McGill University
Ph.D. candidate
Supervisor: Corinne Maurice
Start: 2018-09-01
End: 2022-09-01
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Project

Investigating bacteriophage-bacteria interactions in inflammatory bowel disease
The gut microbiota is a complex collection of bacteria, viruses, archaea, and various eukarya. As these organisms are important in maintaining immune homeostasis, alterations in the composition of the microbiota have been associated with several diseases, including inflammatory bowel diseases (IBD). Most studies which have investigated the role of the microbiota in IBD have focused specifically on interactions between bacterial communities and the human host. However, this picture remains incomplete, as bacteriophages (phages) occupy the gut at similar abundances to their bacterial hosts. In several ecosystems, phages have been shown to powerful modulators of bacterial community abundance, diversity, and metabolism. Given that phage communities are also imbalanced in IBD, it is thought that they may drive relevant changes in the bacterial community that contribute to IBD progression. We hypothesize that IBD-derived phages differentially modulate bacterial community abundance, diversity, and physiology in comparison to phages derived from healthy individuals. To determine the role of phages on bacterial communities, we will extract phage and bacterial communities from IBD patients and healthy controls. First, bacterial communities from each group will be transplanted to germ-free mice. After a 3 week period of colonization, IBD-derived or healthy-derived phages will be given to these mice. Epifluorescence microscopy and flow cytometry will be used to assess phage and bacterial abundance. SybrGreen staining of bacterial communities combined with flow cytometry will give us readouts of bacterial activity following phage treatment. Bacterial and viral metagenomics on mouse fecal pellets will be used to assess changes to the bacterial community and link phages to their hosts. Together, our data will shed light on the extent to which phages influence bacterial community structure in the context of IBD.

Keywords

Inflammation, Human Gut Microbiota, Bacteriophages

Publications

1- Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System
Sinha, Anshul, Corinne F. Maurice
2019 Mediators of Inflammation

2- PmrC (EptA) and CptA Negatively Affect Outer Membrane Vesicle Production in Citrobacter rodentium
Sinha, Anshul, Sammy Nyongesa, Charles Viau, Samantha Gruenheid, Frédéric J. Veyrier, Hervé Le Moual,
2019 Journal of Bacteriology

3- The role of two branched-chain amino acid transporters inStaphylococcus aureusgrowth, membrane fatty acid composition and virulence
Kaiser, Julienne C., Suranjana Sen, Anshul Sinha, Brian J. Wilkinson, David E. Heinrichs
2016 Molecular Microbiology