Multi Organ In Vitro Systems to Understand Organismal Responses to Chemical Stressors

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There is an unmet need across the biosciences for model systems that can mimic and interrogate physiological systems more closely and thus be predictive of the whole organism. For example, in my primary field (environmental toxicology), strategies rely heavily on animal testing that are prohibitively time-consuming and expensive and raise ethical concerns. While in vitro systems exist, they are far from a complete representation of the whole organism. Despite decades of research using in vitro models, we as a community have not critically interrogated the validity of these models and few efforts have tried to relate in vitro-in vivo responses. The long-term objective of my program is to establish an integrated, multi-organ in vitro system that can: a) be predictive of the whole organism [scientific goal]; b) advance fundamental understanding of animal (avian) biology particularly in response to toxic insults [scientific goal]; c) inform chemicals management decisions by stakeholders (industry, government) [applied / regulatory goal]; and d) generate novel scientific tools for use across disciplines and taxa [technological goal]. The short-term objective of my program is to improve the design of, and integrate, in vitro models along the gut-liver-brain axis under the overarching hypothesis that measurements of contaminant uptake and toxic response in the in vitro systems will reflect those in vivo. The work will be performed mainly in an avian (chicken) model and focus on mercury as a model chemical stressor. The program will lead to the development of an integrated multi-organ in vitro system that aims to mimic biological systems more closely and ultimately predicts whole organismal outcomes, thus addressing key scientific, applied, regulatory and technological needs in our field (and the broader biological sciences). There is high likelihood that the research will influence policy and be adopted given my national and international leadership roles in project themes (toxicity testing, mercury) that anchor the work; notably regulatory changes in Canada (CMP) and elsewhere are now demanding these new types of tools. Research and training objectives will be integrated by having students: a) involved in all aspects of the research cycle (from design to conduct to dissemination); b) partake in research translation activities (e.g., engage with stakeholders); and c) conduct research that is integrative (molecular to organismal), comparative (e.g., multiple organisms, etc.) and linked to policy (e.g., Minamata Convention; CMP chemicals management).