Michael L. Nielsen

ORCID: 0000-0002-0067-9039
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About
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Research Areas
  • Advanced Proteomics Techniques and Applications
  • Mass Spectrometry Techniques and Applications
  • Ubiquitin and proteasome pathways
  • PARP inhibition in cancer therapy
  • DNA Repair Mechanisms
  • RNA modifications and cancer
  • Genomics and Chromatin Dynamics
  • Analytical Chemistry and Chromatography
  • CRISPR and Genetic Engineering
  • RNA and protein synthesis mechanisms
  • Metabolomics and Mass Spectrometry Studies
  • RNA Research and Splicing
  • Epigenetics and DNA Methylation
  • Glycosylation and Glycoproteins Research
  • Toxin Mechanisms and Immunotoxins
  • Peptidase Inhibition and Analysis
  • Cancer-related gene regulation
  • Calcium signaling and nucleotide metabolism
  • Fungal and yeast genetics research
  • Cancer-related Molecular Pathways
  • Microtubule and mitosis dynamics
  • Endoplasmic Reticulum Stress and Disease
  • Signaling Pathways in Disease
  • Electrostatic Discharge in Electronics
  • Protein Degradation and Inhibitors

Novo Nordisk Foundation
2016-2025

University of Copenhagen
2016-2025

Foundation Center
2011-2024

Novozymes (Denmark)
2021

Uppsala University
2004-2020

University of Cambridge
2020

Marie Curie
2020

University of Iceland
2020

National Museum of Denmark
2020

University of Rochester
2015

Lysine Acetylation Catalog Covalent posttranslational modification is an essential cellular regulatory mechanism by which the activity of proteins can be controlled. Advances in mass spectrometry made it possible for Choudhary et al. (p. 834 , published online 16 July) to assess prevalence lysine acetylation throughout whole proteome. much more widespread than previously appreciated and occurs on participating all sorts biological functions. influence susceptibility phosphorylation...

10.1126/science.1175371 article EN Science 2009-07-16

Abstract Intrinsically disordered proteins can phase separate from the soluble intracellular space, and tend to aggregate under pathological conditions. The physiological functions molecular triggers of liquid demixing by separation are not well understood. Here we show in vitro vivo that nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates demixing. PAR levels markedly induced at sites DNA damage, provide evidence PAR-seeded results rapid, yet transient fully reversible...

10.1038/ncomms9088 article EN cc-by Nature Communications 2015-08-19

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...

10.1016/j.cels.2017.05.009 article EN cc-by Cell Systems 2017-06-01

Modifying the Modifier Covalent modification of proteins provides an important means whereby their function is regulated. Hydroxylation, catalyzed by oxygenase enzymes, plays role in response to hypoxia, for example. The human protein Jmjd6 has been thought act as oxygenase, catalyzing demethylation histone H3 at arginine-2 and H4 arginine-3. Webby et al. (p. 90 ) now show that interacts with messenger RNA splicing factor U2AF65 acts hydroxylate this lysine residues, modifications also seen...

10.1126/science.1175865 article EN Science 2009-07-02

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces organic acids hydrolytic enzymes high amounts, some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. strain (CBS 513.88) has already been sequenced, versatility this species compel additional exploration. We therefore undertook whole-genome sequencing acidogenic wild-type (ATCC 1015) produced a...

10.1101/gr.112169.110 article EN cc-by-nc Genome Research 2011-05-04

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to astrocyte-to-neuron lactate shuttle hypothesis, taken up by astrocytes and converted lactate, which then oxidized neurons. Here we show, using two-photon imaging of near-infrared 2-deoxyglucose analogue (2DG-IR), preferentially neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake sensory stimulation was associated with sharp increase...

10.1038/ncomms7807 article EN cc-by-nc-nd Nature Communications 2015-04-23

The covalent attachment of ubiquitin to proteins regulates numerous processes in eukaryotic cells. Here we report the identification 753 unique lysine ubiquitylation sites on 471 using higher-energy collisional dissociation LTQ Orbitrap Velos. In total 5756 putative substrates were identified. Lysine residues targeted by ubiquitin-ligase system show no sequence feature. Surface accessible located ordered secondary regions, surrounded smaller and positively charged amino acids are preferred...

10.1074/mcp.m110.003590 article EN cc-by Molecular & Cellular Proteomics 2010-12-08

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,...

10.1021/pr3000249 article EN Journal of Proteome Research 2012-04-27

Arginine methylation is prevalent throughout the proteome and regulates localization function of splicing RNA transport factors.

10.1126/scisignal.aaf7329 article EN Science Signaling 2016-08-30

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...

10.1074/mcp.m112.017905 article EN cc-by Molecular & Cellular Proteomics 2012-07-13

ADP‐ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage viral infection is involved intra‐ extracellular signaling, chromatin transcriptional regulation, protein biosynthesis, cell death. ADP‐ribosylation catalyzed ADP‐ribosyltransferases (ARTs), which transfer ADP‐ribose from NAD + onto substrates. The modification, occurs as mono‐ or poly‐ADP‐ribosylation, reversible due...

10.1111/febs.16142 article EN cc-by-nc-nd FEBS Journal 2021-07-29

Although protein ADP-ribosylation is involved in diverse biological processes, it has remained a challenge to identify ADP-ribose acceptor sites. Here, we present an experimental workflow for sensitive and unbiased analysis of endogenous sites, capable detecting more than 900 modification sites mammalian cells mouse liver. In cells, demonstrate that Lys residues, besides Glu, Asp Arg are the dominant vivo targets during oxidative stress. normal liver tissue, find residues be predominant...

10.1038/ncomms12917 article EN cc-by Nature Communications 2016-09-30

Abstract Small ubiquitin-like modifiers (SUMOs) are post-translational modifications that play crucial roles in most cellular processes. While methods exist to study exogenous SUMOylation, large-scale characterization of endogenous SUMO2/3 has remained technically daunting. Here, we describe a proteomics approach facilitating system-wide and vivo identification lysines modified by native SUMO2. Using peptide-level immunoprecipitation enrichment strategy, identify 14,869 sites human cells...

10.1038/s41467-018-04957-4 article EN cc-by Nature Communications 2018-06-19

ADP-ribosylation is a widespread post-translational modification (PTM) with crucial functions in many cellular processes. Here, we describe an in-depth ADP-ribosylome using our Af1521-based proteomics methodology for comprehensive profiling of sites, by systematically assessing complementary proteolytic digestions and precursor fragmentation through application electron-transfer higher-energy collisional dissociation (EThcD) electron transfer (ETD), respectively. Although ETD spectra yielded...

10.1074/mcp.tir119.001315 article EN cc-by Molecular & Cellular Proteomics 2019-02-24

The recent proliferation of novel mass spectrometers such as Fourier transform, QTOF, and OrbiTrap marks a transition into the era precision spectrometry, providing 2 orders magnitude boost to resolution, compared low-precision ion-trap detectors. We investigate peptide de novo sequencing by spectrometry explore some differences when analysis data. demonstrate how dramatically improved performance with paves way for approaches identification that are based on direct sequence lookups, rather...

10.1021/pr060271u article EN Journal of Proteome Research 2006-11-18
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