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 many of these models with few efforts that 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) be used in ecological risk assessments by stakeholders (industry, government) [applied goal]; and d) generate novel scientific tools for use across disciplines and taxa [technological goal]. The short-term objective of my program is to couple together in vitro models along the gut-liver-brain axis under the overarching hypothesis that measurements of contaminant exposure and hazard in the coupled in vitro models will reflect those in vivo at both the organ- and organismal-level. The work will mainly be performed in an avian (chicken) model and focus on mercury as a 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, and technological needs in our field and across the broader biological sciences. The work here spans pertinent exposure and hazard measures, and thus can help deepen understanding of toxic responses and how organisms cope with contaminants. Two main themes (toxicity testing, mercury) of this work are based on large, international efforts that I am substantially involved with, thus findings from this program will directly inform end users and policy. Research and training objectives will be integrated by having students involved in all aspects of the research cycle (from design to conduct to dissemination) and partake in research translation activities (e.g., engage with stakeholders), and providing opportunities for students to conduct research that is integrative (molecular to organismal) and comparative (e.g., multiple organisms, measures, etc.).