A5075849428- Gut microbiota and health
- Enzyme Catalysis and Immobilization
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Structure and Function
- HIV Research and Treatment
- Biofuel production and bioconversion
- Toxoplasma gondii Research Studies
- CRISPR and Genetic Engineering
- Clostridium difficile and Clostridium perfringens research
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Child Nutrition and Water Access
- Bacteriophages and microbial interactions
- Legume Nitrogen Fixing Symbiosis
- Protein Structure and Dynamics
- Herpesvirus Infections and Treatments
- Microbial Natural Products and Biosynthesis
- Microbial Community Ecology and Physiology
- Parasitic Infections and Diagnostics
- Escherichia coli research studies
- Dye analysis and toxicity
- RNA modifications and cancer
- Protist diversity and phylogeny
- Transgenic Plants and Applications
Hospital for Sick Children
2018-2025
University of Toronto
2013-2025
SickKids Foundation
2018-2024
Great Ormond Street Hospital
2021
University College London
2021
Canada Research Chairs
2018
University of New Brunswick
2018
The human HD domain protein SAMHD1 is implicated in the Aicardi-Goutières autoimmune syndrome and restriction of HIV-1 replication myeloid cells. Recently, this has been shown to possess dNTP triphosphatase activity, which proposed inhibit response by hydrolyzing cellular dNTPs. Here, we show that purified full-length also possesses metal-dependent 3'→5' exonuclease activity against single-stranded DNAs RNAs vitro. In double-stranded substrates, preferentially cleaved 3'-overhangs RNA...
Esterases receive special attention because of their wide distribution in biological systems and environments importance for physiology chemical synthesis. The prediction esterases' substrate promiscuity level from sequence data the molecular reasons why certain such enzymes are more promiscuous than others remain to be elucidated. This limits surveillance space esterases potentially leading new versatile biocatalysts insights into role cellular function. Here, we performed an extensive...
The continuous growth of global plastics production, including polyesters, has resulted in increasing plastic pollution and subsequent negative environmental impacts. Therefore, enzyme-catalyzed depolymerization synthetic polyesters as a recycling approach become focus research. In this study, we screened over 200 purified uncharacterized hydrolases from metagenomes sequenced microbial genomes identified at least 10 proteins with high hydrolytic activity against polyesters. These include the...
Abstract Metagenomics has made accessible an enormous reserve of global biochemical diversity. To tap into this vast resource novel enzymes, we have screened over one million clones from metagenome DNA libraries derived sixteen different environments for carboxylesterase activity and identified 714 positive hits. We validated the esterase 80 selected genes, which belong to 17 protein families including unknown cyclase-like proteins. Three metagenomic enzymes exhibited lipase activity, seven...
Carboxylic acid reductases (CARs) selectively reduce carboxylic acids to aldehydes using ATP and NADPH as cofactors under mild conditions. Although CARs attracts significant interest, only a few enzymes have been characterized date, whereas the vast majority of yet be examined. Herein authors report that 12 bacterial reduces broad range bifunctional containing oxo-, hydroxy-, amino-, or second carboxyl groups with several showing activity toward 4-hydroxybutanoic (4-HB) adipic acids. These...
Abstract Commensal protists and gut bacterial communities exhibit complex relationships, mediated at least in part through host immunity. To improve our understanding of this tripartite interplay, we investigated community functional dynamics between the murine protist Tritrichomonas musculus intestinal bacteria healthy B-cell-deficient mice. We identified dramatic, protist-driven remodeling resident microbiome growth activities, parallel with changes, which were accelerated absence B cells....
Cas4 proteins, a core protein family associated with the microbial system of adaptive immunity CRISPR, are predicted to function in adaptation step CRISPR mechanism. Here we show that SSO0001 from archaeon Sulfolobus solfataricus has metal-dependent endonuclease and 5'→3' exonuclease activities against single-stranded DNA, as well ATP-independent DNA unwinding activity toward double-stranded DNA. The crystal structure revealed decameric toroid formed by five dimers each protomer containing...
Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders has led ongoing debate over their administration. To better understand impact on gut microbiota, we analyse the bacterial, protozoal, fungal helminth communities stool samples collected from subset 80 children at 12 24 months age, previously enrolled into large cluster randomized controlled trial micronutrient...
Abstract Tritrichomonas musculus is a commensal protist colonizing the large intestine of laboratory mice. Parasite colonization reshapes gut microbiome and modulates mucosal immunity. This parasite refractory to axenic culture. In order facilitate functional genomic investigations we assembled 193.49 Mbp high quality reference genome from FACS-purified parasites recovered monocolonized mice using an integrated approach that combined long-read (PacBio Oxford Nanopore) sequencing technologies...
The shrimp Rimicaris exoculata dominates the fauna in deep-sea hydrothermal vent sites along Mid-Atlantic Ridge (depth, 2,320 m). Here, we identified and biochemically characterized three carboxyl esterases from microbial communities inhabiting R. gill that were isolated by naive screens of a chamber metagenomic library. These proteins exhibit low to moderate identity known esterase sequences (≤52%) each other (11.9 63.7%) appear have originated unknown species or genera Proteobacteria...
Clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated Cas proteins comprise a prokaryotic RNA-guided adaptive immune system that interferes with mobile genetic elements, such as plasmids phages. The type I-E CRISPR interference complex Cascade from Escherichia coli is composed of five different 61-nt-long guide RNA (crRNA). crRNAs contain unique 32-nt spacer flanked by repeat-derived 5′ handle (8 nt) 3′ (21 nt). part crRNA directs to DNA targets. Here, we...
Due to a lack of systematic diagnostics, our understanding the diversity and role eukaryotic microbiota in human health is limited. While studies have shown fungal communities be significant modulators health, information on prevalence taxa such as protozoa helminths has been limited small number species for which targeted molecular diagnostics are available. To probe microbes their relationships with other members microbiota, we applied silico experimental approaches design novel...
Maf (for multicopy associated filamentation) proteins represent a large family of conserved implicated in cell division arrest but whose biochemical activity remains unknown. Here, we show that the prokaryotic and eukaryotic exhibit nucleotide pyrophosphatase against 5-methyl-UTP, pseudo-UTP, 5-methyl-CTP, 7-methyl-GTP, which most abundant modified bases all organisms, as well canonical nucleotides dTTP, UTP, CTP. Overexpression protein YhdE E. coli cells increased intracellular levels dTMP...
Immunoglobulin (Ig) A supports mucosal immune homeostasis and host–microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial microbes in induction IgA remains elusive. Here, we demonstrate that permanent colonization with protozoan Tritrichomonas musculis (T.mu) promotes T cell–dependent, class-switch recombination, intestinal accumulation IgA-secreting plasma cells (PC). T.mu specifically drives expansion follicular helper a...
One of the final steps in morphogenetic pathway phage λ is packaging a single genome into preformed empty head structure. In addition to terminase enzyme, chaperone, FI protein (gpFI), required for efficient DNA packaging. this study, we demonstrate an interaction between gpFI and major protein, gpE. Amino acid substitutions that reduced strength also decreased biological activity gpFI, implying binding essential function gpFI. We show two-domain C-terminal domain responsible activity. Using...
During chronic infection, the single celled parasite, Toxoplasma gondii , can migrate to brain where it has been associated with altered dopamine function and capacity modulate host behavior, increasing risk of neurocognitive disorders. Here we explore alterations in dopamine-related behavior a new mouse model based on stimulant (cocaine)-induced hyperactivity. In combination cocaine, infection resulted heightened sensorimotor deficits impairment prepulse inhibition response, which are...
Abstract Commensal protists and gut bacterial communities exhibit complex relationships, mediated at least in part through host immunity. To improve our understanding of this tripartite interplay, we investigated community functional dynamics between the murine protist Tritrichomonas musculus ( T. mu ) intestinal bacteria healthy B cell-deficient mice. We identified dramatic, protist-driven remodeling resident microbiome growth activities, parallel with changes, accelerated absence cells....
ABSTRACT Immunoglobulin(Ig) A antibodies are the most abundant supporting mucosal immune homeostasis and host-microbiota interactions. Driven by gut commensal microbes, IgA-secreting plasma cells (PC) differentiate through T cell-dependent (Td) or cell independent (Ti) mechanisms. While bacteria within microbiota known for their ability to promote IgA, role of non-bacterial microbes on induction IgA remains elusive. Here, we demonstrate that permanent colonization with protozoan...