In the hidden moments of early embryonic development, organisms set up their internal map: heart on the left, liver on the right, digestive tract twisted just so. It’s a biological design so precise that even tiny missteps can mean grave congenital birth defects. But Nanette Nascone-Yoder, a professor and University Faculty Scholar in the College of Veterinary Medicine, is determined to make sense of those maps. 

The National Institutes of Health has awarded Nascone-Yoder a $2.8 million grant, along with her co-investigator Julio Belmonte, an assistant professor of physics. Over the next five years of collaboration, their goal is to discover how internal organs establish their asymmetrical shapes and positions. “We want to understand what happens when it goes perfectly, so we can better understand what happens when it goes imperfectly,” says Nascone-Yoder. 

They’re tackling this challenge on two fronts: in a physical (or wet) lab and in a virtual (or in silico) one. In the Department of Molecular Biomedical Sciences wet lab, Nascone-Yoder’s team is decoding left-right organ asymmetry in frog embryos, chosen for their transparency during organ development. By focusing first on the stomach, a relatively simple organ, the team gains a template for unraveling the intricacies of more complex organs, like the heart. 

Concurrently, Belmonte’s computational model of the embryonic organs creates an in silico laboratory — virtual, but consistent with the laws of nature. Having a simulated testing ground greatly accelerates understanding, says Belmonte: “We can test multiple hypotheses at a higher speed and lower cost compared with physical experiments.”

“It’s a privilege to have someone work on the same problem from a completely different perspective and get similar results.”
— Nanette Nascone-Yoder

Belmonte’s physics team and Nascone-Yoder’s developmental biology team share observations. “It’s a privilege to have someone work on the same problem from a completely different perspective and get similar results,” says Nascone-Yoder. 

Those results could mean progress in unraveling the mystery of early embryonic development, a significant scientific victory. And it could have more immediate and personal impact on families facing scary diagnoses. “Our work could have implications for understanding the underlying causes of many different types of common birth anomalies, including congenital heart defects and intestinal malrotation,” says Nascone-Yoder. “If we can prevent or mitigate that, we can save families from heartache.”  

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