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��M�� and Collaborators Receive $1.68 Million NIH Grant

Alex Keene, Ph.D., an associate professor in ��MŮ��’s Charles E. Schmidt College of Science and a faculty member of the Jupiter Life Science Initiative. (Photo by Alex Dolce)

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A neuroscientist from ��MŮ��’s (JLSI) and collaborators from the and recently received a four-year, $1.68 million R01 research grant from the National Institutes of Health’s (NIH) National Institute of General Medical Sciences (NIGMS) for a project titled, “Understanding Complex Trait Architecture through Population Genomics.”

, Ph.D., an associate professor in ��MŮ��’s and a JLSI faculty member, is working together with fellow principal investigators, , Ph.D., an assistant professor in the College of Biological Sciences at the University of Minnesota, and , Ph.D., an assistant investigator at Stowers Institute for Medical Research, on this collaborative project that utilizes genomic and transgenic technology in Mexican cavefish (Astyanax mexicanus) to identify genetic loci that contribute to sleep, feeding, and metabolism.

“The Mexican cavefish exhibits a dramatic evolution of sleep loss, hyperphagia or overeating, and obesity compared to a surface fish of the same species,” said Keene. “They provide a unique and powerful model for identifying genetic factors regulating these traits.”  

As a result of living in total and permanent darkness in a small location in northeast Mexico, the eyeless, tiny blind Mexican cavefish has evolved sleeplessness, requiring far less sleep than their river-dwelling relatives. These fish have been studied for nearly 100 years for their fascinating traits, yet little is known about how their behavior evolves. Because of their lack of sleep, they provide a great model to study human sleep disorders such as insomnia.

“Because the cave environment differs dramatically from the rivers inhabited by surface fish, cavefish have evolved robust differences in foraging and feeding behavior, raising the possibility that differences in nutrient availability contribute to the evolution of sleep loss in cave populations,” said Keene. “Furthermore, multiple cave populations have evolved substantial reductions in sleep duration and enhanced sensory systems, and our prior research suggests that sleep loss is evolutionary and functionally associated with sensory and metabolic changes.”   

There are more than 29 different populations of cavefish and many of them evolved independently. Keene and his research team have generated transgenic fish lines and are able to image brain activity and genetically map anatomical differences between these Mexican cavefish populations.  

“Sleep and metabolic disorders present an enormous health burden globally and investigating the genes and neural circuits that regulate sleep loss will help to shed light on the interaction between insomnia, obesity, and metabolic disorders,” said Keene. “In addition, this research project has the potential to identify whether shared genetic architecture underlies changes in these traits, providing insight into the relationship between sleep loss and metabolic disorders.”

Beyond their immediate scientific goals, Keene, McGaugh and Rohner will establish transgenic and genomic tools and techniques to provide a valuable resource that can be applied to address questions beyond the scope of the grant project, including investigating eye-degeneration and autism.

JLSI is aimed at building educational and research capabilities in the life sciences on ��MŮ��’s in Jupiter, and is a collaborative effort between the Charles E. Schmidt College of Science and the .

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