Ms Lu Li
Chinese Language Instructor
The Confucius Institute
An objective analysis of the impact of stress
A fascination with human biology and the desire to understand how the body works led Dr Lin Kooi Ong to biomedical science – and now neuroscience where he’s exploring the impact of stress on our health.
As Lin was concluding his undergraduate degree in biomedical science he connected with Professor Peter Dunkley who was the inspiration who honed Lin’s interest in the workings of the brain. Working with Peter first on his Honours year, and then his PhD, Lin’s fascination with the way that the brain works has driven him to specialise in neuroscience research.
“A lot of the basic science about the brain is still unexplored and unknown. We know it’s there, but what’s really happening in the brain with its network and cells all the way to the molecular level?” Lin asks.
With his research, Lin is focused on an increasingly common 21st century health problem – persistent stress. “A lot of people will say ‘Oh, I’m so stressed!’ but, as a neuroscientist with a biochemistry background, I’m really interested in defining what stress is and how it impacts on our health and wellbeing.”
Lin explains that the concept of stress can be confusing as the term is often used interchangeably with distress. “Stress, in a biological way, is the destruction of homeostasis – it impacts on our cell balance. Whereas distress is more of an emotionally unpleasant feeling.”
“As a scientist, I like things to be objective,” Lin says. “We need to be able to classify something such as a physical stressor: which is any threat which has a direct effect on your body or your cells.”
Lin’s research is exploring the parts of the brain which are activated during stress: primarily the catecholaminergic systems such as the locus coeruleus, the ventral tegmental area and the substantia nigra. These neurons transmit dopamine, noradrenaline and adrenaline as chemical messengers or neurotransmitters. “When you are stressed different parts of the brain region get fired up and stimulated. In the short term there are benefits to this, it keeps us alert and prepared for any danger,” Lin explains.
However, when stress is prolonged the effects on the body can be detrimental. During a period of stress the heart rate and blood pressure can be elevated and we get an adrenaline rush. “A small amount of stress is positive, it can improve our resilience and make us adapt to the next stressful event. But if the stress or distress load is high and it remains so for a long time, then it starts to shut down our body system.”
The potential health outcomes associated long-term stress are bleak, with stroke, heart disease and even Parkinson’s disease linked to long-term stress.
Could stress be a risk factor for Parkinson’s disease?
In late 2016 Lin and his team published results from a study linking stress to the development of Parkinson’s disease. With many neurodegenerative diseases, around five – ten per cent of the risk is due to genetic factors, but the remaining 90 per cent is due to idiopathic or unknown factors. “What’s causing the neurodegeneration is still unexplored and researchers are still trying to tease out what are the main components that really cause the brain to slowly die off.”
Taking literature from military doctors who documented Parkinson’s-like symptoms in soldiers after the war, Lin and the team recreated this in the lab through inducing mild stress in mouse modelling. The results showed that after six weeks parts of the brain starts to die off. “This part of the brain controls the motor functions so it’s an important discovery,” Lin adds.
“We think that chronic stress would be a potential risk factor for the development of Parkinson’s disease. It’s not surprising, because while 20 or 30 years ago a lot of neurodegenerative diseases only occurred in people aged over 60, but now it’s getting pushed earlier to around 40-years-old.”
“Age is always a risk factor for neurodegenerative diseases and many other diseases. As you age your body replenishes itself more slowly and all the biological systems get slower. But when you chronically stress the body for long enough the ageing process gets shifted to a younger age,” Lin explains. “So it’s not surprising to see younger people getting stroke, developing hypertension, Parkinson’s and dementia.”
Stress and stroke
The impact of stress on stroke is another area that Lin’s working on because not only does stress have an effect on increasing the risk of stroke, but it can also play a role in making rehabilitation even more difficult.
“One of the things that our lab is doing is using two-way Translational Research to use basic science to investigate what happens in the clinical population, fit it back into basic scientific modelling to investigate potential therapeutic responses, then move it forward to the human population,” Lin says. “So basically moving from bench, to bedside, and bedside to bench. Back and forward.”
Over the course of last few years, Lin and his team used preclinical models to replicate ongoing stress in brain repair after stroke in humans. “We have published many critical preclinical studies (Sage 2016, Sage 2017, Neuroscience 2017) providing evidence that chronic stress is bad for stroke recovery.”
“Excitingly, we are also working on a number of potential therapeutic interventions for stroke recovery. While in their early phases, these interventions, appear to promote neuroplasticity and ameliorate post-stroke cognitive decline.”
It’s hoped that this work will allow the team to develop enough evidence-based research to allow them to move forwards in the public health sphere. One option is through the development of public health campaigns for stress reduction, something Lin feels could be very useful.
Collaborations and ‘hair-brained’ ideas
The NHMRC Centre for Research Excellence in Stroke Recovery and Rehabilitation and the John Hunter Hospital Charitable Trust support Lin in developing and validating a way to measure stress load in an objective and very non-invasive manner – through hair! “One of the things about the stress hormone, cortisol is that it’s deposited in hair, we can extract and measure its levels,” Lin says. “If we take the average hair growing speed, which is around a centimetre a month, this allows us to look at stress periods in a retrospective way.”
“This is a more objective way of measuring stress than asking volunteers in a questionnaire – and also removes limitations around memory and recall,” Lin explains.
We are now working with the Hunter New England Area Health service, in collaboration with researchers at the Florey Institute, to implement the first longitudinal study of stress levels in stroke survivors using an objective biometric evaluation. This work aligns well with the new HMRI Stroke Register where the leading stroke researchers in the Hunter can work with volunteers who are prepared to collaborate with our researchers who are looking to understand stroke.
Lin is collaborating with a range of leading researchers in the Hunter such as Professor Michael Nilsson, Associate Professor Rohan Walker, Associate Professor Coralie English, Associate Professor Phillip Dickson and Professor Deb Hodgson on a wide array of projects around stroke and neuroscience. “We are so lucky to have all these inspiring leaders in our university,” Lin says. “We need to think big and collaboration for leading change in medical research.”
As an early career researcher, Lin’s passionate about ensuring promoting the work that our ECRs do, particularly in the community. Lin is Early Career Researcher Representative for the School of Biomedical Science and Pharmacy Research Committee and was previously the Deputy Newcastle Convenor of the Australian Society for Medical Research (ASMR). “This group of researchers need to be promoted so that government, the public and institutions can see the valuable work they’re doing and keep that work in Australia.”
“I’m a big fan of this quote from the Australian of the year, Professor Alan Mackay-Sim, ‘We must invest in young scientists,’” says Lin.
Also passionate about funding, Lin can see the evidence of public donations from the community in the work our researchers do at HMRI. “Sometimes even a small donation can spark a breakthrough and lead to real changes in health and wellbeing,” Lin concludes.
Science Fiction and the Science of Friction
A scientist improving the efficiency of machinery smaller than a human cell, whilst using salt to extract harmful gas from the air, may sound like the stuff of imagination, but Dr Hua Li is real and looking to change the world.
An early career researcher, Hua’s research interests centre on advanced industrial fluids. Her fluids of choice are Ionic liquids (ILs).
Composed of salt in a liquid state, ILs are solvent-free electrolytes with unique properties making them superior to conventional industrial lubricants, adsorbents, and solvents.
With negligible vapor pressure, high ionic conductivity, and high temperature stability, ILs are set to smash the current limitations of industry and take us directly to space.
As well as using ILs to develop high performance and cost-effective lubricants, Hua is aiming to reduce the impact of industry by utilising ILs as anthropogenic gas adsorbents.
Hua is a principal research member for the UON’s Priority Research Centre for Advanced Fluids And Interfaces.
“At the PRC, we aim to connect our research to industry, and we really hope to convert what we find in small scale for use in large-scale industry.”
Lubricity on any scale
From the largest machines involved in resource mining to the smallest nanoscale devices, friction is a constant consideration in the design and maintenance of machinery.
Lubricants are essential to reduce friction and wear in industrial applications.
“But it is very difficult to lubricate lightweight metal surfaces such as aluminum, and titanium,” Hua explains.
“As a result, high density metals that cost a lot of energy, such as iron and steel are still used in industry as moving parts.”
“We are aiming to change that.”
Nanoscale devices working on an atomic or molecular level come with their own set of challenges regarding wear, friction, and heat.
“Linking tribological performance at the nanoscale and macroscale remains a considerable challenge for the development of new and more effective lubricants,” Hua explains.
Cost is another factor.
“ILs have proven to reduce friction but are quite expensive,” Hua says.
“So instead of replacing common lubricant oils, we are working on dissolving ILs into conventional lubricants.”
But the addition of just how much Ionic liquid is needed to alter lubricity?
“Even by adding one percent ILs, the lubricity significantly improves, so our work in that area is very promising,” Hua states.
Hua is also utilising the fact that ionic liquids are electrolytes to further increase their effectiveness as a lubricant.
“ILs are composed solely of cations and anions which have positive and negative charges,” Hua says.
“Lubricity can be externally controlled in situ by application of a potential to a metal surface.”
“Using this method, we can tune the structure of a boundary layer of ILs.”
Hua is correlating experimental results to computational simulations, to reveal the details of the boundary layer response, and how tribology alters with the boundary layer structure at the ionic liquid-electrode surface.
“The tunable nature of ILs enables cause/effect relationships to be teased out in ways not possible for conventional lubricants, so I am working on that.”
Not working in a vacuum
It was the potential future application of ILs that first attracted Hua to this area of study.
“In the future when we go into space, we will be working in a vacuum,” Hua says.
“Common liquids will be affected by the vacuum, but ILs are a great candidate for use in instruments and other applications in outer space.”
Hua found motivation for the other aspect of her work a bit closer to home.
“I came from China where the amount of pollutants in the air is very significant,” Hua says.
“I want to do something to contribute to fixing that, to make something better for the next generation.”
Focusing on flue gas, Hua’s immediate priority in this area is to design Ionic fluids with specific structures designed to collect or adsorb a target gas such as carbon dioxide or sulfur dioxide.
“The dream is then to design further methods to harvest the gas in pure form for reuse in other applications.”
When asked about projected time frame for such an innovation, Hua answers that support is the only variable that may delay this important innovation.
Fortunately, support does not seem to be lacking for Hua’s research.
Despite only beginning work on gas adsorption in early 2016, Hua has already secured funding from many quarters.
Hua scored a Priming Grant from The Global Connections fund, an initiative of the Australian Government aimed to promote collaboration between Australian Researchers and Small to Medium Enterprises (SMEs).
This project will see her working closely with a SME in China looking specifically at adsorption of nitric oxide (NO) from flue gas.
A grant from the National Natural Science Foundation of China will be used on a mechanism study of flue gas denitrification.
Collaborators at Deakin University as well as in several Chinese and European universities round out Team Li.
One day Hua hopes to have even more fans.
“If I can achieve something in this area, I would perhaps consider myself a hero,” she says, smiling.
But for now, it’s back to work.
Better eating, better breathing
Turning familiar anecdotes into effective antidotes, Professor Lisa Wood's nutritional biochemistry research is proving there are crucial links between what we eat and how we breathe.
Professor Lisa Wood has developed something of a research niche. The enterprising educator and investigator studies both nutrition and inflammation, creatively combining the two to provide evidenced based dietary advice on respiratory disease management.
"I didn't have a particular interest in respiratory when I started," she recalls.
"Exploring nutritional approaches to disease management was a direction I took when I saw an unmet need."
Evolving this specialist area for the past 15 years, however, Lisa has made a number of significant discoveries. Together with her team at the Hunter Medical Research Institute (HMRI), the leader of the Nutrition Research group in the Priority Research Centre for Asthma and Respiratory Diseases examines the mechanisms by which dietary factors, including antioxidants, fatty acids, obesity and soluble fibre, affect the biochemical and physiological outcomes of respiratory disease. Principally demonstrating that short-term nutritional manipulation can modify blood lipid profiles, airway inflammation, asthma control, lung function and responses to asthma medications, such as Ventolin, she's also put science behind some 'very strong' perceptions and hearsay.
"People seem to know food is important in the management of asthma and other respiratory diseases even though there is so little data available," she claims.
"It's a curious thing."
The ambitious academic is similarly aiming to highlight 'great' community interest in this scope of research.
"What we do is incredibly translatable and applied," Lisa concedes.
"This is because people are trying to manage their asthma by changing their diet and as such, they need to be provided with specific guidelines."
Lisa began her research career with a PhD in Nutrition and Dietetics in 2001. Collaborating with the University of Newcastle and Westmead Children's Hospital during the four-year project, she studied the relationship between antioxidants and oxidative stress in young cystic fibrosis patients.
"People with this disease have a very different eating pattern. They are recommended a high-fat/high-energy diet because they don't absorb food properly," the nutritional biochemist explains.
"Eating lots of calorie-rich foods means they'll get enough energy to grow."
Lisa's investigation explored the effect of high fat diets in these patients and also identified a link between lung health and antioxidant levels in the body.
"Increasing antioxidant levels was found to be associated with improved lung function in patients with cystic fibrosis," she divulges.
Continuing this work on antioxidants with the HMRI's Respiratory Research Group from 2002-2006, the National Health and Medical Research Council Australian Training Research Fellow looked to translate some of her PhD research to another airways disease – asthma.
"It has a very different pathology to cystic fibrosis," she asserts.
"But it was again about using nutritional approaches to combat inflammation."
Moving to whole food interventions this time around, Lisa delivered antioxidants to asthma patients in the form of fruit and vegetables. The 'high' fruit and vegetable diet group consumed two serves of fruit and five serves of vegetables per day to meet current dietary guidelines, while the 'low' fruit and vegetable diet group consumed one serve of fruit and two serves of vegetables per day, which is the usual intake for Australian adults.
"We compared what people should be eating with what they are actually eating," she says.
"In a three-month period we found that those in the 'low' group had more than twice the risk of having an asthma attack than those in the 'high' group."
"So consuming lots of fruits and vegetables, which are high in antioxidants and soluble fibre, is important in controlling and reducing intermittent asthma flare-ups."
Hoping this research is as translatable as it is applied, Lisa is now in the process of undertaking a similar study with children.
"Asthma is more prevalent in young people so we're really hoping we can use the dietary approach to reduce their risk of picking up a viral infection or having it move on to an exacerbation," she reveals.
"The other great thing about a high fruit and vegetable diet is that it has multiple health benefits."
"It's an appealing strategy."
Foods that harm and foods that heal
Lisa extended her studies to investigate the roles of fatty acids and obesity in respiratory disease after procuring the prestigious University of Newcastle Brawn Fellowship in 2007. Seeking to examine the effects of different types of dietary fats on different types of bronchodilators, the interdisciplinary researcher demonstrated for the first time that nutritional factors could modulate airway inflammation and pharmacological responses.
"Bronchodilators are drugs that widen the bronchi. An example is Ventolin which is taken by inhalation to alleviate asthma symptoms," she clarifies.
"The key observation underpinning this project is that when people eat lots of fatty foods, it reduces the efficacy of their Ventolin."
"Bronchodilators are the first thing people go to when they're experiencing an asthma flare-up, so it's important we understand why they don't work as well when high-fat foods are consumed."
"It has major implications for the health and safety of asthmatics who are experiencing a potentially life-threatening asthma episode."
Currently working with bariatric surgeons at Lake Macquarie and Lingard Private Hospitals to explore the role of adipose tissue macrophages in obese asthma, Lisa is adding yet another dimension to her research. Fat samples collected during bariatric surgery are brought back to the labs at HMRI, to understand how this tissue could be driving airway inflammation.
"When someone is obese, they develop fat around their organs," the Associate Editor of Respirology explains.
"But it doesn't just sit there doing nothing – the fat actively releases chemicals into the bloodstream."
"Those chemicals then reach different organs and damage them, and this is why obesity is related to so many other diseases."
Hypothesising the same thing happens in asthma, Lisa is after scientific proof that chemicals in the bloodstream also reach the lungs and stop them working efficiently.
"Once you know what the tissue is actually doing you can get creative in how you prevent its effects," she reveals.
"Having this understanding opens up the way to develop new therapies."
Simultaneously running a clinical trial to examine the effects of soluble fibre on the gut microbiome and immune responses in asthma, Lisa is addressing airway inflammation from multiple angles.
"No one has ever done an intervention to see if fibre supplements affect the airways in humans," she says.
"It's only been done in animals, with exciting results."
"Now we are extending the investigation to humans."
Engaging the next generation
Combining this research expertise with more than a decade's worth of teaching experience, Lisa also teaches undergraduate students and supervises a team of PhD students at the University of Newcastle. Chiefly focusing on the biochemical and nutritional aspects of human health, both roles have a strong synergy with her multidisciplinary research endeavours.
"I'm very lucky that I get to teach what I am researching," she admits.
"It gives me an opportunity to talk to students with similar interests and feed them into the research groups at the HMRI and University's Priority Research Centre for Asthma and Respiratory Diseases."
"Most of the members of my team actually come through the undergraduate programs."
A 'very proud' leader both in and out of the laboratory, Lisa has nothing short of praise when it comes to commenting further on her colleagues' collective work ethic.
"Data from five of our recent publications was included in last year's National Asthma Council 'Australian Asthma Handbook', which was very rewarding," she says.
"We're finally starting to provide definitive advice after all these years of research."
A complete picture
Lisa's research hope for the not-so-distant future is two-pronged – provide a comprehensive plan on how people should approach their diet when they have a disease involving airway inflammation, and secure more funding opportunities for work that is of increasing interest to the general public.
"They're the ultimate goals," she declares.
"Any research that crosses disciplines can be difficult to fund because it doesn't fit into any one category – but to me, that's the research that is most worthwhile."
Dr Rebecca Lim is a Senior Lecturer and chief investigator who is primarily interested in balance and the vestibular system. She also has a strong background in auditory (hearing) research, which involves neighboring regions in the inner ear and brain stem.
Rebecca's most recent work has focused on the function of central vestibular neurons in the brainstem that go on to influence spinal motoneuron and postural muscle activity. In addition, she also leads an NHMRC-funded study that aims to characterise the anatomical and functional development of vestibular hair cells and primary afferent neurons.
Rebecca uses fluorescent immunolabeling paired with cutting-edge microscopy to study the expression of synaptic and neuronal proteins within the inner ear and brain. Like Professor Alan Brichta, she collaborates closely with vestibular experts worldwide as well as other HMRI-affiliated neuroscientists. Lim is currently supervising multiple PhD students, and is the course coordinator of Anatomy for the Biomedical Sciences. Notably, Rebecca is also a faculty member of the Australian Course in Advanced Neuroscience (ACAN), a technical training course for early career neuroscience researchers.
How does 'basic science' research – the study of single cells, receptors and neuronal circuits – contribute to the improvement of clinical outcomes for patients with vestibular dysfunction?
Balance is a complex multifaceted sense, comprising sensory hair cells that detect motion, nerve fibres that transmit information to (and from) the brain, and vestibular neurons that process motion signals. Together these components evoke reflexes to maintain visual, postural, and gait stabilisation.
We are still learning how the individual components of the vestibular system interact under normal conditions. This is the first step. Once we know how the normal system works, we go to the next step, and begin to determine the underlying causes of vestibular disorders and develop therapies to minimise the impact of loss of balance function.
A Better Start in Life
Associate Professor Linda Newman's far-reaching research in early childhood education is expanding the Faculty of Education and Arts' international footprint.
Associate Professor Linda Newman forged an interest in social justice while working as a childcare centre director in the 1970s, when she realised that children with special needs were not well catered for in mainstream early childhood education.
Her development of outreach programs to bridge that gap eventually led to a new career as a teaching and research academic and, several decades on, those principles remain a driving force in her work.
Newman juggles administrative and teaching tasks in the Early Childhood program in the Faculty of Education and Arts with a substantial research agenda that takes her to places as diverse as Chile and South Africa - and often to the poorest parts.
"My research interests have always been closely aligned to my work with children, families and teachers, and more recently curriculum and pedagogy," says Newman, whose doctoral studies into professional ethics led to the development of the widely used Ethical Response Cycle [available in Newman & Pollnitz (2005). Working with Children and Families: Professional, Legal and Ethical Issues].
Newman and Professor James Albright are part of a team working with three South African universities - Fort Hare, Western Cape and North-West - to build capacity among academics for developing teacher education programs for the kindergarten-equivalent Grade R (or reception year). Enrolments in Grade R, a non-compulsory pre-primary year for five-year-olds, have increased considerably in that country as part of a national education improvement plan.
"To date their teacher education has been geared towards children starting school later so there is a shortage of teachers trained in early childhood and a great need to build that teaching capacity," Newman says. "The Early Childhood team at Newcastle is working with partner universities and will also do some research around the introduction of early childhood education in South African schools."
Three South African students are undertaking postgraduate study in Newcastle as part of the collaboration and the next phase will be to investigate research partnerships.
Newman is also an investigator on an overseas project called Futuro Infantil Hoy (loosely translated as Children's Futures Today), which is focused on building engagement between communities and early childhood centres in very poor neighbourhoods in the port city of Antofagasta, in northern Chile.
"Despite the extreme poverty, they do have early childhood centres and university-qualified staff, but there had been no tradition there of encouraging families to be involved in their children's education and support their learning at home," Newman says.
Newman and colleagues from the University of Western Sydney, her former employer, have worked alongside the centres introducing teaching methods and initiatives that promote family involvement, such as inviting parents to workshops and documenting children's work with digital photography. These measures have led to increased confidence in the work of the centres and better learning outcomes.
"It has helped raise expectations: parents are now saying to us, 'I can see a future for my child,' " Newman says.
The project has fostered international collaboration, with a study team from Chile having visited Newcastle last year, and Newman says the research has wide application beyond the community in which they are working.
"Everything we are developing and doing there we bring back into our own teaching," she says. "It is a two-way knowledge flow, and there is always scope here for improving interaction between families and early childhood centres."