BSc, Biological Sciences and Biotechnology, BSc, Solid State Physics, Tsinghua University, Beijing, China
PhD, MPh, MSc, Molecular, Cellular and Biophysical Studies, Columbia University
Growing up in China, Ron Yu, PhD, loved looking at the stars, and considered studying astrophysics in college. But when a top-ranking university in Beijing offered him a spot in a new biological sciences program, even waiving the extensive college entrance exam, he couldn’t say no. That decision was one among many paving the way for Yu to become a leading authority on the complex neural circuitry of behavior. “Life is full of happy accidents,” he says.
At Tsinghua University, Yu added physics classes to his already grueling schedule and graduated with a major in biology and a minor in physics. He was accepted into graduate programs at Northwestern University in Chicago, his first choice, and Columbia University in New York City. Then fate intervened again. Northwestern wasn’t able to process the paperwork for his student visa. Columbia was. It was another happy accident. At Columbia, working with Lorna Role, PhD, on ion channels, Yu discovered the joy of recording electrical signals from cells. He built his own electrophysiology rig from scratch, mesmerized as he watched neurons respond to different stimuli.
“With electrophysiology, you can really see that happening right in front of your eyes,” explains Yu, who likens the process to a conversation. “You expect the neurons to fire one way, and sometimes they do, and sometimes they don’t. When they don’t, you try to figure out what they’re trying to tell you.”
Yu didn’t start studying genetics and molecular biology until his postdoctoral position in 1996. He began to work on a collaborative project between Role and the legendary Richard Axel, MD, at Columbia University. In 1991, Axel had cloned the first odorant receptors, for which he was awarded the Nobel Prize in 2004. A serendipitous hallway chat about the “molecular shenanigans” Axel employed to remove cell types from the nervous system by deleting certain transcription factors was a lightbulb moment for Yu. The transcription factors were like switches. When one switch is on, a principal neuron, like one connecting the nose to the brain, is generated. When switched off, or when the gene is deleted, then those cells never have the chance to develop. “I realized one can harvest the power of genetics to study the function of the nervous system,” he says. Working at Columbia and then at the Stowers Institute, which he joined in 2005, Yu has combined molecular genetics, electrophysiology, optical imaging, and studies of animal behavior to explore the biology of behavior.
In his time outside the lab, Yu enjoys classical music. He likes to stay active, running, swimming, and exercising in the Kansas City area. He got into competitive inline skating while a postdoc in New York, and still straps the skates on from time to time. And on a clear night, you might find him and his wife gazing at the night sky with his two children. “It’s kind of a pity that the youth today don’t get to see the stars much,” he says. “We tend to bring our kids where they’ll be away from the city lights to give them that experience.”
The Yu Lab investigates the complex connections between neurons that link sensation to behavior. In particular, he and his team study the mouse olfactory system, which detects odors, and the related vomeronasal system, which detects pheromones. Uncovering the mechanisms at work could advance scientific understanding of the development of nervous system and neurological diseases.
“Communication is all mediated through our senses,” Yu explains. “Our eyes are not cameras and our noses are not simple chemical detectors. The brain has a way of synthesizing information and relating it to our memory. Our experience changes how we perceive things. We’re having a lot of fun figuring out how.”
The Yu Lab was the first to establish a mouse line using genetic tools to detect calcium signals in the nervous system, a major advance in the field. Up to that point, researchers had to rely on invasive techniques to watch a neuron’s response. This development allowed researchers to record signals for hundreds of cells simultaneously. Using this technique, Yu and his team reported in a groundbreaking 2008 Science paper how completely different sets of neurons respond to male or female pheromones. They shared another breakthrough discovery in 2014 in Science of a brief “critical period” in the mouse olfactory system to fix neuronal wiring problems — a window that lasts until about a week after mice are born. Yu and his team have also identified two classes of pheromone receptors crucial for the mating process in mice, a landmark finding reported in eLife in 2014.
Going forward, Yu’s team is continuing to study the molecular mechanisms that control the critical period, with grant support from the NIH’s National Institute on Deafness and Other Communicative Disorders. The researchers also plan to investigate how developmental and aging processes affect the sense of smell. The inability to smell is often the earliest sign of neural degenerative diseases such as Alzheimer’s and Parkinson’s. The lab also has taken a turn toward physiological and theoretical studies of how neuronal information is processed by the brain circuits.