A5058616980- Advanced Proteomics Techniques and Applications
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- Identification and Quantification in Food
- Genomics and Phylogenetic Studies
- Pleistocene-Era Hominins and Archaeology
- Genomics and Chromatin Dynamics
- Forensic Anthropology and Bioarchaeology Studies
- Microtubule and mitosis dynamics
- Genetic diversity and population structure
- Enzyme Structure and Function
- Receptor Mechanisms and Signaling
- Bioinformatics and Genomic Networks
- vaccines and immunoinformatics approaches
- Peptidase Inhibition and Analysis
- Advanced biosensing and bioanalysis techniques
- Gene expression and cancer classification
- Neuroscience and Neuropharmacology Research
- RNA modifications and cancer
- Oral microbiology and periodontitis research
- Paleopathology and ancient diseases
- Digestive system and related health
- Sirtuins and Resveratrol in Medicine
- Veterinary Equine Medical Research
Novo Nordisk (Denmark)
2022
Novo Nordisk Foundation
2012-2021
University of Copenhagen
2012-2021
Max Planck Institute of Biochemistry
2009-2010
Statens Serum Institut
2006
Lysine acetylation is a major posttranslational modification involved in broad array of physiological functions. Here, we provide an organ-wide map lysine sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 on 4,541 proteins and the data set as web-based database. demonstrate that displays site-specific sequence motifs diverge between cellular compartments, with significant fraction nuclear conforming to consensus G-AcK AcK-P. Our reveals...
Highlights•Multi-shot proteomics quantifies the protein levels of 12,200+ genes in HeLa cells•This essentially complete proteome has coverage similar to next-gen RNA-seq•Deep major PTMs is achieved without specific enrichment•The approach extendable other human cell lines and patient samplesSummaryThis study investigates challenge comprehensively cataloging from a single-cell type using mass spectrometry (MS)-based shotgun proteomics. We modify classical two-dimensional high-resolution...
Quantitative phosphoproteomics has transformed investigations of cell signaling, but it remains challenging to scale the technology for high-throughput analyses. Here we report a rapid and reproducible approach analyze hundreds phosphoproteomes using data-independent acquisition (DIA) with an accurate site localization score incorporated into Spectronaut. DIA-based achieves order magnitude broader dynamic range, higher reproducibility identification, improved sensitivity accuracy...
Advances in proteomics are continually driven by the introduction of new mass spectrometric instrumentation with improved performances. The recently introduced quadrupole Orbitrap (Q Exactive) tandem spectrometer allows fast acquisition high-resolution higher-energy collisional dissociation (HCD) spectra due to parallel mode operation, where generation, filling, and storage fragment ions can be performed while simultaneously measuring another ion packet analyzer. In this study,...
Comprehensive mass spectrometry (MS)-based proteomics is now feasible, but reproducible quantification remains challenging, especially for post-translational modifications such as phosphorylation. Here, we compare the most popular techniques global phosphoproteomics: label-free (LFQ), stable isotope labeling by amino acids in cell culture (SILAC) and MS2- MS3-measured tandem tags (TMT). In a mixed species comparison with fixed phosphopeptide ratios, find LFQ SILAC to be accurate techniques....
Posttranslational modifications of proteins increase the complexity cellular proteome and enable rapid regulation protein functions in response to environmental changes. Protein ubiquitylation is a central regulatory posttranslational modification that controls numerous biological processes including proteasomal degradation proteins, DNA damage repair innate immune responses. Here we combine high-resolution mass spectrometry with single-step immunoenrichment di-glycine modified peptides for...
Progress in proteomics is mainly driven by advances mass spectrometric (MS) technologies. Here we benchmarked the performance of latest MS instrument benchtop Orbitrap series, Q Exactive HF-X, against its predecessor for applications. A new peak-picking algorithm, a brighter ion source, and optimized transfers enable productive MS/MS acquisition above 40 Hz at 7500 resolution. The hardware software improvements collectively resulted improved peptide protein identifications across all...
Analysis of phosphorylated proteins from the hearts mice given drugs targeting β-adrenergic receptors may aid in treating heart disease.
Shotgun proteomics is a powerful technology for global analysis of proteins and their post-translational modifications. Here, we investigate the faster sequencing speed latest Q Exactive HF mass spectrometer, which features an ultra-high-field Orbitrap analyzer. Proteome coverage evaluated by four different acquisition methods benchmarked across three generations instruments (ProteomeXchange data set PXD001305). We find analyzer to be capable attaining above 20 Hz, it routinely exceeds 10...
Seven-transmembrane receptors (7TMRs) signal through the well described heterotrimeric G proteins but can also activate protein-independent signaling pathways of which impact and complexity are less understood. The angiotensin II type 1 receptor (AT1R) is a prototypical 7TMR an important drug target in cardiovascular diseases. “Biased agonists” with intrinsic “functional selectivity” that simultaneously blocks Gαq protein activity activates AT1R confer perspectives treatment In this study,...
Information on extracellular signals and conditions is often transduced by biological systems using cascades of proteinphosphorylation that affect the activity enzymes, localization proteins gene expression. A model to study signal transduction response yeast Saccharomyces cerevisiae osmotic changes as it shares many central themes with information processing modules in higher eukaryotes. Despite considerable progress our understanding this pathway, scale dynamics system have not been...
Abstract Large-scale mass spectrometry-based peptidomics for drug discovery is relatively unexplored because of challenges in peptide degradation and identification following tissue extraction. Here we present a streamlined analytical pipeline large-scale peptidomics. We developed an optimized sample preparation protocol to achieve fast, reproducible effective extraction endogenous peptides from sub-dissected organs such as the brain, while diminishing unspecific protease activity. Each...
The composition of ancient oral microbiomes has recently become accessible owing to advanced biomolecular methods such as metagenomics and metaproteomics, but the utility metaproteomics for analyses is less explored. Here, we use quantitative characterize dental calculus associated with remains 21 humans retrieved during archeological excavation medieval (ca. 1100-1450 CE) cemetery Tjærby, Denmark. We identify 3671 protein groups, covering 220 bacterial species 81 genera across all samples....
Denmark has an extraordinarily large and well-preserved collection of archaeological skin garments found in peat bogs, dated to approximately 920 BC – AD 775. These objects provide not only the possibility study prehistoric costume technologies, but also investigate animal species used for production garments. Until recently, identification was primarily performed by light scanning electron microscopy or analysis ancient DNA. However, efficacy these methods can be limited due harsh, mostly...
Significance GHB is a natural brain metabolite of GABA, previously reported to be neuroprotective. However, the high-affinity binding site for has remained elusive almost 40 y. We here unveil CaMKIIα, highly important neuronal kinase, as long-sought-after target. Via specific interaction within central hub domain analogs act stabilize oligomer complex. This potentially explains pronounced neuroprotective effects in cultured neurons exposed chemical insult and mice ischemia. The postischemic...
Abstract Peptides play important roles in regulating biological processes and form the basis of a multiplicity therapeutic drugs. To date, only about 300 peptides human have confirmed bioactivity, although tens thousands been reported literature. The majority these are inactive degradation products endogenous proteins peptides, presenting needle-in-a-haystack problem identifying most promising candidate from large-scale peptidomics experiments to test for bioactivity. address this challenge,...
The Ndc80 complex establishes end-on attachment of kinetochores to microtubules essential for chromosome segregation. subunit is characterized by an N-terminal region, that binds directly microtubules, and a long coiled-coil region interacts with Nuf2. A loop in generates kink the structure disrupts but exact function this not clear. Here we show human cells. Cells expressing mutants are unable align chromosomes stable kinetochore fibers absent. Through quantitative mass spectrometry...