Guoqiang Yu is forging new computational tools to shed light on the role of astrocytes—vitally important cells in the human brain. Astrocytes are little understood, but their impaired function may be associated with brain diseases such as Alzheimer's, stroke, epilepsy, and schizophrenia.
Yu, an assistant professor of ECE, is working on two RO1 grants from the National Institutes of Health (NIH) to help researchers understand astrocyte-neuron communication.
Astrocytes, from the Greek "star cells" in reference to their shape, are workhorses of the central nervous system. They wrap around neurons, nursing and protecting them; help to repair damaged tissue; maintain ion balance; and provide nutrients to nerve tissue.
Unlike neurons, astrocytes do not generate electrical impulses. They communicate among themselves and with neurons through chemical signals—including waves of calcium ions (Ca2+)—which aid the formation and function of synapses (connections between neurons) throughout the brain.
"A deeper understanding of the back-and-forth signaling between astrocytes and neurons in health and disease could lead to novel therapies for brain disorders," says Yu.
Researchers can observe these signals with advanced imaging, including microscopy and fluorescence, however the ability to analyze and interpret the data has lagged far behind, says Yu. "This has slowed the progress of brain disorder therapies," he says.
Correcting the lag
Yu, in collaboration with experimental neuroscientists from the University of California, Davis, is leading a $2.5 million grant from the National Institutes of Health to address this discrepancy. By developing novel computational tools, which draw strength from a variety of advanced machine learning techniques like graph-structured tensor decomposition (GSTD), the research team will analyze the cellular properties of calcium signaling in a single astrocyte.
Then, because so much of an astrocyte's function depends on how it operates within a network, the team will develop computational tools to analyze the properties of calcium signaling in a population of cells.
"The study of astrocytes at the network level has been unduly ignored so far," says Yu. "But we can gain insight into these inner workings by leveraging our experience in network biology and probabilistic modeling."
Finally, the team will package the developed computational tools into a user-friendly software program for experimental scientists. All source code will be available through public open-source hosting websites, so that anyone can modify and tailor the code to their specific application and need.
Understanding the injured brain
Yu's computational tools are already being put to work. He is currently collaborating with Stefanie Robel, an assistant professor at the Virginia Tech Carilion Research Institute, on another grant from the National Institutes of Health. Led by Robel, this project will test the hypothesis that astrocyte dysfunction induced by traumatic brain injury is a root cause of post-traumatic epilepsy.
"After years of assuming that neurological diseases are caused by direct damage to neurons, we now know that impaired astrocyte function precedes and is essential for the progression of many of these diseases," says Robel.
After identifying the primary cause of astrocyte dysfunction, the researchers will be monitoring neurons in areas with abnormal astrocytes to see if they become "hyperexcitable," which is a prerequisite for the development of epilepsy.
Yu and his team will be analyzing 2-photon in vivo imaging data acquired by Robel's team.