Just as Gotham City uses the Bat Signal to call for Batman’s aid, a new tool developed by Sanford-Burnham scientists should serve as the cellular equivalent for children with genetic diseases known as congenital disorders of glycosylation (CDG). In a new report appearing online June 12 in The FASEB Journal, the scientists describe how they used a green fluorescent protein originally isolated from jellyfish to identify the presence of genes—known and unknown—associated with CDG. By being able to identify exactly which genes are defective, researchers can develop therapies to correct the root causes of these diseases, rather than merely treating the symptoms.
Glycosylation is a process in which enzymes coat proteins and other cellular components with sugar molecules. These sugars help cells “stick” together and help proteins fold and work properly, among other things. When a child inherits a defective gene that encodes a glycosylation enzyme, he or she is born with CDG. Symptoms of CDG vary widely, and can include intellectual disability, digestive problems, seizures, or low blood sugar.
“We hope this glowing protein will help light the path for the discovery of new genes that cause genetic disorders in children,” said Hudson Freeze, Ph.D., director of Sanford-Burnham’s Genetic Disease Program and senior author of the study. “It’s not Harry Potter’s magic wand, but we hope it will offer a way to test for new therapies in these kids. They’re counting on us.”
To make this advance, Dr. Freeze and colleagues, including postdoctoral researcher Marie-Estelle Losfeld, Ph.D., engineered cells from children with glycosylation disorders so they would glow to indicate when there was a glycosylation problem related to a defective or missing gene. Once the problematic, glowing cells were “rescued” by inserting a healthy gene into the cell or correcting a defective gene’s function, the cells stopped glowing. This new tool may be used in high-throughput screening to identify therapeutic molecules that improve glycosylation in defective cells, including stem cells. In addition, this advance may serve as the foundation for a new diagnostic tool for patients.
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Meet a few of the kids who’ve already benefited from Dr. Freeze’s work:
Mason
Liam
Rocket