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The Old Well surrounded by yellow flowers.Biologists Celia Shiau and En Yang at UNC-Chapel Hill have been awarded a competitive Chan Zuckerberg Initiative (CZI) grant to tackle unsolved grand challenges in neurodegenerative diseases and fundamental neuroscience. The awards were announced on Feb. 21.

Shiau is an associate professor and Yang is an assistant professor in the department of biology in UNC’s College of Arts and Sciences. Shiau has a secondary appointment in microbiology and immunology in UNC’s School of Medicine.

headshot of Celia Shiau
Celia Shiau

The scientists received a 2024 CZI Neuroscience Collaborative Pairs Pilot Project Award for their project “Mapping Cholesterol Dynamics across Brain-wide Neural Circuits.” This is only the second cycle of these awards since 2018. The awards are given to a pair of investigators and their teams to use innovative, interdisciplinary approaches to tackle new and bold directions of neuroscience.

The CZI Neurodegeneration Challenge Network brings together experimental scientists from diverse research fields to accelerate fundamental neuroscience and neurodegenerative disease research that leads to the development of new strategies for the treatment and prevention of neurodegenerative disorders.

Through their project, Shiau and Yang will study cholesterol dysregulation, which has been linked to a variety of neurological disorders including those causing severe cognitive decline, but the basic questions of exactly how cholesterol is properly maintained for normal brain function remains poorly understood. Scientists still do not understand how irregular brain or body cholesterol levels are associated with altered cognitive abilities.

“We’re diving deep into understanding how cholesterol affects the brain, especially in diseases like Alzheimer’s and after brain injuries,” Yang said. “We’re not just looking at what happens in the brain itself but also considering how cholesterol from the body might impact brain health.”

Headshot of En Yang
En Yang

Shiau and Yang will employ high-dimensional analysis of this complex process by leveraging their complementary expertise. They will use the translucent larval zebrafish as an experimental model to directly visualize and manipulate cholesterol dynamics in the brain and whole body. Combined with cellular-resolution whole-brain activity imaging and computational modeling in behaving animals in controlled virtual reality environments, they will seek to understand how cholesterol impacts brain-wide neural circuits and cognitive functions such as learning and memory.

“The vision of CZI to support science that takes new and bold directions allows investigators to go after big questions they dream of asking but are not possible without the support of high-risk projects and the right fusion of expertise,” Shiau said.

The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges — from eradicating disease and improving education to addressing the needs of local communities.

“This exciting work highlights how research into fundamental biological mechanisms in experimentally tractable organisms like zebrafish can inform our ability to understand, and hopefully one day treat, neurodegenerative diseases,” said Bob Duronio, professor and chair of the department of biology. “It also illustrates how collaborative work from researchers with overlapping but distinct expertise and perspectives is what truly drives innovation.”

Learn more about Pairs Pilot Project Award grantees.



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