A5054440360- RNA and protein synthesis mechanisms
- SARS-CoV-2 and COVID-19 Research
- Bacteriophages and microbial interactions
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Cancer-related gene regulation
- RNA regulation and disease
- RNA Research and Splicing
- Animal Virus Infections Studies
- Bacterial Genetics and Biotechnology
- Plant Virus Research Studies
- Virus-based gene therapy research
- Plant Gene Expression Analysis
- Enzyme Structure and Function
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- DNA and Nucleic Acid Chemistry
- Biopolymer Synthesis and Applications
- Metabolism, Diabetes, and Cancer
- Insect Pest Control Strategies
- Insect Utilization and Effects
- Exercise and Physiological Responses
Novo Nordisk (Denmark)
2017-2024
Novo Nordisk (United Kingdom)
2020
Recombinant Technologies (United States)
2020
University of Copenhagen
2011-2017
Lund University
2010
University of Oxford
2008
Genomics (United Kingdom)
2008
Uppsala University
1999-2006
Osaka University
2002
To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its functionality, focusing on insulin secretion, proliferation, apoptosis ER stress, with objective to assess potential screening platform identification of novel anti-diabetic drug candidates.EndoC-βH1 was transplanted into mice validation in vivo functionality. Insulin secretion evaluated cultured monolayer pseudoislets, well diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, stress responses...
Abstract Globally, the COVID-19 pandemic has had extreme consequences for healthcare system and led to calls diagnostic tools monitor understand transmission, pathogenesis, epidemiology, as well evaluate future vaccination strategies. In this study, we have developed novel, our knowledge, flexible ELISA-based assays specific detection of human SARS-CoV-2 Abs against receptor-binding domain, including an Ag sandwich ELISA relevant large population screening three isotype-specific in-depth...
Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from humans to animals has been reported for many domesticated species, including farmed minks. The identification novel spike gene mutations appearing in minks raised major concerns about potential immune evasion and challenges the global vaccine strategy. One genetic variant, known as "cluster five," arose among Denmark resulted a complete shutdown world's largest mink production. However, functional properties this new...
NAC (NAM/ATAF/CUC) plant transcription factors regulate essential processes in development, stress responses and nutrient distribution important crop model plants (rice, Populus, Arabidopsis), which makes them highly relevant the context of optimization bioenergy production. The structure DNA-binding domain ANAC019 has previously been determined by X-ray crystallography, revealing a dimeric predominantly β-fold structure, but mode binding to cognate DNA remained elusive. In present study,...
Dynamic methylations and demethylations of histone lysine residues are important for gene regulation facilitated by methyltransferases demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2-specific demethylase belonging to the JmjC domain-containing family (JHDMs). Several studies have linked KDM5B breast, prostate skin cancer, highlighting its potential as a drug target. However, most inhibitor focused on other JHDMs, inhibitors remain be explored. Here, we report expression,...
Abstract Tools to monitor SARS-CoV-2 transmission and immune responses are needed. We present a neutralization ELISA determine the levels of Ab-mediated virus preclinical model focused immunization strategy. The is strongly correlated with elaborate plaque reduction test (ρ = 0.9231, p < 0.0001). potency convalescent sera correlates IgG titers against receptor-binding domain (RBD) spike 0.8291 0.8297, respectively; 0.0001) lesser extent protein N 0.6471, vaccine NMRI mice models using...
The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases many European countries. incidence domination likely due to a fitness advantage that could be driven by receptor-binding domain (RBD) residue change (N501Y), which also independently other variants of concern such as beta/B.1.351 gamma/P.1 strains. Here, we present functional characterization variant show an eightfold...
How low can you go? The natural substrate for the epigenetic regulators PHF8, JmjD2A, and JmjD2C (lysine demethylases), a peptide consisting of 39 amino acid residues, be truncated to 14, 8, 4 acids, respectively, while maintaining catalytic activity (see picture). Inhibitors were prepared by attaching small molecules substrates. Selective inhibition over JmjD2A PHF8 was possible.
Identification of inhibitors histone-lysine demethylase (HDM) enzymes is important because their involvement in the development cancer. An ELISA-based assay was developed for identification HDM KDM4C a natural products library. Based on one hits with affinity low μM range (1, catechol), subset structurally related compounds selected and tested against panel HDMs. In this subset, two (2 10) had comparable affinities towards KDM6A but no effect PHF8. One inhibitor restored H3K9me3 levels...
The recent identification and rise to dominance of the P.1 B.1.351 SARS-CoV-2 variants have brought international concern because they may confer fitness advantages. same three positions in receptor-binding domain (RBD) are affected both variants, but where 417 substitution differs, E484K/N501Y co-evolved by convergent evolution. Here we characterize functional immune evasive consequences RBD mutations. E484K N501Y result gain-of-function with two different outcomes: confers a ten-fold...
Posttranslational modifications (PTMs) of the histone H3 tail such as methylation, acetylation and phosphorylation play important roles in epigenetic signaling. Here we study effect some these PTMs on demethylation rates methylated lysine 9 vitro using peptide substrates mimicking H3. Various combinations with other were employed to possible cross-talk effects by comparing enzyme kinetic characteristics. We compared kinetics for truncated demethylases KDM4A KDM4C containing only catalytic...
We have determined the structures of complexes between phage MS2 coat protein and variants replicase translational operator in order to explore sequence specificity RNA-protein interaction. The 19-nt RNA hairpins studied substitutions at two positions that been shown be important for specific binding. At one these positions, -10, which is a bulged adenosine (A) stem wild-type hairpin, were made with guanosine (G), cytidine (C) non-native bases, 2-aminopurine (2AP) inosine (I). other...
To investigate ligand selectivity between the oncogenic KDM4C and tumor repressor protein KDM6A histone demethylases, were enzymatically characterized, subsequently, four compounds tested for inhibitory effects. 2,4-dicarboxypyridine (R)-N-oxalyl-O-benzyltyrosine (3) are both known to bind a close homolog 3 binds in part of cavity that accommodates side chain position 11 3. The inhibition measurements showed significant KDM6A. This demonstrates despite very similar active site topologies,...
Abstract The histone demethylase PHF8 catalyzes demethylation of mono‐ and di‐methylated Lys9 on H3 (H3K9me1/2), is a transcriptional activator involved in the development cancer. Affinity specificity towards H3K9me2 affected by interaction with both catalytic domain PHD reader domain. latter specifically recognizes tri‐methylated Ly4 H3. A fragment tail Lys4 was used as template for structure‐based design cyclic, cell‐penetrating peptide that exhibits micromolar binding affinity to...
Wie weit kann man gehen? Das natürliche Substrat der epigenetischen Regulatoren PHF8, JmjD2A und JmjD2C (Lysindemethylasen), ein aus 39 Aminosäuren bestehendes Peptid, auf 14, 8 bzw. 4 gekürzt werden, ohne dass die katalytische Aktivität verlorengeht (siehe Bild). Inhibitoren wurden hergestellt, indem kleine Moleküle an gekürzten Substrate angefügt wurden. Eine selektive Inhibierung von gegenüber PHF8 war möglich. Detailed facts of importance to specialist readers are published as...
Three investigators, with varying levels of experience, independently built and refined the structure Escherichia coli ribokinase at 2.6 A resolution. At end refinement/rebuilding processes models had essentially converged, although each its own particular pattern remaining errors. The subsequent refinement same 1.8 resolution allowed an overall quality check lower models, analysis which graphics-based tools were generally most efficient in locating these Criteria are useful application...
Abstract SARS-CoV-2 transmission from humans to animals has been reported for many domesticated species, including cats, dogs and minks. Identification of novel spike gene mutations appearing in minks raised major concerns about potential immune evasion challenges the global vaccine strategy. The genetic variant, known as “cluster-five”, arose among farmed Denmark resulted a complete shutdown world’s largest mink production. However, functional properties this new variant are not...
Abstract Globally, the COVID-19 pandemic has had extreme consequences for healthcare system and calls diagnostic tools to monitor understand transmission, pathogenesis epidemiology, as well evaluate future vaccination strategies. Here we have developed novel flexible ELISA-based assays specific detection of SARS-CoV-2 antibodies against receptor-binding domain (RBD): An antigen sandwich-ELISA relevant large population screening three isotype-specific in-depth diagnostics. Their performance...