- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- Origins and Evolution of Life
- RNA Research and Splicing
- Genetics, Bioinformatics, and Biomedical Research
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- Evolution and Genetic Dynamics
- Biochemical and Molecular Research
- Plant Virus Research Studies
- Biomedical and Engineering Education
- Plant Disease Resistance and Genetics
- Biosensors and Analytical Detection
- Molecular Biology Techniques and Applications
- Lymphoma Diagnosis and Treatment
- SARS-CoV-2 detection and testing
- Nutrition, Genetics, and Disease
- Advanced Fluorescence Microscopy Techniques
Simon Fraser University
2016-2025
University of Alberta
2009
Plant Industry
2005
Whitehead Institute for Biomedical Research
1997-2003
Massachusetts Institute of Technology
1994-2003
Canadian Nuclear Laboratories
1996
Atomic Energy (Canada)
1993
The RNA world hypothesis regarding the early evolution of life relies on premise that some sequences can catalyze replication. In support this conjecture, we describe here an molecule catalyzes type polymerization needed for ribozyme uses nucleoside triphosphates and coding information template to extend primer by successive addition up 14 nucleotides—more than a complete turn helix. Its activity is general in terms sequence length RNAs, provided 3′ terminus pairs with template. also quite...
Because RNA lacks strong intrinsic fluorescence, it has proven challenging to track molecules in real time. To address this problem and allow the purification of fluorescently tagged complexes, we have selected a high affinity aptamer called Mango. This binds series thiazole orange (fluorophore) derivatives with nanomolar affinity, while increasing fluorophore fluorescence by up 1,100-fold. Visualization Mango single-molecule microscopy, together injection imaging Mango/fluorophore complex...
The diversity of microRNAs and small-interfering RNAs has been extensively explored within angiosperms by focusing on a few key organisms such as Oryza sativa Arabidopsis thaliana . A deeper division the plants is defined radiation gymnosperms, with latter comprising commercially important conifers. conifers are expected to provide information regarding evolution highly conserved small regulatory RNAs. Deep sequencing provides means characterize quantitatively profile in understudied these....
Abstract Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the proteins available study proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar existing proteins, and be compatible with established live fixed cell protein strategies. Here, we report microfluidics-based selection three new high-affinity Mango fluorogenic aptamers....
Our current understanding of biology suggests that early life relied predominantly on RNA for catalysis and replication. Here, we report the isolation an polymerase ribozyme called B6.61 exhibits superior extension fidelity relative to its progenitor, Round-18 polymerase. The was selected from a mutagenized pool containing ∼ 9 × 10 14 sequence variants through use novel large-scale in vitro compartmentalization system. polymerized all tested primer–template (PT) complexes faster than...
Leishmania use exosomes to communicate with their mammalian hosts and these secreted vesicles appear contribute pathogenesis by delivering protein virulence factors macrophages. In other eukaryotes, were found carry RNA cargo, such as mRNAs small non-coding RNAs, capable of altering recipient cell phenotype. Whether leishmania also contain RNAs which they are able deliver bystander cells is not known. Here, we show that indeed compare contrast the content released donovani braziliensis.We...
Abstract Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis strongly associated with molecular subgroup, although the driver mutations that distinguish two main subgroups remain poorly defined. Through integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes non-coding loci are commonly mutated in DLBCL. Our has identified novel cis -regulatory sites, implicates recurrent 3′ UTR NFKBIZ as a mechanism...
RNA molecules play vital roles in many cellular processes. Visualising their dynamics live cells at single-molecule resolution is essential to elucidate role metabolism. aptamers, such as Spinach and Mango, have recently emerged a powerful background-free technology for live-cell imaging due fluorogenic properties upon ligand binding. Here, we report novel array of Mango II aptamers fixed with high contrast sensitivity. Direct comparison MS2-tdMCP-mCherry dual-labelled mRNAs show marked...
RNA silencing is an evolutionarily conserved process in eukaryotes that represses gene expression by using 21- to 24-nt guide RNAs mediate mRNA cleavage or translational inhibition. Plants have two distinct groups of silencing-associated small (smRNAs): the micro (miRNAs) and interfering (siRNAs). A recent report Yu et al. [Yu, B., Yang, Z., Li, J., Minakhina, S., M., Padgett, R. W., Steward, & Chen, X. (2005) Science 307, 932-935] has shown plant miRNAs are modified at their 3′ termini...
Plants produce small RNAs to negatively regulate genes, viral nucleic acids, and repetitive elements at either the transcriptional or post-transcriptional level in a process that is referred as RNA silencing. While silencing has been extensively studied across different phyla of animal kingdom (e.g., mouse, fly, worm), similar studies plant have focused primarily on angiosperms, thus limiting evolutionary plants. Here we report an unexpected phylogenetic difference size distribution among...
Several RNA aptamers that bind small molecules and enhance their fluorescence have been successfully used to tag track RNAs in vivo, but these genetically encodable tags not yet achieved single-fluorophore resolution. Recently, Mango-II, an binds TO1-Biotin with ∼1 nM affinity enhances its by >1500-fold, was isolated selection from the pool yielded original Mango. We determined crystal structures of Mango-II complex two fluorophores, TO3-Biotin, found despite high affinity, ligands adopt...
The effective tracking and purification of biological RNAs RNA protein complexes is currently challenging. One promising strategy to simultaneously address both these problems develop high-affinity aptamers against taggable small molecule fluorophores. Mango a 39-nucleotide, parallel-stranded G-quadruplex aptamer motif that binds with nanomolar affinity set thiazole orange (TO1) derivatives while inducing 10 3 -fold increase in fluorescence. We find has large its thermal stability upon the...
A processive RNA replicator The World Hypothesis suggests that, before modern life, there were molecules that capable of carrying genetic information and driving chemical reactions, a task gradually replaced by DNA enzymes in biology. Central to this theory is an replicase mediating general replication RNA. Using laboratory evolution, Cojocaru et al. isolated promoter-based polymerase ribozyme analogous modern-day protein polymerases, clamps onto templates increase its processivity, making...
In baker's yeast, genes encoding ribosomal proteins often exist as duplicate pairs, typically with one 'major' paralog highly expressed and a 'minor' less that undergoes controlled expression through reduced splicing efficiency. this study, we investigate the regulatory mechanisms controlling of minor uS4 protein gene (RPS9A), demonstrating its is repressed during vegetative growth but upregulated meiosis. This differential RPS9A mediated by two transcription factors, Rim101 Taf14. Deletion...
A rotational band based on the proton ${\mathit{h}}_{11/2}$ orbital has been observed to high spin (79/2\ensuremath{\Elzxh}) and frequency (\ensuremath{\Elzxh}\ensuremath{\omega}\ensuremath{\simeq}1.0 meV) in nucleus $_{51}^{113}\mathrm{Sb}$. The measured transition quadrupole moment is ${\mathit{Q}}_{0}$=4.4\ifmmode\pm\else\textpm\fi{}0.6 e b, consistent with an axial prolate deformation of ${\mathrm{\ensuremath{\beta}}}_{2}$\ensuremath{\simeq}0.32. large interaction strength...