A healthy brain is a happy brain.
The American Brain Foundation recognizes that 1 in 6 people worldwide is affected by brain disease or a neurological disorder ranging from Alzheimer’s disease to epilepsy, stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and more.
The large number of people who live with one or more of these conditions also comes with a huge cost burden – about $760 billion each year in the U.S. alone.
Guoqiang Yu, professor in the Bradley Department of Electrical and Computer Engineering, and his team of researchers at Virginia Tech have been awarded $3.43 million by the National Institutes of Health (NIH) to explore new methods of treatment that would promote healing and alleviate some of the financial burden.
To do this, Yu and his team will build computational tools and models to better understand the functional role of astrocytes in the brain. Until now, most of the research and treatment of brain diseases and disorders has been primarily focused on neurons, but those research findings haven’t delivered much relief for the patients.
The astrocyte is the most abundant glial cell in the brain. Glial cells hold the nerve cells in place and help them function the way they should. Astrocytes significantly outnumber neurons in the human brain. Long thought to be primarily a passive cell, the astrocyte has been increasingly recognized as an essential player with an active regulatory role in neural circuitry and behaviors, such as decision-making, memory, and learning.
Yu, who specializes in the fields of bioinformatics and neuroinformatics, hopes that by focusing his research on astrocytes, new and more effective treatments can be developed and used to save lives.
“Astrocytes participate in almost all aspects of brain function, so it is expected that the proposed tools we are creating will have a very broad impact,” said Yu. “We anticipate that this research will create opportunities for application in basic mechanistic studies such as synaptogenesis, neuroimmunology, myelination, and blood-brain barrier. We also expect applications to various diseases such as Alzheimer's disease, autism, epilepsy, and Parkinson’s disease.”
The hope is that a deeper understanding of astrocytes in the brain will help advance the development of new drugs and other treatments. Additionally, the team’s work will focus on the brain’s system of complex signaling, or the way information is transmitted from one area to another. Because this process also occurs in other organs, the tools developed for astrocytes could be broadly applied to medical conditions affecting other areas of the body.
Yu will focus on the project’s machine learning aspects as well as bioimage analysis and algorithm and software development. An award-winning researcher, he has a proven track record when it comes to knowledge of biology. He did postdoctoral training at Stanford University School of Medicine and has published several papers with a biomedical focus. His hope is to utilize that expertise to improve the lives of many.
“As an engineer, I have always been interested in solving challenging and complex problems. Recent advancements in biotechniques generate needs and provide opportunities for the invention of new and sophisticated computational methods,” said Yu. “Understanding how the brain works and dysfunctions remains a huge task. We hope our expertise in machine learning and mathematical modeling can contribute to resolving this ultimate scientific mystery and further addressing the continuingly increasing mental health problems in society.”
The five-year project includes a subcontract of $800,000 to University of California, Davis (UC Davis). Lin Tian, a professor and vice chair of the Department of Biochemistry and Molecular Medicine at UC Davis Health, serves as co-investigator of the project. The team is collaborating with Tian to establish an imaging and analytic protocol that examines the astrocyte calcium in a stem cell-derived brain model based on preliminary data that Tian has collected from a previous study of her own.
The UC Davis team will also contribute to the overall goal of the project by developing color-shifted sensors. Those sensors will allow researchers to analyze and study multiple images at once. Viewing multiple images at once will allow the team to understand the interaction between astrocytes and other cells like neurons, oligodendrocytes and microglia.
Yu’s team is also working closely with Misha Ahrens of the Howard Hughes Medical Institute’s Janelia Research Campus. Ahrens, a leading expert in brain imaging, is well-known for conducting brain and behavior studies using zebrafish as a model organism. Ahrens provided the team with valuable preliminary data on astrocytes and their role in decision making.
The subcontract and research contributions from other universities are extremely important to the overall success of the project, said Yu.
“We are working in an interdisciplinary field. Collaborating with other researchers from peer institutions, we can achieve things none of us can achieve alone,” said Yu. “New ideas can often be inspired by the interaction. Very importantly, different angles can be inspected through the collaboration so that a more complete picture can be seen.”
Yue "Joseph" Wang, the Grant A. Dove Professor in the Virginia Tech College of Engineering and co-principal investigator of the project, is responsible for applying systems theory to understand astrocyte’s calcium signaling.
Wang, who previously has been involved in molecular analysis of Parkinson’s disease and mental disorders, is optimistic about the impact this work could have on the nearly 1 billion people around the world with neurological disease.
“The discoveries from this project will provide novel insights about the active functional roles of astrocytes in neural circuitry and behavior that could be useful for improved understanding and interventions,” said Wang.
The NIH Research Project Grant Program (R01) providing funds for the project is the original and historically oldest grant used by the organization. It tasks the investigator with completing a project based on their interests and competencies while upholding the mission of the NIH. That mission is to “seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.”