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Biologist Awarded Grant to Study Effects of Chemicals in the Environment on Embryos

Biologist Awarded Grant to Study Effects of Chemicals in the Environment on Embryos

An associate professor of molecular biosciences at the University of Texas at Austin is one of two individuals this year to receive a Sustaining Outstanding Achievement in Research (SOAR) award from the National Institute of Dental and Craniofacial Research. Johann Eberhart was awarded the eight-year, $7.6 million grant to study the genetic and environmental causes of human birth defects of the head and face, which now occur in up to 5% of all births.

Some previous research in the Eberhart lab has centered around Fetal Alcohol Spectrum Disorder, a condition that can include abnormal facial features, learning disabilities, vision or hearing problems and speech and learning delays. With this new grant, Eberhart will expand his research to discover how genes interact with chemicals other than alcohol that people encounter in their daily lives and how these interactions may affect developing embryos.

"There are more than 80,000 synthetic chemicals in our environment and 3,000 of them are found in measurable quantities in our bodies. What most of them do to human embryos is completely unknown," Eberhart said. "Part of our work is to identify those that might have the most deleterious outcomes."

The head and face are incredibly complex systems in vertebrates. Because their development depends on the interaction and integration of many different types of cells in order to function correctly, a lot can go wrong.

Eberhart has done most of his work using zebrafish to model the effects for human embryos. Zebrafish are useful because they develop externally, and their embryos are clear; this makes it simple to see how the cells that make the head and face respond to genetic and environmental variables.

Eberhart and his team of collaborators previously found several genetic mutations that heighten sensitivity to alcohol in zebrafish, making fish embryos with those mutations more likely to develop FASD compared to other embryos. They have found evidence that those same genes identified in zebrafish may also sensitize humans to embryonic alcohol exposure.

"It was known that there were genetic influences on the outcomes of prenatal alcohol exposure, but what those genes were wasn't very well known," Eberhart said.

An image of nerves in the head of an embryonic zebra fish. Image courtesy of the Eberhart Lab.

Eberhart plans next to screen what effect certain chemicals have on gene expression, protein production and more.

"We could look at hundreds of these chemicals and see what they are doing in zebrafish," he said, "and then potentially apply that back to human populations to see if they are causing other birth defects."

One chemical his team is already examining is piperonyl butoxide, an agent found in a variety of household products, including insecticides. There is evidence that it can affect a critical signaling pathway that is required for cell differentiation in embryonic development, a pathway that is also affected by alcohol exposure.

"Everybody probably has some of this chemical in their household," Eberhart said. "So then, you can imagine that it's a simple combination of drinking, and a genetic mutation that disrupts a signaling pathway, but then there's this other thing in your house. You're getting an exposure that you don't even know about."

Eberhart hopes to use the grant to move from understanding interactions among genes and environmental factors to understanding how the interactions affect the production and localization of proteins by cells in the craniofacial complex, with the eventual aim of forestalling preventable birth defects.

The SOAR grant is intended to provide longer-term support for mid-career scientists with outstanding records of research productivity, mentorship and professional service to the research community.

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Sunday, 08 December 2019

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