Dr. Dayu Lin
Associate Professor Institute of Neuroscience & Department of Psychiatry, New York University Langone Medical Center
Postdoctoral Fellow California Institute of Technology
PhD in Neurobiology Duke University
Dr. Dayu Lin was not feeling optimistic as she prepared to try out a new technique called “optogenetics”. She had been trying to stimulate neurons in a particular part of the brain called the ventromedial hypothalamus (VMH), which previous studies suggested might be important for aggression. She expected that electrically stimulating this region in mice would cause them to fight with other mice, yet for half a year she’d only induced flight, never fight. Was her hypothesis incorrect, or was something going wrong in her experiments?
Dayu was ready to give up, but her postdoctoral advisor convinced her to use this new “optogenetics” trick - a method of using blue light to activate specific populations of neurons - to give the experiment one last try. As she expected from her many failed experiments, the first four mice she tried from her final cohort of six mice ran away as soon as she turned on the blue light to stimulate the VMH. But then, to her utter shock, when she turned on the light for mouse #5, it approached another mouse and began to attack! Dayu couldn’t believe her eyes. She flicked on the light again and again, and every time, mouse #5 began to fight. Feeling emboldened, she prepared another cohort of six mice, and this time, 5 out of 6 began to fight when she optogenetically stimulated that area. This success after months of frustration gave rise to a groundbreaking paper on how this brain area controls aggression and launched her academic career. Today, Dayu is an Associate Professor of Neuroscience at New York University, and her lab continues to unravel the neural circuits underlying aggression and other innate, social behaviors.
Dayu’s love for neuroscience came about gradually out of a more general interest in biology. At her university in Shanghai, China, where she grew up, there was no neurobiology major or even a neurobiology department. She became more interested in the brain while working on an undergraduate project related to Alzheimer’s disease, but even at the time that she was applying for graduate schools in the United States, her interests in biology were still very broad. While she applied for programs ranging from genetics to bioinformatics, she ultimately decided to join the neurobiology graduate program at Duke University. There, in her third research rotation with Dr. Larry Katz, she heard her first spikes while doing intracellular recordings from anesthetized animals. She was mesmerized by her first experience interacting with the brain in real time, stunned that she was literally hearing what was going on inside. Her interests only grew from there. She ultimately joined Larry’s lab and went on to study how complex odors are represented in the olfactory bulb. She discovered that individual olfactory bulb neurons called mitral cells were activated by specific compounds within complex odors, such as urine. She also identified a particular compound in male mouse urine which was attractive to female mice and drove a disproportionately large number of mitral cells to respond; in other words, the compound was a highly salient social cue that the olfactory bulb seemed to care about a lot.
These findings in the olfactory system led Dayu to become especially interested in innate social behaviors. That interest led her to her postdoctoral fellowship with Dr. David Anderson at CalTech, and it was in David’s lab that she made the seminal discovery about the VMH’s importance in aggression. She realized later that her months of failed experiments from electrically stimulating the VMH were likely due to the fact that the VMH is very small and packed with different functions. In fact, the specific part of the VMH that Dayu found to be important for aggression - the ventrolateral subdivision of the VMH (VMHvl) - is right next to another small region that is important for defensive behaviors. Thus, in her electrical stimulation experiments, she was likely stimulating both of these regions, and the drive for defensive behavior took precedence over the drive for aggression. Dayu points out that this is a common theme in the neural circuits underlying different types of innate, social behaviors; often, very different behaviors, like fight and flight, have nearby or even shared “nodes” in their underlying circuits. This is why Dayu’s lab studies not only aggression but also other innate social behaviors, such as sexual behaviors, that have overlapping circuitry. While her lab is currently focused on gaining a basic mechanistic understanding of these behaviors and how they are subject to change through experience, she imagines future work in her lab also looking at how these circuits go awry in states of hyper-aggression and violence.
In starting her own lab, Dayu was reminded of advice she received from her most influential mentor: her graduate advisor, Larry Katz. She recalls asking him what was the secret to being a successful scientist, and his response, after some thought, was “people”. Over time, Dayu has come to see the truth in that statement. The hardest part of starting her own lab, but what has ultimately helped her and her lab be successful, was identifying and attracting the best people. She draws energy from the people in her lab, as well as new ideas and perspectives for thinking about scientific questions. She also finds it immensely gratifying to witness her trainees’ own “ah-ha!” moments when they first discover something no one else in the world knows - like her own milestone moment when her mouse #5 began to fight instead of flee.
While Dayu always had the goal of becoming a PI in the back of her mind, she encountered moments of doubt and a critical decision point that nearly led her on a very different path. Three years into her postdoc with a great deal more work yet to do, she found herself in the difficult situation of having a two-year old child and a husband with a job on the opposite side of the country. Wanting to be reunited with her family, she decided to interview for a position where her husband worked and was offered the job. She was then faced with an agonizing decision: leave academia and take the job with twice her present salary and the promise of reuniting with her family, or continue to pursue her dream of becoming a PI? Unsure what to do, she burst into her advisor’s office and asked whether he thought she was “faculty material”. David responded with an emphatic, “Of course”. With the encouragement of her husband to pursue her dream and with David’s support to go on the job market immediately so that she could be together with her family as soon as possible, Dayu decided to give it a shot. Happily, she was ultimately offered a position at NYU and was able to reunite with her family and become a faculty member.
Dayu is so successful and passionate about her work that it’s hard to imagine that she nearly took a different path. In that critical decision moment, she says she realized that she could find other opportunities to change directions if a faculty job didn’t work out or if she was unhappy, but it would be much harder to return to an academic career if she decided to leave at that time. Even though it was a difficult decision, she is glad that she turned down the job offer to pursue her passion. Clearly things have worked out in her favor, and her lab continues to conduct ground-breaking research uncovering how circuits in the brain support the generation and modulation of innate social behaviors. And whenever they do new experiments in pursuit of milestone moments with fundamental new discoveries, they always use cohorts of at least six mice.
Check out Megan’s interview with Dayu on October 2nd, 2019 below!
