A5055496875- Ubiquitin and proteasome pathways
- Cellular transport and secretion
- Protein Degradation and Inhibitors
- Autophagy in Disease and Therapy
- Biotin and Related Studies
- Click Chemistry and Applications
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Cell Image Analysis Techniques
- Fish biology, ecology, and behavior
- Genetics, Aging, and Longevity in Model Organisms
- Ethics in Clinical Research
- Epigenetics and DNA Methylation
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Genomics and Phylogenetic Studies
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
- Digestive system and related health
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2019-2025
Fred Hutch Cancer Center
2024
A progressive loss of protein homeostasis is characteristic aging and a driver neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics proteomics. We detected reduction correlation between mRNA, mainly due to post-transcriptional mechanisms that account for over 40% age-regulated proteins. These changes cause stoichiometry several complexes, including...
The small intestine is responsible for nutrient absorption and one of the most important interfaces between environment body. During aging, changes epithelium lead to food malabsorption reduced barrier function, thus increasing disease risk. drivers these alterations remain poorly understood. Here, we compare proteomes intestinal crypts from mice across different anatomical regions ages. We find that aging alters epithelial immunity, metabolism, cell proliferation accompanied by...
Thanks to the plummeting costs of continuously evolving omics analytical platforms, research centers collect multiomics data more routinely. They are, however, confronted with lack a versatile software solution harmoniously analyze single-omics and interpret data. We have developed iSODA, web-based application for analysis single- The tool emphasizes intuitive interactive visualizations designed user-driven exploration. Researchers can access variety functions ranging from simple...
Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite relevance human disease drug development, no method currently exists monitor composition interactions vivo animal models. To fill this gap, we developed a strategy based on tagging proteasomes with promiscuous biotin ligases generated new mouse model enabling quantification by...
Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite relevance human disease drug development, no method currently exists monitor composition interactions vivo animal models. To fill this gap, we developed a strategy based on tagging proteasomes with promiscuous biotin ligases generated new mouse model enabling quantification by...
Proximity-dependent biotinylation is an important method to study protein-protein interactions in cells, for which expanding number of applications has been proposed. The laborious and time-consuming sample processing limited project sizes so far. Here, we introduce automated workflow on a liquid handler process up 96 samples at time. automation not only allows higher numbers be processed parallel but also improves reproducibility lowers the minimal input. Furthermore, combined with shorter...
Mutations in lysosomal genes cause neurodegeneration and neurological storage disorders (LSDs). Despite their essential role brain homeostasis, the cell-type-specific composition function of lysosomes remain poorly understood. Here, we report a quantitative protein atlas lysosome from mouse neurons, astrocytes, oligodendrocytes, microglia. We identify dozens novel proteins reveal diversity across cell types. Notably, discovered SLC45A1, mutations which monogenic disease, as neuron-specific...
Aging and neurodegeneration entail diverse cellular molecular hallmarks. Here, we studied the effects of aging on transcriptome, translatome, multiple layers proteome in brain a short-lived killifish. We reveal that causes widespread reduction proteins enriched basic amino acids is independent mRNA regulation, it not due to impaired proteasome activity. Instead, identify cascade events where aberrant translation pausing leads reduced ribosome availability resulting remodeling independently...
SUMMARY Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite relevance human disease drug development, no method currently exists monitor composition interactions vivo animal models. To fill this gap, we developed a strategy based on tagging proteasomes with promiscuous biotin ligases generated new mouse model enabling...
Summary A progressive loss of protein homeostasis is characteristic aging and a driver neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics proteomics. We detected reduction correlation between mRNA, mainly due to post-transcriptional mechanisms that account for over 40% age-regulated proteins. These changes cause stoichiometry several complexes, including...
Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite relevance human disease drug development, no method currently exists monitor composition interactions vivo animal models. To fill this gap, we developed a strategy based on tagging proteasomes with promiscuous biotin ligases generated new mouse model enabling quantification by...
Abstract Omics technologies including genomics, proteomics, metabolomics, and lipidomics allow profound insights into health disease. Thanks to plummeting costs of continuously evolving omics analytical platforms, research centers collect multi-omics data more routinely. They are, however, confronted with the lack a versatile software solution harmoniously analyze single-omics merge interpret data. We have developed iSODA, an interactive web-based application for analysis single-as well as...
We introduce an automated workflow for proximity dependent biotinylation on a liquid handler to process up 96 samples at time,combined with shorter chromatography gradients and data-independent acquisition increase analysis throughput enable reproducible protein quantitation
We introduce an automated workflow for proximity dependent biotinylation on a liquid handler to process up 96 samples at time,combined with shorter chromatography gradients and data-independent acquisition increase analysis throughput enable reproducible protein quantitation
Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite relevance human disease drug development, no method currently exists monitor composition interactions vivo animal models. To fill this gap, we developed a strategy based on tagging proteasomes with promiscuous biotin ligases generated new mouse model enabling quantification by...
ABSTRACT Post-translational modifications (PTMs) regulate protein homeostasis and function. How aging affects the landscape of PTMs remains largely elusive. Here, we reveal changes in hundreds ubiquitylation, acetylation, phosphorylation sites brain mice. We show that has a major impact on ubiquitylation 29% are affected independently abundance, indicating altered PTM stoichiometry. found subset these to be also short-lived killifish Nothobranchius furzeri , highlighting conserved phenotype....
Abstract Proximity dependent biotinylation is an important method to study protein-protein interactions in cells, for which expanding number of applications has been proposed. The laborious and time consuming sample processing limited project sizes so far. Here, we introduce automated workflow on a liquid handler process up 96 samples at time. automation does not only allow higher numbers be processed parallel, but also improves reproducibility lowers the minimal input. Furthermore, combined...
Gene duplication enables the emergence of new functions by lowering evolutionary pressure that is posed on ancestral genes. Previous studies have highlighted role specific paralog genes during cell differentiation, for example, in chromatin remodeling complexes. It remains unexplored whether similar mechanisms extend to other biological and regulation conserved across species. Here, we analyze expression paralogs human tissues, development neuronal differentiation fish, rodents humans....
Abstract Gene duplication enables the emergence of new functions by lowering general evolutionary pressure. Previous studies have highlighted role specific paralog genes during cell differentiation, e.g., in chromatin remodeling complexes. It remains unexplored whether similar mechanisms extend to other biological and regulation is conserved across species. Here, we analyze expression paralogs human tissues, development neuronal differentiation fish, rodents humans. While ~80% are...