Zebrafish are making a big splash at the Virginia Tech Carilion Research Institute. Smaller than a human’s pinky finger, the translucent fish offer a perfect view into their developing brains.
“They’re small enough that we can see every neuron in their body through a light microscope,” said Albert Pan, an associate professor in the VTCRI Developmental and Translational Neurobiology Center (DTNC). “We can follow the full process of neuronal development in zebrafish. It’s a dynamic model to understand the developmental aspect of psychiatric disorders in humans.”
Pan moved his laboratory this summer from the Medical College of Georgia at Augusta University to join the VTCRI, where he also serves as the Commonwealth Research Commercialization Fund Eminent Research Scholar in Developmental Neuroscience.
Pan earned his doctoral degree in neural development under the mentorship of neuroscientist Joshua Sanes, working on nerve regeneration and axon outgrowth in mice. While finishing up his doctoral training with Sanes at Harvard University, Pan became intrigued with zebrafish as an animal model to study brain development and various neurological disorders. In 2005, Alex Schier, a zebrafish developmental biologist had just been recruited to Harvard from New York University.
“At a departmental retreat, Alex showed a movie of hundreds of nerve fibers sprouting in all directions in a live zebrafish and I was just blown away,” Pan recalled. “I was also tired of waiting weeks after weeks for mice that may or may not have the correct combinations of genetic modifications I need. Getting 200 zebrafish embryos to work with every week sounded really appealing.”
Pan soon joined Schier’s lab as a postdoctoral fellow and began developing new tools to visualize neurodevelopment in zebrafish. At Harvard, Pan adapted the Brainbow technique for zebrafish, which is a way to fluorescently label cells in a wide array of vibrant colors. Michael Fox, an associate professor and director of the VTCRI Developmental and Translational Neurobiology Center, also uses the Brainbow technique in his lab at the VTCRI to track retinal development.
Pan also developed a virus-based neuronal tracer, allowing for the systematic mapping of the zebrafish brain.
“One limitation of conventional neuronal dyes is that the dye does not spread from cell to cell,” Pan said. “There is no way to find out how neurons are connected to each other via synaptic connections.”
In collaboration with Connie Cepko, a professor of genetics and ophthalmology at Harvard Medical School, Pan used a virus to infect neurons and make the neurons express different colors. The virus fluorescently labels neuronal connections and never gets diluted.
“It’s a great technical challenge, but now we can quantify neuron types and study specific populations, such as zebrafish with a gene associated with neuropsychiatric conditions such as autism spectrum disorder,” Pan said.
At the VTCRI, Pan plans to improve upon the virus technique, and use it to examine genetic lesions and how they influence the development of connections in the brain and how neurological deficits affect simple motor behaviors like eye movements.
“My work intersects with a lot of the research programs already in place here,” Pan said. “It’s a vibrant and active scientific community. I feel that the people here are on the leading edge of their respective fields. It’s an opportunity to learn.”
Pan is also enjoying the amenities of Roanoke. In his first month here, he achieved several area hiking feats with his wife, Yushen, and two children, 10-year-old Meribel and 6-year-old Thomas. “It’s nice that people embrace living in Roanoke—it’s not just a suburb of a big city where people disappear on the weekends,” Pan said. “The mountains are certainly a plus!”
Pan isn’t the only one pleased to be in Roanoke.
“We’re glad to have Albert here,” Fox said. “He complements existing strengths in the development of neural circuits that exist at VTCRI, but he brings with him an entirely new toolkit and set of approaches that add strength to the research portfolio of the center and the institute. In zebrafish, we can begin to model human psychiatric disorders and identify potential therapeutic targets.”
Michael Friedlander, executive director of the VTCRI, echoed Fox’s sentiment.
“Although technical advances are critical to drive the very leading edge of neuroscience, the intellectual creativity and boldness to explore concepts beyond the comfort zone of the field are also key attributes of innovation and discovery – Albert Pan has both,” Friedlander said.