Carbon-based nanomaterials (CNMs) may be among the most useful engineered nanomaterials for different applications, although our understanding of the toxicity and potential impact of carbon-based nanomaterials on human and ecosystems is still in its infancy. Among the various toxicity effects observed, genotoxicity (the damage to genes from chemicals) is of particular concern to human and other lives because genotoxicity from nanomaterial (nanogenotoxicity) can potentially cause cells to mutate and eventually lead to cancer. This study will demonstrate the application of a new high-throughput, rapid and effective nanogenotoxicity assay platform and a new mechanism-driven hierarchical model framework that will be tested. The results of the research will fill in the urgent knowledge gap in mechanistic understanding of the environmental and health impact of CNMs. This research has significant benefits to the environment and public health protection. The outcome from the research will aid strategies related to nanoscience and technology, as well as elucidate the environmental and health implications of nanomaterials, which will help bridge the gap between scientific research, creation of commercial products and public health protection. In terms of broader impact on the community, the synergized arrays of education outreach and public education programs will present the technology, benefits, and societal and environmental impact of nanotechnology to a wide range of audiences at many levels. For example, PI Gu had initiated the BEST (Biotechnology for the Environment, Showcase and Training) program as part of a CAREER award. With this proposal, she will be able to expand that program, as well as collaborate with additional existing programs (e.g. a RET program, NEU CONNECTIONS, etc) to promote training of students and teachers. Both PIs will also work with the Boston Museum of Science to create multimedia that disseminates research to the public.
This project proposes to perform a comprehensive and systematic genotoxicity assessment of a variety of well-characterized carbon-based nanomaterials (CNMs), using a newly developed high throughput toxicogenomics-based 3-D gene/protein expression profiling technique, with the aim to relate nanogenotoxicity with CNMs' physicochemical and structural properties and, explore prototype mechanism-driven QSAR (Quantitative Structure Activity Relationships) model. Genotoxicity of four different CNMs (SWCNT, fullerene C60, carbon black and graphene) and their variations will be evaluated by measuring the NM-induced expression alteration in genes and proteins that are indicative or essential for the known DNA damage and repair pathways, using the newly developed molecular genotoxicity assay platform and, with the extension to multiple species across different taxonomic levels (bacteria, yeast and human). Dose-response relationships and molecular genotoxicity endpoints will be determined using the molecular effect level index (MELI) recently proposed by us. To validate the proposed molecular assay and confirm the genotoxicity of CNMs tested, conventional phenotypic genotoxcity assays will be performed in parallel. An array of modern techniques will be employed to determine the purity, elemental composition, dimension, surface chemistry, aggregate size and state, zeta potential, hydrophilicity etc. of the CNMs. A prototype nanogenotoxicity QSAR model with hierarchical structures that integrates current QSAR framework with molecular bioassay information through correlative links among CNMs descriptors, DNA damage mechanism-specific molecular endpoints and phenotypic genotoxicity endpoints will be explored.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
