Engineering an in vitro lung model for air pollutant deposition and toxicology

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DESCRIPTION (provided by applicant): The candidate's overall career goal is to become a leading, independent researcher in the field of air pollution and air pollution effects on public health. Career objectives related to this grant are to: a) enhance the candidate's knowledge of pulmonary biochemistry and physiology, b) develop technical expertise in cellular toxicology, and c) develop an independent research program that integrates the fields of mechanistic toxicology with air pollution physics and exposure assessment. The long term goal of this research is to establish mechanistic, dose-response relationships between inhaled air pollutants and lung disease. Merging the fields of in vitro toxicology and exposure assessment is a necessary step in realizing this goal. Therefore, the immediate objective is to develop a realistic, physiological model for air pollutant deposition in vitro. The investigator's model will accomplish this task by approximating particle size-specific deposition patterns of particulate aerosols to pulmonary epithelial cells housed within a state-of-the-art in vitro lung model. This model will be developed, calibrated, and finally validated against the existing state-of-the-art model. In vitro toxicology can be employed as a relatively low-cost, rapid screening method for elucidating these mechanisms across many cell types. Establishing a link between exposure and health effect 1) provides a means for further innovations in the prevention and treatment of pulmonary disease, specifically allowing for more targeted (and resource-intensive) in vivo experimentation to follow from in vitro screening tests, 2) allows for intervention and control strategies targeted to reduce specific toxic components of ambient air pollution, and 3) helps provide the necessary information for regulating agencies to set more protective, health-based standards.