Nowe spostrzeżenia mogą utorować drogę nowym metodom leczenia bezsenności
Bezsenność to zaburzenie snu charakteryzujące się trudnościami z zasypianiem lub utrzymaniem snu, co prowadzi do chronicznego zmęczenia i upośledzenia funkcjonowania w ciągu dnia. Może to być spowodowane różnymi czynnikami, w tym stresem, lękiem, depresją, schorzeniami i niezdrowymi nawykami dotyczącymi snu.
Biolog Texas A&M, Alex Keene, wraz ze swoim zespołem wykorzystał mapowanie wariantów do genów, predykcyjną metodę genomiki, aby wykazać, że gen Pig-Q odgrywa rolę w regulacji snu u ludzi, much i danio pręgowanego.
Wysiłek finansowany przez National Institutes of Health, składający się z naukowców z Texas A&M University, Perelman School of Medicine na University of Pennsylvania i Children’s Hospital of Philadelphia (CHOP), wykorzystał ludzką genomikę do odkrycia nowej ścieżki genetycznej, która reguluje śpią u ludzi i muszek owocowych. Ten przełom może doprowadzić do opracowania nowych metod leczenia bezsenności i innych zaburzeń związanych ze snem.
Alex Keene, genetyk i biolog ewolucyjny Texas A&M, współpracował z Allanem Packiem i Philipem Gehrmanem z University of Pennsylvania oraz Struanem Grantem ze Szpitala Dziecięcego w Filadelfii (CHOP) nad innowacyjnymi badaniami. Ich odkrycia zostały niedawno opublikowane w czasopiśmie
“There is an abundance of human genome-wide association studies (GWAS) that identify genetic variants associated with sleep in humans,” Keene said. “However, validating them has been an enormous challenge. Our team used a genomics approach called variant-to-gene mapping to predict the genes impacted by each genetic variant. Then we screened the effect of these genes in fruit flies.
“Our studies found that mutations in the gene Pig-Q, which is required for the biosynthesis of a modifier of protein function, increased sleep. We then tested this in a vertebrate model, zebrafish, and found a similar effect. Therefore, in humans, flies, and zebrafish, Pig-Q is associated with sleep regulation.”
Keene says the team’s next step is to study the role of a common protein modification, GPI-anchor biosynthesis, on sleep regulation. In addition, he notes that the human-to-fruit flies-to-zebrafish pipeline the team developed will allow them to functionally assess not only sleep genes but also other traits commonly studied using human GWAS, including neurodegeneration, aging, and memory.
“Understanding how genes regulate sleep and the role of this pathway in sleep regulation can help unlock future findings on sleep and sleep disorders, such as insomnia,” said Gehrman, an associate professor of clinical psychology in psychiatry at Penn and a clinical psychologist with the Penn Chronobiology and Sleep Institute. “Moving forward, we will continue to use and study this system to identify more genes regulating sleep, which could point in the direction of new treatments for sleep disorders.”
Keene’s research within his Center for Biological Clocks Research-affiliated laboratory lies at the intersection of evolution and neuroscience, with a primary focus on understanding the neural mechanisms and evolutionary underpinnings of sleep, memory formation, and other behavioral functions in fly and fish models. Specifically, he studies fruit flies (Drosophila melanogaster) and Mexican cavefish that have lost both their eyesight and ability to sleep with the goal of identifying the genetic basis of behavioral choices which factor into human disease, including obesity, diabetes, and heart disease.
Reference: “Variant-to-gene mapping followed by cross-species genetic screening identifies GPI-anchor biosynthesis as a regulator of sleep” by Justin Palermo, Alessandra Chesi, Amber Zimmerman, Shilpa Sonti, Matthew C. Pahl, Chiara Lasconi, Elizabeth B. Brown, James A. Pippin, Andrew D. Wells, Fusun Doldur-Balli, Diego R. Mazzotti, Allan I. Pack, Phillip R. Gehrman, Struan F.A. Grant and Alex C. Keene, 6 January 2023, Science Advances.
DOI: 10.1126/sciadv.abq0844
The study was funded by the National Institutes of Health.
