Progress, and Applications
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NIEHS Creates National Center for Toxicogenomics
The outpouring of human genome data and the development of large-scale, rapid, efficient technologies to probe them have transformed the field of toxicology and engendered a new specialty toxicogenomics. Researchers in this new field study gene response to environmental stressors and toxicants and seek to understand the role played in disease by gene-environment interactions. The use of DNA microarray and proteomic techniques to assess changes in gene and protein expression is a rapidly growing research area that will have a large impact in many areas, including the environmental health sciences.
To develop the field of toxicogenomics and coordinate an international research effort, the NIH National Institute of Environmental Health Sciences (NIEHS) created the National Center for Toxicogenomics (NCT). NCT aims to promote advances in toxicogenomics and catalyze their application to the prevention and amelioration of environmentally related diseases.
The establishment of NCT was announced in December 2000 by NIEHS Director Kenneth Olden and Deputy Director Samuel Wilson. NCT Director is Raymond Tennant, NIEHS. Toxicogenomic strategies under development through NCT are based on microarrays containing thousands of messenger RNA (mRNA) fragments, the intermediary products of active genes, to create "gene-expression profiles." Using bioinformatics tools, researchers combine these data with those from protein-expression profiles to determine how disease may be influenced by environmental factors. NCT's goal is to combine these microarray-based strategies into a unified approach, together with the informatics infrastructure necessary to understand it.
This challenge exemplifies the ongoing paradigm shift occurring across the life sciences. Researchers are moving toward monitoring cellular events on a large-scale, global level that will facilitate a broader view of how living systems respond to specific stresses, drugs, and toxicants. Data generated by such research will provide extraordinarily detailed information on coordination profiles for cellular networks of responding genes and proteins, help define important target molecules for toxicity studies, and suggest future biomarkers and alternative testing procedures.
Experiments using such microarray technologies also will help define complex regulatory circuitry within a cell, tissue, or organ that is responding to specific stressors. Studies may help pinpoint locations and time points for effectively interceding in a cascade of biochemical and molecular events influenced by environmental stressors, making possible the early diagnosis of cellular responses and the prevention of or intervention in human disease.
Other NCT goals are to increase understanding of the pathways involved in biological response to environmental stressors and how these changes differ with genetic and dose differences; establish a publicly available relational database of toxicogenomics research; and promote collaborative research that will combine toxicology and disease pathology with gene-expression profiling, proteomics, and single- nucleotide polymorphism analysis using the Chemical Exposure in Biological Systems Data Base. A symposium on Gene Expression and Proteomics in Environmental Health Research will be held December 3 4 in Bethesda, Maryland. [James K. Selkirk, Deputy Director NCT, 919/541-2548, Fax: -1460]
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Last modified: Wednesday, October 29, 2003
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