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Environmental Factor, July 2015

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Tox21 tools promoted at UC Davis meeting

By Virginia Guidry

Linda Birnbaum, Ph.D.

“The purpose of Tox21 is to support the evolution of toxicology from a mostly observational science to a predominantly predictive science focused upon mechanism-based, biological observations,” Birnbaum said. (Photo courtesy of Christopher Portier)

A delegation of scientists from NIEHS and the National Toxicology Program (NTP) promoted high throughput screening tools at a meeting June 18-19 at the University of California, Davis. Led by NIEHS and NTP Director Linda Birnbaum, Ph.D., they joined a number of high-profile NIEHS grantees (see text box), discussing use of the innovative methods for identifying environmental toxicants.

The event, "Elucidating Environmental Dimensions of Neurological Disorders and Diseases: Understanding New Tools from Federal Chemical Testing Programs," was organized by the Environmental Defense Fund (EDF) in partnership with NIEHS, NTP, and the U.S. Environmental Protection Agency (EPA).

“The overall goal was to introduce these tools to researchers who might not be familiar with them,” said Kris Thayer, Ph.D., NTP deputy director for analysis.

Faster testing for toxic effects

The Tox21 program, a collaboration involving NTP, EPA, National Institutes of Health Chemical Genomics Center, and the U.S. Food and Drug Administration, uses high throughput screening to research and test chemicals of toxicological concern. The automated approach provides a rapid and low cost method of systematically testing the impacts of many chemical compounds at varying concentrations on cells and model tissues.

Birnbaum outlined three main goals of Tox21:

  • Prioritize chemicals needing further study
  • Identify mechanisms contributing to toxicity
  • Develop models to test biological response in humans

After potential toxicants are identified, toxicologists can use observational studies and systems biology approaches to explore how dose and timing of exposure contribute to toxicity.

Putting HTS into action

In addition to background from Birnbaum and NTP Associate Director John Bucher, Ph.D., presenters described HTS assays in detail and lessons learned by researchers thus far. Some attendees also participated in what organizers described as genius bars, where they received step-by-step instructions on accessing Tox21 tools. Instructors included experienced researchers such as NTP molecular toxicologist Scott Auerbach, Ph.D., and Nisha Sipes, Ph.D., of the NTP Biomolecular Screening Branch.

To encourage junior researchers to learn about and use the HTS tools, NTP provided eight travel awards to basic scientists outside of the federal government. One of the awardees, Merja Jaronen, Ph.D., research fellow at Brigham and Women´s Hospital and Harvard Medical School, remarked, “I am about to test some of the compounds in a zebrafish model of neurodegeneration, and it was extremely interesting, as well as valuable, to learn about the databases and see how other people have benefited from these tools.”

Providing resources and moving forward

Another hallmark of Tox21 is that the data are available to researchers in publicly available databases, with multiple search capabilities. For example, NTP provides a library of compounds that impact neural cells. “The 80 compounds include known developmental neurotoxicants as well as chemicals of environmental interest, such as flame retardants and polycyclic aromatic hydrocarbons,” Birnbaum said.

A number of new developments are on the horizon for Tox21. Researchers plan to increase the use of normal human cells in testing. There is emphasis on measuring impacts on messenger ribonucleic acids (RNA), also called transcriptomics, because of RNA’s role in transcribing genetic information for protein synthesis.

The goal is to select more than 1,500 sentinel human genes that have full pathway coverage and can predict the gene expression of the rest of the transcriptome with high accuracy, dubbed the Human S1500 Gene Set, for use in HTS. To parallel the 1500 sentinel human genes (S1500), a mouse S1500 and a zebrafish S1500 are also under development.

(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison.)


Speakers and Moderators

Leonard Abbeduto, Ph.D, UC Davis MIND Institute
Scott Auerbach, Ph.D., NTP
Tina Bahadori, Ph.D., EPA
Linda Birnbaum, Ph.D, NIEHS
Jeffrey Bronstein, M.D., Ph.D., UC Los Angeles
John Bucher, Ph.D., NTP
Thomas Burke, Ph.D., EPA
Elaine Faustman, Ph.D., University of Washington
Irva Hertz-Picciotto, Ph.D., UC Davis
Keith Houck, Ph.D., EPA
Valerie Hu, Ph.D., George Washington University
Seth Kullman, Ph.D., North Carolina State University
Pamela Lein, Ph.D., UC Davis
Matt Martin, Ph.D., EPA
Jennifer McPartland, Ph.D., EDF
Craig Newschaffer, Ph.D., Drexel University
Chirag Patel, Ph.D., Harvard University
Heather Patisaul, Ph.D., North Carolina State University
Christopher Portier, Ph.D., EDF
Francisco Quintana, Ph.D., Harvard University
Robert Ring, Ph.D., Autism Speaks
Peter Schmidt, Ph.D., National Parkinson Foundation
Gina Solomon, M.D., California Environmental Protection Agency
Robert Tanguay, Ph.D., Oregon State University
Caroline Tanner, M.D., Ph.D., San Francisco Veteran's Affairs Medical Center
Kristina Thayer, Ph.D., NTP
Russell Thomas, Ph.D., EPA
Ray Tice, Ph.D., NTP (Retired)
Sarah Vogel, Ph.D., EDF



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