A5041173857- Legionella and Acanthamoeba research
- Vibrio bacteria research studies
- Bacterial biofilms and quorum sensing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Autophagy in Disease and Therapy
- Enzyme Structure and Function
- Hydrocarbon exploration and reservoir analysis
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- Petroleum Processing and Analysis
- RNA and protein synthesis mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Toxoplasma gondii Research Studies
- Olfactory and Sensory Function Studies
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Analytical Chemistry and Chromatography
- Genomics and Phylogenetic Studies
- Genetic Syndromes and Imprinting
- Metabolomics and Mass Spectrometry Studies
- Parasitic Infections and Diagnostics
University of Toronto
2014-2024
MaRS
2021
Public Health Ontario
2012-2017
Tufts University
2009-2012
Howard Hughes Medical Institute
2012
Massachusetts Institute of Technology
2001-2009
Center for Human Genetics
2007-2009
Harvard University
2007-2009
Massachusetts General Hospital
2007-2009
Whitehead Institute for Biomedical Research
2003-2004
Abstract Background Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller species, larger noncoding transcripts are also thought to be highly abundant mammalian cells. To search for large RNAs that might control gene expression or mRNA metabolism, we used Affymetrix arrays identify polyadenylated displaying nuclear enrichment. Results This screen identified no more than three transcripts; XIST , and two unique enriched (...
Abstract Pathogens deliver complex arsenals of translocated effector proteins to host cells during infection, but the extent which these are regulated once inside eukaryotic cell remains poorly defined. Among all bacterial pathogens, Legionella pneumophila maintains largest known set substrates, delivering over 300 via its Type IVB , Icm/Dot translocation system. Backed by a few notable examples effector–effector regulation in L. we sought define this phenomenon through systematic analysis...
ABSTRACT The intracellular bacterial pathogen Legionella pneumophila modulates a number of host processes during growth, including the eukaryotic ubiquitination machinery, which dictates stability, activity, and/or localization large proteins. A L. proteins contain eukaryotic-like motifs typically associated with ubiquitination. Central among these is family five F-box-domain-containing . Each translocated to cytosol by Dot/Icm type IV protein translocation system infection. We show that...
The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer fitness consequences associated foreign gene acquisition. Loss of results in severe growth defects Salmonella, but underlying reasons were unclear. An experimental evolution approach was employed determine which secondary mutations could compensate for loss Salmonella. Six independently derived S. Typhimurium hns mutant strains serially passaged 300 generations...
The Gram-negative bacterium, Legionella pneumophila, is a protozoan parasite and accidental intracellular pathogen of humans. We propose model in which cycling through multiple hosts the environment holds L. pneumophila state evolutionary stasis as broad host-range pathogen. Using an experimental evolution approach, we tested this hypothesis by restricting to growth within mouse macrophages for hundreds generations. Whole-genome resequencing high-throughput genotyping identified several...
Abstract Coagulase-negative staphylococci and Staphylococcus aureus colonize similar niches in mammals conceivably compete for space nutrients. Here, we report that a coagulase-negative staphylococcus, chromogenes ATCC43764, synthesizes secretes 6-thioguanine (6-TG), purine analog suppresses S. growth by inhibiting de novo biosynthesis. We identify 6-TG biosynthetic gene cluster other including epidermidis , pseudintermedius capitis . Recombinant strains harbouring this operon produce and,...
Pseudomonas aeruginosa is an opportunistic pathogen that causes antibiotic-resistant infections with high mortality rates, particularly in immunocompromised individuals and cystic fibrosis patients. Due to the increasing frequency of multidrug-resistant P. infections, there great need for development alternative therapeutics.
Over 20 years ago, two groups independently domesticated Legionella pneumophila from a clinical isolate of bacteria collected during the first recognized outbreak Legionnaires' disease (at 1976 American Legion's convention in Philadelphia). These laboratory strains, JR32 and Lp01, along with their derivatives, have been disseminated to number laboratories around world form cornerstone much research conducted on this important pathogen date. Nevertheless, no exhaustive examination genetic...
Mucosal-associated Escherichia coli are commonly found in inflamed tissues during inflammatory bowel disease (IBD). These bacteria often possess an adherent and invasive phenotype but lack virulence-associated features of well-described intestinal E. pathogens, diverse serology phylotypes, making it difficult to correlate strain characteristics with exacerbations disease.The genome sequences 14 phenotypically assigned adherent-invasive (AIEC) isolates obtained from biopsies patients IBD were...
Legionella pneumophila translocates the largest known arsenal of over 330 pathogenic factors, called "effectors," into host cells during infection, enabling L. to establish a replicative niche inside diverse amebas and human macrophages. Here, we reveal that effectors MavC (Lpg2147) MvcA (Lpg2148) are structural homologs cycle inhibiting factor (Cif) adjacent gene, lpg2149, produces protein directly inhibits their activity. In contrast canonical Cifs, both contain an insertion domain...
CRISPR–Cas is a bacterial and archaeal adaptive immune system that uses short, invader-derived sequences termed spacers to target invasive nucleic acids. Upon recognition of previously encountered invaders, the can stimulate secondary spacer acquisitions, process known as primed adaptation. Previous studies adaptation have been complicated by intrinsically high interference efficiency most systems against bona fide targets. As such, date has studied within context imperfect sequence...
Although only partially understood, multicellular behavior is relatively common in bacterial pathogens. Bacterial aggregates can resist various host defenses and colonize their environment more efficiently than planktonic cells. For the waterborne pathogen Legionella pneumophila, little known about roles of autoaggregation or parameters which allow cell-cell interactions to occur. Here, we determined endogenous exogenous factors sufficient take place L. pneumophila. We show that isolates...
Clustered regularly interspaced short palindromic repeats with CRISPR-associated gene (CRISPR-Cas) systems are widely recognized as critical genome defense that protect microbes from external threats such bacteriophage infection. Several isolates of the intracellular pathogen Legionella pneumophila possess multiple CRISPR-Cas (type I-C, type I-F and II-B), yet targets these remain unknown. With recent observation at least one (II-B) plays a non-canonical role in supporting replication,...
The number of autosomal mammalian genes subject to random monoallelic expression has been limited highly specific the function chemosensory neurons or lymphocytes, making this phenomenon difficult address systematically. Here we demonstrate that asynchronous DNA replication can be used as a marker for identification novel with and identify p120 catenin, gene involved in cell adhesion, belonging class. is widely expressed; its presence available lines allowed us quantitative aspects...
A number of genes in the mammalian genome are expressed from only one two alleles either an imprinted or random manner. Those belonging to class include X-linked subject X inactivation, as well a autosomal genes, including odorant receptors, immunoglobulins, T-cell interleukins, natural killer-cell receptors and pheromone receptors. Monoallelically display unusual property asynchronous replication for those whose transcription is randomly monoallelic, also random. In mice, recent work has...
Legionella pneumophila is the primary etiologic agent of legionellosis, a potentially fatal respiratory illness. Amongst sixteen described L. serogroups, majority clinical infections diagnosed using standard methods are serogroup 1 (Sg1). This high prevalence Sg1 hypothesized to be linked environmental specific advantages and/or increased virulence strains belonging Sg1. The genetic determinants for this remain unknown primarily due limited genomic information available non-Sg1 strains....