NIEHS-led research collaboration received National Institutes of Health (NIH) Director’s Challenge Innovation Award.

Coble runs the NIEHS Vivarium, where he helps ensure that researchers working with research animals receive the support they need and that the facility provides exceptional animal care and scientific support. (Photo courtesy of Steve McCaw/NIEHS)

Led by Dondrae Coble, DVM, head of the Directorate of Comparative Medicine, the grant will fund the construction of several animal enclosures designed to help researchers observe the effects of 115 environmental chemicals on behavior. Enclosures help ensure that observations disturb research animals, especially fruit flies and mice, as little as possible. Additionally, the researchers will use the grant to create a system to collect, analyze, store, and share the data collected during the experimentation process.

The ultimate goal is to reduce the environmental chemicals most likely to cause potential neurodevelopmental disorders in fruit flies and mice from 115 to 10, which can then translate to the potential for these chemicals to cause neurodevelopmental disorders in human children.

The effort brings together collaborators from the NIEHS Division of Intramural Research (DIR) and the Division of the National Toxicology Program (DNTP), as well as the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering.

“The proposed project led by Dr. Coble, a recent NIEHS recruit from Nationwide Children’s Hospital and The Ohio State University, is highly meritorious and is precisely the type of innovative, high-risk/high-reward research that the intra- NIH muros was designed to support,” said Darryl Zeldin, MD, Scientific Director of DIR. “I am thrilled that he and his outstanding research team have received this highly competitive award.”

The award follows previous NIEHS research also using holistic systems physiology pioneered by Brian Berridge, DVM, Ph.D., Scientific Director of DNTP – an animal modeling method that simultaneously measures the effects of environmental factors from multiple systems . The method reduces the number of research animals while increasing the amount of information collected.

“As a laboratory animal medicine veterinarian, I want to use animals in the most responsible and appropriate way,” Coble said. “If there are opportunities to refine our techniques or reduce the use of animals, that’s something I’m interested in.”

Applying self-driving car research to health

The development of round-the-clock observation instrumentation for animal enclosures is tapping into an unlikely source: machine vision capabilities pioneered by autonomous vehicle research. Machine vision occurs when artificial intelligence (AI) is applied to real-time image and video processing using deep neural networks, which are used to train the AI ​​to select features and learn as you go.

Jesse Cushman, Ph.D. Cushman said the project’s approach can be used not only as a model to extrapolate impacts to humans, but also to other species, such as bees or aquatic invertebrates. (Photo courtesy of Steve McCaw/NIEHS)

“There are lots of ways we’re being tracked all the time — with smartwatches, apps, and sensors in our clothes — and now we’re incorporating that into animal models,” said Jesse Cushman, Ph.D., director of the basic neurobehavioral laboratory.

Just as a self-driving car can tell the difference between a person and a stop sign, the machine vision used in the speakers will be trained to tell the difference between behaviors that transcend species, such as grooming, eating, sleeping and interacting with. others, as well as differentiating between species-specific behaviors like wing-stretching in fruit flies and foraging in mice.

By observing how environmental chemicals affect the behavior of fruit flies and mice, researchers can extrapolate these effects to how they might impact human development.

“Globally, cross-species extrapolation is a foundation of what we do in science,” Cushman said. “Regulators attach great importance to these live studies, but they are very expensive and time-consuming – which is what we are trying to solve with this approach. It is essential to have live data across the body to understand the total impact of compounds. Our goal is to create an automated, scalable, and high-throughput method to perform behavioral research better for animals. We see this as a foundational technology for integrating holistic perspectives.

(Kelley Christensen is a contract writer for the NIEHS Office of Communications and Public Liaison.)