The IU Consortium for Environmental Genomics and Toxicology (CEGT) is an alliance of The Center for Genomics and Bioinformatics, the Center for Environmental Health, the School of Public and Environmental Affairs, and the Center for Research in Environmental Sciences. It represents a collaboration among IU-Bloomington and IU School of Medicine units that transcends traditional customary boundaries between human health science and research on environmental sciences and policy. This alliance seeks to better understand how transcriptional (genomic) signatures of pollutant-induced stress can both diagnose threats to ecosystems and provide crucial clues on their effects on human health.
The NIH National Toxicology Program estimates that >80,000 chemicals are manufactured in the United States. Two to three thousand (2000-3000) new compounds are introduced annually, and additional chemicals are produced as byproducts. Only a small minority of these chemicals (approximately 6 percent) are tested for their toxic effects, despite strong evidence that environmental toxins play major roles in both human and environmental health.
Many diseases (e.g., cancer, lung disease, diabetes) and chronic conditions (birth defects, asthma, reproductive problems) are preventable, in part, by limiting exposures to environmental stressors. Traditional methods in toxicology--lethality doses (LD) in mammals--are too slow and too expensive, and they provide no information about the underlying basis of toxicity. CEGT aims to provide (i) better and more efficient ways to screen substances for their harmful effects, and (ii) more robust and facile approaches for uncovering the biological processes that are affected.
The researchers will use high-throughput assays in Daphnia to characterize the effects of chemicals on gene expression and their dosage sensitivity. Daphnia, the water flea, is one of the most widely used organisms in environmental toxicology and the CGB has led in the study of its genomics. These assays are faster, more sensitive, less expensive, and more informative than traditional methods. A pattern of gene expression (a signature) carries information about the chemical's effects on the organism's underlying biochemistry. Partnering with IU specialists in informatics, scientists at the Center for Environmental Health will use this information to unravel the biochemical consequences in human cells.
Daphnia, the water flea
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The growing number of genomic tools now available for Daphnia research are presently used to understand how animals acclimate to changes in their environment and whether the genes responsible for a physiological response are the same genes that lead to a population's genetic adaptation to chronic ecological stress.
Despite over 100 million years of Daphnia adapting to a huge variety of aquatic settings, modern populations are facing new challenges. In North America, 80,000 chemicals are released by human activities in the environment every year. The outcome of combining chemical mixtures with familiar ecological stressors on aquatic populations is largely unknown. Nor are the mechanisms for chemical toxicity and its long-term effects on ecosystems known.
Yet for over 50 years, water fleas have been used by environmental protection agencies to set regulatory limits on pollution. Experiments done on Daphnia represent over 10 percent of all half million records within toxicological databases. Daphnia ranks Number 2 as a standard test species around the globe because of its importance as a conduit species for toxicants and its sentinel position in aquatic food webs. |
They plan to screen relatively well-understood chemical pollutants (metals, PCBs, agricultural chemicals) in a "proof of principle" demonstration of how prior results can be quickly and inexpensively replicated using genomics techniques and to demonstrate that much more information can be garnered by these approaches. Other chemicals representing emerging threats to water quality and human health (e.g., pharmaceuticals, personal care products, polybrominated flame retardants [PBDEs]) will also be screened. Finally, they plan to investigate mixtures of compounds. The interactions of toxicants are often complex, non-linear (e.g., antagonism, synergism), and important, but they are seldom investigated because of limitations of existing approaches.
This approach will lead to methods that can both diagnose the nature of environmental exposures (using Daphnia as a sentinel organism) and provide key information to guide the biochemical study of those effects in humans. And by providing a database of signatures for comparison with the effects of novel compounds, it will catalyze the development of a far richer understanding of toxicology within humans and across species boundaries.
Cadmium effects
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Microarray experiments to classify gene responses to stress
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