The Connaught Global Challenge award supports University of Toronto-based research with a focus on addressing the biggest challenges in the international community, and the GEMINI project is doing exactly that. Led by Drs. Jennifer Gommerman and Kenneth Croitoru, the Generational differences in Environmental exposures caused by Migration: Impact on Incidence of Inflammatory disease (GEMINI) is attempting to understand how migration from South Asian countries (including: Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka) to Toronto can affect the gut microbiota and the risk of developing chronic disease. Specifically, the team is interested in investigating the differences in the microbiome between first generation (those who migrated from South Asia) and second generation (the offspring born in Canada) South Asian Canadians. These microbial differences may be associated with the differential incidence of chronic inflammatory diseases observed between the generations of South Asian Canadians. The Connaught Fund bolsters multi-disciplinary and international collaboration; as such, a symposium was held in November that brought together world-renowned leaders in the fields of microbiota, genetics and inflammation to discuss and provide input on the GEMINI project.

Image Credit: Patricia Kambitsch
Image Credit: Patricia Kambitsch

MICROBIOME
The first day began with Dr. Eytan Wine (University of Alberta) describing how gut microbes are sensors and mediators of disease, acting between the genetics of the host and the environment to alter disease development. Diet, one of the main environmental factors influencing the microbiota, was examined by Dr. Jeremiah Faith (Icahn School of Medicine at New York) whose lab reported that increased dietary protein resulted in greater intestinal bacterial biomass and inflammation. This effect was dependent on microbes, as no effect was observed in germ-free mice. To follow-up, his lab is investigating the biomass and microbiota composition of zoo animals with varying diets (coolest project ever!). Next, Dr. Ken Cadwell (New York University) described the significant effect of mouse norovirus infection on intestinal morphology and inflammation. Finally, Dr. Charles O. Elson (University of Alabama) gave a fascinating Easton seminar on the immune-microbiota dialogue, particularly the antibody response to microbial antigens.

GENES x ENVIRONMENT
Dr. Bruce Vallance (University of British Columbia) illustrated the regulatory role of the inflammasome and caspase signalling within the intestinal tract. Very much on point with the focus of the day, Dr. Kevan Jacobson (BC Children’s Hospital) reported that the offspring of South Asian migrants to British Columbia had increased incidence of inflammatory bowel disease, equivalent to that of non-South Asian Canadians. Lastly, Dr. Thad Stappenbeck (Washington University) detailed the importance of Paneth cell morphology and its use as a potential biomarker. Moreover, his team has identified that smoking alters both Paneth cell morphology and the microbiota in mice with an IBD-associated autophagy mutation.

IMMUNE RESPONSE

Image Credit: Patricia Kambitsch
Image Credit: Patricia Kambitsch

As a pioneer in host immune-microbe interactions, Dr. Kathy McCoy (University of Calgary) chronicled multiple levels of host immunity as they are driven by microbes. She detailed the findings on how both exposure in utero and through milk are key for offspring colonization, with maternal antibodies being critical for capturing microbial products and mediating the effects. The concept of the “multi-biome” was introduced by Dr. Lisa Osborne (University of British Columbia), whose work investigating the crosstalk between host, helminth and viral infection opens a new avenue of microbiome studies.The second day began with Dr. Frits Koning (Leiden University) outlining the results of CyToF analysis of mucosal immune signatures. He was followed by Dr. Maria Rescigno (University of Milano) who emphasized the importance of mouse strains by showing the significant difference in IgA levels between BALB/c and C57BL/6 mice, which resulted in altered bacterial uptake into Peyer’s patches.

GWAS & META-ANALYSIS
The next talks focused on gene-microbiome associations. Dr. Andre Franke (University of Kiel) and Dr. Judy Cho (Icahn School of Medicine at Mount Sinai) both portrayed genetic analysis as a gateway to learning drivers of disease.

ENVIRONMENTAL DETERMINANTS
As a reminder that environmental factors are complex, Dr. Gilaad Kaplan (University of Calgary) gave an overview of the global rise in IBD. He highlighted the importance of identifying environmental risk factors since innovation can alter the environment and thus the impact on IBD incidence. Dr. Jens Walter (University of Alberta) highlighted how environmental factors can interrupt the symbiosis between hosts and their microbiota, resulting in interference and disease development. To close the symposium, Dr. Howard Hu (Dalla Lana School of Public Health) provided an epidemiological perspective, emphasizing the different types of environmental exposures, their timing and dosing.

Overall, the meeting provided an interesting overview of the multiple levels of research looking into host-microbiota interactions and the countless environmental factors that can alter these interactions. It also provided a nice platform for researchers to share their experiences in dealing with the multitude of environmental controls that are becoming necessary in microbiota studies. At the end of the day, we have barely scratched the surface of understanding the complex bidirectional relationship between a host and its microbiota, but with multi-disciplinary collaborations such as the GEMINI project, we are starting to learn how to ask and address the questions we have.


In addition to traditional presentations…
…the organizers added two ‘special features’ to the symposium. During each talk, two artists were translating what was said into a visual summary of the data (presented on artboards), which were on display for the rest of the meeting. This was especially helpful for the other feature: panel discussions on “big data” and “how to design a mouse experiment”. The take-home message from the “big data” panel was to meet with statisticians before beginning experiments, as early interactions between experts of informatics and statistics is essential for the development of effective “big data” analytical plans and will maximize data reliability. For the “mouse experiments” panel, Dr. Thad Stappenbeck took charge and examined the plethora of environmental factors that can influence mouse work, including: diet, water acidification, diurnal light cycle, caging conditions, infection history, etc. Ultimately, the more we discuss these topics and share our experiences, the more we can standardize practices and improve reproducibility.

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Ashleigh Goethel

I am a 3rd year PhD candidate in the department of Immunology. Curiosity and a love of nature is what drew me to biology and what drives me forward. Outside of the lab, I enjoy hiking, skiing, playing volleyball, taking my dog to the dog park, and cooking. In an alternate universe, I'd love to be an interior designer or a chef - there is nothing I enjoy more than cooking a wonderful meal and sharing it with friends and good wine!

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