A5015123316- Immune Cell Function and Interaction
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- T-cell and B-cell Immunology
- Pediatric health and respiratory diseases
- Molecular Biology Techniques and Applications
- Diabetes and associated disorders
- Influenza Virus Research Studies
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Cell Image Analysis Techniques
- Whipple's Disease and Interleukins
- Biopolymer Synthesis and Applications
- Respiratory and Cough-Related Research
- Chromosomal and Genetic Variations
- Allergic Rhinitis and Sensitization
- Polyamine Metabolism and Applications
- Microtubule and mitosis dynamics
- Animal testing and alternatives
- Psoriasis: Treatment and Pathogenesis
- Neuroinflammation and Neurodegeneration Mechanisms
- Microscopic Colitis
Ottawa Hospital
2025
Ottawa Hospital Research Institute
2025
Trudeau Institute
2007-2020
The Francis Crick Institute
2013-2016
Wellcome Sanger Institute
2012-2015
Immune Regulation (United Kingdom)
2007
Medical Research Council
2004-2007
University of Birmingham
2007
St. Jude Children's Research Hospital
2000
Mutations in whole organisms are powerful ways of interrogating gene function a realistic context. We describe program, the Sanger Institute Mouse Genetics Project, that provides step toward aim knocking out all genes and screening each line for broad range traits. found hitherto unpublished were as likely to reveal phenotypes known genes, suggesting novel represent rich resource investigating molecular basis disease. many unexpected detected only because we screened them, emphasizing value...
Current influenza vaccines elicit Abs to the hemagglutinin and neuraminidase envelope proteins. Due antigenic drift, these must be reformulated annually include proteins predicted dominate in following season. By contrast, vaccination with conserved nucleoprotein (NP) elicits immunity against multiple serotypes (heterosubtypic immunity). NP is generally thought convey protection primarily via CD8 effector mechanisms. However, significant titers of anti-NP are also induced, yet involvement...
Abstract Immunity to heterosubtypic strains of influenza is thought be mediated primarily by memory T cells, which recognize epitopes in conserved proteins. However, the involvement B cells this process controversial. We show study that influenza-specific are insufficient protect mice against a lethal challenge with virulent strain absence cells. contribute protection multiple ways. First, although non-neutralizing Abs themselves do not provide any infection, they reduce weight loss, lower...
Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4), which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by disruption causes proportionate, growth failure that characteristic syndrome unknown. By generating hypomorphic allele Cenpj, we have developed mouse (Cenpj(tm/tm)) recapitulates many clinical features syndrome, including...
Abstract Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, immune system functions, and many other physiological processes. However, mechanisms S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members spinster 2 (Spns2) member major facilitator superfamily known to mediate cell culture. Spns2 was also shown control activities zebrafish vivo play a critical role cardiovascular...
C57BL/6N (B6N) is becoming the standard background for genetic manipulation of mouse genome. The B6N, whose genome very closely related to reference C57BL/6J genome, versatile in a wide range phenotyping and experimental settings large repositories B6N ES cells have been developed. Here, we present series studies showing baseline characteristics fed high-fat diet (HFD) up 12 weeks. We show that HFD-fed mice increased weight gain, fat mass, hypercholesterolemia compared control diet-fed mice....
Abstract The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines next 5 years gain a better understanding of mammalian gene function, provide an invaluable resource scientific community for follow up studies. Phenotyping includes generation standardized biobank paraffin embedded tissues each line, but histopathology is not routinely performed. In collaboration with Pathology Core Centre Modeling Human...
The NF-kappaB family of transcription factors is vital to all aspects immune function and regulation in both the hemopoietic stromal compartments environments. Recent studies mouse models deficient for specific members have revealed critical roles these proteins process secondary lymphoid tissue organogenesis. In this study, we investigate role member NF-kappaB2 lymph node development lymphocyte recruitment. Inguinal nodes nfkappab2(-/-) mice are reduced size cellularity, most notably B cell...
Homozygosity for Slc25a21tm1a(KOMP)Wtsi results in mice exhibiting orofacial abnormalities, alterations carpal and rugae structures, hearing impairment inflammation the middle ear. In humans it has been hypothesised that 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved disease acidaemia. Unexpectedly, no acidaemia-like symptoms were observed animals homozygous despite confirmation this allele reduces Slc25a21 expression 71.3%. To study complete knockout, an allelic series...
Experimental studies suggest that the probiotic yeast Saccharomyces boulardii can mitigate symptoms of inflammatory bowel disease. However, these results are equivocal and S therapy has not gained widespread acceptance in clinical practice. To assess whether therapeutic properties might be improved upon, we engineered to overproduce secrete spermidine, a pro-regenerative natural metabolite. We employed CRISPR gene deletion transposon-mediated integration manipulate expression key enzymes...
Inducible Bronchus Associated Lymphoid Tissue (iBALT) is an ectopic lymphoid tissue that develops in the early postnatal period and associated with severe forms of chronic lung diseases, including obstructive pulmonary disease, rheumatoid hypersensitivity pneumonitis asthma, suggesting iBALT may exacerbate these clinical conditions by promoting larger or faster immune responses lung. However, despite link between pathology formation, role pathogenesis remains unknown. Here we tested whether...
Knowledge of the expression profile a gene is critical piece information required to build an understanding normal and essential functions that gene, any role it may play in development or progression disease. High throughput, large scale efforts are on-going internationally characterise reporter tagged knockout mouse lines. As part effort, we report open access adult resource which 424 genes has been assessed up 47 different organs, tissues sub-structures using lacZ gene. Many specific...
Abstract Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic formed in the lung after pulmonary infection or inflammation. This local structurally similar to conventional secondary organs (SLOs), with separated B and T cell areas, specialized stromal cells dendritic (DCs). The presence of iBALT typically associated pathology advanced disease, particularly patients chronic obstructive disease (COPD), rheumatoid fibrosis infections, suggesting that functions exacerbate immune...