How zebrafish could help unlock new approaches to treating human stress

In the thick of job hunting and her postdoc, Professor Soojin Ryu’s sleepless nights provided her first personal insight into the impact of stress on the brain and behaviour. The revelation would shape a research career that is transforming understanding of stress.

“One day it struck me – when I’m stressed I don’t sleep. I got to thinking about the impact of that on the body and on a person’s life, and the consequences are huge. If you’re stressed and not sleeping you can start behaving like an unpleasant human being – agitated and short-tempered, and ultimately you can become really sick. As a modern society, we’ve decided to ramp up our stress hormone to the point that it’s life-threatening. I find that fascinating.”

Now, Soojin has joined the University of Exeter as Mireille Gillings Professor of Neurobiology, heading up a group that studies zebrafish to examine how acute and chronic stress change behaviour and its longer term consequences on the body and brain.

In her early career, in Berkley, Soojin worked in cells, but found the research ultimately unsatisfying. “I spent a number of years working on cell culture, but then I’d ask myself – ‘ is that what’s really happening in the body’?”

She wanted to work in small vertebrate, in which changes in response to hormonal fluctuations occur quickly. She chose zebrafish as the best option, pioneering a new animal model to study stress by discovering important aspects of how they respond to stress.

“Of course, zebrafish are really very different from humans, but it’s important to recognise which aspects are similar,” Soojin said. “I realised that the evolutionarily ancient brain stress response is similar in both humans and zebrafish.”

At the Max Planck Institute in Germany, Soojin started her own research, creating a genetically-modified zebrafish in which scientists are able to manipulate stress hormone levels at will. Published in Nature Communications, the work helped address some of the difficulties researchers had encountered in studying stress. In her last post at the University of Mainz, Soojin was part of a network applying basic stress research to human resilience.

“Some level of stress hormone is beneficial, but once it hits a certain level, it becomes detrimental to the body and brain,” explained Soojin. “Stress can be life-saving. Our stress hormone levels rise shortly before we awake and it helps ensure our systems are ready to respond. The stress hormone is fundamental to animal survival. We need the right level of stress for the appropriate situation and our bodies need to be able to regulate that to be healthy. We know that depressed people have different patterns of stress hormone where that regulation can falter.

“For the first time, our zebrafish model allows us to precisely control both the stress hormone level and the duration which is necessary to understand different effects of stress. That’s why it’s so exciting for the future of stress research.”

One important aspect of securing the Gillings Fellowship was a commitment to promoting women in science, an issue close to the heart of philanthropist Mireille Gillings. Soojin has mentored a number of female scientists and has organised workshops and meetings for women in neuroscience, to discuss the issues they identified as important. Her interest also stems from a personal passion driven by her need to balance work with parenting her eight-year-old daughter Leia. “As a mother, I am deeply committed to helping women combine scientific career with family,” she said.

“I’m delighted to join Exeter. Having seen how successful our model is, I’m passionate about collaborating with people who are working on human health to form a translational network to ensure it benefits people as swiftly as possible. Exeter has a strong focus on mental health and has amazing growth potential. I’m looking forward to working with my new colleagues to explore new treatment targets.”

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