- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Fungal and yeast genetics research
- Bacterial Genetics and Biotechnology
- Vibrio bacteria research studies
- Genetics, Bioinformatics, and Biomedical Research
- Genomics and Chromatin Dynamics
- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- RNA and protein synthesis mechanisms
- Scientific Computing and Data Management
- Chromosomal and Genetic Variations
- Genomics and Phylogenetic Studies
- interferon and immune responses
- Pneumonia and Respiratory Infections
- MicroRNA in disease regulation
- RNA Research and Splicing
- Plant Molecular Biology Research
- CRISPR and Genetic Engineering
- Retinal Development and Disorders
- Antibiotic Resistance in Bacteria
- Viral gastroenteritis research and epidemiology
- RNA regulation and disease
- RNA modifications and cancer
- Fermentation and Sensory Analysis
Trinity College Dublin
2016-2025
Simon Fraser University
2004-2009
University of Saskatchewan
2008
The Arabidopsis genome contains numerous large duplicated chromosomal segments, but the different approaches used in previous analyses led to interpretations regarding number and timing of ancestral large-scale duplication events. Here, using more appropriate methodology a recent version sequence annotation, we investigate scale segmental duplications . We protein similarity searches detect blocks genome, level synonymous substitution between genes estimate relative ages containing them,...
Abstract The sole human cathelicidin peptide, LL-37, has been demonstrated to protect animals against endotoxemia/sepsis. Low, physiological concentrations of LL-37 (≤1 μg/ml) were able modulate inflammatory responses by inhibiting the release proinflammatory cytokine TNF-α in LPS-stimulated monocytic cells. Microarray studies established a temporal transcriptional profile and identified differentially expressed genes monocytes presence or absence LL-37. significantly inhibited expression...
Bacterial transcriptional networks consist of hundreds transcription factors and thousands promoters. However, the true complexity in a bacterial pathogen effect environments encountered during infection remain to be established. We present simplified approach for global promoter identification bacteria using RNA-seq-based transcriptomic analyses 22 distinct infection-relevant environmental conditions. Individual RNA samples were combined identify most 3,838 Salmonella enterica serovar...
More than 50 y of research have provided great insight into the physiology, metabolism, and molecular biology Salmonella enterica serovar Typhimurium (S. Typhimurium), but important gaps in our knowledge remain. It is clear that a precise choreography gene expression required for infection, basic genetic information such as global locations transcription start sites (TSSs) has been lacking. We combined three RNA-sequencing techniques two sequencing platforms to generate robust picture S....
Article2 September 2008Open Access InnateDB: facilitating systems-level analyses of the mammalian innate immune response David J Lynn Corresponding Author Department Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada Centre for Microbial Diseases Immunity Research, University Vancouver, Search more papers by this author Geoffrey L Winsor Calvin Chan Nicolas Richard Matthew R Laird Aaron Barsky Computer Science, Jennifer Gardy Fiona M Roche Timothy...
A variety of innate immune responses and functions are dependent on time day, many inflammatory conditions associated with dysfunctional molecular clocks within cells. However, the functional importance these has yet to be fully characterized. NRF2 plays a critical role in system, limiting inflammation via reactive oxygen species (ROS) suppression direct repression proinflammatory cytokines, IL-1β IL-6. Here we reveal that core clock protein, BMAL1, controls mRNA expression Nrf2 E-box...
The response to an innate immune challenge is conditioned by the time of day, but molecular basis for this remains unclear. In myeloid cells, there a temporal regulation induction lipopolysaccharide (LPS) proinflammatory microRNA miR-155 that correlates inversely with levels BMAL1. BMAL1 in lineage inhibits activation NF-κB and protects mice from LPS-induced sepsis. Bmal1 has two miR-155-binding sites its 3'-UTR, and, LPS, binds these target sites, leading suppression mRNA protein humans....
Salmonella enterica serovar Typhimurium is arguably the world's best-understood bacterial pathogen. However, crucial details about genetic programs used by bacterium to survive and replicate in macrophages have remained obscure because of challenge studying gene expression intracellular pathogens during infection. Here, we report use deep sequencing (RNA-seq) reveal transcriptional architecture activity infection murine macrophages, providing new insights into strategies pathogen a...
Abstract Background Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity nervous system development. Here we catalogue all the extracellular LRR (eLRR) worms, flies, mice humans. We use convergent evidence from several transmembrane-prediction motif-detection programs, customised algorithm, LRRscan, to identify eLRR proteins, hierarchical clustering method based...
We know a great deal about the genes used by model pathogen Salmonella enterica serovar Typhimurium to cause disease, but less global gene regulation. New tools for studying transcripts at single nucleotide level now offer an unparalleled opportunity understand bacterial transcriptome, and expression of small RNAs (sRNA) coding responsible establishment infection. Here, we define transcriptomes 18 mutants lacking virulence-related regulatory systems that modulate SPI1 SPI2 Type 3 secretion...
Leptospirosis, an emerging zoonotic disease with worldwide distribution, is caused by spirochetes belonging to the genus Leptospira. More than 500,000 cases of severe leptospirosis are reported annually, >10% these being fatal. Leptospires can survive for weeks in suitably moist conditions before encountering a new host. Reservoir hosts, typically rodents, exhibit little no signs but shed large numbers organisms their urine. Transmission occurs when mucosal surfaces or abraded skin come into...
Significance Invasive nontyphoidal Salmonella disease is a major and previously neglected tropical responsible for an estimated ∼390,000 deaths per year in Africa, largely caused by variant of Typhimurium called ST313. Despite the availability >100,000 genomes, it has proven challenging to associate individual SNPs with pathogenic traits this dangerous bacterium. Here, we used transcriptomic strategy identify single-nucleotide change promoter region crucial phenotypic differences African...
Salmonella enterica is comprised of genetically distinct 'serovars' that together provide an intriguing model for exploring the genetic basis pathogen evolution. Although genomes numerous isolates with broad variations in host range and human disease manifestations have been sequenced, functional links between phenotypic differences among these serovars remain poorly understood. Here, we conduct high-throughput genomics on both generalist (Typhimurium) human-restricted (Typhi Paratyphi A) at...
The severity of bovine respiratory infections has been linked to a variety factors, including environmental and nutritional changes, transportation, social reorganization weaned calves. Fatal infections, however, usually occur when primary viral infection compromises host defences enhances the secondary bacterial infection. This viral-bacterial synergy can by number different mechanisms disease challenge models have developed analyse responses during these infections. A herpesvirus-1 (BHV-1)...
The role played by microRNAs (miRs) as common regulators in physiologic processes such development and various disease states was recently highlighted. Retinitis pigmentosa (RP) linked to RHO (which encodes rhodopsin) is the most frequent form of inherited retinal degeneration that leads blindness, for which there are no current therapies. Little known about cellular mechanisms connect mutations within eventual photoreceptor cell death apoptosis.Global miR expression profiling using...
Abstract Genomic approaches can be exploited to expose the complexities and conservation of biological systems such as immune network across various mammalian species. In this study, temporal transcriptional expression profiles were analyzed in human bovine monocytic cells response TLR-4 agonist, LPS, presence or absence their respective host defense peptides. The cathelicidin peptides, LL-37 myeloid antimicrobial peptide-27 (BMAP-27), are homologs, yet they have diverged notably terms...
The RpoS sigma factor protein of Escherichia coli RNA polymerase is the master transcriptional regulator physiological responses to a variety stresses. This stress response comes at expense scavenging for scarce resources, causing trade-off between tolerance and nutrient acquisition. favors non-functional rpoS alleles in nutrient-poor environments. We used experimental evolution explore how natural selection modifies regulatory network strains lacking when they evolve an osmotically...
We report the first investigation of binding Salmonella enterica LeuO LysR-type transcription regulator to its genomic targets in vivo. Chromatin-immunoprecipitation-on-chip identified 178 sites on chromosome S. serovar Typhimurium strain SL1344. These were distributed across both core and horizontally acquired genome, included housekeeping genes known contribute virulence. Sixty-eight co-bound by global repressor protein, H-NS. Thus, while may function as an H-NS antagonist, these functions...
Salmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and well-characterized ST19 4/74 that gastroenteritis across globe revealed extensive synteny. To understand how 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach involved global gene expression...
Salmonella enterica serovar Typhimurium ( S . Typhimurium) is a zoonotic pathogen that causes diarrheal disease in humans and animals. During salmonellosis, colonizes epithelial cells lining the gastrointestinal tract. has an unusual lifestyle begins within endocytic-derived -containing vacuole (SCV), followed by escape into cytosol, cell lysis bacterial release. The cytosol more permissive environment than SCV supports rapid growth. physicochemical conditions encountered genes required for...
Abstract The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and particular suggest that VWF may play an important regulating inflammatory responses. However, the molecular mechanisms through which exerts its immuno-modulatory effects remain poorly understood. In this study, we report binding...