A5039323966- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- PARP inhibition in cancer therapy
- Bacteriophages and microbial interactions
- Antimicrobial Resistance in Staphylococcus
- DNA and Nucleic Acid Chemistry
- Protein Structure and Dynamics
- Integrated Circuits and Semiconductor Failure Analysis
- Antibiotic Resistance in Bacteria
- RNA modifications and cancer
- Vibrio bacteria research studies
- Hematological disorders and diagnostics
- Machine Learning in Bioinformatics
- Nanoparticle-Based Drug Delivery
- Fungal Infections and Studies
- COVID-19 Clinical Research Studies
- Toxin Mechanisms and Immunotoxins
- Pain Mechanisms and Treatments
- bioluminescence and chemiluminescence research
- Synthesis and Characterization of Heterocyclic Compounds
- Ion-surface interactions and analysis
- Chemistry and Stereochemistry Studies
- SARS-CoV-2 and COVID-19 Research
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
University of Oxford
2020-2021
KU Leuven
2015-2020
Rega Institute for Medical Research
2015-2020
VIB-VUB Center for Structural Biology
2014-2016
Vrije Universiteit Brussel
2011-2016
Viral macrodomains possess the ability to counteract host ADP-ribosylation, a post-translational modification implicated in creation of an antiviral environment via immune response regulation. This brought them into focus as promising therapeutic targets, albeit close homology some human raised concerns regarding potential cross-reactivity and adverse effects for host. Here, we evaluate structure function macrodomain SARS-CoV-2, causative agent COVID-19. We show that it can antagonize...
Abstract Poly(ADP-ribose) polymerase 1 (PARP1) and PARP2 are recruited activated by DNA damage, resulting in ADP-ribosylation at numerous sites, both within PARP1 itself other proteins. Several inhibitors currently employed the clinic or undergoing trials for treatment of various cancers. These drugs act primarily trapping on damaged chromatin, which can lead to cell death, especially cells with repair defects. Although is thought be caused catalytic inhibition PARP-dependent modification,...
Abstract Poly(ADP-ribosyl)ation (PAR) is a versatile and complex posttranslational modification composed of repeating units ADP-ribose arranged into linear or branched polymers. This scaffold linked to the regulation many cellular processes including DNA damage response, alteration chromatin structure Wnt signalling. Despite decades research, principles mechanisms underlying all steps PAR removal remain actively studied. In this work, we synthesise well-defined branch point molecules...
Cytoplasmic aggregation and nuclear depletion of TAR DNA-binding protein 43 (TDP-43) are hallmarks several neurodegenerative disorders. Yet, recapitulating both features in cellular systems has been challenging. Here, we produced amyloid-like fibrils from recombinant TDP-43 low-complexity domain demonstrate that sonicated trigger pathology human cells, including induced pluripotent stem cell (iPSC)-derived neurons. Fibril-induced cytoplasmic inclusions acquire distinct biophysical...
Toxin-antitoxin (TA) modules are pairs of genes essential for bacterial regulation upon environmental stresses. The mazEF module encodes the MazF toxin and its cognate MazE antitoxin. highly dynamic possesses an N-terminal DNA binding domain through which it can negatively regulate own promoter. Despite being one first TA systems studied, transcriptional Escherichia coli remains poorly understood. This paper presents solution structure C-terminal truncated E. a MazE-DNA model with palindrome...
The Staphylococcus aureus genome contains three toxin–antitoxin modules, including one mazEF module, SamazEF. Using an on-column separation protocol we are able to obtain large amounts of wild-type SaMazF toxin. protein is well-folded and highly resistant against thermal unfolding but aggregates at elevated temperatures. Crystallographic nuclear magnetic resonance (NMR) solution studies show a well-defined dimer. Differences in structure dynamics between the X-ray NMR structural ensembles...
Cellular proteomes are distributed in multiple compartments: on DNA, ribosomes, and inside membranes, or they become secreted. Structural properties that allow polypeptides to occupy subcellular niches, particularly after crossing remain unclear. We compared intrinsic extrinsic features cytoplasmic secreted of the Escherichia coli K-12 proteome. between cytoplasmome secretome sharply distinct, such a signal peptide-agnostic machine learning tool distinguishes from proteins with 95.5%...
TRPM3 channels play important roles in the detection of noxious heat and inflammatory thermal hyperalgesia. The activity these ion somatosensory neurons is tightly regulated by µ-opioid receptors through signaling Gβγ proteins, thereby reducing TRPM3-mediated pain. We show here that directly binds to a domain 10 amino acids solve cocrystal structure this together with Gβγ. Using data mutational analysis full-length we pinpoint three their interacting partners Gβ
The pyrimidine-containing Trojan horse antibiotics albomycin and a recently discovered cytidine-containing microcin C analog target the class II seryl- aspartyl-tRNA synthetases (serRS aspRS), respectively. active components of these compounds are competitive inhibitors that mimic aminoacyl-adenylate intermediate. How they effectively substitute for interactions mediated by canonical purine group is unknown. Employing nonhydrolyzable aminoacyl-sulfamoyl nucleosides substituting base with...
mazEF modules encode toxin-antitoxin pairs that are involved in the bacterial stress response through controlled and specific degradation of mRNA. Staphylococcus aureus MazF MazE constitute a unique module under regulation sigB operon. A MazF-type mRNA interferase is combined with an antitoxin unknown fold. Crystals S. (SaMazF) were grown space group P2(1)2(1)2(1). The crystals diffracted to 2.1 Å resolution likely contain two SaMazF dimers asymmetric unit.