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CURRENT PROJECTS

Air pollution

Oxidative stress as a potential target of environmental contaminants: development of sex-specific co-culture models

The long-term objective of this research program is to elucidate the sex-specific effects of environmental exposures on oxidative stress pathways using newly-developed male and female co-culture models of various tissues, first starting with the airway. With a push in recent years to reduce our use of animals in risk assessment and toxicity studies, integrating a sex-specific approach in the development of physiologically relevant in vitro assays is particularly relevant. Emerging evidence suggests that genes located on the sex chromosomes contribute to inherent sex differences in oxidative stress. While the question of sex dysmorphism in oxidative stress following environmental exposure is being explored in animal models, most, if not all in vitro assays do not consider this aspect. Additionally, we do not understand the sex-specific impacts of many industrial chemicals on these mechanisms. My research program aims to tackle this critical research need. This NSERC-Discovery Grant (DG) program will develop and use three-dimensional (3D) cell-cultures to delineate sex-specific differences in oxidative stress responses following exposure to chemicals emitted by unconventional natural gas exploitation. Unconventional natural gas (UNG) is a key industry in Canada, and recent work from our group and others revealed its impacts on local air quality.

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This program will further our understanding of the sex-specific mechanisms underlying the oxidative stress response triggered by exposure to chemicals. This NSERC-DG is expected to contribute to the availability of biologically relevant cellular models for broad use in toxicological risk assessment and aspires to advance the fields of toxicology, cell biology, and molecular biology.

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Principal Investigator:

Élyse Caron-Beaudoin

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There’s something in the air: disentangling the role of airborne microbes and pollutants in the inflammatory response of asthma along a latitudinal gradient in Canada

Asthma is an inflammatory respiratory disease that affects over 3.8 million Canadians, approximately a quarter of which are children. Few studies have investigated the morbidity of asthma in Northern
Canada, but Inuit children have been found to have lower prevalence of asthma compared to other
Indigenous and non-Indigenous children. This is interesting because asthma is not only influenced by genetics but also by environmental factors. Therefore, where an individual lives has a significant impact on the risk of developing asthma and its severity. This can be due to exposure to allergens but also to other protective or inflammatory processes. For example, recent studies have found that growing up in areas with diverse microbial communities such as farmland can decrease the likelihood of developing asthma, by helping human-associated microbes (the microbiome) train the immune system. More directly, certain airborne microorganisms have been found to have a protective role against the development of asthma by preventing serious inflammation of the airways.

Microorganisms are not the only aspect of air quality that can contribute to asthma. Pollutants associated with resource extraction, transportation, as well as consumer and commercial products can have the opposite effect and induce inflammation and oxidative damage to the airways thus contributing to severity of symptoms. Airborne environmental microbes and pollutants therefore have opposite effects in asthma, and these factors are highly specific to where a person lives. However, it is unclear how these two variables intersect, and how together they may promote or impede the presentation of asthma. Our goal is to investigate how air quality may contribute to inflammation and asthma in an in vitro co-culture cell model of the human respiratory tract. We will sample 4 regions along a gradient varying in population size, but also in vegetation and land use: Scarborough (Ontario, population ~632k), Saguenay (Quebec, ~69k), Kuujjuarapik (Nunavik, ~686) and Resolute Bay (Nunavut, ~198).

At all sites, we will measure air pollutants (volatile organic compounds, trace elements, particulate matter), pollen, and microbial communities for characterization through metagenomic sequencing. Airborne microbes will also be collected and concentrated from each site. In the lab, we will expose a co-culture cellular model of the human respiratory airway to these field microbes. The co-culture will also be exposed to varying concentrations of pollutants, representative of our field data. We will then measure indicators of oxidative stress and inflammation, to quantify the role of both microbes and pollutants in asthma and identify organisms that protect from inflammation. We hypothesize that the diversity of airborne microbes in an environment will have a protective effect in our northern sites. We also expect airborne pollutant levels representative of our Northern sites to induce less inflammation.

This study proposes to use a novel approach to understand how the environment shapes the etiology of asthma. Our mechanistic approach will allow us to disentangle the role of the major environmental variables in inflammation of respiratory airways, and to identify the drivers of asthma along a latitudinal gradient in Canada.

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Nominated Principal Investigator:

Catherine Girard (Université du Québec à Chicoutimi)

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Co-Investigators:

Catherine Laprise (Université du Québec à Chicoutimi)

Isabelle Laforest-Lapointe (Université de Sherbrooke)

Caroline Duchaine (Université Laval)

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My role:

Co-Principal Investigator

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Collaborators and community partners: 

Ana Blanchard (Centre de recherche du CHU Sainte-Justine)

Makivik Nunavik Research Center

Nunavut Arctic College

FUNDING

Natural Sciences and Engineering Research Council of Canada (NSERC)

Fonds de Recherche Québec

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