A5020511389- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Probiotics and Fermented Foods
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Microscopic Colitis
- Mycobacterium research and diagnosis
- Inflammatory Bowel Disease
- T-cell and B-cell Immunology
- Dietary Effects on Health
Wellcome Sanger Institute
2017-2022
Human health and disease have increasingly been shown to be impacted by the gut microbiota, mouse models are essential for investigating these effects. However, compositions of human microbiotas distinct, limiting translation microbiota research between hosts. To address this, we constructed Mouse Gastrointestinal Bacteria Catalogue (MGBC), a repository 26,640 high-quality microbiota-derived bacterial genomes. This catalog enables species-level analyses mapping functions interest identifying...
Abstract Experimental mouse models are central to basic biomedical research; however, variability exists across genetically identical mice and facilities making comparisons difficult. Whether specific indigenous gut bacteria drive immunophenotypic in of human disease remains poorly understood. We performed a large-scale experiment using 579 laboratory from single animal facility, designed identify the causes widely used dextran sulphate sodium model inflammatory bowel disease. Commonly...
The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans. Here, we used the murine CMV (MCMV) model infection determine that limits herpesvirus-associated pathogenesis without directly preventing virus replication. Instead, promoted cellular immunity through virus-induced lymphopenia, apoptosis-independent NK death, loss T cells. Viral...
The mammalian gut microbiota consists of hundreds anaerobic bacterial species that shape intestinal homeostasis and influence host immune responses. Although the causal roles specific human in health disease are emerging, role indigenous bacteria driving immunophenotypic variability mouse models remains poorly understood. We performed a large-scale experiment using 579 laboratory mice designed to identify validate causes widely used dextran sulphate sodium (DSS) model inflammatory bowel...
Abstract Mouse models are essential for biomedical science and drug discovery, yet it is not known how the bacteria in mouse microbiota – important determinants of phenotypes health disease –affect their relevance to human disease. To interrogate taxonomic functional differences between gut microbiotas, we developed Microbial Genome Collection (MMGC), a compilation 276 genomes from cultured isolates 45,218 metagenome-assembled (MAGs) 1,960 publicly available metagenomes. The MMGC reveals...
ABSTRACT By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation. Specifically, phenotyping 530 knockout mouse lines identified 140 monogenic “hits” (>25%), most which had never hitherto been implicated in immunology. Furthermore, they were conspicuously enriched genes for humans show poor tolerance loss-of-function. The also exposed dense...
Abstract The gut microbiota has been identified as a leading cause of irreproducibility in mouse models, but current resources are insufficient to address this core challenge immunology research. Furthermore, although models central tools for biomedical science, it is not known how the bacteria – important determinants immunological phenotypes affect their ability recapitulate human disease. To better characterise and facilitate its functional taxonomic comparison microbiota, we developed...