Worm studies may help understanding of parasitic disease

Researchers at the UT Southwestern Medical Center have discovered a molecule that activates genes involved in the development and reproduction of caenorhabditis elegans (C elegans), a common research worm about the size of a pinhead.

In the study, the scientists describe how the molecule, called a ligand, acts like a hormone, the first such hormonal ligand identified in C elegans. Like a key fitting into a lock, the newfound ligand binds to a protein in the cell’s nucleus called a nuclear receptor, a receptor designated DAF-12. Once that binding occurs, DAF-12 activates other genes that allow the worm to develop through its normal stages, reach maturity and reproduce.

When the researchers blocked that hormonal signal by engineering mutant worms that couldn’t manufacture the ligand, the mutants’ development stopped before they reached maturity. Instead the worms went into a ‘resting’ stage called the dauer diapause, in which they don’t eat or reproduce. When the researchers provided the mutants with the missing ligand, it prevented the dauer stage, and the animals continued to develop normally.

“This pathway in worms is remarkably similar to hormonal pathways in humans,” said Dr David Mangelsdorf, chairman of pharmacology at UT Southwestern and senior author of the study.

The UT Southwestern research may be useful in understanding hormone replacement therapy and also in the fight against human disease, as the dauer diapause stage of C elegans is very similar to the infective state of parasitic nematodes. According to the World Health Organization, such parasites infect about two billion people worldwide.