Multiscale Modeling of Nano Effects on Major Human Organs in the Body
ABSTRACT: Although nanomaterials have demonstrated potential for widespread applications, toxicology of these materials has not been thoroughly evaluated under different exposure scenarios. We propose to develop a comprehensive software tool integrating multidisciplinary physiology and systems biology approaches for modeling nanomaterial uptake, disposition, transport within the body and toxicity incorporating phenomena at different scales to address this challenge. Uptake and deposition will be simulated using actual 3D representation of target organs. The high fidelity models will be integrated to compartmental models representing other organs using systemic vascular and lymphatic system generated via novel wire models. In Phase I, we will demonstrate the tool for nanoparticle inhalation. The cellular toxicity model for the lung will be constructed using gene expression data of nanoparticle exposed tissue and the output from the physiological model. A detailed cellular-scale model of the biological pathways and a minimal model of this pathway will be developed to identify critical interactions, map the activation patterns of the output nodes and determine their cellular localization. The dosage of nanoparticles accumulated within the cell and transported out will be determined and communicated to the physiological model for transport calculations. This novel framework will yield the level of exposure to organ under consideration. BENEFIT: The predictive software tool will enable knowledge-based understanding of nanotoxicity, thereby leading to development of nanomaterial exposure rules, and design and deployment of effective practices and countermeasures to mitigate adverse effects. The proposed software tool has tremendous market potential that includes nanomaterials based manufacturers, pharmaceutical companies and inhalational device manufacturers.
Small Business Information at Submission:
Senior Contracts Specialist
CFD Research Corporation
215 Wynn Dr., 5th Floor Huntsville, AL -
Number of Employees: