A5055574665- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Cellular transport and secretion
- Mass Spectrometry Techniques and Applications
- Protease and Inhibitor Mechanisms
- Protein Degradation and Inhibitors
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Microtubule and mitosis dynamics
- Biotin and Related Studies
- S100 Proteins and Annexins
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Click Chemistry and Applications
- Blood Coagulation and Thrombosis Mechanisms
- Pancreatic function and diabetes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Lymphoma Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
- Protein purification and stability
- Chemokine receptors and signaling
- Genetics and Neurodevelopmental Disorders
- Enzyme Structure and Function
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2021-2025
Fred Hutch Cancer Center
2024
Technische Universität Berlin
2020-2023
Wellcome Centre for Cell Biology
2018-2020
University of Edinburgh
2018-2020
Helmholtz Zentrum München
2009-2017
Ludwig-Maximilians-Universität München
2015-2017
German Center for Lung Research
2015-2017
Max Planck Institute of Neurobiology
2010-2011
Max Planck Society
2010
While AlphaFold2 can predict accurate protein structures from the primary sequence, challenges remain for proteins that undergo conformational changes or which few homologous sequences are known. Here we introduce AlphaLink, a modified version of algorithm incorporates experimental distance restraint information into its network architecture. By employing sparse contacts as anchor points, AlphaLink improves on performance in predicting challenging targets. We confirm this experimentally by...
Neutrophils play a pivotal role in the defense against bacterial, viral and fungal infections are important mediators acute inflammatory response. At same time, neutrophils also volved sterile responses that triggered by endogenous ligands. A series of immediate effector functions expression proinflammatory genes enable to initiate immune response injurious agent. Among these, interleukin-1β (IL-1β) plays key orchestration Induction IL-1β leads production cytosolic pro-IL-1β, which requires...
Trypsin is the most used enzyme in proteomics. Nevertheless, proteases with complementary cleavage specificity have been applied special circumstances. In this work, we analyzed characteristics of five protease alternatives to trypsin for protein identification and sequence coverage when S. pombe whole cell lysates. The heavily impacted number proteins identified. Proteases higher led more than lower specificity. However, AspN, GluC, chymotrypsin, proteinase K largely benefited from being...
Background Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell is characterized by the t(2;5) chromosomal translocation, resulting in expression of a fusion protein formed nucleophosmin (NPM) and ALK. Recently, we reported abnormal transcription factor CCAAT/enhancer binding protein-beta (C/EBPβ) ALK-positive lymphomas, demonstrated its dependence on NPM-ALK activity.Design Methods In this study, role C/EBPβ proliferation survival lymphomas was investigated, as well mechanism...
Significance Common single-amino acid variations of proteins are traditionally regarded as functionally neutral polymorphisms because these substitutions mostly located outside relevant surfaces. In this study, we present an example a coding sequence variation, which, show here, confers risk for large artery atherosclerotic stroke. The single-residue variation M1(A213V) in serpin family A member 1 ( SERPINA1 ) [encoding alpha-1 antitrypsin (AAT)] is situated the protease-reactive inhibitory...
Cross-linking mass spectrometry has become an important approach for studying protein structures and protein–protein interactions. The amino acid compositions of some regions impede the detection cross-linked residues, although it would yield invaluable information modeling. Here, we report on a sequential-digestion strategy with trypsin elastase to penetrate low density trypsin-cleavage sites. We exploited intrinsic substrate-recognition properties specifically target larger tryptic...
An imbalance between neutrophil-derived proteases and extracellular inhibitors is widely regarded as an important pathogenic mechanism for lung injury. Despite intense efforts over the last three decades, attempts to develop small-molecule neutrophil elastase have failed in clinic. Here we discover intrinsic self-cleaving property of mouse that interferes with action inhibitors. We show conversion single-chain (sc) into a two-chain (tc) by self-cleavage near its S1 pocket altered substrate...
Chronic staphylococcal osteomyelitis can persist for long time periods causing bone destruction. The ability of Staphylococcus aureus to develop chronic infections is linked its capacity invade and replicate within osteoblasts osteocytes switch a dormant phenotype called small colony variants. Recently, were described as main reservoir this pathogen in tissue. However, the mechanisms involved persistence S. these cells are still unknown. Here, we investigated interaction between or during...
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...
Preconditioning with lipopolysaccharide (LPS) induces neuroprotection against subsequent cerebral ischemic injury, mainly involving innate immune pathways. Microglia are resident cells of the central nervous system (CNS) that respond early to danger signals through memory-like differential reprogramming. However, cell-specific molecular mechanisms underlying preconditioning not fully understood. To elucidate distinct on microglia, we compared these proteomic profiles in response LPS and...
During myogenic differentiation the cellular architecture and proteome of muscle stem cells myoblasts undergo extensive remodeling. These molecular processes are only partially understood display alterations in disease conditions as well during aging resulting impaired regeneration. Here, we used mass spectrometry to quantify temporal dynamics more than 6000 proteins differentiation. We identified actin nucleator leiomodin 1 (LMOD1) among a restricted subset cytoskeletal increasing abundance...
During myogenic differentiation the cellular architecture and proteome of muscle stem cells myoblasts undergo extensive remodeling. These molecular processes are only partially understood display alterations in disease conditions as well during aging resulting impaired regeneration. Here, we used mass spectrometry to quantify temporal dynamics more than 6000 proteins differentiation. We identified actin nucleator leiomodin 1 (LMOD1) among a restricted subset cytoskeletal increasing abundance...
We present a concise workflow to enhance the mass spectrometric detection of crosslinked peptides by introducing sequential digestion and crosslink identification software Xi. Sequential enhances peptide selective shortening long tryptic peptides. demonstrate our simple 12-fraction protocol for multi-protein complexes cell lysates, quantitative analysis, high-density crosslinking, without requiring specific crosslinker features. This overall approach reveals dynamic protein-protein...
Abstract Posttranslational mechanisms play a key role in modifying the abundance and function of cellular proteins. Among these, modification by advanced glycation end products has been shown to accumulate during aging age-associated diseases but specific protein targets functional consequences remain largely unexplored. Here, we devise proteomic strategy identify sites carboxymethyllysine modification, one most abundant products. We over 1000 carboxymethylation mouse primary human cells...
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...
ABSTRACT During myogenic differentiation the architecture and proteome of muscle stem cells undergo extensive remodeling. These processes are only partially understood display impairments in age disease. Here, we used mass spectrometry to analyze dynamics during differentiation. We identified actin nucleator Leiomodin 1 (LMOD1) among a restricted set proteins that increase abundance early phases LMOD1 is expressed by vivo its levels with aging. Knockdown primary myoblasts severely affected...
Mutations in the IER3IP1 (Immediate Early Response-3 Interacting Protein 1) gene can give rise to MEDS1 (Microcephaly with Simplified Gyral Pattern, Epilepsy, and Permanent Neonatal Diabetes Syndrome-1), a severe condition leading early childhood mortality. The small endoplasmic reticulum (ER)-membrane protein plays non-essential role ER-Golgi transport. Here, we employed secretome cell-surface proteomics demonstrate that absence of results mistrafficking proteins crucial for neuronal...
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...
Abstract High abundance proteins like protease inhibitors of plasma display a multitude interactions in natural environments. Quantitative analysis such vivo is essential to study diseases, but have not been forthcoming, as most methods cannot be directly applied complex biological environment. Here, we report quantitative microscale thermophoresis assay capable deciphering functional deviations from vitro inhibition data by combining concentration and affinity measurements. We obtained...
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