September 2016 edition 27
ihbi
Institute of Health and Biomedical Innovation
IN THIS ISSUE
ADVANCES Infection research takes ‘disarm, not kill’ approach Impetus to treat medical conditions using 3D printing Team hones in on molecule to address cancer resistance Technology taps into motivation to build healthy lifestyles Robotics research aiming to improve knee surgery Executive Director’s report
Centre: Professor Lynne Daniels
Professor Stewart Trost
Prevention better than cure for addressing global obesity rates Context is important in preventative health research. Studies need to take into account how people behave, how easily they can accommodate preventative measures into their lives – and how willing they are. Context is a major driver in shaping obesity prevention research at IHBI. IHBI Professor Stewart Trost is considering how best to ensure obesity prevention programs borne from evidencebased research are rolled out to the community and have a real health impact. He is establishing the Queensland node of the Centre of Research Excellence (CRE) in the Early Prevention of Obesity in Childhood. OBESITY A term used to describe somebody who is very overweight with a high degree of body fat. PREVENTION The best way to prevent becoming overweight, or obese, is through a healthy diet and regular exercise. It is important for parents to provide support to their children to be physically active from an early age. A HEALTHY DIET • Limit intake of fats, salt and sugar •
Avoid white bread, white rice, pastries, sugary drinks and other highly processed food
Increase •
consumption of plant foods, particularly fruits, vegetables, legumes, whole grains and nuts
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Drink water
The CRE aims to reduce the prevalence of obesity and obesityrelated behaviours, especially in children under five years of age. Among the key lifestyle links to obesity are a poor diet, inadequate sleep and insufficient activity. Professor Trost says there is no single tool that has been demonstrated to be effective for use with infants, toddlers and Preschool-aged children. He is working with IHBI colleague Professor Lynne Daniels, who leads the PEACH (Parenting, Eating and Activity for Child Health) program, with the aim of arming parents with the skills and confidence to enable the whole family to eat better and be more active. Professor Daniels works with more than 800 Queensland families with children above the healthy weight range and is reporting some reduction in weight; improvements in diet and activity levels; and increased parent confidence to manage eating and activity for their family. However, Professor Trost aims to prevent children reaching an unhealthy weight. While learning from some of the behaviours that Professor Daniels reports, he is aware of the different motivations he needs to understand for prevention strategies. “There is a knowledge gap in determining the most effective obesity prevention programs for children up to the age of five,” he says. “For a start, we have not yet identified the most accurate way of monitoring of obesity-related behaviours, given there is a large variation in activity, sleep and diet among children.”
The CRE aims to develop rapid, validated measuring tools for obesity-related behaviours so that prevention strategies can be designed and rolled out through user-friendly online resources. The prevention strategies will also be evaluated for costeffectiveness, acceptability, sustainability and scalability. Professor Trost takes seriously his goal of reducing the prevalence of obesity among children in order to transform the health trajectories of the next generation. “It is a major health issue in Australia that we need to address. We are doing the research, but we need to be consultative to ensure we understand what drives obesity-related behaviours. “Translating research into practice also requires an understanding of the policy context and how to engage clinical practitioners and parents in the community.” One in five children and adolescents are either overweight or obese, with predictions that 65 per cent of young Australians will be overweight or obese by 2020. About 80 per cent of obese adolescents will become obese adults, placing them at risk of developing type 2 diabetes, liver problems, respiratory disorders and cardiovascular disease. Funding for the CRE was secured from the National Health and Medical Research Council in a bid led by the University of Sydney. IHBI researchers will collaborate with CRE partners at the University of South Australia, the University of Sydney and Deakin University.
Infection research takes ‘disarm, not kill’ approach Many common infections that used to be treated successfully with antibiotics are showing resistance, making them virtually untreatable and lethal. IHBI’s Dr Makrina Totsika is working on new therapeutics that show promise in disarming bacteria that can cause infections. Dr Makrina Totsika
The World Health Organisation has highlighted the very high rates of resistance to antibiotics in bacteria that cause most common human infections, such as cystitis and diarrhoea. The bacterium E. coli is listed as a pathogen of international concern because of its high resistance rate and more than 200 million infections annually around the world. Dr Totsika says it is important to distinguish between harmless, or even beneficial, bacteria and harmful ones known as pathogens. While researchers aim to target pathogens, their solutions must protect what they call commensal microflora, micro-organisms found on body surfaces that are harmless and often form a mutually beneficial relationship with their human hosts. WHAT ARE ANTIBIOTICS? Antibiotics are medicines used to prevent and treat infections mainly caused by bacteria. They do not work for viral infections, such as the flu or common cold. WHY ARE ANTIBIOTICS FAILING? Due to overuse and misuse of antibiotics in medicine and agriculture, many bacteria-causing diseases such as urinary tract infections, bloodstream infections, foodborne diarrhoea and even tuberculosis, are now resistant to most available antibiotics. This means prescriptions will no longer work and doctors are resorting to last-line drugs. Alarmingly, these are also increasingly failing as resistance rates increase and spread among bacteria. HOW CAN WE PREVENT RESISTANCE? Minimising unnecessary prescribing and overprescribing of antibiotics for humans and animals can prevent antibiotic resistance. Using alternative medicines, such as antivirulence antimicrobials, could reduce the number of antibiotic prescriptions worldwide.
Dr Totsika is using the support of a QUT Vice Chancellor’s Research Fellowship to focus her research on a pathogen’s virulence factors. These factors are known to be involved in determining a pathogen’s ability to cause disease and are often missing from commensal bacteria. She is developing a novel class of antimicrobials that will disarm pathogens by targeting virulence mechanisms rather than trying to kill them, as antibiotics aim to do. “Because antibiotics are designed to kill pathogens, their use inevitably selects for bacteria in the population with natural genetic changes that allow them to grow in the presence of antibiotics,” Dr Totsika says. “Resistance is a natural phenomenon as old as bacteria but antibiotic overuse and misuse has led to the alarming rates of resistance we see today worldwide. “I am developing novel anti-virulence antimicrobials that will be a much-needed alternative to failing antibiotics and will impose less selection pressure for resistance development,” Dr Totsika says. “The aim is to inhibit pathogen mechanisms that will selectively eliminate infecting bacteria, without harming the host and the commensal microbiota.” Dr Totsika aims to target a pathogen’s adherence, a critical first step in the infection process. Adhesins are cell-surface appendages of bacteria that enable adherence to other cells or to a body’s surfaces. Adhesins are a type of virulence factor. Bacteria are typically found attached to surfaces and in immobile clusters known as biofilms. Adhesins serve both as anchors and provide surface recognition, allowing the targeting
of bacteria to a particular surface such as a specific tissue type or even medical implants. Evaluating several inhibitors that block bacterial adhesion will enable Dr Totsika to progress them to anti-adhesion therapeutics that can treat and prevent infection, slow a pathogen’s resistance and prevent disruption of a person’s commensal flora. “My work has already significantly advanced our understanding of bacterial adherence: from adhesin gene identification to adhesin structure and function. The understanding is now guiding us in developing novel anti-adhesion therapeutics that can block bacterial adherence and be used to treat infections.” Through two ongoing National Health and Medical Research Council (NHMRC) project grants involving collaboration with leading experts in Australia and the US, Dr Totsika’s research is expected to lead to next-generation antimicrobials that will be tailored to each patient’s infection. With a recent relocation to QIMR-Berghofer as part of IHBI’s growing Infectious Diseases program, Dr Totsika will be able to advance her research through access to specialist infectious diseases research laboratories and co-location with health and medical professionals at the Royal Brisbane and Women’s Hospital at Herston. Dr Totsika’s success in research, combined with excellence in communication and community engagement, have been recognised with a joint Queensland Young Tall Poppy of the Year Award in August.
Impetus to treat medical conditions using 3D printing 3D printing is already having a major impact in advanced manufacturing and has the potential to significantly change personalised treatment of challenging medical conditions. IHBI researchers are at the forefront, with plans to develop technologies and train the next generation of engineers, clinicians and scientists. IHBI researchers are leading the Australian Research Council (ARC) Training Centre in Additive Biomanufacturing, established this year with new ARC funding in collaboration with research peers, industry and clinicians.
Additive biomanufacturing, another term for 3D printing, will enable the researchers to custom-design and manufacture medical implants as well as scaffolds that encourage cell growth and tissue regeneration.
IHBI Professor and Chair Dietmar W Hutmacher will lead the centre, with support from IHBI Professor Yin Xiao and associate professors Mia Woodruff and Travis Klein.
Professor Hutmacher says they must first overcome three challenges, involving the 3D printers, the bio-inks they use and their introduction into in hospitals and clinics. “3D printers must be developed for a range of materials to engineer a variety of tissues in a manner that is suitable for clinical applications,” he says.
Their aim is to develop technologies that can be introduced in hospitals and clinics to treat damage and defects from injuries and disease, with a focus on muscoskeletal applications. WHAT IS ADDITIVE MANUFACTURING? It refers to a process in which successive layers of material are formed under computer control to create the object. The term 3D printing is increasingly used as a synonym for additive manufacturing. WHAT WILL THE ARC TRAINING CENTRE IN ADDITIVE BIOMANUFACTURING DO? It will bring together leading researchers and industry to develop and translate technologies into personalised treatments of challenging medical conditions. WHAT MEDICAL CONDITIONS WILL BE TARGETED? The aim is to develop additive biomanufacturing technology platforms for muscoskeletal disorders such as bone and cartilage defects. The centre will also investigate additive biomanufacturing for use in advancing radiotherapy and better tissue integration of Cochlear implants. WEBSITE https://www.qut.edu.au/research/our-research/student-topics/advanced-fabrication-oftissue-engineering-scaffolds-using-melt-electrospinning
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Associate Professor Klein will also work with clinicians at St Vincent’s Health and the Peter MacCallum Cancer Centre on the clinical use of additive biomanufacturing, including in advancing radiotherapy, customising 3D printed titanium implants and developing therapies for cartilage defects. Professor Hutmacher says the centre aims to establish and grow a new sector in the advanced manufacturing industry. “The centre will address the training priorities of advanced manufacturing techniques; product design and development; and product innovation.”
For example, the printers need to work in such a way and use specific bioinks to design and fabricate implants with biomaterials such as hydrogels, biodegradable polymers, ceramics and metals. Some will remain in the body. Other implants will encourage the correct tissue to grow and then dissolve in time as the tissue replaces it.
The centre is expected to train 12 PhD students and three postdoctoral research fellows in its first four years of operation, providing them with technological and business development skills. “We want them to be skilled up to form the backbone of a new generation of innovators in the Australian additive biomanufacturing sector, with a global perspective and impact,” Professor Hutmacher says.
Professor Hutmacher will lead a program working with national and international industry partners Anatomics, Osteopore and Cochlear to develop multi-material and multifunctional printers that can manufacture medical devices and implants in large quantities.
It builds on a collaboration between QUT, the University of Wollongong, the University Medical Centre Utrecht in the Netherlands and the University of Würzburg in Germany that has established a Dual Masters in Biofabrication program.
Professor Xiao and associate professors Woodruff and Klein will work with peers to consider the special requirements for bio-inks to deliver formulations with controlled biodegradability and bioactivity on a large scale.
Professor Xiao leads the Australia-China Centre for Tissue Engineering and Regenerative Medicine at IHBI, involving collaboration with internationally recognised universities and research institutes in China and providing access to a talent pool of students suitable for recruitment to the new training centre.
Image: (left to right) Professor Dietmar Hutmacher, Dr Daniela Loessner, PhD Candidate Christoph Meinert
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Team hones in on molecule to address cancer resistance Dr Brett Hollier
Androgen deprivation therapy (ADT) is the best treatment option when prostate cancer spreads, but it comes with a risk of the disease developing therapy resistance. IHBI’s Dr Brett Hollier is working on a solution to block the resistance.
Dr Hollier is an expert in cancer biology at IHBI’s Australian Prostate Cancer Research Centre – Queensland (APCRC-Q), using a Young Investigator Project Grant from Cancer Australia, the Cure Cancer Australia Foundation and the Prostate Cancer Foundation of Australia to address prostate cancer metastasis and therapy resistance. PROSTATE CANCER INCIDENCE Prostate cancer accounts for about 30 per cent of all cancers diagnosed in Australian men and is responsible for more than 3000 deaths annually. COMMON SYMPTOMS • difficulty in starting to urinate •
blood in the urine or semen
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discomfort when urinating
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a slow flow of urine that is difficult to stop
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decreased libido.
He is not aiming to replace ADT, but to find a way to address resistance that ultimately occurs in the vast majority of patients. The aim is to develop a therapeutic that can be given to patients in combination with ADT. “Patients generally respond to ADT. It leads to tumour regression,” Dr Hollier says. “But after 18 to 36 months many patients relapse and we have found high levels of a protein to be predictive of this relapse.” At the centre of the research is the molecule Neuropilin-1 (NRP1) that Dr Hollier has identified as being involved in prostate cancer metastasis and therapy resistance. “Prostate cancer metastasis encompasses a complex series of events,” Dr Hollier says. “Research during the past decade has demonstrated that cancer cells can adapt to ADT and modify their biology to take on properties of other cell types to survive these therapies, termed tumour cell plasticity.”
REDUCING THE RISK There is no evidence protective factors can stop prostate cancer development, but they can improve overall health and possibly reduce the risk. Diet: Eat nutritious meals. Exercise: There is some evidence to show that regular exercise can be protective for cancer. Exercise at least 30 minutes of a day.
Dr Hollier is working with APCRC-Q colleagues and international collaborators on a number of related research projects, with funding from the National Health and Medical Research Council (NHMRC) and a Prostate Cancer Foundation of Australia Movember Revolutionary Team Award. The work aims to better understand cancer cell plasticity to identify new targets for therapeutic intervention. “The ultimate goal of our research program is to develop novel targeted therapies to improve clinical responses of prostate cancer patients to ADT,” Dr Hollier says. The APCRC-Q is based at the Translational Research Institute, co-located at Brisbane’s Princess Alexandra Hospital (PAH) to provide an environment that encourages collaboration with clinicians and facilitates research into diagnostic biomarkers, therapeutics and treatments.
While cell plasticity has beneficial effects during normal embryonic development and wound healing, it can also facilitate cancer metastasis and therapy resistance.
“The team assembled is uniquely placed to rapidly translate discoveries into the clinical setting to improve the treatment options and outcomes for men with aggressive forms of prostate cancer,” Dr Hollier says.
“I have identified NRP1 expression to be altered during cell plasticity and be elevated in metastatic prostate cancer cell lines and patient samples,” Dr Hollier says. “Suppression of NRP1 leads to a significant reduction in invasive and metastatic behaviour.
He is involved in a pilot trial, working with APCRC-Q Executive Director Professor Colleen Nelson and PAH clinicians to investigate the benefits of the anti-diabetic drug Metformin, in combination with ADT, on the disease progression of men with advanced prostate cancer.
“The hypothesis I am testing is that targeting NRP1 will reduce primary tumour invasion and metastasis as well as halt disease progression towards a lethal therapy resistance.”
Technology taps into motivation to build healthy lifestyles Professor David Kavanagh
Technology makes it easier to roll out the same healthcare services in both metropolitan areas and in rural communities. IHBI researchers are embracing technology including robots, phone apps and websites to improve the lives of people with chronic illnesses such as diabetes and address problems with alcohol use, smoking, physical inactivity and diet.
ONTRACK (WWW.ONTRACK.ORG.AU) Online services supporting people to achieve mental and physical health and wellbeing, including programs focusing on depression, alcohol and mental illness. E-MENTAL HEALTH IN PRACTICE (WWW.EMHPRAC.ORG.AU) Offering e-mental health training and support for health practitioners and service providers working with Indigenous people. BABY STEPS (WWW.BABYSTEPS.ORG.AU) Uses IHBI research to enhance the wellbeing of new mums and dads, aiming to prevent episodes of perinatal depression. FUNCTIONAL IMAGERY TRAINING TRIAL Low-cost way to help people change behaviours using mental imagery, regardless of where they live. Addresses Alcohol Use Disorder, a common problem with substantial health and social impacts. BREAKUP SHAKEUP (SEARCH AT ITUNES.APPLE.COM) Ideas for fun, easy things to do to help young people cope after a breakup. Demonstrates that planning activities and increasing social support will help in recovering faster and helps them overcome moments of despair. MUSIC eSCAPE (SEARCH AT ITUNES.APPLE.COM) For young people with mild levels of stress or distress. Lets them create a mood map of their music library, develop playlists to match a mood and create a music journey to express, enhance or change their mood.
IHBI Professor David Kavanagh is leading research that aims to help people strengthen and sustain their motivation for leading healthy lifestyles. An important component is mental imagery. The research aims to train people to use imagery in everyday situations and determine if it affects their quality of life. Professor Kavanagh’s team also aims to understand whether increased training delivery costs through use of technology are offset by greater gains and a decreasing dependence on healthcare. “Prevention and early intervention are important,” Professor Kavanagh says. “We want to catch people early and help them make decisions that will optimise their later health and wellbeing.” When the treatments are delivered via the web or phone, they also have the potential to increase treatment access to people in rural and remote communities. Professor Kavanagh’s team has started a large trial that compares three forms of motivational intervention on Alcohol Use Disorder, tracking their outcomes for 12 months and examining their relative cost-effectiveness. To maximise the accessibility of the treatments, they are all delivered by phone – and in some cases are supported by mobile phone apps. “We are aiming to build in the participants an ability to effectively self-manage alcohol misuse, particularly when
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they are dealing with periods of acute temptation and craving,” Professor Kavanagh says. “We have strong and sustained results to date. It gives us a realistic expectation that the program will have substantial impact.” The recent acquisition of robots has opened the door to a new area of research for Professor Kavanagh’s team at the Centre for Children’s Health Research. In collaboration with clinicians from the adjacent Lady Cilento Children’s Hospital, PhD student Nicole Robinson plans to use robots to improve the glycaemic control in teenagers with type 1 diabetes. Ms Robinson will use the robots to help teenagers become more adept at controlling their blood sugar, by restricting highcarbohydrate snacking and using insulin effectively. She expects the participants will find it easy to talk to the robots about the issues and will find the sessions highly engaging. “The research is important,” Professor Kavanagh says. “Nonadherence to diabetes regimens in teenagers has very serious potential consequences, including a greater risk of retinopathy, kidney disease, neural and cardiovascular disease.” Similarly, technology that attracts teenagers is being used to help them cope with a romantic breakup and enhance their mood using music. Phone apps funded by the Young and Well CRC, Breakup Shakeup and Music eSCAPE, have high acceptability and utility ratings from users on iTunes and have been tested in randomised controlled trials by the team.
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Dr Anjali Jaiprakash
Robotics research aiming to improve knee surgery Knee surgery has developed in recent decades, with the introduction of keyhole technologies, but the process remains manual, complex and demanding for clinicians. IHBI’s Dr Anjali Jaiprakash is part of research to introduce robotics to improve precision and reduce the risk of unintended tissue damage.
WHY PERFORM ARTHROSCOPIES? The advantage over traditional open surgery is that the joint does not have to be opened up fully. For knee arthroscopy only two small incisions are made: one for the arthroscope and one for the surgical instruments to be used in the knee cavity. This reduces recovery time and may increase success because of reduced trauma to the connective tissue. WHERE DO YOU USE ARTHROSCOPIES? It is technically possible to do an arthroscopy on almost every joint, but is most commonly used for the knee, shoulder, elbow, wrist, ankle, foot and hip. WHAT CAN AN ARTHROSCOPY REPAIR? Arthroscopy diagnoses several knee problems, such as a torn meniscus or a misaligned kneecap. It can also be used to repair the ligaments of the joint.
EXECUTIVE DIRECTOR’S REPORT
IHBI research aims to provide better health in our lifetime, with a focus on prevention, intervention and translation; partnerships with clinicians and industry; use of the latest technology; and impact on improving clinical practices. Dr Brett Hollier is applying many of those elements in his work to develop a solution to block therapy resistance when prostate cancer spreads, with support from Cancer Australia and the Cure Cancer Foundation. He is collaborating with leading national and international researchers and clinicians; using cutting-edge facilities at the Australian Prostate Cancer Research Centre – Queensland; and is part of a pilot trial that shows promise in therapeutically addressing progression of advanced prostate cancer. Dr Makrina Totsika is another IHBI researcher working on new therapeutics. The aim is to disarm bacteria that can cause infections and overcome present treatment challenges because of antibiotic resistance. Dr Totsika has secured National Health and Medical Research Council funding; collaborates with research leaders in Australia and the US; and has access to the equipment, facilities and expertise at QUT and QIMR Berghofer.
“It is a multi-faceted project,” Dr Jaiprakash says. “It involves an understanding of surgery, orthopaedic research, robotics, design and advanced manufacturing.” Support from an Advanced Queensland Early Career Research Fellowship will enable her to extend collaborations with global orthopaedics company Stryker, the Prince Charles Hospital Foundation and the Holy Spirit Northside Hospital. Knee arthroscopies are well-established procedures with more than four million performed at a cost to the global healthcare system of more than $19 billion annually. The complexity and length of procedures pushes surgeons to their mental and physical limits and increases the risk of unintended tissue damage and resulting pain, longer recovery and scarring. “There are presently no robotically-assisted technologies being used in knee arthroscopies. They are performed entirely manually,” Dr Jaiprakash says. “Major challenges are the confined spaces within the joint and the complex maneuvers of the leg that are needed to access the joint and perform the surgery. This presents an opportunity for the use of robotic technology but also highlights the great complexity in identifying robotic solutions.”
Dr Jaiprakash is also collaborating with IHBI orthopaedic surgeon Professor Ross Crawford, who led Australia’s first robot-operated hip surgery earlier this year, resulting in national media coverage and a meeting with Prime Minister Malcolm Turnbull during the recent federal election. Professor Crawford has an ongoing collaboration with Stryker, with his clinical research leading to the redesign of a subset of the company’s Exeter Total Hip implant and assisting in development of a new range of Exeter stems for hip operations. The team has set its sights on reducing hospital stays during recovery from knee surgery from an average of 6.1 days to 4.9, allowing hospitals to treat more patients, reduce waiting lists and improve efficiencies. Robotic technology has the potential to advance surgery on other body areas, such as hip, shoulder, ankle or wrist procedures. Beyond orthopaedics, the technology has the potential to improve efficiencies and decrease complications in procedures such as laparoscopic surgery, colonoscopies and endoscopies. “The development of autonomous robotic arthroscopic surgery is a ground-breaking field within medicine,” Dr Jaiprakash says.
Dr Jaiprakash is working with IHBI Professor Jonathan Roberts, considered one of Australia’s leading robotic scientists and tasked with advancing QUT research in medical robotics.
“In the future such technology has the potential to allow for the treatment of a greater number of surgical cases in locations such as rural and regional Queensland via the integration of telemedicine coupled with improved training regimes and availability of skilled surgeons.”
Technology, translation and collaboration with clinicians and industry are all part of Dr Anjali Jaiprakash’s research in orthopaedics. She works with surgeons, robotic scientists and industry to better understand the challenges and design tools and practices to advance knee surgery with the use of robotics.
Professor Dietmar W Hutmacher is leading establishment of another centre, using IHBI’s firmly-established research capabilities in additive biomanufacturing as the platform for training the next generation of engineers, clinicians and scientists using new national funding.
Prevention is a primary concern for Professor David Kavanagh, who aims to help people strengthen and sustain their motivation for leading healthy lifestyles, using technology such as robots, phone apps and websites.
Professor Hutmacher is a biofabrication expert who will lead development of 3D printing technologies that can be introduced in hospitals and clinics to treat damage and defects from injuries and disease such as bone and cartilage defects.
Professor Kavanagh aims to improve the lives of people with chronic illnesses such as diabetes and address problems related to alcohol use, smoking, physical inactivity and diet in order to improve health and decrease dependence on healthcare.
The research is varied, but the people working in IHBI laboratories, clinics and advanced computing facilities have much in common. They all strive to translate their research so it can make an impact, improving the lives and health of people.
Similarly, Professor Stewart Trost has a focus on prevention as he leads the establishment of the Queensland node of a Centre of Research Excellence. The centre aims to reduce the prevalence of obesity and obesity-related behaviours among children, with a focus on addressing key lifestyle links such as poor diet, inadequate sleep and insufficient activity.
Professor Lyn Griffiths Executive Director, IHBI
© QUT 2016 22376
Dr Jaiprakash is working with surgeons and industry to better understand the challenges and design tools and practices to advance knee surgery with the use of robotics. The work includes the use of cameras to capture 3D images that will enable analysis of arthroscopic procedures; working with surgeons to identify issues such as visibility and ergonomics during surgery; and design of a robot that will move a patient’s leg with precision to maximise access.
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