Molecular, Cellular and Organism High-Throughput Screening for Hazard Assessment - Theme 2 (HTS)
Leader: André Nel
The overarching goal of Theme 2 is to develop high throughput screening (HTS) approaches that can be carried out in tissue culture cells, bacteria, yeasts and zebrafish embryos to develop predictive toxicology paradigms that relate potentially hazardous ENM properties to adverse biological outcomes in cells and terrestrial and aquatic organisms/animals. To do so, we have developed a number of robust scientific platforms relating molecular and cellular injury responses to nanomaterial properties that could pose environmental risk and therefore useful for high content toxicological screening, dosimetry calculation and safe-by design approaches. High content or high throughput screening is done in close collaboration with other CEIN themes to prioritize CEIN’s ability to address important nanomaterials through expedited hazard and risk ranking. For the first five years of the center, we utilize OECD’s prioritization of primary nanomaterials such as metals, metal oxides, silicas and carbon nanotubes (CNT) nanomaterials for acquisition, synthesis and characterization by Theme 1. The availability of these compositional and combinatorial ENM libraries has allowed us to focus on and develop a number of biological endpoints on which to base HTS. The studies in Theme 2 inform investigators in Themes 2-5 about the key material types and properties that should be considered for fate and transport studies as well as for study in terrestrial, marine and freshwater ecosystems. The rich data sets emerging from the HTS studies has been instrumental in the development of quantitative structure-activity relationships, machine learning analyses and hierarchical ranking of ENM hazard by Theme 6. Theme 2 is leveraging the automated high throughput screening (HTS) infrastructure of the UCLA Molecular Screening Shared Resource (MSSR), which is an associated Center Core facility (see Core Report). The MSSR Core perform automated screening with robotic equipment that allows assessment of luminescence-based reporter gene activity, epifluorescence microscopy that assesses multi-parameter sub-lethal and lethal cellular injury responses, multiplex quantification of pro-inflammatory and cellular injury response markers in the supernatant, as well as high throughput screening and imaging of zebrafish embryos and larvae.
1. Development of High Throughput Screening and Predictive Toxicology by Using Mammalian and Fish Cell Lines To Study Nanomaterial Toxicity
2. Development of High Content Screening of Nanoparticle Toxicity Using Zebrafish Models
3. Linking the Physicochemical Properties of a Library of Multiwall Carbon Nanotubes (MWCNTs) to Toxicological Outcomes at Cellular Level That Reflect Pathogenic Potential In The Lungs of Mice
4. Property-Activity Analysis of Silica Nanoparticles, Including the Relationship of Surface Chemistry To Their Toxicological Potential
5. High Throughput Screening to Determine the Mechanistic Toxicology of Engineered Nanomaterials in Bacteria
6. Assessment of The Role of Metal Oxide Energy Structure on The Biological Effects and Potential Toxicity of This Class of Nanomaterials
7. Linking The Physicochemical Properties of a Library of Single-Walled Carbon Nanotubes (SWCNTs) to Toxicological Outcomes at Cellular Level That Could Also Reflect Their Pathogenic Potential In Vivo
8. Study of the Role of Aspect Ratio of Mesoporous Silica Nanoparticle on Cellular Uptake in Mammalian Cells
9. Reporter Gene Cell-based Assays for High Throughput Screening to Determine Sub-Lethal Toxicity of Nanomaterials (Completed Aug 2011)
10. Study of the Biological Effects of Long Aspect Ratio CeO2 On Inflammasome Activation And the Generation of Cytotoxicity
11. Toxicological Assessment of Cationic Nanoparticles With Different Surface Charge Densities in Differentiated in Undifferentiated Bronchial Epithelial Cells
Core Activity D - Molecular Shared Screening Resource
