A5084846822- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Ferroptosis and cancer prognosis
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- Genetics, Aging, and Longevity in Model Organisms
- Gene Regulatory Network Analysis
- Gene expression and cancer classification
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- Genomics and Chromatin Dynamics
- Plant Virus Research Studies
- Cancer, Hypoxia, and Metabolism
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Mass Spectrometry Techniques and Applications
- Metabolism, Diabetes, and Cancer
- Evolution and Genetic Dynamics
- Bacterial Genetics and Biotechnology
- Insect Resistance and Genetics
- Genetic Mapping and Diversity in Plants and Animals
University of Toronto
2013-2023
Donnelly College
2019
Occupational Cancer Research Centre
2016
Princeton University
2006-2013
Institute for Integrative and Experimental Genomics
2010-2013
Mount Sinai Hospital
2013
Lunenfeld-Tanenbaum Research Institute
2013
Hospital for Sick Children
2013
SickKids Foundation
2013
Ontario Institute for Cancer Research
2013
RNA interference (RNAi) was first recognized in Caenorhabditis elegans as a biological response to exogenous double-stranded (dsRNA), which induces sequence-specific gene silencing. RNAi represents conserved regulatory motif, is present wide range of eukaryotic organisms. Recently, we and others have shown that endogenously encoded triggers silencing act through elements the machinery regulate expression protein-coding genes. These small temporal RNAs (stRNAs) are transcribed short hairpin...
Double-stranded RNA induces potent and specific gene silencing through a process referred to as interference (RNAi) or posttranscriptional (PTGS). RNAi is mediated by RNA-induced complex (RISC), sequence-specific, multicomponent nuclease that destroys messenger RNAs homologous the trigger. RISC known contain short (∼22 nucleotides) derived from double-stranded trigger, but protein components of this activity are unknown. Here, we report biochemical purification effector cultured Drosophila...
We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and 350,000 positive interactions. This comprehensive maps interactions essential gene pairs, highlighting genes as densely connected hubs. Genetic profiles enabled assembly of hierarchical model cell function, including modules corresponding to protein complexes pathways, biological processes, cellular compartments. Negative...
RNA interference (RNAi) is a flexible gene silencing mechanism that responds to double-stranded by suppressing homologous genes. Here, we report the characterization of RNAi effector complexes (RISCs) contain small interfering RNAs and microRNAs (miRNAs). We identify two putative RNA-binding proteins, Drosophila homolog fragile X mental retardation protein (FMRP), dFXR, VIG (Vasa intronic gene), through their association with RISC. FMRP, product human locus, regulates expression numerous...
In a diverse group of organisms including plants, Caenorhabditis elegans , Drosophila and trypanosomes, double-stranded RNA (dsRNA) is potent trigger gene silencing. several model systems, this natural response has been developed into powerful tool for the investigation function. Use interference (RNAi) as genetic recently extended to mammalian cells, being inducible by treatment with small, ≈22-nt RNAs that mimic those produced in first step silencing process. Here, we show some cultured...
We present a liquid chromatography−mass spectrometry (LC−MS) method that capitalizes on the mass-resolving power of orbitrap to enable sensitive and specific measurement known unanticipated metabolites in parallel, with focus water-soluble species involved core metabolism. The reversed phase LC method, cycle time 25 min, involves water−methanol gradient C18 column tributylamine as ion pairing agent. MS portion full scans from 85 1000 m/z at 1 Hz 100 000 resolution negative mode stand alone...
Trigenic interactions in yeast link bioprocesses To dissect the genotype-phenotype landscape of a cell, it is necessary to understand between genes. Building on digenic protein-protein interaction network, Kuzmin et al. created trigenic by using synthetic genetic array (see Perspective Walhout). Triple-mutant analyses indicated that majority genes with associations functioned within same biological processes. These converged networks identified landscape. Although overall effects were weaker...
Highlights•Interspecies systems biology paradigm links genetics to metabolites•Vitamin B12 is produced by the Comamonas, but not E. coli, diet•Vitamin affects development, fertility, and propionic acid toxicity•Vitamin accelerates development via SAM metabolismSummaryDiet greatly influences gene expression physiology. In mammals, elucidating effects mechanisms of individual nutrients challenging due complexity both animal its diet. Here, we used an interspecies approach with Caenorhabditis...
The mitochondrial inner membrane contains a large protein complex that functions in organization and formation of contact sites. was variably named the site complex, organizing system, structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify nomenclature term "mitochondrial cristae system" its subunits Mic10 Mic60.
Abstract Glioblastoma (GBM) is a deadly cancer in which stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as promising target GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition suppresses the cohort 46 patient-derived GBM cell cultures, with proneural subtype showing greater sensitivity. We causes widespread disruption splicing across...
The ability of transcriptional activation domains (TADs) to signal ubiquitin-mediated proteolysis suggests an involvement the ubiquitin-proteasome pathway in transcription. To probe this involvement, we asked how ubiquitylation regulates activity a transcription factor containing VP16 TAD. We show that TAD signals through Met30 ubiquitin-ligase and is also required for activate requirement circumvented by fusion ubiquitin activator, demonstrating activator essential activation. propose...
Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The non–Shiga toxin–associated HUS (atypical [aHUS]) has been shown to be a disease complement dysregulation. Mutations in plasma regulators factor H I widely expressed membrane cofactor protein (MCP; CD46) have described recently. This study looked for MCP mutations panel 120 patients with aHUS. In this cohort, approximately 10% aHUS (11 patients;...
Histone deacetylases (HDACs) are important for gene regulation and the maintenance of heterochromatin in eukaryotes.Schizosaccharomyces pombe was used as a model system to investigate functional divergence within this conserved enzyme family.S. has three HDACs encoded by hda1 ؉ , clr3 clr6 genes.Strains mutated these genes have previously been shown display strikingly different phenotypes when assayed viability, chromosome loss, silencing.Here, differences substrate binding pocket identify...
Abstract Background High-throughput cDNA synthesis and sequencing of poly(A)-enriched RNA is rapidly emerging as a technology competing to replace microarrays quantitative platform for measuring gene expression. Results Consequently, we compared full length 2-channel expression in the context differential Because its comparable cost microarray, our study focused on data obtainable from single lane an Illumina 1 G sequencer. We highly replicated microarray experiment profiling two divergent...
Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis inheritance in Saccharomyces cerevisiae. In addition, used perform targeted double-mutant analysis detecting another nine genes synthetic defects biogenesis. This represents an increase of about 25% over previously known...
Abstract Background: The wide availability of genome-scale data for several organisms has stimulated interest in computational approaches to gene function prediction. Diverse machine learning methods have been applied unicellular with some success, but few extensively tested on higher level, multicellular organisms. A recent mouse prediction project (MouseFunc) brought together nine bioinformatics teams applying a diverse array methodologies mount the first large-scale effort predict...
Significance We used the model eukaryote Saccharomyces cerevisiae to investigate which genes are important for survival of heat stress. Previously, this question was addressed by examining turned on mild stress; in study, we examined gene-deletion mutants increased sensitivity lethal This approach reveals that these two sets largely nonoverlapping, demonstrating mutant analysis is a powerful complementary gene-expression analysis. In addition, many identified as involved metabolism or...
Maintaining balanced growth in a changing environment is fundamental systems-level challenge for cellular physiology, particularly microorganisms. While the complete set of regulatory and functional pathways supporting proliferation are not yet known, portions them well understood. In particular, governed by mechanisms that highly conserved from unicellular to multicellular organisms, disruption these processes metazoans major factor development cancer. this paper, we develop statistical...
Despite rapid progress in characterizing the yeast metabolic cycle, its connection to cell division cycle (CDC) has remained unclear. We discovered that a prototrophic batch culture of budding yeast, growing phosphate-limited ethanol medium, synchronizes spontaneously and goes through multiple cycles, whereas fraction cells G1/G0 phase CDC increases monotonically from 90 99%. This demonstrates cycling does not require synchrony carbon-source limitation. More than 3,000 genes, including most...