A National Institutes of Health-funded effort involving researchers from Texas A&M University, the University of Pennsylvania’s Perelman School of Medicine, and the Children’s Hospital of Philadelphia (CHOP) uses human genomics to identify novel genes involved in sleep regulation in Drosophila. identified the route. This is a new insight that could pave the way for new treatments for insomnia and other sleep-related disorders.
Alex Keene, a geneticist and evolutionary biologist at Texas A&M, collaborated with Allan Pack of Penn, Philip Gehrman, and Struan Grant of CHOP in a groundbreaking study published in Science Advances.
“Major efforts have been made to discover sleep genes using human genome studies,” said Keene. “There are studies with hundreds of thousands of individuals. But validation and testing in animal models is very important in understanding function. Each brings different specialties that enable the ultimate effect of collaboration.”
According to Keene, the most exciting part of the team’s work is developing the pipeline from real human genome data, rather than model organisms.
“There are a wealth of human genome-wide association studies (GWAS) identifying genetic variants associated with sleep in humans,” Keane said. “However, it was very difficult to validate them. Our team used a genomics approach called variant-to-gene mapping to predict which genes would be affected by each genetic variant. We screened for the effects of these genes in Drosophila.
“In our study, we found that mutations in the gene Pig-Q, which is required for the biosynthesis of modifiers of protein function, increased sleep. We then tested this in the vertebrate model zebrafish. , similar effects were seen.Thus, Pig-Q is associated with sleep regulation in humans, flies and zebrafish.”
According to Keene, the team’s next step is to study the role of GPI-anchored biogenesis, a common protein modification, in sleep regulation. Additionally, he notes that with the human-to-fruit-to-fly-to-zebrafish pipeline his team has developed, sleep genes as well as neurodegeneration, aging, memory, and more are commonly studied using human GWAS. Other characteristics can also be evaluated functionally, he said.
“Understanding how genes regulate sleep and the role of this pathway in sleep regulation will help clarify future discoveries regarding sleep and sleep disorders such as insomnia.” Penn Time Biology and Sleep Institute. “Future research using this system to identify more genes that regulate sleep could point the way to new treatments for sleep disorders.”
At the Center for Biological Clock Research, Keen’s research lies at the intersection of evolution and neuroscience, focusing on understanding the neural mechanisms and evolutionary underpinnings of sleep, memory formation, and other behavioral functions in fly and fish models. focus. Specifically, I study Drosophila (Drosophila melanogaster) and a Mexican bloodline that has lost both sight and sleep with the goal of identifying the genetic basis of behavioral choices that contribute to human diseases such as obesity, diabetes and heart disease.