An illustration of human brain activity. Credit: Getty Images

Yubing Sun and Jun Yao Obtain NSF Award to Create More Lifelike Brain Organoids

Jun Yao (left) and Yubing Sun
Jun Yao (left) and Yubing Sun

Yubing Sun, associate professor of mechanical and industrial engineering, and Jun Yao, associate professor of electrical and computer engineering, have received a three-year, $564,510 award from the U.S. National Science Foundation (NSF) to create more lifelike neural organoids – in vitro tissues artificially grown from stem cells that closely resemble parts of, and are excellent tools for studying, the human brain. 

Their NSF research will develop more realistic neural organoids that better mimic real human-brain structures and embody more accurate interactions among various regions of the brain. 

“Very briefly, this project is to derive better brain organoids and track their development using our unique engineering tools,” says Sun, the project’s principal investigator. “Neural organoids are excellent tools to study the development of human brains. However, they do not fully represent the brain structure. It is also difficult to record neuronal activities for a long time in neural organoids.”

Sun goes on to say that current, state-of-the-art, neural organoids are still restricted by their “lack of regionalization,” or the inability to mimic real human-brain structures realistically and simulate life-like interactions among those structures. What’s more, current neural organoids lack the proper electrical hardware to monitor their development continuously over extended periods of time. 

“This project aims to transcend these key limitations by developing an engineered neural-organoid system that is properly regionalized and innervated with a tissue-like electronic mesh system capable of chronic monitoring and stimulation for improved studies of circuitry development in the neocortex,” says Yao, co-principal investigator on the project.

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To address all these challenges, Sun and Yao are pursuing three key objectives. First, a new approach will be developed to derive neural organoids that better mimic brain structures. Those improved organoids will be assembled to represent true-to-life interactions between various brain regions.

The second objective is to incorporate tissue-like, ultra-flexible, mesh electrodes into these new organoids. Mesh electrodes are known to have minimal impacts on cells and can safely monitor the electrical activities of neurons on a continual basis. Previously, Sun, Yao, and their collaborators had successfully demonstrated the integration of this kind of tissue-like mesh system into in vitro cardiac tissue. Now they are confident that similar technology can be applied to the more sophisticated brain organoids for their advancement.

The third objective is to investigate if the act of applying electrical stimulation to neural organoids can significantly accelerate their maturation, which usually takes several months before they’re ready for research purposes. 

As Sun and Yao conclude, “Together, this project will lead to improved neural-organoid models and new knowledge of human-brain development.” 

The project will also support various educational and outreach activities, including new course development, undergraduate research projects, and paid internship programs. 

Sun and Yao add that “Highly motivated regional high-school, undergraduate and graduate students from diverse backgrounds will have opportunities to engage in stem-cell research, which will facilitate the recruitment and retention of students in this exciting field.”