research matters - IHMRI - UOW

Looking outside the square for solutions to schizophrenia…p8

Inside: Streptococcal infections and blood type Is there a link?…p3

Aboriginal Healthy Hearts Research Workshop New initiative to address high rates of coronary heart disease…p11

ILLAWARRA HEALTH AND MEDICAL RESEARCH INSTITUTE

VISIONS

RESEARCH MATTERS

INSPIRED

autumn

2017

Cyclists spin funds for

cancer research

CONTENTS Cyclists spin funds for cancer research

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FEATURE: Streptococcal infections and blood type: is there a link?

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IHMRI tackles the science of gender equality

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Dame Bridget Ogilvie Awards and Scholarships

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Career Advancement Scholarships

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FEATURE: Protein deposits: the black holes of motor neurones

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COVER STORY: Inspired visions: looking outside the square for solutions to schizophrenia

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FEATURE: Long-term impact of neonatal abstinence syndrome tracked with NAPLAN data 10 Aboriginal Healthy Hearts Research Workshop

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FEATURE: Scientists, practitioners and the community unite to fight cancer

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New Scientific Advisory Committee Members provide guidance on Research

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2017 IHMRI Grants Scheme

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Project Air Strategy partner with Mission Australia

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Australian Society for Medical Research Scientific Meeting

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EVENTS: Save the date

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Cover image: Dr Katrina Green and PhD candidate Ashleigh Osborne. Photo by Simon Bullard.

Professor Marie Ranson accepts a donation from Tour de Cure cyclists at Westpac Bank in the Crown Street Mall.

Cancer charity Tour de Cure donates $10,000 to translational research at IHMRI. Inspirational pedal power was on colourful display when cyclists on a gruelling three-day Westpac Tour 200 event made a pit stop in Wollongong on 6 March to donate $10,000 to IHMRI cancer researcher Professor Marie Ranson and prominent local Oncologist, Professor Philip Clingan OAM. The Westpac Tour 200 is one of more than a dozen Tour de Cure events held around Australia each year that raise money to fight cancer. The tours have already raised $3.1 million this year. Clad in bright orange and blue lycra, the large group of cyclists made a spectacular entrance to the Crown Street Mall. Although weary from blustery conditions, nothing could diminish their enthusiasm. The group had ridden around the Southern Highlands, the Shoalhaven and the Illawarra, delivering donations along the way to selected cancer charities. Professor Ranson gave a short speech to thank the group for their support and explained how she would use the donation to support Phase II clinical trials of Deflexifol, the innovative chemotherapy solution for malignant colorectal cancer. “This project started as basic research involving Illawarra researchers and students in the laboratories of IHMRI,” explained Professor Ranson. “We recently finished Phase I clinical trials of Deflexifol in Wollongong. The results were extremely promising. Deflexifol increased quality of life for terminally ill cancer patients by reducing the side effects such as weight loss and venous inflammation,” she said. “Phase II trials are now required in order to get the drug to market.” Professor Philip Clingan, who led the Phase I trial with 39 patients, will again lead the Phase II trial, which will recruit patients locally and regionally.

Illawarra Health and Medical Research Institute Ltd Building 32, University of Wollongong, NSW 2522 t: +61 2 4221 4333 f: +61 2 4221 8130 e: [email protected] w: www.ihmri.uow.edu.au ACN 130692 849

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Several other collaborators at IHMRI and the University of Wollongong played an important role in the early phases of Deflexifol’s development, including Dr Tamantha Stutchbury and Dr Kara Vine; medicinal chemists Emeritus Professor John Bremner and Dr Julie Locke; and Commercialisation Manager Dr Gavin Dixon. The project has received support from many local organisations in the past, including the Illawarra Cancer Carers; Kiama, Minnamurra and Gerringong Sunrise Rotary; The Robert East Memorial Fund; Southern Medical Day Care Centre; the Gay Bates Memorial Foundation and UOW Alumni.

IHMRI RESEARCH MATTERS – AUTUMN 2017

Streptococcal infections and blood type: is there a link?

OUR NEWS

FEATURE

Senior Research Fellow, Dr Martina Sanderson-Smith and Post-Doctoral Researcher, Dr David De Oliveira. Photo by Todd Hardingham.

IHMRI infectious disease scientists have found that people with a common blood group could be more susceptible to Streptococcal infections. IHMRI Senior Research Fellow, Dr Martina Sanderson-Smith and Post-Doctoral Researcher, Dr David De Oliveira, from the University of Wollongong’s School of Biological Sciences, have published these recent findings in a top-ranking international microbiology publication, mBIO. There are many different types of Streptococcal infection, from mild sore throats to deadly infections of the blood or organs. Repeated infections can lead to chronic conditions, such as rheumatic heart disease. “Rather than focussing on how Streptococcus spreads like other studies, we took a different approach. We know that some people are more susceptible to Streptococcal infections. We wanted to see if there are other biological reasons that increase the risks, and understand why some people suffer repeated infections,” explains Dr Martina Sanderson-Smith. For his PhD thesis, Dr De Oliveira studied Streptococcus pyogenes (Group A Streptococcus or GAS), that is responsible for over 500,000 deaths worldwide each year. Using IHMRI’s state-of-the-art laboratories, he investigated a highly virulent clone

WWW.IHMRI.UOW.EDU.AU

of GAS (M1T1 GAS) that is present in many cases of pharyngitis and invasive infections. Dr De Oliveira found that people with blood group O could be more prone to infections caused by M1T1 GAS. The O blood group is the most common group among urban populations in western countries, including Australia. “This streptococcus interacts with, and attaches to, numerous sugar molecules that sit on blood cells,” explains Dr David De Oliveira. “These sugar molecules, known as glycans, are prevalent in group O blood. Our data suggests that these glycans act as a bridge for the M1T1 GAS to colonise humans, allowing it to flourish in the body.” Their work has already captured the attention of the medical research world. The researchers will present their findings at international conferences later in the year, including The Lancefield International Symposium on Streptococci and Streptococcal Disease. To progress understanding of the link between Streptococcus and blood groups, they will embark on a new project— studying saliva samples taken from people colonised with GAS, in collaboration with researchers at the Murdoch Childrens Research Institute.

The researchers also hope one day to take their findings out of the laboratory and into new treatments for people suffering from Streptococcal infections. “One of the outcomes we are striving for is a non-antibiotic treatment for children with sore throats,” states Dr Martina Sanderson-Smith. “A sore throat is one of the most common reasons children are prescribed antibiotics, but we are becoming more aware that antibiotic overuse can be a problem, so developing non-antibiotic treatments for bacterial infections is important.” Dr Sanderson-Smith and Dr De Oliveira worked with other researchers from the Department of Chemistry and Biomolecular Sciences at Macquarie University; the Australian Infectious Diseases Research Centre at the University of Queensland; the Centre for Immunity, Infection and Inflammation at the University of California, San Diego; and the Institute for Glycomics at Griffith University. This project was partly funded by an IHMRI Career Development Grant to Dr De Oliveira. Read the full paper: De Oliveira DMP, Hartley-Tassell L, Everest-Dass A, et al. 2017. Blood group antigen recognition via the group A streptococcal M protein mediates host colonization. mBio 8:e02237-16. http://goo.gl/U2DErD

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OUR NEWS

tackles the science of gender equality IHMRI

In the spirit of International Women’s Day, IHMRI hosted an inaugural event on 6 March to recognise, support and celebrate female researchers in the Illawarra region. Lunch with Dame Bridget Ogilvie brought together a very diverse group of women working in health and medical research, including senior academics and clinician researchers, early and mid-career researchers, as well as PhD candidates. Held at The Grange Golf Club, the event was not only a wonderful networking opportunity, but also a platform to raise issues that hamper the career progression of female researchers, particularly those living in regional areas.

Heema Vyas, Professor Judy Raper, Dame Bridget Ogilvie, Professor Maureen Lonergan, Dr Martina Sanderson-Smith and Professor Robin Anderson. Photo by Mark Newsham.

IHMRI plans to make Lunch with Dame Bridget Ogilvie an annual event. IHMRI will also continue to work alongside the University of Wollongong’s (UOW)

Science Australia Gender Equity (SAGE) initiative to strengthen and progress the careers of women in science in the Illawarra region.

Keynote address Dame Bridget Ogilvie (AC, DBE, SCD, FRS, FAA) is a renowned scientist who has had an influential career. Following a twenty-year research career in immunology, Dame Bridget has been at the helm of many great research institutes, advisory councils and funding bodies, including the Wellcome Trust, Medicines for Malaria Venture and Cancer Research UK. She now serves as the patron of IHMRI and hosted the inaugural event to address gender equity issues in the Illawarra region. Dame Bridget Ogilvie delivered a powerful and inspiring keynote address, reflecting on times when she was the only female in an agricultural science degree, and warning of the dangers of

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complacency when it comes to gender equality, stressing, “we cannot afford to waste the ability of half of our population.” Drawing on her experiences in research and executive leadership positions, Dame Bridget Ogilvie also spoke about the cultural and social differences between men and women that persist in the workplace. She proposed two strategies for improving the standing of women in research—acknowledging the effects of female and male behaviour in professional settings, and addressing unconscious social bias against women at a community level.


Dame Bridget Ogilvie delivering her keynote address. Photo by Mark Newsham.

OUR NEWS

Panel discussion Senior, early-career and emerging women researchers further explored these issues during a panel discussion led by Dr Melina Georgousakis, founder of Franklin Women—an organisation that brings together like-minded women in health and medical research to create opportunities for personal and professional development and career progression. “Great things happen when women in diverse health research roles connect: from unique research collaborations,

to sharing contacts and resources or just having someone to talk to who understands what you are going through,” says Melina. The panellists spoke about broad issues, like the significance of a critical mass of female leaders for gender equality, and offered practical suggestions, such as employing a research assistant to cover maternity leave. They also discussed financial support, salary equity, flexibility when returning to work and social support.

An appetite for change Gender imbalance in health and medical research, and the loss of women from senior research roles, is well documented in Australia and internationally. Women comprise more than half of science PhD graduates and earlycareer researchers in Australian universities and institutes, but less than 20 per cent of senior academics are women. These trends are evident within IHMRI: women represent 42 per cent of our research community with more female than male PhD students and doctoral holders; but significantly, fewer female researchers are at the professorial level.

Panellists left to right: Mr David Rae, UOW Workforce Diversity Officer and SAGE representative; Dr Martina Sanderson-Smith, Senior Lecturer in Molecular Biology, UOW; Professor Maureen Lonergan, Director of Renal Services, ISLHD; Professor Robin Anderson, Head of the Translational Breast Cancer Program, Olivia Newton John Cancer Research Institute; Dame Bridget Ogilvie; Dr Melina Georgousakis, founder of Franklin Women; Professor Melissa Wake, Professor of Paediatrics, Child and Youth Health, University of Auckland; Professor Judy Raper, Deputy Vice-Chancellor of Research and Innovation, UOW; Associate Professor Sally Inglis, Principal Research Fellow, University of Technology Sydney; Heema Vyas, PhD candidate, UOW. Photo by Mark Newsham.

Many women choose to leave academic careers in science because of barriers to career progression, such as career disruptions for mothers and unconscious bias against women. This can affect the promotion of women to leadership roles, as well as their grant funding success.

Naming competition Attendees had to put on their thinking caps for a competition to find a name for a local networking group for women working in health and medical research in the Illawarra. There were some very creative and interesting ideas. Notable mentions included: I-WISH (Illawarra Women In Science and Health); and WITCHAS (Women of the Illawarra making Tremendous Contributions in Health And Science). However, the winning table by popular vote was FLOURISH in the Illawarra (Females Leading Outstanding Research In Science and Health). Congratulations to the winning team of Dame Bridget Ogilvie, Distinguished Professor Gordon Wallace AO, Vicky Wallace, Senior Professor Linda Tapsell AM, Monica Birrento, Emma Hawksworth, Dr Sue Fitzpatrick and Zehra Boz on table three. Winners of the naming competition from table three, Monica Birrento and Emma Hawksworth. Photo by Mark Newsham.


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OUR NEWS

Dame Bridget Ogilvie Awards and Scholarships

IHMRI is championing the equality of women in the workforce, delivering new awards and a scholarship initiative designed to reward research excellence and provide career development to women in health and medical research. IHMRI has initiated two new awards to celebrate outstanding work by female IHMRI researchers with the inaugural recipients receiving $3000 each. Dame Bridget Ogilvie (AC, DBE, SCD, FRS, FAA) announced the winners at Lunch with Dame Bridget Ogilvie on 6 March. Associate Research Fellow Dr Rebecca Stanley received the Dame Bridget Ogilvie Citation Award, which recognises research excellence in outstanding publications by an early-mid career female researcher. To determine the recipient with the highest percentage of highly cited publications in their field of research IHMRI adapted a methodology used by Thomson Reuters for their Women in Citation Award. IHMRI received nineteen nominations for this award. Dr Stanley is a childhood health researcher focused on culturally appropriate school, afterschool, and community-based interventions to increase physical activity, reduce sedentary behaviour and promote healthy lifestyles in children and adolescents, particularly in Indigenous communities. Dr Stanley is also outstanding in being awarded one of the first NSW Health

Left to right: Dr Rebecca Stanley, Dame Bridget Ogilvie and Kelly Lambert. Photo by Mark Newsham

Early-Mid Career Fellowships last year for her project to develop an after-school Aboriginal cultural activity program for children living in the Shoalhaven region. Dr Stanley hopes to use her award to travel to Canada where she can learn from researchers who work with Indigenous peoples, and bring those skills to her own work with local Aboriginal communities. Kelly Lambert received the Dame Bridget Ogilvie Clinical Excellence Award, which recognises outstanding contribution to clinical practice by an early-mid career female researcher. Research Central at the Illawarra Shoalhaven Local Health District (ISLHD) nominated six clinicians for consideration for this award. A clinical dietician at The Wollongong Hospital, Kelly is an active member of the renal unit at The Wollongong Hospital and ISLHD’s Research Central.

She is enrolled in a PhD sponsored by the ISLHD/UOW Clinical PhD Scholarship Program, investigating early recognition of cognitive impairment in renal patients. Kelly won this award for the demonstrable translation of her research to improve care of patients with chronic kidney disease. Her research empowers patients to manage their own health. Although in the early stages of her research career, she is clearly establishing a national and international profile. Kelly would like to use the award to visit clinical researchers in Chicago to learn about questioning styles to use with patients who have poor health literacy. “I’d like to see [their methods] in practice to see how they apply [them] so that I could adapt it here in Australia. It is really opportune that I have received this award,” she says.

Career Advancement Scholarships The Dame Bridget Ogilvie Career Advancement Scholarships will provide funding to support female researchers, with a PhD or equivalent clinical experience, at any stage of their career to assist financially with an opportunity to enhance their career profile.

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This could include leadership training, participating in leadership roles (honorary), primary care assistance to allow attendance of a conference or a grant review panel, or put toward assistance during grant writing or reporting periods or for a significant publication.

IHMRI RESEARCH MATTERS –- SUMMER AUTUMN 2017 2017

There are two scholarships available of $1500 each. IHMRI will award the scholarships annually. Applications for the inaugural scholarships closed 31 May 2017. For more information visit http://goo.gl/PWRNVI

OUR NEWS

FEATURE

Protein deposits: the black holes of motor neurones PhD candidate Isabella Lambert-Smith and Principal Research Fellow Dr Justin Yerbury. Photo by Simon Bullard.

A five-year international research project led by IHMRI scientists has uncovered new insights into causes of motor neurone disease (MND). According to the MND Association, about 2000 Australians, including almost 30 in the Illawarra-Shoalhaven, suffer from the disorder in which the nerve cells (neurones) controlling the muscles that enable us to move, speak, breathe and swallow begin to degenerate and die. There is no effective treatment or cure and most people with MND die within 3-5 years of diagnosis. In rare cases, like that of eminent physicist and cosmologist Professor Stephen Hawking, life span is much longer. The research, which is led by IHMRI Principal Research Fellow Dr Justin Yerbury with the assistance of Senior Professor Mark Wilson and PhD student Isabella Lambert-Smith, from the University of Wollongong’s School of Biological Sciences, focuses on the protein molecules found in motor neurons. Proteins are important because they are the second most abundant molecule in the body after water. The researchers discovered proteins that do not normally interact will gather into deposits within motor neurons.


Dr Yerbury, who met with Professor Stephen Hawking at the University of Cambridge in April, said a strong analogy can be made between the research findings and Professor Hawking’s work in physics and cosmology. “There are almost as many protein molecules in a human body as there are stars in the universe and we liken the deposits of proteins within motor neurons to black holes,” he said. “They are dense accumulations that attract a whole range of proteins that become lost to the cell when they are sucked in. The biological properties of motor neurons make them vulnerable to this attack. “In this study we wanted to chip away at one of the biggest questions about this disease—why do motor neurons die while other groups of neurons and tissues in the body remain unaffected. “We believe that motor neurons are particularly vulnerable to losing proteins to their cellular black holes. This has brought us one step closer to explaining why only motor neurons die off in MND.”

Dr Yerbury and Ms Lambert-Smith, who worked with researchers from the University of Cambridge; CRG Barcelona; Universitat Pompeu Fabra; UNSW; and North Western University, hope this new understanding of the molecular origins of MND will provide a target for more effective treatment or therapies in the future. They are now actively testing potential therapeutics with Research Fellow Dr Kara Vine from UOW’s School of Biological Sciences. This research has received international attention, with publication in top-ranking international journal, PNAS (Proceedings of the National Academy of Sciences of the United States of America). Read the full paper: Ciryam P, Lambert-Smith I, Bean D, et al. Spinal motor neuron protein supersaturation patterns are associated with inclusion body formation in ALS. PNAS April 10 2017, doi:10.1073/pnas.1613854114. http://goo.gl/VXTIv7

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OUR NEWS

COVER STORY

Inspired visions: looking outside the square for solutions to schizophrenia

Senior Professor Xu-Feng Huang, Professor Nadia Solowij, Dr Katrina Green and PhD candidate Ashleigh Osborne. Photo by Simon Bullard.

Hallucinations, delusions, disorganised speech and social withdrawal. These are just some of the symptoms of schizophrenia—a debilitating brain disorder that affects the way a person behaves, thinks, and sees the world. According to the Schizophrenia Research Institute, people with schizophrenia have two and a half times the death rate of the general population, with

life expectancy reduced by up to 18 years. It ranks among the top 10 causes of disability in developed countries worldwide.

Two projects by collaborative teams of IHMRI researchers at the University of Wollongong (UOW) are tackling schizophrenia from two very different angles and in unexpected ways.

Cannabis compound has potential to unlock new cognitive treatment for schizophrenia

insights about the therapeutic potential of CBD during a detailed review of 27 existing studies.

IHMRI researchers have discovered that an active compound in cannabis plants may alleviate cognitive impairment, providing a vital opportunity in the treatment of schizophrenia.

“From this review, we found that CBD will not improve learning and memory in healthy brains, but may improve aspects of learning and memory in illnesses associated with cognitive impairment, including Alzheimer’s disease, as well as neurological and neuro-inflammatory disorders,” project leader, Dr Katrina Green said. “Evidence suggests that CBD is neuroprotective and can reduce cognitive impairment associated with use of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis.”

The compound, Cannabidiol (CBD), can influence learning, memory and attention, offering potential solutions to several core symptoms of schizophrenia that can be a challenge to alleviate with existing medicines, such as cognitive impairment and social withdrawal. The researchers hope that this knowledge will be used to develop new and improved medications for schizophrenia—a debilitating mental illness that ranks among the top 10 causes of disability in developed countries worldwide.

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Although current antipsychotic medications are effective against the delusions and hallucinations of schizophrenia, they are less effective in treating the cognitive and negative symptoms, such as social withdrawal and blunted emotional expression. Current medications can also have negative side effects, such as weight gain and movement disorder. PhD candidate Ashleigh Osborne and her supervisors, Dr Katrina Green and Professor Nadia Solowij from UOW, initially uncovered the fascinating


This evidence inspired Ms Osborne to investigate whether CBD can improve cognitive impairment in a rodent model of schizophrenia, together with her supervisors and research team members, Senior Professor Xu-Feng Huang and PhD candidate Ilijana Babic.

Reversing the cause of schizophrenia

“These findings are interesting because they suggest that CBD may be able to treat some of the symptoms of schizophrenia that are seemingly resistant to existing medications. In addition, CBD treatment did not alter body weight or food intake, which are common side effects of antipsychotic drug treatment.” Dr Green said the team was excited about the results but further testing was needed to determine whether CBD has the same beneficial effects in people with schizophrenia. They are now examining changes in neurotransmitter signalling pathways in the brain that result from CBD treatment in order to uncover the underlying therapeutic mechanisms. The study review was published in the high impact journal, Neuroscience and Biobehavioral Reviews (Osborne et al., Jan 2017. 72:310324 http://goo.gl/AdAP9U), while the experimental findings were recently published in Nature journal, Neuropsychopharmacology, (Osborne et al., http://goo.gl/oj02Lh). These studies were supported by the National Health and Medical Research Council (Project Grant 1007593 to Professor Nadia Solowij), the Australian Research Council (Future Fellowship FT110100752 to Professor Nadia Solowij) and a Faculty of Science, Medicine and Health Advancement Grant (2015/ SPGA-S/02 to Dr Katrina Green and Senior Professor Xu-Feng Huang). Ashleigh Osborne is supported by an Australian Government Research Training Program Scholarship. Please note the researchers do not endorse the use of cannabis products to treat schizophrenia, as some ingredients, such as THC, have the potential to aggravate symptoms. This research examined one isolated compound of the cannabis plant within controlled laboratory settings. People diagnosed with a mental illness should always consult their medical practitioners about any issues with their current medication.


COVER STORY

“We found that CBD was able to restore recognition and working memory, as well as social behaviour to normal levels,” Ms Osborne said.

Distinguished Professor Gordon Wallace AO, Senior Professor Xu-Feng Huang and Dr Qingsheng (Kiefer) Zhang. Photo by Mark Newsham.

IHMRI researchers have developed a potential new treatment for schizophrenia that targets its underlying cause. ARC Centre of Excellence for Electromaterials Science (ACES) Director Distinguished Professor Gordon Wallace AO has joined forces with Senior Professor Xu-Feng Huang from UOW’s School of Medicine to explore options for treating a recently discovered neural connection deficit that causes schizophrenia.

The paper’s lead author, Dr Qingsheng (Kiefer) Zhang, said the study involved delivering electrical stimulation to brain cells from mice of three genotypes.

The pair saw an opportunity to apply a biocompatible polymer and protocol developed previously by ACES for Cochlear implant studies, to address the neural connection deficit.

“First, we found that the diseased cells indeed have a reduced neurite outgrowth and a reduced capacity for communication compared to the healthy cells. We also found that using conductive polymer mediated electrical stimulation can regenerate the neurite network and synapses responsible for communication between cells,” he reveals.

“The polymer we developed promotes neurite outgrowth using electrical stimulation, and in parallel there was mounting evidence linking a lack of neural connectivity and schizophrenia,” states Professor Wallace. The polymer and its protocol could help to recreate those connections. “In diseased brain cells, we see a reduction in the surrounding network of cells, called neurites, that facilitate communication between cells,” explains Senior Professor Huang. “We now know that this deficit is the primary pathology underlying schizophrenia, leading to symptoms like psychosis, social withdrawal or cognitive dysfunction.” With the help of a National Health and Medical Research grant, the two teamed up to look at the effectiveness of the ACES electrical stimulation method on diseased schizophrenia cells from mice.

“We applied electrical stimulation to brain cells from healthy mice and mice with two different kinds of diseased genes which are known to be linked to schizophrenia,” Dr Zhang states.

The research could be significant for the some 200,000 Australians living with schizophrenia. “People living with schizophrenia rely on a limited number of drugs—with a range of debilitating side effects—to treat the symptoms of the disease without targeting the underlying cause. This early stage research is a step in the right direction for treating its cause,” concludes Professor Huang. Read the full paper: Zhang Q, Esrafilzadeh D, et al. Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1KO and DISC1-LI Mice. Scientific Reports 7, Article number: 42525 (2017) doi:10.1038/ srep42525 http://goo.gl/jX7DPi

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FEATURE

Long-term impact of neonatal abstinence syndrome tracked with

NAPLAN data

IHMRI researchers have found babies withdrawing from addictive drugs in the womb have poor long-term school results. When a woman uses addictive drugs during pregnancy, her baby is likely to suffer from Neonatal Abstinence Syndrome (NAS) when born. Babies with NAS have similar withdrawal symptoms to adult drug users who are trying to quit, including vomiting, diarrhoea, tremors, fever and sweating. Previous research by Professor Ian Wright from the University of Wollongong’s (UOW) School of Medicine, and his colleagues, found that newborn children diagnosed with NAS have an increased risk of a prolonged hospital stay. These children are also more likely to be re-hospitalised in childhood for maltreatment and trauma, as well as mental and behavioural disorders. Although researchers suspected that children with NAS might be at risk of ongoing neurodevelopmental and cognitive problems, the difficulties of long-term follow up with these patients made it difficult to test this theory. Until now. To help fill this knowledge gap, Professor Wright joined a research team led by Dr Ju-lee Oei from the University of New South Wales (UNSW), that also included Professor Ted Melhuish from UOW’s Early Start Research Institute. The team conducted a long-term study using National Assessment Program for Literacy and Numeracy (NAPLAN) results to trace the downstream effect of NAS on educational outcomes. Introduced in 2008, NAPLAN is a compulsory curriculum-based test for all students in years three, five, seven and nine in Australia.

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Paediatrician Professor Ian Wright. Photo by Paul Jones.

The researchers compared a group of 2,234 babies born with NAS in New South Wales between 2000 and 2006, with a control group of 4,330 children matched for gestation, socioeconomic status and gender, and with other NSW children born during the same time period. They then analysed the mean test results of each group in schooling years three, five and seven from NAPLAN data. “The findings are stark,” says Professor Ian Wright. “By year three, mean test scores for children with NAS were significantly lower than the two other cohorts, and results deteriorate even more by high school. By year seven, children with NAS scored lower than other children in year five.” The outlook for children born with NAS is complex. School performance is an important indicator of childhood development, and failure at school can lead to poor outcomes in adult life, including psychiatric and physical illness, unemployment, delinquency, crime, drug use and intergenerational disadvantage. Dysfunctional parental behaviour stemming from continued

IHMRI RESEARCH MATTERS –- SUMMER AUTUMN 2017 2017

drug use makes for a disruptive home environment, which may also affect a child’s performance at school—and this was acknowledged by the researchers. With NAS one of the fastest growing public health problems in the world, this study could not be more timely. “We believe that this study provides a compelling reason to support children with NAS beyond the withdrawal stage to minimise risk of school failure and its consequences,” states Professor Wright. “Interestingly, significant geographical variation exists in this data, suggesting that these outcomes are not inevitable for children exposed to drugs or staying with their families.” “The high risk of poor academic performance in this vulnerable group of children is applicable to all countries. Strategies to address this risk, and prevent poor adult outcomes and intergenerational vulnerability, should be urgently addressed.” Read the full paper: Oei JL, Melhuish E, Uebel H, et al. Neonatal Abstinence Syndrome and High School Performance. Paediatrics. 2017;139 (2):e20162651

Healthy Hearts

RESEARCH CENTRAL

NEWS

Aboriginal

Research Workshop

New initiative to address high rates of coronary heart disease in Indigenous people. Coronary heart disease (CHD) in Aboriginal and Torres Strait Islander peoples is a pressing national health issue. Overall, the death rate from CHD is twice as high in Indigenous people as in non-indigenous people. Indigenous people are also more likely to suffer CHD at an earlier age. According to statistics from the Federal Government’s Australian Institute of Health and Welfare, Indigenous people are 10 times more likely to die from CHD aged 25-37, seven times as likely to die from CHD aged 35-44, and four and half times as likely to die from CHD aged 5564 than non-indigenous people. To explore potential solutions to these issues, Research Central from the Illawarra Shoalhaven Local Health District (ISLHD) facilitated the Aboriginal Healthy Hearts Research Workshop on 30 March at City Beach Function Centre. The workshop was a first of its kind for the region, gathering together a diverse group of people, including national health experts, doctors, public servants and representatives from local Indigenous communities. “The Workshop is the first step in this collaborative initiative. We want to understand the scope of the problem in our area, discuss examples of successful intervention strategies, and define what further research is needed,” states Professor Leonard Arnolda, Clinical Director of IHMRI. Chief Executive of the ISLHD, Margot Mains, delivered opening remarks at the workshop.

Alec Trindall and IHMRI Clinical Director Professor Leonard Arnolda at the Aboriginal Healthy Hearts Research Workshop organised by ISLHD’s Research Central and supported by IHMRI.

The keynote guest speaker was Professor Alex Brown, a medical doctor originally from the Shoalhaven who is now Leader of the Aboriginal Health Unit at the South Australian Health and Medical Research Institute (SAHMRI). He was joined by Pauline Brown, Director Aboriginal Health Strategy, at ISLHD, as well as Dr Scott Winch, Academic Leader, Indigenous Health, at the University of Wollongong (UOW). In addition to local Aboriginal people with heart disease, other speakers included:

IHMRI and ISLHD’s Research Central will use the insights gained from the workshop to develop a translational grant application, targeting strategies to reduce CHD in the Illawarra. The initiative was inspired by the Close the Gap Campaign, a government strategy that aims to reduce disadvantage among Aboriginal and Torres Strait Islander people with respect to life expectancy, child mortality, access to early childhood education, educational achievement, and employment outcome.

• Dr Marianne Gale, NSW Ministry of Health • Dr Rowena Ivers, Senior Medical Officer, Illawarra Aboriginal Medical Service • Clinical Honorary Associate Professor Marianna Milosavljevic, Manager of Research, ISLHD • Bronia Kandl, CNC and Anne O’Neill, CNC, Shoalhaven Cardiac Rehabilitation service, ISLHD • Sandra McCreanor, CNC Illawarra Cardiac Rehabilitation service, ISLHD. Professor Alex Brown from the South Australian Health and Medical Research Institute (SAHMRI).


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OUR NEWS

FEATURE

Scientists, practitioners and the community unite to fight cancer

Professor Peter Metcalfe. Photo by Paul Jones.

IHMRI connects scientists and medical practitioners to help solve pressing health challenges in our communities. Our collaborative and multi-disciplinary approach is finding new ways of diagnosing and treating one of Australia’s most pervasive diseases.

IHMRI researchers awarded funding to develop world-first radiotherapy system The Cancer Council NSW funded project will make radiation therapy safer and more effective Forty percent of cancer patients in Australia receive radiation therapy. One of the difficulties with current treatment techniques, which map out the cancer ahead of the radiotherapy, is that tumours move during treatment, for example when the patient breathes. Magnetic Resonance Image (MRI)-guided radiotherapy now allows the cancer and surrounding organs to be viewed in real time as it is being treated, but at present it is impossible to check the radiation dose in real time. A team of IHMRI researchers within the University of Wollongong’s Centre for Medical Radiation Physics (CMRP) aims to solve this problem by perfecting a novel radiation dosimetry (radiation dosage measurement) system that operates with MRI-linear accelerators. To support this vital work, the Cancer Council NSW has awarded IHMRI researcher Professor Peter Metcalfe from CMRP a $427,195 project grant to develop a worldfirst system to ensure the safe delivery of radiation doses to cancer patients.

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Other IHMRI researchers on the project are Distinguished Professor Anatoly Rozenfeld, Dr Marco Petasecca, and Dr Brad Oborn from the Illawarra Cancer Care Centre. They are collaborating with Associate Professor Gary Liney from the Ingham Institute for Applied Medical Research, Associate Professor Lois Holloway from Liverpool Hospital and Professor David Thwaites from the University of Sydney. Professor Metcalfe said the end benefits of the three-year study will enable technology such as the MRI-linear accelerator to be used to their full potential, resulting in safer, more accurate and more effective treatment for patients. “It’s mainly for the cancers that are difficult to visualise and treat—lung, breast, oesophagus, pancreas, kidney, rectal tissue, liver, cervix, prostate and lymph nodes—all the tricky ones,” Professor Metcalfe states. “These cancers are difficult to target using current technology because they are near healthy organs that need to be


avoided. The main thing with radiotherapy is avoiding other surrounding organs. So if you can reduce the size of the radiation field and hit the target more exactly you can spare the healthy organs.” “Professor Rozenfeld and Dr Petasecca’s dosimeters are very, very high resolution. We can usually measure doses in square centimetres but these dosimeters actually measure the edges of the field out to 20 microns resolution.” Professor Metcalfe said that working with Cancer Council NSW really brought home the importance of the project. “The big thing with Cancer Council NSW is that they give you a consumer to have on the project, and that consumer is usually someone who has been a patient,” he explains. “They help you write the grant to show what the advantage is going to be to the consumer – the patient – and you keep them at your meetings throughout the project and they give feedback on what they think about what you are doing in your research.” “You feel a real responsibility when you’ve got a grant from Cancer Council NSW because you’ve seen the women and men doing Daffodil Day and Relay for Life. They’ve really worked their butts off to raise this money, so you’d better do some good work.”

Protein study reveals new insights into bowel cancer

Bowel cancer, also known as colorectal cancer, is one of the most common forms of cancer in Australia, and the incidence is increasing, particularly among younger people. Bowel Cancer Australia estimates that 20,000 people will be diagnosed with the disease in 2020. Bowel cancer is one of the more deadly forms of cancer—second only to lung cancer in the number of lives it claims each year. If diagnosed early doctors can successfully treat a patient with bowel cancer. Unfortunately, fewer than 40 per cent of patients with bowel cancer have their disease detected during the early stages, reducing their chances of survival. Therefore, medical practitioners urgently need new biomarkers that can detect early-stage disease and even early growth, such as adenoma. Carcinoembryonic antigen (CEA), still the most widely accepted prognostic marker in bowel cancer, is mainly used for disease monitoring after therapy, since elevated CEA levels are only detected at later stages of the disease. A team of IHMRI researchers at the University of Wollongong (UOW), with the help of medical practitioners in the Illawarra, have uncovered new insights into translationally controlled tumour protein (TCTP) that could pave the way

FEATURE

IHMRI scientists and doctors uncover potential new way to assist in early detection and monitoring of bowel cancer for new and improved ways to diagnose and treat bowel cancer. “TCTP is involved in numerous biological processes in the human body. It protects cells from a range of stresses and is involved in the cellular DNA damage repair system. However it is also involved in cell growth and the development of different types of cancers,” explains Associate Professor Ulrich Bommer. The team, which included Research Fellow Dr Kara Vine and Dr Alistair Lochhead, investigated how TCTP behaves in the early development of bowel cancer and during chemotherapy. “Our research shows that TCTP levels are already elevated in the early stages of bowel cancer development. This means that TCTP could be explored as a biomarker to assist in the detection of early tumour growth and to identify patients with a high TCTP status,” reveals Associate Professor Bommer. The researchers also found that TCTP might protect cancer cells against chemotherapy treatment. “In bowel cancer cells which are treated with 5-fluorouracil (5-FU) and oxaliplatin, two chemotherapeutic drugs frequently used in bowel cancer treatment, we found that TCTP levels are particularly high. We suspect that TCTP may be

responsible for making the cancer cells resistant to the anti-cancer treatments,” states Dr Vine. The researchers believe this insight could make TCTP suitable as a potential biomarker for chemo-resistance and as an anti-cancer drug target in chemoresistant tumours. Further research is required to explore these theories. The team comprised researchers from UOW’s Schools of Medicine and of Biological Sciences, as well as Medical Practitioners from Southern.IML Pathology and from The Wollongong Hospital. Funding for the project was obtained through a URC small grant from UOW’s School of Medicine and through a grant from the IHMRI Small Grants Program. It was the aim of these grant programs to facilitate exactly such types of collaborative projects. Read the full paper: Bommer et al. Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin. Cell Communication and Signaling (2017) 15:9. http://goo.gl/th1LDT

Cannabis trial for nausea relief in cancer patients IHMRI researcher and Medical Oncologist, Professor Morteza Aghmesheh, will oversee a clinical trial at Wollongong Hospital to study whether medicinal cannabis can alleviate nausea and vomiting in cancer patients receiving chemotherapy. Wollongong Hospital is one of seven in New South Wales selected to be part of the world-first trial, which is led by the Chris O’Brien Lifehouse in Sydney. Twenty carefully selected cancer patients in the Illawarra will participate. The trials will be conducted in The Wollongong Hospital’s state-of-the-art Illawarra Cancer Care Centre. “We’re excited Wollongong Hospital is able to take part in this world-first trial,” explains Professor Aghmesheh. “The medicinal cannabis is being trialled in patients where standard treatments for nausea have failed, and who meet the eligibility criteria.”


Carly Leighton, Cancer Clinical Trials Manager, Illawarra Shoalhaven Cancer & Haematology Network and Professor Morteza Aghmesheh, Principal Investigator for The Wollongong Hospital.

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NEW OUR NEWS

Scientific

Advisory Committee Members provide guidance on Research

The Scientific Advisory Committee (SAC) supports IHMRI’s Executive Management Team, ensuring our research program is scientifically and clinically relevant, and directed towards solving ‘real world’ health and medical problems. Chaired by IHMRI’s Executive Director, Professor David Adams, the SAC offers advice on our research priorities and research strengths, as well as guidance on funding opportunities.

six external members who serve for an initial term of three years. Drawn from a range of external Australasian institutions and universities, the external committee members are highly successful and experienced international researchers.

The new external committee members visited IHMRI on 6 March for the first time, together with IHMRI Patron, Dame Bridget Ogilvie (AC, DBE, SCD, FRS, FAA).

Members

Professor David Adams recently appointed the following external members from a list of nominees as members of IHMRI’s SAC for 2017-2019.

The SAC consists of up to eight members, including IHMRI’s Executive Director and Clinical Director, and up to

All of the members are new, apart from Professor Christos Pantelis who served on the previous SAC from 2014-2016.

They attended the first SAC meeting, which included a tour of the IHMRI headquarters, attendance at the Lunch with Dame Bridget Ogilvie, and in the afternoon visited The Wollongong Hospital, meeting with ISLHD researchers and IHMRI theme leaders. The SAC will meet again at an IHMRI translational research workshop in September.

Professor Robin Anderson

Professor Mark Cooper AO

Professor Christos Pantelis

The SAC also participates in reviews of research initiatives and provides a broad perspective of national and international trends in health and medical research.

Head, Translational Breast Cancer Program

Head of Department of Diabetes

Olivia Newtown John Cancer Research Institute

Monash University

Scientific Director of the Melbourne Neuropsychiatry Centre University of Melbourne

Research focus: genetic regulation of metastasis, primarily in breast cancer; identifying new targets for molecular based therapy for patients with progressive disease

Research focus: diabetes and its three major complications: kidney disease, heart disease and blindness

Research focus: psychosis; schizophrenia; early developmental disorders in children; biomarkers in neurodegenerative and psychotic disorders

Professor Perry Bartlett

Professor David Craik

Professor Melissa Wake

Director of the Queensland Brain Institute University of Queensland Research focus: molecular neuroscience; brain stem cells

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Institute for Molecular Bioscience University of Queensland

Cure Kids Professor of Child Health Research, Department of Paediatrics and the Liggins Institute University of Auckland

Research focus: peptides and protein structures in drug and insecticide design

IHMRI RESEARCH MATTERS - AUTUMN 2017

Research focus: population paediatrics; children’s health and development

OUR NEWS

2017 IHMRI Grants Scheme Supporting vital health and medical research in the Illawarra-Shoalhaven. Every year IHMRI assists health and medical research in the region by providing grants to academic/clinician researchers and medical professional researchers. In 2017, seven grants are available across two schemes, providing $130,000 in total. To help early career researchers develop their skills and expertise, IHMRI will offer three Career Development Grants worth up to $10,000 each. To support collaborative research projects that target important health

issues in the Illawarra, IHMRI will offer four Collaborative Research Grants, worth up to $25,000 each. These grants are for projects co-led by allied health professionals/clinicians and academic researchers. Applications close 12 June 2017. For more information about the Grants Program, including eligibility requirements and application forms, visit http://goo.gl/N8A1oQ or email IHMRI’s Research Development team at [email protected]

Project Air Strategy partner with Mission Australia IHMRI researchers with the University of Wollongong’s Project Air Strategy will help Mission Australia evaluate their Dialectical Behaviour Therapy (DBT) program at Triple Care Farm. Triple Care Farm, located on 110 acres in the Southern Highlands, is a residential program for young people (aged 16-24) experiencing homelessness, substance abuse, mental illness, or acute behavioural problems. The research team will evaluate the effectiveness of DBT in treating adolescents and young adults experiencing substance misuse over a two-year period. DBT combines practices from cognitive behaviour therapies and eastern philosophy, including the practice of mindfulness.


A grant to Mission Australia from NSW Health is funding the research. The IHMRI researchers include Professor Brin Grenyer and Research Fellow Dr Denise Meuldijk. As well as offering services for health professionals and organisations who work with people with personality disorders, Project Air Strategy also offers research services such as literature reviews, guideline development, clinical trials, outcome studies and more. For more information visit www.projectairstrategy.org

Australian Society for Medical Research Scientific Meeting Congratulations to the following students who have been awarded sponsorship by IHMRI to attend this year’s Australian Society for Medical Research Scientific Meeting on 2 June at Westmead Hospital, Sydney. • Rachelle Balez: Investigating the distribution and neuroprotective effect of alphatocopherol in induced pluripotent stem cell derived neurons. Supervised by Dr Lezanne Ooi and Associate Professor Todd Mitchell. • Monique Bax: Ubiquitin Proteasome System Dysfunction in Amyotrophic Lateral Sclerosis Patient Induced Pluripotent Stem CellDerived Motor Neurons. Supervised by Dr Lezanne Ooi and Dr Justin Yerbury. • Ashleigh Osborne: Muscarinic M1 receptor density alterations in the brain following cannabidiol treatment in a prenatal infection model of schizophrenia. Supervised by Dr Katrina Green and Professor Nadia Solowij. • Jay Perry: Skin Deep: Understanding Metastatic Non-Melanoma Skin Cancer. Supervised by Professor Marie Ranson and Associate Professor Ron Sluyter. • Reece Sophocleous: Characterisation of the canine P2X4 receptor channel and its relevance to human health and disease. Supervised by Associate Professor Ron Sluyter and Dr Lezanne Ooi. Thank you to all those students who applied for sponsorship. All applications received were highly competitive with the IHMRI Executive facing a difficult task in selecting the final five. For those students who may still be interested in attending and presenting at the workshop please contact the organisers of the meeting directly https://asmr.org.au/asmr-mrw/nsw/

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EVENTS

Save the date Put these events in your diary Throughout the year, IHMRI hosts, supports and promotes seminars, theme meetings, workshops and symposia, with many events timed to coincide with visits by national and international speakers. To RSVP email [email protected] Seminar, 21 June

Seminar, 19 July

Speaker: Professor Tony Okely from UOW’s Early Start Research Institute

Speaker: Professor Margaret Morris from the University of NSW

Topic: Whole body calorimetry studies in pre-schoolers, children and adolescents Time: 12:00pm – 1:00pm Venue: Conference Room 1, Block C, Level 8, The Wollongong Hospital

July Dementia and Driving Public Lecture Researchers from UOW’s Dementia and Driving project have organised this lecture to increase knowledge and understanding of approaches to dementia and driving retirement. Participants will learn how to support informed decisions by individuals with early dementia diagnosis, in partnership with their GPs, other practitioners, family members and carers. The lecture will be held on Monday 3 July in building 28 at the University of Wollongong, 5.30pm – 7.00pm. For more information visit, http://goo.gl/uO010x.

September Translational Cancer Research Workshop Medical practitioners, scientists and members of the local community will come together for the second Translational Cancer Research Workshop on Friday 8 September at Panorama House, Bulli Tops.

Topic: How can diet impact brain function and behaviour? Time: 12:30pm – 1:30pm

Community Address, 21 August Speaker: Professor John Mattick, Executive Director of the Garvan Institute for Medical Research Topic: The transformational impact of genomics and machine learning on biomedical discovery and healthcare

Venue: IHMRI, Building 32 University of Wollongong

Time: 5:30pm – 7:30pm

Organised by the Centre of Oncology Education & Research Translation (CONCERT), Research Central at the Illawarra Shoalhaven Local Health District and IHMRI, the one-day networking workshop will cover a range of topics in cancer research and care, including chemotherapy dosing, robotic surgery, biobanking and much more.

To register, visit the website at www. drugdeliveryaustralia2017.com. For great savings, register before 21 August 2017 to secure the early bird rate.

For more information, please contact ISLHD’s Research Central on 4253 4892 or email [email protected]

October 2017 Drug Delivery Australia Conference: Colloids on the Coast The Australian Chapter of the Controlled Release Society invites you to the 2017 Drug Delivery Australia Conference: Colloids on the Coast. Colloids on the Coast will bring together prominent scientists from pharmaceutical, medicinal, biological, engineering, and chemistry backgrounds to discuss emerging technologies in drug delivery science. Supported by IHMRI, Colloids on the Coast will be held at City Beach Function Centre, 23 – 24 October 2017.

Venue: City Beach Function Centre

November 3rd International Proteostasis and Disease Symposium UOW’s Proteostasis and Disease Research Centre (PDRC) and IHMRI are proud to host the 3rd International Proteostasis and Disease Symposium. The PDRC will offer a fresh and cuttingedge program, featuring national and international researchers at the forefront of this field, including Professor Christopher Dobson FRS (University of Cambridge, UK) and Professor Richard Morimoto (Northwestern University, USA). The Symposium will be held at the Novotel Northbeach, 20-22 November 2017. To register, visit www.proteostasissymposium.org.au. Early bird rates end on 18 August. If you have any questions, please email proteostasis-2017@uow. edu.au.

Research Matters is a publication of the Illawarra Health and Medical Research Institute, a joint initiative of the Illawarra Shoalhaven Local Health District and University of Wollongong. IHMRI’s purpose is to build a regionally relevant, but internationally and nationally recognised centre of health and medical research, targeting health improvements through novel treatments, better clinical practice and preventative health.

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