Stellar Science Foundation (SS-F) is dedicated to “advancing the world through the power of science.” Upholding the philosophy of “People-Centric”—born from people, connecting people, and expanding through people—SS-F pursues the essence of scientific research and seeks to amplify its impact.
The “Inventor’s Vision” series highlights the work of “Stellar Inventors,” researchers who approach science with unparalleled perspectives and imagination. By delving into their motivations, worldviews, and human qualities, the series aims to uncover the potential of “People-Centric” science.
In the inaugural installment, we interviewed Yu Hayashi, whose research focuses on answering the question, “Why do we sleep?” In a groundbreaking paper published in Cell in September 2024, Dr. Hayashi identified nerve cells responsible for regulating REM sleep in humans. This discovery has garnered significant attention for its potential to contribute to the early detection and treatment of conditions such as Parkinson’s disease.
Reflecting on his journey, Dr. Hayashi expresses, “It’s truly fortunate to have encountered such a compelling research theme like sleep.” He emphasizes that the essence and allure of research lie in “unexpected discoveries.” From his childhood fascination with living organisms to becoming a leading researcher probing the mysteries of sleep, this is his story.
Rarely is research ‘predictable.’
── Dr. Hayashi, after more than a decade of work culminating in the discovery of nerve cells responsible for regulating REM sleep, we’re excited to explore the motivations and personal journey behind your achievement. What moments in your research bring you the most excitement?
The most exhilarating moments are when unexpected discoveries emerge, especially when they’re still known only to me and a few in my lab.
For instance, I was thrilled to discover that blood flow during REM sleep was much higher than anticipated. Previously, it was thought that REM sleep and the wakeful state during physical activity were similar. Observing the blood flow revealed a completely different state, which was both surprising and fascinating.
── Unexpected discoveries, indeed.
Discoveries that diverge from expectations are integral to research. In fact, it’s almost rare for things to progress exactly as hypothesized.
For example, a neural circuit we believed activated REM sleep turned out to strongly suppress it instead. Nature often delivers outcomes contrary to the hypotheses we, as researchers, construct. That’s precisely why the time and resources invested in experiments are worthwhile.
── Encountering completely unexpected results is the true essence of research and one of its most fulfilling moments, isn’t it?
Yes, absolutely. Sleep research is filled with mysteries, and that’s precisely what makes it such a fascinating topic. We still don’t fully understand why sleep is essential for humans.
I hope that we’ll uncover the answer in the future, and I want to get as close to it as possible. I truly feel fortunate to have come across such a compelling research theme as sleep.
From a childhood fascination with animals to a focus on sleep research
── It’s inspiring that you consider yourself so “fortunate” to have found this research theme. Could you share your roots and journey leading to this discovery? What fascinated you as a child?
I’ve always loved living creatures, especially animals.
I had a particular fondness for fish. As a child, I lived in Texas, where I often went fishing. I caught black bass, bluegill, and catfish in rivers. Unlike Japan, even catfish thrived in the sea. While I didn’t know much about Japanese fish, I enjoyed imagining them through picture books my grandparents sent me from Japan, including species like sea bream.
In fifth grade, my family moved to Fukuoka, where I spent the rest of my elementary school years. Fukuoka’s rich natural environment, particularly the biodiversity in the Muromi River, left a lasting impression on me.
── At that time, the keyword “sleep” hadn’t yet appeared in your research, had it?
That’s correct. Reflecting back on my senior year of high school, when I was considering my future academic path, my interest was still centered on biology. In particular, I was fascinated by how living organisms could perform complex behaviors without being explicitly taught.
When I entered university, I joined the laboratory of Professor Takeo Kubo, who studied various organisms like honeybees. There, my research focused on nematodes, but I eventually shifted to studying the brain and its developmental mechanisms. That was the starting point for my focus on sleep research.
For example, honeybees undergo distinct behavioral changes as they age—starting as nurse bees caring for the brood, then becoming guards at the entrance of the hive, and finally transitioning to foragers venturing outside. Even in university, I was captivated by such animal behavior and ecology.
To better understand animal behavior, the brain became a key area of focus. Naturally, I developed an interest in the brain and began studying its development through a cellular biology approach. Over time, I wanted to explore more complex neurobiological methods, which eventually led me to focus on sleep.
── So it was through delving into animal behavior and ecology in university that you encountered the theme of “sleep.” When did you officially begin studying sleep?
It was during my postdoctoral work in the laboratory of Dr. Shigeyoshi Itohara at RIKEN. Prior to that, as a graduate student, I had been researching the neural development of nematodes.
Interestingly, I recently had an opportunity to conduct experiments using nematodes in my current lab. While my research now focuses on REM sleep, I’ve noticed many parallels between non-REM sleep and the sleep-like states observed in nematodes and mice. The experience I gained from studying nematodes continues to inform my work, and I believe it will remain valuable in the future.
“Sleep Manipulation Medicine” to Extend Healthy Lifespans
── Was there a specific moment when you decided to pursue a career as a researcher?
Hmm… I wouldn’t say there was a definitive moment. I didn’t participate in job hunting; instead, I went straight into a doctoral program. As I continued enjoying the research in front of me, I naturally found myself on this path. So, it’s hard to pinpoint a specific turning point.
That said, I’ve always found research enjoyable, ever since I started working on my undergraduate thesis. Even though I didn’t initially have the confidence to see myself as a researcher, the joy of research itself was a constant.
── Looking back now, what were some key turning points in your journey as a researcher?
There are a few, but the biggest turning point was undoubtedly shifting to sleep research during my postdoctoral stage. Another significant milestone was becoming an independent researcher at the relatively young age of 32, establishing my own lab.
I set up my lab when Tsukuba University established its Sleep Research Institute. Taking on the role of a principal investigator (PI) while my track record was still limited was daunting. However, in hindsight, it was an excellent decision. Being a PI and conducting research differs significantly from doing research as a postdoc or student.
For example, as a PI, I had to find everything for myself, including the lab space and office. Up until then, I had worked in environments prepared by my mentors. As a PI, I had to start from scratch, building the research environment myself. Setting up a facility for genetic experiments, in particular, involved overcoming numerous hurdles, requiring extensive negotiations. Taking on these challenges early on provided valuable training that has had a lasting impact on my career.
── It seems like the shift in your role brought new challenges, which significantly influenced your activities as a researcher.
Absolutely. Another pivotal experience was joining Tsukuba University’s Sleep Research Institute, where I had the opportunity to work with Dr. Masashi Yanagisawa, a prominent sleep scientist. Dr. Yanagisawa, who had extensive research experience in the U.S., often mentioned how some American researchers could publish papers in top journals like Nature or Cell at a pace of about one per year. However, Dr. Yanagisawa focused on producing extremely impactful discoveries every few years, a style I greatly admired.
Dr. Yanagisawa also strongly believed that researchers should be freed from administrative tasks. He allocated significant resources to support staff and infrastructure, enabling researchers to focus solely on their work.
One of Dr. Yanagisawa’s guiding principles was, “Truth is stranger than hypothesis.” This encapsulates the idea of uncovering unexpected discoveries in research. This philosophy profoundly influenced me. Dr. Yanagisawa’s firm beliefs and approach have been invaluable lessons in shaping me as a researcher.
── Reflecting on your journey, what societal challenges do you hope to address through your research moving forward?
Even among otherwise healthy individuals, it’s been observed that REM sleep declines significantly in those over 90 years old. Developing solutions to address this issue and extend healthy lifespans is one of my primary visions.
We refer to this field as “Sleep Manipulation Medicine,” and we aim to develop it into a new branch of medical science. Currently, our research focuses on understanding the abnormalities associated with REM sleep. Specifically, we are investigating whether activating the nerve cells we recently discovered can improve cognitive function and reduce inflammation in patients with Parkinson’s disease, dementia, and depression.
Improving sleep not only addresses issues like insomnia but can also enhance overall health and contribute to the prevention of various diseases. To achieve this, we will continue to iterate and refine our approaches.
(Text: Tomohiro Kurimura, Photos: Kayo Sekiguchi, Interview and Editing: Masayuki Koike)
