A5028345838- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- RNA modifications and cancer
- MicroRNA in disease regulation
- interferon and immune responses
- Evolution and Genetic Dynamics
- RNA and protein synthesis mechanisms
- Parasite Biology and Host Interactions
- Extracellular vesicles in disease
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Animal Genetics and Reproduction
- RNA regulation and disease
- MXene and MAX Phase Materials
- Physiological and biochemical adaptations
- Insect symbiosis and bacterial influences
- Magnesium Alloys: Properties and Applications
- Nematode management and characterization studies
- RNA Interference and Gene Delivery
- Electrocatalysts for Energy Conversion
- Pluripotent Stem Cells Research
- Parasitic Infections and Diagnostics
- Circadian rhythm and melatonin
University of Toronto
2014-2024
University of Massachusetts Chan Medical School
2008-2010
Howard Hughes Medical Institute
2010
Science Oxford
2005
Universidad de Salamanca
2005
Pasadena City College
2005
Bethesda University
2005
Seattle University
2005
United States Department of Justice
2005
Massachusetts Institute of Technology
2002-2005
Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode Caenorhabditis elegans contains an expanded family of 19 functional AGO proteins, many which have not been fully characterized. In this work, we systematically analyzed every C. using CRISPR-Cas9 genome editing introduce GFP::3xFLAG tags. We characterized the expression patterns each throughout development, identified RNA binding complements, and determined effects...
Gametogenesis is a thermosensitive process in numerous metazoans, ranging from worms to man. In Caenorhabditis elegans, variety of RNA-binding proteins that associate with germ-line nuage (P granules), including the Piwi-clade argonaute PRG-1, have been implicated maintaining fertility at elevated temperature. Here we describe role two AGO-class paralogs, alg-3 (T22B3.2) and alg-4 (ZK757.3), promoting thermotolerant male fertility. A rescuing GFP::alg-3 transgene localized P granules...
Argonaute (AGO) proteins interact with distinct classes of small RNAs to direct multiple regulatory outcomes. In many organisms, including plants, fungi, and nematodes, cellular RNA-dependent RNA polymerases (RdRPs) use AGO targets as templates for amplification silencing signals. Here, we show that RdRPs function sequentially produce target endogenous loci in Caenorhabditis elegans . We DCR-1, the RdRP RRF-3, dsRNA-binding protein RDE-4 are required biogenesis 26-nt a 5′ guanine (26G-RNAs)...
Extracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here, we describe a Argonaute protein (exWAGO) that secreted in extracellular vesicles (EVs) released by the gastrointestinal nematode Heligmosomoides bakeri, at multiple copies per EV. Phylogenetic gene expression analyses demonstrate exWAGO orthologues highly conserved abundantly expressed related...
The EBNA1 protein of Epstein-Barr virus (EBV) plays multiple roles in EBV latent infection, including altering cellular pathways relevant for cancer. Here we used microRNA (miRNA) cloning coupled with high-throughput sequencing to identify the effects on miRNAs two nasopharyngeal carcinoma cell lines. affected a small percentage both lines, particular, upregulating let-7 family miRNAs, let-7a. let-7a were verified by demonstrating that silencing EBV-positive carcinomas downregulated...
Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify conserved helicase Aquarius/EMB-4 as direct essential link between small pathways transcriptional machinery Caenorhabditis elegans. Aquarius physically interacts with germline HRDE-1. is required initiate small-RNA-induced heritable HRDE-1...
Parental infection can result in the production of offspring with enhanced immunity phenotypes. Critically, mechanisms underlying inherited are poorly understood. Here, we show that Caenorhabditis elegans infected intracellular microsporidian parasite N. parisii produce progeny resistant to microsporidia infection. We determine kinetics response and intergenerational prevents host-cell invasion by Nematocida enhances survival bacterial pathogen Pseudomonas aeruginosa demonstrate is induced...
The Caenorhabditis elegans genome encodes nineteen functional Argonaute proteins that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact csr-1 locus two isoforms. These isoforms differ by an additional 163 amino acids present in N-terminus of CSR-1a. Using CRISPR-Cas9 editing introduce GFP::3xFLAG into long (CSR-1a) and short...
CRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control Cas9 activity so that the timing, tissue specificity, and accuracy editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors CRISPR-Cas systems, well suited purpose. A number anti-CRISPR proteins have been shown to potently inhibit subgroups but their maximal inhibitory is generally restricted specific homologs....
Chorion gene amplification in the ovaries of Drosophila melanogaster is a powerful system for study metazoan DNA replication vivo. Using combination high-resolution confocal and deconvolution microscopy quantitative realtime PCR, we found that initiation elongation occur during separate developmental stages, thus permitting analysis these two phases Bromodeoxyuridine, origin recognition complex, factors minichromosome maintenance proteins (MCM)2–7 proliferating cell nuclear antigen were...
As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite being preserved among diverse nematodes, conservation divergence function targets pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. briggsae characterize pathway, its their evolution....