Currently, there are over 80,000 chemicals in use and approximately 2000 new chemicals are introduced into use every year. Regulatory agencies have recognized the need for alternative toxicological methods and models to decrease the time and expense of current toxicity testing protocols. In association with the National Toxicology Program (NTP), our group is developing C. elegans as an alterative organism for in vivo toxicological testing. Short life cycles, easy and inexpensive maintenance and culturing, and detailed biological knowledge has allowed for the development of rapid, low-cost toxicity tests that readily lend themselves to mechanistic studies of toxicant actions. Because of the evolutionarily conserved nature of the stress-response and other relevant pathways, it is likely that responses elicited in C. elegans will be applicable to understanding similar processes in higher organisms, including humans.? ? Our group has developed methods to measure the toxicity of known and suspected developmental and neurological toxicants. Protocols are regularly used to assess the effects of chemicals on the growth, size, reproduction, feeding, or movement of C. elegans. These technologies are based on a 96 well format, and required the adaptation of liquid handling robotics to C. elegans biology. The COPAS Biosort platform is similar to a fluorescence-activated cell sorter system and is used for dispensing and measuring C. elegans characteristics including length, optical density and fluorescence. Using this technology, our group is able to reliably quantify biological responses in a whole organism in a high throughput format.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES102046-02
Application #
7594024
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2007
Total Cost
$1,678,434
Indirect Cost
City
State
Country
United States
Zip Code
Behl, Mamta; Rice, Julie R; Smith, Marjo V et al. (2016) Editor's Highlight: Comparative Toxicity of Organophosphate Flame Retardants and Polybrominated Diphenyl Ethers to Caenorhabditis elegans. Toxicol Sci 154:241-252
Boyd, Windy A; Smith, Marjolein V; Co, Caroll A et al. (2016) Developmental Effects of the ToxCastâ„¢ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits. Environ Health Perspect 124:586-93
Rice, Julie R; Boyd, Windy A; Chandra, Dave et al. (2014) Comparison of the toxicity of fluoridation compounds in the nematode Caenorhabditis elegans. Environ Toxicol Chem 33:82-8
Song, Min Ok; Mattie, Michael D; Lee, Chang-Ho et al. (2014) The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Exp Cell Res 322:39-50
Harrington, James M; Boyd, Windy A; Smith, Marjolein V et al. (2012) Amelioration of metal-induced toxicity in Caenorhabditis elegans: utility of chelating agents in the bioremediation of metals. Toxicol Sci 129:49-56
Boyd, Windy A; McBride, Sandra J; Rice, Julie R et al. (2010) A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay. Toxicol Appl Pharmacol 245:153-9
Leung, Maxwell C K; Goldstone, Jared V; Boyd, Windy A et al. (2010) Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo. Toxicol Sci 118:444-53
Tvermoes, Brooke E; Boyd, Windy A; Freedman, Jonathan H (2010) Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans. J Cell Sci 123:2124-34
Boyd, Windy A; Smith, Marjolein V; Kissling, Grace E et al. (2009) Application of a mathematical model to describe the effects of chlorpyrifos on Caenorhabditis elegans development. PLoS One 4:e7024
Smith, Marjolein V; Boyd, Windy A; Kissling, Grace E et al. (2009) A discrete time model for the analysis of medium-throughput C. elegans growth data. PLoS One 4:e7018

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