A5062503368- Genetics, Aging, and Longevity in Model Organisms
- Helminth infection and control
- Circadian rhythm and melatonin
- Lipid Membrane Structure and Behavior
- Alzheimer's disease research and treatments
- Lysosomal Storage Disorders Research
- Insect and Arachnid Ecology and Behavior
- Physiological and biochemical adaptations
- Cholinesterase and Neurodegenerative Diseases
- Tardigrade Biology and Ecology
- Prion Diseases and Protein Misfolding
- Tryptophan and brain disorders
- Biomedical Research and Pathophysiology
- Mitochondrial Function and Pathology
- Parasites and Host Interactions
- Cellular Mechanics and Interactions
- Monoclonal and Polyclonal Antibodies Research
- Parasite Biology and Host Interactions
- Computational Drug Discovery Methods
University of Toronto
2019-2024
University Health Network
2024
Krembil Research Institute
2024
Toronto Western Hospital
2024
Cellular Research (United States)
2022
York University
2016
How the cuticles of roughly 4.5 million species ecdysozoan animals are constructed is not well understood. Here, we systematically mine gene expression datasets to uncover spatiotemporal blueprint for how chitin-based pharyngeal cuticle nematode Caenorhabditis elegans built. We demonstrate that correctly predicts patterns and functional relevance development. find as larvae prepare molt, catabolic enzymes upregulated genes encode chitin synthase, cross-linkers, homologs amyloid regulators...
Abstract The nematode Caenorhabditis elegans is a bacterivore filter feeder. Through the contraction of worm’s pharynx, bacterial suspension sucked into pharynx’s lumen. Excess liquid then shunted out buccal cavity through ancillary channels made by surrounding marginal cells. We find that many worm-bioactive small molecules ( a.k.a . wactives) accumulate inside cells as crystals or globular spheres. screens for mutants resist lethality associated with one crystallizing wactive we identify...
Mitochondrial dysfunction is one of the leading causes neurological disorders in humans. perturbations lead to adaptive mechanisms that include HIF-1 stabilization, though consequences increased levels following mitochondrial stress remain poorly understood. Using Caenorhabditis elegans, we show a hif-1 loss-of-function mutation confers resistance towards toxin ethidium bromide (EtBr) and suppresses EtBr-induced production ROS. In mammals, PD-related gene DJ-1 known act as redox sensor...
The cuticles of ecdysozoan animals are barriers to material loss and xenobiotic insult. Key this barrier is lipid content, the establishment which poorly understood. Here, we show that p-glycoprotein PGP-14 functions coincidently with sphingomyelin synthase SMS-5 establish a polar within pharyngeal cuticle nematode C . elegans We coincidentally expressed in epithelium surrounds anterior where localizes apical membrane. pgp-14 sms-5 also peak expression at time new synthesis. Loss...
With the increasing prevalence of anthelmintic resistance in animals recorded globally, and threat human helminths, need for novel drugs is greater than ever. Most research aimed at discovering leads relies on high throughput screening (HTS) large libraries synthetic small molecules industrial academic settings West, even though it tropical countries that are most plagued by helminth infections. Tropical countries, however, have advantage possessing a rich flora may yield natural products...
Abstract The nematode worm Caenorhabditis elegans is a bacterivore filter feeder. Through the contraction of worm’s pharynx, bacterial suspension sucked into pharynx’s lumen. Excess liquid then shunted out buccal cavity through ancillary channels that are made from specialized pharyngeal cells called marginal cells. characterization our library worm-bioactive small molecules ( a.k.a. wactives), we found more than one third wactives visibly accumulate inside as crystals or globular spheres....
Abstract Roughly 4.5 million species of ecdysozoan animals repeatedly shed their old cuticle and construct a new one underneath to accommodate growth. How cuticles are constructed is not well understood. Here, we systematically mine gene expression datasets uncover the spatiotemporal blueprint for how chitin-based pharyngeal nematode Caenorhabditis elegans built. We demonstrate that correctly predicts patterns functional relevance development. find as larvae prepare molt, catabolic enzymes...
Abstract Understanding how to pharmacologically manipulate amyloids is an essential step towards managing dozens of amyloid-based human diseases. Here, we present a pipeline that yields small molecule antagonists amyloidogenesis. Screens for molecules perturb the development nematode C. elegans revealed 24 distinct scaffolds crystalize on non-luminal face pharyngeal cuticle. Consistent with amyloid-like nature cuticle, 25% these are known bind nanomolar affinity. The growing crystals...