A5067322380- Fungal and yeast genetics research
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Photosynthetic Processes and Mechanisms
- DNA Repair Mechanisms
- Biochemical Analysis and Sensing Techniques
- Cardiovascular Function and Risk Factors
- Electric and Hybrid Vehicle Technologies
- Biotin and Related Studies
- Gene Regulatory Network Analysis
- 3D Printing in Biomedical Research
- Microbial Natural Products and Biosynthesis
- Erythrocyte Function and Pathophysiology
- Plant-based Medicinal Research
- Protein Structure and Dynamics
- Cardiomyopathy and Myosin Studies
- Studies on Chitinases and Chitosanases
- Marine Sponges and Natural Products
- Carcinogens and Genotoxicity Assessment
- Bioactive Natural Diterpenoids Research
Concordia University
2018-2022
British Columbia Children's Hospital
2017-2018
University of British Columbia
2012-2018
Child and Family Research Institute
2012-2016
The regulated expansion of membrane contact sites, which mediate the nonvesicular exchange lipids between organelles, requires recruitment additional site proteins. Yeast Vps13 dynamically localizes to contacts that connect ER, mitochondria, endosomes, and vacuoles is recruited prospore in meiosis, but its targeting mechanism unclear. In this study, we identify sorting nexin Ypt35 as a novel adaptor recruits endosomal vacuolar membranes. We characterize an interaction motif N terminus...
Sorting nexins are PX domain-containing proteins that bind phospholipids and often act in membrane trafficking where they help to select cargo. However, the functions cargo specificities of many sorting unknown. Here, a high-throughput imaging screen was used identify new nexin yeast Saccharomyces cerevisiae. Deletions 9 different were screened for mislocalization set green fluorescent protein (GFP)-tagged found at plasma membrane, Golgi or endosomes. This identified 27 require 1 more their...
Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson's disease and spastic ataxia. Recent evidence suggests that different paralogs transport lipids between organelles at membrane contact sites. How isoform is targeted to not known. We have shown localization yeast Vps13 protein membranes requires a conserved six-repeat region, Adaptor Binding (VAB) domain, which binds...
The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, are non-functional, which may due presence of fungal sterol ergosterol instead cholesterol. Here we engineer produce cholesterol and introduce diverse mu, delta, kappa create sensitive biosensors that recapitulate agonist binding profiles antagonist inhibition. Additionally, receptor variants,...
P4-ATPases are a family of putative phospholipid flippases that regulate lipid membrane asymmetry, which is important for vesicle formation. Two yeast flippases, Drs2 and Neo1, have nonredundant functions in the recycling synaptobrevin-like v-SNARE Snc1 from early endosomes. activity needed to form vesicles its own trafficking, suggesting flippase localization linked. However, role Neo1 endosomal not well characterized. To identify novel regulators trafficking at endosomes, we first...
The retromer complex facilitates the sorting of integral membrane proteins from endosome to late Golgi. In mammalian cells, efficient recruitment endosomes requires lipid phosphatidylinositol 3-phosphate (PI3P) as well Rab5 and Rab7 GTPases. However, in yeast, role Rabs recruiting is less clear. We identified novel physical interactions between Saccharomyces cerevisiae VPS9-domain Rab5-family guanine nucleotide exchange factors (GEFs) Muk1 Vps9. Furthermore, we a new yeast VPS9...
Abstract The genetic tractability of the yeast Saccharomyces cerevisiae has made it a key model organism for basic research and target metabolic engineering. To streamline introduction tagged genes compartmental markers with powerful Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) - CRISPR-associated protein 9 (Cas9)-based genome editing tools, we constructed Markerless Yeast Localization Overexpression (MyLO) CRISPR-Cas9 toolkit 3 components: (1) set optimized...
Heterotetrameric adaptor protein complexes are important mediators of cargo sorting in clathrin-coated vesicles. The cell type-specific expression alternate μ chains creates distinct forms AP-1 with altered sorting, but how these subunits confer differential function is unclear. Whereas some studies suggest the specify localization to different cellular compartments, others find that two present same vesicle recognize cargo. Yeast have AP-1, which differ only chain. Here we show variant...
Cells depend on robust DNA damage recognition and repair systems to maintain genomic integrity for survival in a mutagenic environment. In the pathogenic yeast Candida albicans, subset of genes involved response damage-induced genome instability morphological changes has been found regulate virulence. To better understand virulence-linked network, we screened methyl methane sulfonate (MMS) sensitivity within GRACE conditional expression collection identified 56 hits. One these potential...
The polytopic yeast protein Chs3 (chitin synthase III) relies on a dedicated membrane‐localized chaperone, Chs7, for its folding and expression at the cell surface. In absence of forms high molecular weight aggregates is retained in endoplasmic reticulum (ER). Chs7 was reported to be an ER resident protein, but role transport not well characterized. Here, we show that itself exits localizes with bud neck intracellular compartments. We identified mutations C‐terminal cytosolic domain do...
ABSTRACT The genetic tractability of the yeast Saccharomyces cerevisiae has made it a key model organism for basic research and target metabolic engineering. To streamline introduction tagged genes compartmental markers with powerful CRISPR-Cas9-based genome editing tools we constructed Markerless Yeast Localization Overexpression (MyLO) CRISPR-Cas9 toolkit three components: (i) set optimized S. pyogenes Cas9-guide RNA (gRNA) expression vectors five selectable option to either pre-clone or...
ABSTRACT The yeast Saccharomyces cerevisiae is a powerful tool for studying G protein-coupled receptors (GPCRs) as they can be functionally coupled to its pheromone response pathway. However, some exogenous GPCRs, including the mu opioid receptor, are non-functional in yeast, which may due presence of fungal sterol ergosterol instead animal cholesterol. We engineered produce cholesterol and introduced human creating an biosensor capable detecting peptide DAMGO at EC 50 62 nM opiate morphine...
Membrane contact sites are regulated through the controlled recruitment of constituent proteins. Yeast vacuolar protein sorting 13 (Vps13) dynamically localizes to membrane at endosomes, vacuoles, mitochondria, and endoplasmic reticulum under different cellular conditions is recruited prospore during meiosis. Prior our recent work, mechanism for localization was largely unknown. We identified Ypt35 as a novel Vps13 adaptor endosomes nucleus-vacuole junction. Furthermore, we discovered...
Abstract Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson’s disease and spastic ataxia. Recent evidence suggests that different paralogs transport lipids between organelles at membrane contact sites. How isoform is targeted to not known. We have shown localization yeast Vps13 protein membranes requires a conserved six-repeat region, Adaptor Binding (VAB) domain,...