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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.”

Mireille Gillings Fellow will innovate to improve lives of frail older people

Over her career, Professor Sallie Lamb has developed a huge respect for the older people she works with on her ground-breaking rehabilitation programmes.

Professor Lamb, Mireille Gillings Professor of Health Innovation, has recently joined Exeter, having worked with a wide range of patients over the years, and has a specialism in frailty.

“I really admire how tenacious so many older people are,” said Sallie, who joins Exeter from Oxford University. “They’re the most vulnerable, yet they’re the ones who try the hardest and complain the least. I think it’s because they already know what losing their mobility feels like. They want to do everything they can to prevent that further and to get better, and they’re willing to fight for it.”

Sallie’s Fellowship at Exeter will help her develop more tools for older people to combat frailty. She has already had huge success in other areas, developing a programme for the common and often debilitating issue of lower back pain that was acknowledged as one of the most successful innovations in the NHS. The programme uses a cognitive behavioural approach to promote appropriate physical activity, which can effectively reduce symptoms over the long term.

“If you’re in a lot of pain, you feel like you can’t move and that you should lie still in bed – but that creates a vicious cycle of making the symptoms worse. With back pain, you really need to move to relive the symptoms. Our programme teaches people how to pace themselves and what type of activities to select, plus what to do if you get a setback.”

As a marker of the success of the programme, thousands of health professionals have so far undertaken a free online learning course, known as a MOOC, to upskill in the programme.

At Exeter, Sallie’s research will focus on frailty, an area where the College of Medicine and Health has existing expertise including Professors Louise Allen and Vicki Goodwin. “It’s a really exciting opportunity,” said Sallie. “There’s a huge opportunity to drive forward innovation and improve the health and wellbeing of older people – and particularly to improve mobility, which is key to a healthy and active life.

“The funding from the Gillings Foundation is really going to accelerate the development of a strong research programme to complement the existing research going on at Exeter. It’s a huge boost and will really accelerate getting this research to a point where it benefits people in need.”

Sallie is known for her rigorous approach to research, previously leading the Oxford Clinical Trials Research Unit, and will contribute to expanding capacity and expertise in clinical trials and medical statistics in the South West. .

A key aspect of the Fellowship appointments is a commitment to promoting women, a passion shared by entrepreneur Mireille Gillings. Sallie said she found herself in a role model position by leading by example, and as mother to 7-year-old Emelia, she is passionate about promoting work-life balance while enabling career progression.

“I’m also really committed to promoting a culture of teamwork between academic and professional services staff,” said Sallie. “People in professional services roles are absolutely critical and it’s important that’s recognised and valued.

“I’m really excited to join so many excellent scholars at Exeter, at such a dynamic time of growth and development.”

New Fellowship will tackle overlap between cancer and diabetes

Around 415 million people worldwide have diabetes, while 100 million people have cancer. They are unequivocally two of today’s greatest global health challenges. In bringing her world-leading knowledge of cancer to Exeter’s renowned diabetes research team, Professor Chrissie Thirlwell aims to benefit people with both conditions.

The newly-appointed Mireille Gillings Professor of Cancer Genomics will investigate the increased risk of some cancers in type 2 diabetes and obesity.

“If you have type 2 diabetes, you have a 20 – 30 per cent increased risk of developing certain cancers including bowel, liver and pancreatic cancer. The potential mechanisms underlying this increased risk are complex and incorporate lifestyle, dietary and other known risk factors such as obesity. The first step will be to determine any specific mechanisms associated with type 2 diabetes or obesity individually.

“The Mireille Gillings Fellowship has given me the infrastructure and opportunity to bring together my experience of cancer genomics and the wealth of world class research in diabetes and obesity at Exeter. It will accelerate our understanding of the increased cancer risk through utilising genomic data that has already been generated while producing new epigenetic data which will inform us about the impact of lifestyle on cancer risk.”

Chrissie’s expertise neatly crosses over with several research strengths at Exeter’s College of Medicine and Health and the wider university. She has natural synergy with Professors Sian Ellard and Andrew Hattersley in genomics, including a shared involvement with Sian in the 100,000 Genomes Project. Chrissie will join the Genomic Medical Centre team bringing her cancer genomics experience at a pivotal time when the 100,000 genomes project is being completed and DNA sequencing is becoming a routine part of patient care through the delivery of the next 5 million genomes.

The research funded by the Mireille Gillings Fellowship dovetails with several other groups in the RILD allowing new and exciting collaborations including with Professor Tim Frayling in large-scale genome-wide association studies looking for patterns in genes, and Professors Jon Mill and Katie Lunnon in epigenetics, or the study of how genes are activated, and Prof Lorna Harries in how genes are transcribed. Like Professor Noel Morgan, she is also already looking at clusters of cells known as islets in the pancreas, and how they contribute to the development of pancreatic neuroendocrine tumours.

Chrissie plans to apply these burgeoning collaborations to her new research and her body of work studying neuroendocrine tumours – rare tumours that can grow in different body organs. The international collaborations she has established to aid understanding and improve treatment have made her a global authority.

A large aspect of the Gillings Fellowship, supported by entrepreneur Mireille Gillings, is a commitment to promoting women in leadership roles. Through her involvement in UCL Cancer Institute’s Athena SWAN team, where they secured a coveted silver award to recognise commitment to equality, Chrissie realised the extent of a problem that had been invisible to her. “I was at a stage in my career when I wasn’t even aware that so few senior roles were held by women. I naively thought a lot of it was down to personal choice around work-life balance and families. Through working with industry during the UCL Cancer Institute Athena SWAN process, I learned that there were many incredibly capable women who really wanted those opportunities – they just weren’t getting them. I was struck how the statistics are alarmingly similar across the public and private sectors in that only 20% of senior leadership roles are held by women.

“It has to be about the right person with the right skills to do the job, there’s so much evidence that having diversity across all areas in leadership roles and on executive boards, leads to a far more productive workforce.”

Now, the medical oncologist plans to continue her clinical work alongside her research, joining the Royal Devon & Exeter NHS Foundation Trust. She has bold ambitions for the region. “I’m really keen to link with other trusts and create a European Centre of Excellence for the management of neuroendocrine tumours in the South West. We have the expertise across the region and it would mean a huge benefit to patients.

“It always blows people away when I mention the statistic that one in two people born after 1960 will be diagnosed with cancer at some point in their lives. Yet I’ve seen through my working life that prognosis and treatments are continuously improving. We’re moving towards a time where cancer becomes a chronic disease that people live with, rather than die from. There have been recent improvements in early diagnosis, and Exeter’s research has contributed to that through Professor Willie Hamilton’s team, however there’s still more work to be done .
“We’ve also seen major advances in treatment, particularly through immunotherapy, which harnesses the patient’s own immune system to fight cancer cells. Being part of those advances make my job extremely rewarding. When a patient is referred to an oncologist, you generally look after them for life. You get to know them and their families really well, and these days, there’s so much more we can do to improve their prognosis and enable them to live as normal life as possible during and after treatment.”

Chrissie arrives at Exeter at an exciting time. The diabetes research team recently secured a major £6 million award as part of the Government’s modern industrial strategy. The award recognises excellence with capacity to grow, and aims to enable the research to reach the next level, through academic recruitment and investment in infrastructure and facilities.
A keen open water swimmer who swam the English Channel while completing her PhD, Chrissie is looking forward to exploring all that the South West can offer. “The lifestyle is the icing on the cake for me in moving to Exeter,” she said. “It’s such an amazing time to come here. I‘m passionate about education and the expanding Medical Sciences and Medicine programmes present some really exciting opportunities, alongside the many research opportunities. I’ve had an incredible welcome so far and I’m really looking forward to getting stuck in and making a difference.”