A5088019956- Insect symbiosis and bacterial influences
- Plant Virus Research Studies
- CRISPR and Genetic Engineering
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Chromosomal and Genetic Variations
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Insect Resistance and Genetics
- Genomics and Chromatin Dynamics
- vaccines and immunoinformatics approaches
- Malaria Research and Control
- Viral Infections and Vectors
- Computational Drug Discovery Methods
- Hepatitis C virus research
- Animal Genetics and Reproduction
- Vector-Borne Animal Diseases
- Epigenetics and DNA Methylation
- Extracellular vesicles in disease
- Renal and related cancers
- RNA and protein synthesis mechanisms
- Metalloenzymes and iron-sulfur proteins
- interferon and immune responses
- Genetics, Aging, and Longevity in Model Organisms
TropIQ Health Sciences
2024-2025
Institute of Molecular Biology
2018-2024
Radboud University Medical Center
2010-2019
Radboud University Nijmegen
2010-2019
Radboud Institute for Molecular Life Sciences
2010-2019
University Medical Center
2018
Institute of Infection and Immunity
2013
The siRNA pathway is an essential antiviral mechanism in insects. Whether other RNA interference pathways are involved defense remains unclear. Here, we report cells derived from the two main vectors for arboviruses, Aedes albopictus and aegypti, production of viral small RNAs that exhibit hallmarks ping-pong piwi-associated (piRNAs) after infection with positive or negative sense viruses. Furthermore, these produce endogenous piRNAs mapped to transposable elements. Our results show mosquito...
RNA viruses in insects are targets of an interference (RNAi)-based antiviral immune response, which viral replication intermediates or dsRNA genomes processed by Dicer-2 (Dcr-2) into small interfering RNAs (vsiRNAs). Whether dsDNA virus infections controlled the RNAi pathway remains to be determined. Here, we analyzed role DNA infection using Drosophila melanogaster infected with Invertebrate iridescent 6 (IIV-6) as a model. We show that Dcr-2 and Argonaute-2 mutant flies more sensitive...
Little is known about the tolerance mechanisms that reduce negative effects of microbial infection on host fitness. Here, we demonstrate histone H3 lysine 9 methyltransferase G9a regulates to virus by shaping response evolutionary conserved Jak-Stat pathway in Drosophila. G9a-deficient mutants are more sensitive RNA and succumb faster than wild-type controls, which was associated with strongly increased dependent responses, but not major differences viral load. Genetic experiments indicate...
Transposable elements are genomic parasites that expand within and spread between genomes
Identification of novel drug targets is a key component modern discovery. While antimalarial are often identified through the mechanism action studies on phenotypically derived inhibitors, this method tends to be time- and resource-consuming. The discoverable target space also constrained by existing compound libraries phenotypic assay conditions. Leveraging recent advances in protein structure prediction, we systematically assessed Plasmodium falciparum genome 867 candidate with evidence...
RNA interference (RNAi) is a major antiviral pathway that shapes evolution of viruses. We show here Nora virus, natural Drosophila pathogen, both target and suppressor RNAi. detected viral small RNAs with signature Dicer-2 dependent interfering in virus infected Drosophila. Furthermore, we demonstrate the VP1 protein contains RNAi suppressive activity vitro vivo enhances pathogenicity recombinant Sindbis an manner. Cricket paralysis (1A) antagonized Argonaute-2 (AGO2) Slicer induced...
Highlights•Tdrd6a is required for Bucky ball mobility within aggregates, and PGC formation•Maternal Tdrd6a coordinates transcript deposition into future PGCs•A dimethylated tri-RG motif in mediates interaction with Tdrd6a•The essential Balbiani body germ cell formationSummaryPhase separation represents an important form of subcellular compartmentalization. However, relatively little known about how the formation or disassembly such compartments regulated. In zebrafish, (Bb) plasm (Gp) are...
Invertebrate RNA viruses are targets of the host interference (RNAi) pathway, which limits virus infection by degrading viral substrates. Several insect encode suppressor proteins to counteract this antiviral response. We recently demonstrated that dsDNA iridescent 6 (IIV-6) induces an RNAi response in Drosophila. Here, we show is suppressed IIV-6-infected cells and mapped activity protein 340R. Using biochemical assays, reveal 340R binds long dsRNA prevents Dicer-2-mediated processing into...
Coevolution of viruses and their hosts may lead to viral strategies avoid, evade, or suppress antiviral immunity. An example is RNA interference (RNAi) in insects: the host RNAi machinery processes double-stranded into small interfering RNAs (siRNAs) replication, whereas insect encode suppressors RNAi, many which inhibit (vsiRNA) production. Yet, studies have analyzed heterologous systems, due lack experimental systems manipulate genome interest, raising questions about vivo functions...
Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated (piRISC) enter a membraneless organelle called nuage cleave their target RNA, which is stimulated by Gtsf proteins. resulting cleavage product gets loaded into an empty protein form new piRISC complex. However, for occur, RNA substrates, Gtsf-piRISC,...
The antiviral RNA interference (RNAi) pathway processes viral double-stranded (dsRNA) into small interfering RNAs (vsiRNA) that guide the recognition and cleavage of complementary target RNAs. In virus infections, replication intermediates, dsRNA genomes or structured have been implicated as Dicer-2 substrates. a recent publication, we demonstrated DNA virus, Invertebrate iridescent 6, is Drosophila RNAi machinery, proposed overlapping converging transcripts base pair to form substrates for...
RNA interference (RNAi) is an indispensable mechanism for antiviral defense in insects, including mosquitoes that transmit human diseases. To escape this system, viruses encode suppressors of RNAi prevent elimination viral RNAs, and thus ensure efficient virus accumulation. Although the first animal Viral Suppressor (VSR) was identified more than a decade ago, molecular basis suppression by these proteins remains unclear. Here, we developed single-molecule fluorescence assay to investigate...
Abstract Transposable elements are genomic parasites that expand within and spread between genomes 1 . Piwi proteins control transposon activity, notably in the germline 2,3 These recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step this crucial genome immunity system. While processing of precursors is an essential process, many molecular details process remain unknown. We identify novel endoribonuclease, PUCH,...
Abstract Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated (piRISC) enter nuage cleave target RNA, which is stimulated by Gtsf proteins. resulting cleavage product gets loaded into an empty protein form a new piRISC complex. However, for occur, it required that RNA substrates, Gtsf-piRISC are all...
<title>Abstract</title> The identification of novel drug targets for the purpose designing small molecule inhibitors is key component to modern discovery. In malaria parasites, discoveries antimalarial have primarily occurred retroactively by investigating mode action compounds found through phenotypic screens. Although this method has yielded many promising candidates, it time- and resource-consuming misses not captured existing compound libraries assay conditions. Leveraging recent...
Summary In recent years, it has become clear that phase separation represents an important class of subcellular compartmentalization. However, relatively little is known about how the formation or disassembly such compartments regulated. zebrafish, Balbiani body (Bb) and germ plasm (Gp) are phase-separated structures essential for cell specification home to many cell-specific mRNAs proteins. Throughout development, these range from a single large aggregate (Bb), dispersed state back...