A5006953602- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Lipid Membrane Structure and Behavior
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- Nanoparticle-Based Drug Delivery
- Infant Nutrition and Health
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Immune Response and Inflammation
- Glioma Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Glycosylation and Glycoproteins Research
- Protein Structure and Dynamics
- Cell Image Analysis Techniques
- Metabolomics and Mass Spectrometry Studies
- Erythrocyte Function and Pathophysiology
- Polydiacetylene-based materials and applications
- Gut microbiota and health
- Polyamine Metabolism and Applications
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Probiotics and Fermented Foods
University of Victoria
2020-2024
Genome British Columbia
2020-2024
University of Calgary
1999-2012
Ontario Genomics
2012
Centre National de la Recherche Scientifique
2010
Unit of Virus Host Cell Interactions
2010
Université Joseph Fourier
2010
Western University
2007-2008
European Molecular Biology Laboratory
2004
University of Pittsburgh
2001
The HIV-1 envelope glycoprotein (Env) composed of the receptor binding domain gp120 and fusion protein subunit gp41 catalyzes virus entry is a major target for therapeutic intervention neutralizing antibodies. Env interactions with cellular receptors trigger refolding gp41, which induces close apposition viral membranes leading to membrane fusion. energy released during used overcome kinetic barrier drives reaction. Here, we report crystal structure at 2 A resolution complete extracellular...
The three human β-defensins, HBD1–3, are 33–47-residue, cationic antimicrobial proteins expressed by epithelial cells. All have broad spectrum activity, with HBD3 consistently being the most potent. Additionally, has significant bactericidal activity against Gram-positive <i>Staphylococcus aureus</i> at physiological salt concentrations. We compared multimeric state of β-defensins using NMR diffusion spectroscopy, dynamic and static light scattering, analysis migration on a native gel....
The interaction of several tryptophan (Trp)-rich cationic antimicrobial peptides with membranes was investigated. These included tritrpticin, indolicidin, lactoferricin B (Lfcin B), and a shorter fragment (LfcinB 49 ). average environment the Trp residues these assessed from their fluorescence properties, both wavelength maximal emission as well red edge effect. insertion into vesicles differing composition examined using quenching fluorescence, soluble acrylamide nitroxide-labelled...
The membrane-proximal tryptophan-rich region of the HIV transmembrane glycoprotein, gp41, plays an important role in membrane fusion reaction. Using NMR spectroscopy, we have studied tertiary structure a synthetic 19-residue amidated peptide (NH2-KWASLWNWFNITNWLWYIK-CONH2) corresponding to this membrane-mimetic environments. Initial experiments sodium dodecyl sulfate/H2O micelles and trifluoroethanol gave poor results, because low solubility. However, dodecylphosphocholine micelles, obtained...
Tritrpticin is a member of the cathelicidin family, group diverse antimicrobial peptides found in neutrophil granules. The three Trp and four Arg residues sequence VRRFPWWWPFLRR make this Trp-rich cationic peptide. structure tritrpticin bound to membrane-mimetic sodium dodecyl sulfate micelles has been determined using conventional two-dimensional NMR methods. It forms two adjacent turns around Pro residues, distinct fold for peptide-membrane interaction. first turn involves 4-7, followed...
Lactoferricin B (LfcinB) is a 25‐residue antimicrobial peptide released from bovine lactoferrin upon pepsin digestion. The center of LfcinB consists six residues (RRWQWR‐NH 2 ), and it possesses similar bactericidal activity to LfcinB. structure the six‐residue bound sodium dodecyl sulfate (SDS) micelles has been determined by NMR spectroscopy molecular dynamics refinement. adopts well defined amphipathic when SDS with Trp sidechains separated Arg residues. Additional evidence demonstrates...
The powerful antimicrobial properties of bovine lactoferricin (LfcinB) make it attractive for the development new agents. An 11-residue linear peptide portion LfcinB has been reported to have similar activity itself, but with lower hemolytic activity. membrane-binding and membrane-perturbing this were studied together an amidated synthetic version added disulfide bond, which was designed confer increased stability possibly cytotoxic peptides measured against Staphylococcus aureus Escherichia...
Abstract Mouse is the mammalian model of choice to study human health and disease due its size, ease breeding natural occurrence conditions mimicking pathology. Here we design validate multiple reaction monitoring mass spectrometry (MRM-MS) assays for quantitation 2118 unique proteins in 20 murine tissues organs. We provide open access technical aspects these enable their implementation other laboratories, demonstrate suitability proteomic profiling mice by measuring normal protein...
A number of physicochemical characteristics have been described which contribute to the biological activity antimicrobial peptides. This information was used design a novel peptide sequence by using an intrinsically inactive membrane-associated derived from HIV glycoprotein, gp41, as starting scaffold. corresponds tryptophan-rich membrane-proximal region is known interact at interfacial viral membrane and adopts helical structure in presence lipids. Three synthetic peptides were designed...
Abstract Background: Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies. Materials Methods: We used Mendelian randomization (MR) screen 207 metabolites for their role cancer predisposition using independent genome-wide association studies (GWAS) blood metabolite levels (n = 7,824) 29,266 cases/56,450 controls). A nested case–control study (656 cases 1,296 matched...
: Resistant starches, such as high-amylose maize starch and resistant potato (RPS), have prebiotic effects that are linked to improved metabolism at >15 g/day, but the lower doses not been reported.
Histamine from our diet or gut microbes can trigger gastrointestinal disturbances, and resistant potato starch (RPS) has previously been shown to alleviate these symptoms while increasing levels of health-associated bacteria such as Akkermansia through unknown mechanisms. Post hoc exploratory metabolomic analysis serum amino acid, amine, carnitine metabolites in participants consuming 3.5 g/day RPS placebo (n = 48) was performed using liquid chromatography-mass spectrometry determine whether...
Abstract Chemoresistance is a major clinical challenge in the management of glioblastoma (GBM) Temozolomide (TMZ) chemotherapeutic drug choice for GBM; however, therapeutic effect TMZ limited due to development resistance. Recapitulating GBM chemoresistance controlled environment thus essential understanding mechanism chemoresistance. Herein, we present hybrid microphysiological model chemoresistant GBM-on-a-chip (HGoC) by directly co-culturing TMZ-resistant spheroids with healthy neurons...
Cucurbit[7]uril was used to form non-covalent complexes with low-molecular-weight quaternary-ammonium compounds for their indirect analysis by MALDI-MS. By shifting the ion signals a higher and interference-free mass region, distributions of neurine, choline, phosphocholine in rat brain were visualized MALDI imaging high selectivity good sensitivity.
We investigated the effect of homogenization strategy and protein precipitation on downstream quantitation using multiple reaction monitoring mass spectrometry (MRM-MS). Our objective was to develop a workflow capable processing disparate tissue types with high throughput, minimal variability, maximum purity. Similar abundances endogenous proteins were measured in nine different mouse tissues regardless method used; however, had strong positive effects several targets. The best throughput...
Abstract We proteotyped blood plasma from 30 mouse knockout strains and corresponding wild-type mice the International Mouse Phenotyping Consortium. used targeted proteomics with internal standards to quantify 375 proteins in 218 samples. Our results provide insights into manifested effects of each gene at proteome level. first investigated possible contamination by erythrocytes during sample preparation labeled, one case, up 11 differential as erythrocyte originated. Second, we showed that...
Abstract Chemoresistance is a major clinical challenge in management of glioblastoma (GBM). Temozolomide (TMZ) the chemotherapeutic drug choice for GBM; however, therapeutic effect TMZ limited due to development resistance. Recapitulating GBM chemoresistance controlled environment thus essential understanding mechanism chemoresistance. Herein, we present hybrid microphysiological model chemoresistant GBM-on-a-chip (HGoC) by directly co-culturing TMZ-resistant spheroids with healthy neurons...