June 2016 edition 26
ihbi
Institute of Health and Biomedical Innovation
IN THIS ISSUE
ADVANCES Individual patient focus in emerging medical model Childhood a focus of new IHBI research appointment Collaborative effort has schizophrenia in its sights Studies aim to improve eye transplant success rates Saliva shows potential for monitoring athlete health Executive Director’s report
This image: The NordBord Image right: Dr Anthony Shield
World sporting teams line up to use invention based on IHBI research The ultimate measure of success for researchers is to see their invention used around the world. IHBI researcher Dr Anthony Shield is achieving such success with his hamstring testing system, now being sent to major sporting teams in Europe, the US and Australia. Dr Shield invented and built a portable prototype of the NordBord to measure the strength of an athlete’s hamstrings. He then set out with former PhD student David Opar to determine whether weaker football players were more likely than strong ones to sustain a hamstring injury.
“In competitions such as the English Premier League, players are paid enormous sums of money. Clubs can’t afford to have the players sitting on the sideline with an injury. Hamstring strains cost millions of pounds a year.”
Dr Shield’s research continues at IHBI, with a focus on hamstrings and the impacts of injury, ageing and resistance training. He still collaborates with Dr Opar, who now conducts research at the Australian Catholic University.
Along with information such as prior injury history and age, NordBord strength measurements can help determine which players are at high risk of hamstring tears while also serving to review progress in training and during the recovery from injury.
The NordBord is based on a well-known hamstring exercise, the nordic curl. It tests eccentric strength, the amount of force that a muscle can generate while it lengthens. Injuries are known to most frequently occur among athletes with poor eccentric strength or strength imbalances between limbs.
The research focus for Dr Shield has shifted to the effects of prior hamstring injury on muscle activation and architecture.
“Hamstring strains are the number one injury in AFL,” Dr Shield says. “It is the number one injury in soccer and it is among the most frequent in cricket and rugby.
Sensors in the NordBord combine with data capture software to enable clinicians, coaches and high performance staff to accurately determine the hamstring strength of each player.
WHY SET UP A SPIN-OFF COMPANY? They make use of university technologies that might otherwise go undeveloped and provide a mechanisms for involving the inventor of the technology in the process of commercialisation. HOW ARE UNIVERSITY SPIN-OFFS CREATED? Funding from the governments, industry and foundations are used to support scholarly research in science and engineering. Some of the research results in the creation of new technology that is then brought to the attention of the university. The university technologylicensing office may decide to seek intellectual property protection for the invention and move to license the technology.
Thirteen English Premier League clubs, including recent surprise winners Leicester City, are using the NordBoard, along with 12 AFL clubs, five Rugby World Cup national teams, six NRL teams and five different National Institutes of Sport. It is also being sent to European soccer teams, universities and teams in the National Football League, National Collegiate Athletic Association and Major League Baseball in the US. QUT spin-off company Vald Performance manufactures the NordBord in Brisbane. Vald Performance was set up with support from QUT’s technology transfer company qutbluebox and last year received a Federal Government Accelerating Commercialisation grant of $493 000 to aid the commercialisation process. Vald Performance chief executive officer Laurie Malone, chief technology officer Sam James and operations director Christopher Rowe are all QUT graduates, while Dr Shield and Dr Opar maintain advisory roles at the company.
Pain and inactivity among injured athletes can cause neuromuscular inhibition. The inhibition is a potential mechanism for several maladaptations linked to hamstring re-injury, including persistent eccentric hamstring weakness, muscle atrophy and the shortening of muscle fascicles. “There is evidence that athletes returning to competition after hamstring injury with maladaptations are predisposed to further injury,” Dr Shield says. Athletes recovering from hamstring injuries, especially those who have potentially developed maladaptations, need to undertake exercises such as stiff-legged deadlifts or the nordic curl because the eccentric muscle contractions involved build a damage resistance in the muscle, he says. “When athletes have greater eccentric strength in the hamstrings they will have a greater resistance to damage of these fibres. Greater levels of eccentric strength will also help to minimise injury risk during fatiguing running such as during game play.”
Individual patient focus in emerging medical model Personalised medicine is seen as one of the most important avenues for improving healthcare into the future, with care tailored to individual patients based in large part on their genetic make-up. Linking genetic research to patient care is IHBI Professor Matt Brown. Professor Matt Brown
Professor Brown joined IHBI in late February, with an appointment as QUT Director of Genomics and an integral role in a partnership between the university and the Queensland Government’s Metro South Health, a region that includes the Princess Alexandra, Greenslopes and Logan hospitals. Key to the partnership is a research team based at the PA Hospital focusing on cancer and genomics. The team aims to offer services to patients by the end of July, specifically those who have cancers that require chemotherapy. PROFESSOR MATT BROWN QUT’s new Professor and Director of Genomics. Most recently Director of the University of Queensland’s Diamantina Institute. Has a clinical appointment with Metro South Health and is an eminent staff clinician. Queensland Premier’s Fellow and previously a Professor and Fellow of the University of Oxford. Recently published a major study in Nature Genetics that revealed genes as the major cause of five chronic inflammatory diseases: ankylosing spondylitis, Crohn’s Disease and ulcerative colitis (collectively known as inflammatory bowel disease), psoriasis and primary sclerosing cholangitis.
“We will be sequencing samples of the cancers and identifying the mutations – and predicting how the cancer will behave and how the patients will best respond to treatment,” Professor Brown says. The initial focus will be on developing personalised medicine approaches for people with leukaemia, lung, gastric, head and neck, and colorectal cancer. “This is a rapidly growing area of medicine and, although we will initially only target certain cancers, I believe all major cancers will ultimately have such an approach to treatment.”
Professor Brown says techniques used in his research team such as genome sequencing can reveal mutations in DNA that influence diseases including cancer. Sequencing RNA can show a change in levels in response to environmental factors and provide a broader understanding of a person’s state of health. “Personalised medicine has the potential to create a treatment approach specific to individual patients and open the door to better diagnoses, earlier intervention and development of more efficient therapeutics,” he says.
Personalised medicine separates patients into different groups, with medical decisions, treatments and therapeutics tailored to individual patients based on their predicted response or risk of disease. The approach relies on an understanding of the molecular basis of disease, particularly genomics, to provide a clear evidence base on which to group related patients.
Professor Brown’s personalised medicine research will also be conducted in China, flowing from the signing of a recent agreement worth an estimated $18 million with one of country’s largest hospitals. It will establish a research and clinical service provision facility at Wenzhou Medical University’s First Affiliated Hospital, a 6000-bed teaching hospital that looks after an area of 20 million people.
Every person has a unique variation of the human genome. While most variation has no effect on health, an individual person’s health stems from genetic variation combined with behaviours and environmental factors.
“We are very excited about the potential of this partnership to deliver both improved healthcare for large numbers of people but also fantastic research into the causes of common cancer types,” Professor Brown says.
Genome variation is responsible for the relatively low responsiveness to therapeutics among cancer patients, with medicines proving effective for about 25 per cent of them.
TRANSLATIONAL GENOMICS GROUP Has 35 members. Includes QUT Vice-Chancellor’s Research Fellow Associate Professor Paul Leo. Based at the Princess Alexandra Hospital and Translational Research Institute, ensuring the research has clinical relevance. Business development manager Dr Bruce Wyse will ensure close ties to industry and pharmaceutical companies so research can be commercialised.
Childhood a focus of new IHBI research appointment Development in childhood has an important bearing on health and wellbeing for the remainder of a person’s life. IHBI is combining the best minds and latest technology to address a range of childhood diseases, injuries and development issues under the leadership of Professor Geoff Cleghorn.
Professor Geoff Cleghorn
Professor Cleghorn was appointed QUT IHBI Director at the Centre for Children’s Health Research (CCHR), QUT Professor in Child Health and senior paediatrician at the Children’s Nutrition Research Centre at CCHR. He has more than 30 years of experience as a clinician and researcher in paediatrics, paediatric gastroenterology and nutrition. Paediatric gastroenterology involves treating diseases of the gastrointestinal tract, liver and pancreas of children, CENTRE FOR CHILDREN’S HEALTH RESEARCH A stand-alone centre adjacent to the Lady Cilento Children’s Hospital bringing together child and adolescent health researchers to create a critical mass of expertise and specialist knowledge covering childhood cancer, Indigenous health, infectious diseases, physical activity, obesity, burns and wound repair. A partnership involving QUT, the University of Queensland and Queensland Health. IHBI AT CCHR IHBI has a team of 110 researchers and research higher degree students at CCHR. IHBI research areas at CCHR covers: • • • • • • •
Correct gastric tract function and internal health is related to the nutrition that the child or mother receives. During the prenatal period, incorrect nutrition can affect development, most commonly leading to short bowel syndrome, a malabsorption disorder that causes abdominal pain, diarrhea, fluid depletion, weight loss, malnutrition and fatigue. A common problem among newborns is iron deficiency, which can cause anemia, a decrease in the amount of red blood cells or hemoglobin in the blood, lowering its ability to carry oxygen. Symptoms are tiredness, weakness, shortness of breath, increased thirst, confusion and a loss of consciousness. Iron deficiency is caused when the only food that the baby receives is maternal milk that does not fulfill the baby’s nutrition. There is no treatment, as iron will reach normal levels with the weaning process. Professor Cleghorn says the attention applied to the health and wellbeing of vulnerable infants and young children is paramount for the subsequent overall development and health of people throughout their entire life.
Cough, asthma and airways Burns and trauma Respiratory infection Exercise and nutrition Psychology and counselling Paediatric spine research Allergies
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principally acute diarrhea, persistent vomiting, gastritis and problems with gastric tract development.
“Our understanding of perinatal and infant nutrition has led to significant changes in our understanding of this time period,” he says. “QUT’s new and strategic emphasis on child health research and scholarship is both vital and timely.”
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The immaturity of the newborn immune system, smaller body and substantially different physiology from that of adults means child health has important distinctions from areas of research and healthcare that focus on adults. A newborn’s immune system makes young children more susceptible to viral and bacterial infections. “The body size differences between children and adults are paralleled by maturation changes,” Professor Cleghorn says. “Congenital defects, genetic variance and developmental issues are of great concern to pediatricians.” Professor Cleghorn’s research interests include the use of energy expenditure and body composition analysis in a number of disease states including chronic liver disease, cystic fibrosis and general nutritional rehabilitation. He has spoken throughout Asia on a number of nutritional and gastrointestinal topics and been appointed to the academic teaching staff of the Department of Child Health at University of Indonesia as a visiting professor. It includes involvement in several multinational trials in South East Asia and exchanges that bringing trainees to Brisbane to further their paediatric gastrointestinal and nutritional studies with Professor Cleghorn. Professor Cleghorn has been involved in many of the historical and seminal advances in paediatric liver transplantation, including the world’s first successful living related donor liver transplant and the development of the liver cut down technique now universally known as the Brisbane Technique.
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Collaborative effort has schizophrenia in its sights The complexity of schizophrenia has long been a barrier to understanding the disorder, with no definitive understanding of triggers, underlying biology or its unrelenting persistence after onset. IHBI researcher Dr Joanne Voisey is collaborating with US peers to gain a better understanding.
Dr Joanne Voisey
Extensive international study into schizophrenia has so far led to plausible explanations but not necessarily in-depth understanding. Researchers around the world agree that schizophrenia involves a combination of genetic and environmental factors. They believe the emerging research field of epigenetics is best placed to provide explanations of the disorder. SCHIZOPHRENIA A medical condition affecting the normal functioning of the brain, interfering with a person’s ability to think, feel and act. People with schizophrenia have one personality. It is a myth that those affected have a split personality. SYMPTOMS Outside of treatment, people with schizophrenia experience persistent symptoms of what is called psychosis. These include: • Confused
thinking: The everyday thoughts that let us live our daily lives become confused and don’t join up properly. • Delusions: Holding a belief that is not held by others of the same cultural background. • Hallucinations: Seeing, hearing, feeling, smelling or tasting something that is not actually there. Often disembodied voices that no one else can hear. • Associated symptoms: Low motivation and changed feelings. TREATMENT Can reduce and even eliminate the symptoms, generally including a combination of medication and community support. Both are usually essential for the best outcome. •
Medication: Can assist the brain to restore its usual chemical balance. support: Should include information, accommodation, help with finding suitable work, training and education, psychosocial rehabilitation and mutual support groups. Understanding and acceptance is very important.
• Community
Epigenetics refers to changes in gene expression, or the distinction between active and inactive genes, that does not involve changes to the underlying DNA. An example of a mechanism that causes these changes is DNA methylation. Dr Voisey says methylation profiling enables the measurement of the activity of thousands of genes at once. “The methylation profiles allow us to determine differences seen between schizophrenia patients with particular symptom severity and their response to medication,” she says. Dr Voisey is leading IHBI’s collaboration with the Walsh Research Institute in Illinois in the US, using a prestigious Hilton Family Foundation Inc grant of $165 838. An aim of the research is to provide evidence that schizophrenia is a gene-regulation disorder. Such a disorder is characterised by an abnormality or impairment in regulatory mechanisms that govern metabolism, immune response or organ function. “Our objective is to identify specific genes that are dysregulated, so we can target them with improved treatments,” Dr Voisey says. “We also aim to use epigenetics to eventually enable identification of people at risk of developing schizophrenia and provide strategies for effective prevention.” Beyond investigating epigenetic avenues, the collaboration will study environmental factors that can cause altered gene expression. “Researchers are developing effective methods for identifying cancer-prevention genes that have been ‘turned off’ by environmental factors. Our study aims to determine if a similar approach will work in schizophrenia.”
Studies aim to improve eye transplant success rates
It is probable that some people are born with a predisposition to developing schizophrenia and that certain factors, including stress or use of drugs such as marijuana, LSD or speed, can trigger their first episode. Dr Voisey says a key element missing in most research is recognition that schizophrenia may be an ‘umbrella’ term used to describe several different disorders. The Walsh Research Institute has identified three major schizophrenia biotypes based on their database of 3600 diagnosed patients. “Our study is expected to provide sharper, more definitive evidence that schizophrenia is epigenetic in nature, validate the classification of schizophrenia into biotypes and identify specific gene-regulation abnormalities for each biotype,” she says. The ultimate aim is to understand triggers; develop tools for identifying at-risk people and providing early diagnosis; and introduce effective prevention and treatment strategies based on the specific schizophrenia biotypes. “I am excited to be working with the Walsh Research Institute as we have a common goal of discovering better diagnoses and treatment options for patients,” Dr Voisey says. “It is such a debilitating disorder and antipsychotic treatments don’t target individual symptoms. Side effects can be just as negative as some of the schizophrenia symptoms. By identifying DNA methylation patterns we are targeting both environmental and genetic risk factors which may uncover more of the schizophrenia puzzle.”
Associate Professor Damien Harkin
Tissue transplants using donated organs have advanced healthcare and improved the survival rates and lifestyles of millions of people. However, organ donation brings with it medical and logistical challenges that in some cases could be overcome using cultured cells and biomaterials. IHBI vision and eye researcher, Associate Professor Damien Harkin, is leading a collaborative research project aiming to validate techniques and materials for use in corneal tissue reconstructions. The research aims to improve clinical outcomes by reducing the reliance on donor eye tissue, which will eventually be rejected by the immune system, and carries significant logistical and safety issues. HOW MANY CORNEAL TISSUE TRANSPLANTS ARE PERFORMED EACH YEAR IN AUSTRALIA? More than 2000. WHAT ARE THE GREATEST RISK FACTORS FOR THE TRANSPLANTS FAILING? A history of inflammatory eye disease and immune rejection. HOW COULD CULTIVATED CORNEAL ENDOTHELIAL CELLS OVERCOME THAT?
Transplants generally restore structure and function to the most posterior layer of the cornea, the corneal endothelium. The cornea is the transparent part of the eye that covers the iris, pupil and anterior chamber. It governs fluid and solute transport across the cornea surface and maintains the cornea in the slightly dehydrated state required for optical transparency. An accumulation of fluid would disrupt or degrade corneal transparency.
He is working with a multidisciplinary team from the Queensland Eye Institute and the University of Melbourne’s Centre for Eye Research Australia, with support from a National Health and Medical Research Council (NHMRC) Project Grant.
There is no medical treatment that can promote wound healing or regeneration of the corneal endothelium. Present treatment relies on the use of donor corneal transplants.
The research will generate data necessary to advance studies towards a phase I/II clinical trial in patients with corneal endothelial cell dysfunction.
Donor corneal tissue availability is unpredictable, demand is increasing as the population ages and the donor tissue is eventually rejected by the immune system.
“Importantly, this project has the additional significance of bringing together Australia’s two leading research groups aimed at developing cultured CEC implants, combining our respective skills and resources,” Associate Professor Harkin says.
Cultivated corneal endothelial cells (CEC) show potential in providing tissue for multiple patients using material derived from a single donor. Culturing enables cell numbers to be increased a point of critical mass for use in transplants. The potential exists for multiple sheets of CEC to be manufactured to a desired density from each donor cornea.
By improving the purity and efficacy of implanted tissue.
Associate Professor Harkin will work with his collaborators to establish an optimal technique for CEC cultivation and compare two novel materials developed as suitable scaffolds – fibroin membranes and hydrogel films.
“The collaborative approach will also impact positively on subsequent translation of our research outcomes to the clinic on a national scale and serve as an exemplar for research in other areas of national importance.”
CEC implants show potential to instigate repair and regeneration in a patient’s eye, but they need a scaffold to provide physical support during cell culture and implantation.
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Professional sports place a major burden on an athlete’s body. Much consideration needs to be given to injury prevention and recovery, avoiding stress and ensuring a healthy immune system to ward off illness. Now, saliva is being studied at IHBI for monitoring stress and fatigue in athletes.
Monitoring of athletes involves invasive and time-consuming procedures, including the taking of blood. IHBI’s Dr Jonathan Peake sees saliva as an effective alternative because it can be collected quickly, easily, without an invasive procedure or highly-specialised skills. Dr Peake has long been interested in the biology of muscle injury and the effects of treatments such as cold water immersion, icing, anti-inflammatory or antioxidant supplements ATHLETE’S RECOVERY Encompasses a complex range of processes that include: •
refueling the muscle and liver glycogen (carbohydrate) stores
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replacing the fluid and electrolytes lost in sweat
• manufacturing
new muscle protein, red blood cells and other cellular components as part of the repair and adaptation process
• allowing
the immune system to handle the damage and challenges caused by the exercise
USE OF SALIVA Saliva consists of a clear, protein-rich fluid secreted by the salivary glands and trace amounts of various biochemicals present in blood serum that filter into the mouth. As certain health conditions arise, such as cancer or HIV, proteins and substances linked to these diseases can pass from the serum into the saliva. Proteins linked to stress, inflammation or hormone releases, can also pass into saliva. Increased concentrations of the compounds over time make saliva potentially promising for screening and diagnosis. SALIVA TECHNOLOGY APPLICATION RESEARCH SYMPOSIUM www.salivasymposiumbrisbane.com
EXECUTIVE DIRECTOR’S REPORT
IHBI research activities are being expanded into new and emerging areas, with impetus from senior researcher appointments, high-level collaborations and support from national and international funding bodies. Recent senior appointment Professor Matt Brown is an example, bringing with him a background in both genomics research and clinical care. He works with patients at the Princess Alexandra, has a collaboration with Queensland Government’s Metro South Health region and recently signed an agreement with Wenzhou Medical University’s First Affiliated Hospital in China. That enables Professor Brown to use the latest technology and explore genetic make-up as the basis for a new, targeted approach to cancer treatment. Another senior appointment is Professor Geoff Cleghorn, who will lead IHBI research in childhood cancer, Indigenous health, infectious diseases, physical activity, obesity, burns and wound repair at the Centre for Children’s Health Research (CCHR). Co-location of CCHR alongside the Lady Cilento Children’s Hospital will provide the researchers with an opportunity to collaborate with clinicians, support staff, patients and their
and hyperbaric oxygen therapy. His research also takes into account the effects of exercise and nutrition on immune function and the implications for healthy aging and treating chronic diseases. “I compare metabolic, hormonal and inflammatory responses during recovery from different forms of exercise and develop strategies to monitor fatigue and recovery to determine when athletes are ready to return to training and competition,” he says. “I am keen to better understand the underlying mechanisms of how our body responds and adapts to stress.” Part of Dr Peake’s research is conducted in collaboration with the Queensland Academy of Sport, using saliva to assess the balance between stress and arousal in response to exercise. Another collaboration with Professor Maree Gleeson from the University of Newcastle involves studying the effects of exercise intensity on antimicrobial proteins in saliva, known to be linked to mucosal immunity. It includes study of the immune system’s protection of mucous membranes, tissue that secretes mucus, from infection. Associate Professor Chamindie Punyadeera’s recent appointment to IHBI widens the scope of saliva research. Associate Professor Punyadeera aims to use saliva to diagnose head and neck cancers earlier and is also investigating its potential for heart disease.
families to gain greater insights into a host of diseases, injuries and aspects of childhood development. Similarly, Dr Joanne Voisey is collaborating with the Walsh Research Institute in Illinois in the US and using their database of 3600 people with schizophrenia to understand the disorder. With the support of a prestigious Hilton Family Foundation Inc grant, the collaboration will focus on the underlying biology, triggers and people’s response to medication. Improving the clinical outcomes of corneal tissue reconstructions without the need for organ donation is the goal of vision and eye researcher Associate Professor Damien Harkin. He is working with the Queensland Eye Institute and the University of Melbourne’s Centre for Eye Research Australia, with support from the National Health and Medical Research Council (NHMRC).
Adding impetus will be the Saliva Technology Application Research Symposium at QUT on July 8, bringing researchers from around the world to Brisbane for Australia’s first major saliva conference. The symposium will detail emerging research and translational and technological advances in diagnostics, collection devices, rheology, genetics, dentistry and industry involvement. Dr Peake says the conference will enable him to meet potential research collaborators and industry partners, share knowledge and learn about additional avenues for saliva use. “There are some simple point-of-care tests for hormones in saliva,” Dr Peake says. “It would be good to expand this suite so that athletes can get an instant readout on whether they have recovered properly and are ready to return to training or competition.” Beyond that, he is investigating the possibility of using saliva to screen for concussion and improving the sensitivity of saliva screening equipment to benefit areas of health such as sleep and mental disorders. “I work in an important area of research. My work constantly makes me aware of the need to exercise, sleep and eat well.”
Dr Jonathan Peake hopes to follow a similar path, with his first steps in an emerging research area. Dr Peake is investigating the potential of saliva to monitor fatigue in athletes to avoid injury, aid recovery and prevent recurrence. The aim is to develop a monitoring and testing device that uses saliva rather than blood. The common thread of each of the IHBI research initiatives is an appreciation of the importance of collaborating, using the latest technology and looking for new approaches to understand and overcome illness and injury – and bring about better health in our lifetime. Professor Lyn Griffiths Executive Director, IHBI
Ultimately, researchers want to make a difference to the health and wellbeing of people around the world. Dr Anthony Shield has found a market for his invention, the NordBord, among elite international sporting teams. His work is an example of how research, collaboration and strategic thinking came together to create a hamstring testing system and led to a commercialisation success story.
© QUT 2016 22219
Dr Jonathan Peake
Saliva shows potential for monitoring athlete health
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