In a paper published as a "First Release," in the journal Science, lead authors Kirill Martemyanov, PhD, and Brock Grill, PhD, describe how they designed and implemented a new, unbiased approach for decoding the genetic network that controls actions of opioids in a nervous system.
They used a small soil dwelling animal, the nematode worm, to discover something surprising about one of the most-studied drug receptors.
Study - Everything - Response - Surface - Martemyanov
"A study like this makes it clear that even though we may think we know everything there is to know about the opioid response, we're actually just scratching the surface," Martemyanov says.
Their system relies upon the nematode c. elegans, engineered to express the mammalian surface receptor for painkilling drugs, the μ (mu) opioid receptor (MOR). The receptor is not normally found in the worms' DNA, and adding it made the transgenic animals respond to opioids like morphine and fentanyl. The researchers then exposed the worms to mutagens and selected the ones with abnormal responses to opioids. Whole-genome sequencing and CRISPR engineering was then used to pinpoint the genes responsible for those aberrant responses.
Forward - Genetics - Discovery - Receptor - Grill
"Forward genetics -- unbiased genetic discovery -- has never been applied to probing an opioid receptor like this," Grill says. "The opioid epidemic is a huge problem and we don't have good solutions. This type of approach can bring a whole new array of targets and a new way of thinking about and going after an old...
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