complex structures, ascertaining continuous turnover cellular building blocks. Furthermore, they act as regulatory hub for metabolism, being crucially involved regulation major signaling pathways. Currently, ~450 lysosomal proteins can be reproducibly identified single cell line by mass spectrometry, most which are low-abundant, restricting their unbiased proteomic...
Abstract Autophagy is a finely orchestrated process required for the lysosomal degradation of cytosolic components. The final step essential clearing autophagic cargo and recycling macromolecules. Using CRISPR/Cas9-based screen, we identify RNAseK, highly conserved transmembrane protein, as regulator autophagosome degradation. Analyses RNAseK knockout cells reveal that, while maturation intact, severely disrupted. Importantly, protease activity acidification remain intact in absence...
The mass spectrometry-compatible surfactant RapiGest promotes the enzymatic digestion of proteins by facilitating their unfolding while retaining activity. consists a hydrophilic head and hydrophobic tail, which can be separated acid hydrolysis. This allows for removal prior to spectrometric analysis via precipitation solid phase extraction. During in-solution experiments with RapiGest, we noticed high variability in formation precipitates after hydrolysis, implying that is sample-dependent....
Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear which factors contribute to VWM pathogenesis. Here, we investigated the basis of pathogenesis using 2b5
In a currently 13-year-old girl of consanguineous Turkish parents, who developed unsteady gait and polyneuropathy at the ages 3 6 years, respectively, we performed whole genome sequencing identified biallelic missense variant c.424C>T, p.R142W in glypican 1 (GPC1) as putative disease-associated variant. Up to date, GPC1 has not been associated with neuromuscular disorder, hypothesized that this variant, predicted deleterious, may be causative for disease. Using mass spectrometry-based...