Robinson Research Institute Annual Report 2015 Our vision is to achieve life-time health for all children and families, through research excellence.

Our mission is to deliver world-class advances in knowledge of human reproduction, pregnancy and child health, and to inform clinical care, policy and practice that will improve health across generations and global communities.

Contents

Who we are 1 RRI at a glance 2 Message from the Deputy Vice-Chancellor (Research) 3 Message from the Chair 4 Message from the Director 5

Research Priorities 6

Funding Highlights 28 Fellowships and Awards 30 Financials 32

Key Collaborations 33 International Visitor Spotlight 34

Institute Engagement 36 Media Impact 38

Research Groups 39 Fertility and Conception 40 Pregnancy and Birth 48 Early Origins of Health 52 Child and Adolescent Health 56

Fostering Research Excellence 64 Advisory Board 70 Executive Committee 71 Member List 72 Publications 74 Support us 87 Who we are

We focus on the early stages of life to The Robinson Research improve the health and well-being of children and families over the life course Institute is a collective of and across generations, in Australia and internationally renowned around the world. We seek to enable a healthy start through researchers in human fertility choices and mindful conception, nurturing the baby during pregnancy and reproduction, pregnancy birth, strengthening the brain and body in early life, and advancing child and and child health at the adolescent health to treat and prevent University of Adelaide. disease.

Annual Report 2015 1 RRI at a glance

$15m+ 48 $42,800+ competitive funding Research Leaders donations

350+ 4 9 30+ 90+ 380+ Members Research Research Honours PhD publications Themes Priorities students students

5 5 17,300+ 7.5% 120+ Embedded in 5 Top ERA citations by citation Conference SA hospitals ranking of 5 for Research increase from papers all 3 rounds, Leaders 2014 research is well (Google above world Scholar) standard

2 Robinson Research Institute Message from the Deputy Vice-Chancellor (Research)

A vital aspect of any world-class university is delivering impact – real advances that benefit society and improve people’s lives.

With more than 350 talented scientists and demonstrating that the stress hormone clinicians, the Robinson Research Institute cortisol affects brain plasticity and learning; seeks to improve lifetime health for children the discovery that obesity in parents changes and families through research excellence, DNA structure, leading to significantly and translating research discoveries to increased risk of obesity in children; and deliver better clinical care and health policy. defining health function changes in children Addressing the earliest phases of life is the with type 1 diabetes. key to solving many of the major health Looking through this report and reflecting conditions affecting Australians and people on the breadth and depth of the Institute’s across the globe. There is a strong societal research activities, I am confident the Institute and economic case for focussing on will continue to lead the way in transforming preconception, pregnancy and the child to the health of families around the world. deliver great dividends in our community. 2015 was yet another successful year for Professor Mike Brooks the Institute with many significant research Deputy Vice-Chancellor (Research) advances including: the discovery of a genetic contribution to cerebral palsy;

Annual Report 2015 3 Message from the Chair

In an increasingly competitive research environment, the Robinson Research Institute is taking measures to ensure it continues to be a research powerhouse into the future. Its future location in the new Adelaide Medical and Nursing School and the support by the University of Adelaide provide a strong and essential base for the continued success of the Institute.

Collaboration and new partnerships will The Institute continues to demonstrate its also be key and I’m pleased to witness how leading capabilities, achieving an Excellence RRI members are adapting and devising in Research for Australia (ERA) rating of 5 for innovative approaches to tackle big research the third cycle in a row, demonstrating research questions. We can no longer rely on the outputs well above world standard – the only traditional sources of funding such as department in the country to achieve this NHMRC or ARC for research direct costs rating for all three cycles in the discipline of and salaries. It is essential that other avenues paediatrics and reproductive medicine. of funding be explored, requiring a different Thank you once again to the RRI Board mindset and different performance indicators. Members for the commitment, contribution Multi-disciplinary groups are clearly essential, and insight provided to the Institute during with clinicians and researchers working not 2015. We welcome Dr Susan Evans to the just across RRI research groups, but also Board who brings a community perspective with collaborators interstate and around the to our discussions as well as expertise world. Additionally, members are branching in the reproductive health of women. I’d out to form partnerships beyond their especially like to acknowledge the Director, peers, namely with the community, health Professor Sarah Robertson for her vision for professionals and corporates. the future of the Institute and for her inspiring This is in-line with the National Innovation leadership during challenging times. and Science Agenda and with the Research I look forward to continuing to Chair the Strategic Plan of the University of Adelaide. Advisory Board into 2016 and beyond, This vision seeks to match researchers and congratulate the RRI staff on another with industry to find solutions to real world outstanding year. problems. Professor Jock Findlay Chair

4 Robinson Research Institute Message from the Director

2015 was another strong year for the Robinson Research Institute. Our research continues to provide new understanding and practical solutions for important health conditions ranging from infertility through to preterm birth, and debilitating childhood conditions such as diabetes, obesity and infectious disease.

I’m proud of our increasingly collaborative career researchers working in the Institute. approach, with most members now working We developed a funding scheme to seed across research groups and themes, and promising new projects, expanded our with national and international collaborators. mentoring scheme and established a High This enables not just incremental advances Performance Researcher Program to assist but bigger strides forward toward solving selected researchers in developing skills and major problems in reproduction, pregnancy characteristics for enhanced productivity and child health. It is clear that scale and and success. These new initiatives add to coordinated effort is essential to improving our series of funding schemes that support the complex conditions constraining health and enable researchers to work towards the and quality of life for children and families Institute’s priority goals. around the globe. Successes in 2015 are many, but a The Australian research space is changing highlight was securing an NHMRC Centre rapidly. The increasingly competitive research of Research Excellence to examine links environment raises new challenges and between in utero and perinatal events, and compels us to re-examine our focus and later childhood development and learning. ensure the relevance of our research to the Led by Professor John Lynch with a team wider community. To assist us with setting including Professors Michael Sawyer, Claire future directions we commissioned an Roberts and several others, the CRE will external Scientific Advisory Committee (SAC) work to identify how best to protect our in 2015. The SAC comprises renowned children from mental health and learning experts in our field, Prof Moira Clay (Chair), disorders that limit their life chances. I am School building in the West End in early Prof John Aitken, Prof Jonathan Morris AM, delighted that this CRE embodies the RRI’s 2017, and the excitement and challenges Prof Peter Richmond and Prof Melissa Wake. core belief in the paramount importance that move will bring. They have been charged with identifying and of early life foundations of health, and also I am grateful to the University’s continuing providing critical advice on key capabilities, illustrates how multidisciplinary teams can encouragement and confidence in the limitations and opportunities, and guidance achieve more together than on their own. importance of the Institute’s research. We on making sustainable decisions for the In 2016 we will invest effort in key areas that are supported by the dedicated work of future. The first meeting held in November are critical to our future. Priorities will include the Institute’s professional staff, especially generated a helpful vision and plan for strengthening current relationships and Business Manager Marcus Goddard. I also 2016 and beyond, and I sincerely thank the building new diverse research partnerships thank the Advisory Board, and particularly committee for their dedication and valuable so that our skills and capabilities can be best Chair Professor Jock Findlay, for his support recommendations. applied in research that is meaningful to the and guidance. Additionally, we refined our management local, national and international community. I hope you enjoy reading this report and structure, appointing three Deputy Directors, A second goal is to work more closely with learning about the breadth of research effort Professors Claire Roberts and Ray Rodgers emerging research leaders, to ensure the and real value we deliver for the health of and Associate Professor Helen Marshall. Institute is responsive and able to facilitate children and families in Australia and around Together with our new Business Manager their path to future success. Thirdly, we the world. Marcus Goddard, I am confident in the seek to build capacity in cohort and clinical Executive team’s ability to grow the quality studies that are essential for understanding Professor Sarah Robertson and impact of the Institute’s research. which interventions and practises best Director In 2015 we had a special focus on building benefit patients and families. All of this will be effective support for early career and mid- against the backdrop of preparing to relocate to the University’s new Adelaide Medical

Annual Report 2015 5 RESEARCH PRIORITIES We seek to prevent and alleviate infertility

6 Robinson Research Institute Infertility is common; Removal of human growth Guidelines for PCOS hormone from IVF treatment In collaboration with Prof Helena Teede 1 in 6 couples are Prof Rob Norman’s results from the LIGHT and colleagues at , Study led to significant change in the IVF RRI members are developing clinical diagnosed as clinically procedure by showing the prescription of guidelines for the evaluation, management adjunct hormones for poor responders and health care needs of polycystic ovary infertile, costing of IVF treatment is unnecessary. In a syndrome, through the NHMRC Centre for randomised controlled study, his team Research Excellence. Australians more than showed conclusively that the number The guidelines have been distributed to of eggs retrieved, and most importantly every general practitioner and specialist in $360 million per year. the live birth rate does not change when Australia. In 2016 the CRE team will form women are administered hGH, delivering a taskforce to implement their guidelines little benefit to IVF outcomes. This internationally, which will significantly ineffective treatment has previously been impact the health and treatment of millions widely used, at a cost of $1,000 to $2,000 of women around the world living with To address infertility the Robinson per cycle, and is no longer prescribed to PCOS. Research Institute is: women in Australia and internationally. >> Advancing knowledge of the IVF modification Endometriosis drug development physiological processes of gamete With collaborators from 17 centres in The production, conception and early A/Prof Louise Hull is the principle Netherlands, Prof Ben Mol demonstrated embryo development investigator for a clinical trial assessing that IVF with a single embryo transfer or >> Uncovering how diet, infection and a new pharmaceutical drug for in a modified natural cycle were inferior lifestyle choices in women and men endometriosis in South Australia. This to intrauterine insemination through alter fertility and the health of the baby newly formulated GnRH antagonist a randomised controlled trial involving (Elagolix) is for oral use, meaning it is easy >> Understanding how metabolic 602 couples. to administer daily for long periods of conditions such as obesity and diabetes Ben’s results suggest that IVF with single time, compared to the currently available cause infertility and alter fetal growth, and embryo transfer should not replace injectable GnRH antagonists. developing interventions to tackle this intrauterine insemination with mild hyper Adelaide is one of the sites in this >> Improving the process of IVF to make it stimulation as the treatment of first choice multinational, randomised controlled safer, less invasive and more cost effective in couples that are trying to conceive for clinical trial and the Robinson Research an intermediate time. How intrauterine >> Developing new infertility treatments to Institute has partnered with the Pain and insemination compares to no treatment is expand options and to improve success Anaesthesia Research Clinic (PARC) a question that remains to be answered. >> Educating the community on the to conduct this trial in association with importance of early planning for AbbVie. Fertility treatment guidelines conception and parenthood, to reduce In many Asian countries, reproductive IVF Vet Solutions funds new IVF dependence technologies and infertility treatments research into in vitro production are poorly regulated, difficult to access Translational Impact Established by A/Prof Jeremy Thompson, and subject to very little quality control. with A/Prof Robert Gilchrist (UNSW), IVF Despite strong industry standards in Vet Solutions provides mouse embryo BlastGen China, Japan and Korea, other regions assays for the screening of toxicity that typically have unequal access to treatment A/Prof Louise Hull led the Australian may be present in media and disposables and pregnancy rates may be extremely BlastGen clinical trial for IVF patients used in human IVF, improving the efficacy poor. with previous miscarriage. BlastGen and safety of treatments. Additionally, Prof Rob Norman has been President is the next phase of the successful the facility provides consultancy and and Past President of ASPIRE (Asia EmbryoGen trial and is formulated to training for complete bovine IVP and Pacific Initiative on Reproduction), which support blastocyst stage embryo transfer. vitrification to improve fertility in the cattle is establishing minimum care standards, Both BlastGen and EmbryoGen contain industry. The financial returns are fed a quality accreditation system and the signalling molecule GM-CSF, which back into their world-leading research promoting education across the region. protects the embryo from stress, making on in vitro maturation of oocytes, which His role, along with other members of the it stronger and more robust following in conjunction with clinical colleagues in RRI, has been key in establishing new conception. In this new IVF treatment, Brussels, are in Phase 1 clinical trials. the embryo is cultured in an environment guidelines and demonstrates the value of that more closely mimics the natural engaging with professional societies and uterine environment, leading to a higher collaborators across the world. pregnancy success rate.

Annual Report 2015 7 Advances in 2015 Prof Ray Rodgers published an extensive We discovered that the extracellular matrix review of stem cells in the ovary, carefully that forms around oocytes has a specific We discovered that haemoglobin is present and thoroughly assessing conflicting claims signaling function that actively promotes in eggs released into the oviduct, but missing and addressing controversies that have maturation of the oocyte to prepare it at from eggs generated in vitro. A/Prof Jeremy impeded understanding to date. the right time for fertilisation and embryo Thompson and Dr Hannah Brown improved We discovered that the environment development. A/Prof Darryl Russell has embryo viability by adding haemoglobin to surrounding the oocyte exhibits a unique found new biomarkers that identify the oocytes matured in culture. metabolite profile, with distinct localisation healthiest oocytes most likely to form high We discovered that silencing of sex of lipids within follicular fluid and oocytes. quality embryos. chromosomes during male germ cell Ongoing experiments by A/Prof Rebecca We demonstrated that ER stress inhibitor development emerged in evolution after Robker and Prof Rob Norman will determine can improve the development of cow the divergence of egg-laying mammals. whether metabolites are skewed with oocytes exposed to high levels of lipid. Prof Frank Grutzner’s work advances our obesity or aging. A/Prof Rebecca Robker and Dr Melanie understanding of sex chromosome organisation. We demonstrated that measuring the McDowall believe this provides a therapeutic We identified activin-A and follistatin as pattern of microRNAs in blood might have target for improving dairy cow fertility. modulators of the inflammatory network in diagnostic value in identifying women with We demonstrated that seminal fluid factors the human cervical cell response to seminal endometriosis. A/Prof Louise Hull believes utilise Toll-like receptors to induce gene fluid. Prof Sarah Robertson and Dr David that ultimately this will reduce the need for expression changes in female reproductive Sharkey anticipate that better knowledge invasive surgery to diagnose this common cells at conception. Prof Sarah Robertson of this biological process will show that condition. and Dr John Schjenken aim to expand our a father’s contribution to establishing We demonstrated that sleep disturbances understanding of the molecular mechanisms pregnancy goes beyond simple provision of are almost twice as common in women with by which male factors contribute to sperm to fertilise the egg. polycystic ovary syndrome (PCOS) compared promote fertility. We conducted the first detailed characterisation with women of similar age without PCOS. We found that selenium protects the egg of a major signalling pathway Kit ligand/c-Kit Dr Lisa Moran’s findings highlight another from oxygen radicals in the late stages of in human ovaries. A/Prof Rebecca Robker potential consequence of the PCOS condition development. Prof Ray Rodgers’ finding is and Dr Theresa Hickey believe this will help that will inform new treatment advances. vital information for those living in areas with to prevent polycystic ovary syndrome as low levels of selenium in the soil and food. abnormal expression of these genes has been implicated in PCOS.

8 Robinson Research Institute We seek to prevent and alleviate infertility

Mouse embryo stained to identify inner cell mass cells (green) and trophectoderm cells (pink). A/Prof Rebecca Robker and Siew Wong

Annual Report 2015 9 RESEARCH PRIORITIES Optimising growth of the fetus in the womb

10 Robinson Research Institute An average Australian baby weighs 3.4kg with over 6% of babies less than 2.5kg and 12% more than pregnancy does not result in a significantly 4kg. Both small and large babies are at greater risk higher rate of live births in women with a history of recurrent miscarriage. Prof Ben of health complications including disability, adult Mol’s findings have implications for clinical practice in the treatment of women at risk onset diseases and early death. for miscarriage. We identified factors in the female immune response, including specific cytokines and immune cells, that when perturbed affect To understand how and why some the resulting babies range from childhood placental structure and thus fetal growth. babies are born too small or too large, obesity, mild learning and behavioural Prof Sarah Robertson expects that immune and to optimise birth weight, the problems, to severe disabilities such and inflammatory perturbations contribute Robinson Research Institute is: as cerebral palsy, intellectual handicap, to growth disturbances in human fetuses. >> Investigating how birth weight is blindness or even death. We identified genetic variants in the influenced by the interaction between Prof Claire Roberts is seeking to prevent insulin gene family that when carried by genetic and epigenetic factors and the the onset of these complications and the father or fetus, associate with small environment has developed the world’s first screening for gestational age babies. Infant gene >> Developing effective interventions to test that can predict a women’s risk variants also associate with blood flow ensure babies are born at a healthy of developing a pregnancy disorder. in the umbilical artery in mid-gestation. weight Currently testing and validation of the Dr Prabha Andraweera and Prof Claire algorithms is underway. Claire has Roberts and Prof Gus Dekker are >> Educating the community about the garnered the support of a commercial examining a suite of gene variants in risk factors associated with unhealthy partner and hopes this screening test will multiple gene families in relation to fetal birth weight including: diet, alcohol, be implemented worldwide by in the next growth and pregnancy complications. drug usage, smoking, mental few years. health problems, diabetes, BMI and We established the OPRATA (Obesity socioeconomic status and disadvantage in Pregnancy Research and Translation Obesity in pregnancy Alliance) with collaborators in Australia >> Understanding why Indigenous women Prof Jodie Dodd led the LIMIT randomised and the United Kingdom. Prof Jodie are at increased risk of delivering an controlled trial looking at improving Dodd and Prof Julie Owens seek to unhealthy birth weight infant, and outcomes for pregnant women who develop a collaborative and harmonised working with these women to improve were overweight or obese at the start approach towards addressing obesity in outcomes for both mothers and babies of pregnancy. Women who received pregnancy and translating findings into Our work positively impacts the achievable dietary and lifestyle advice practise globally. community through the translation of made significant improvements to their We completed a systematic review on research findings into clinical practice; diet and physical activity, and their babies the impact of dietary intakes in human for example, findings from the LIMIT were less likely to be born with a birth pregnancy on infant birthweight. A/Prof randomised trial and the impact of positive weight over 4kg. Vicki Clifton and Dr Jessica Grieger found changes to women’s diet and physical In 2015 Jodie demonstrated that the that the consumption of whole foods activity during pregnancy have been additional cost of providing this one-on- such as fruit, vegetables, low-fat dairy incorporated into local state-wide clinical one lifestyle advice was offset by improved and lean meats promotes appropriate practice guidelines, and are informing outcomes at birth, through reduced birthweight. More studies are required recommendations in the United Kingdom healthcare costs for both mothers and to understand the impact of dietary and Europe. their babies, providing an impetus to supplementations. change current clinical care. Ongoing We found that non-mendelian polar over- Translational Impact follow-up of children whose mothers dominance in imprinted gene expression participated in this trial will continue to contributes to placental and umbilical Preventing and reducing inform healthcare, particularly the impact cord phenotype. Prof Stefan Hiendleder’s pregnancy complications of maternal diet on early childhood health discovery of parent of origin effects on and development. Approximately 25% of women in their offspring phenotype in cattle is relevant to first ongoing pregnancy in Australia are understanding regulation of fetal growth, affected by one or more of the four major Advances in 2015 and may have practical application in complications: preeclampsia, preterm livestock breeding industry. We demonstrated that daily progesterone birth, intrauterine growth restriction and therapy during the first trimester of gestational diabetes. Health issues for

Annual Report 2015 11 RESEARCH PRIORITIES Preventing early labour and improving outcomes for babies born prematurely

12 Robinson Research Institute >> Developing treatments to improve short Advances in 2015 and long-term health outcomes for 1 in 10 babies are born babies born preterm With colleagues in Montreal and Edmonton, we demonstrated that novel preterm at less than small molecule inhibitors of interleukin-1 Translational Impact signalling prevent infection-associated 37 weeks gestation. preterm birth in mouse models. Prof Hypertensive disorder deliveries Sarah Robertson, Dr Loretta Chin and This carries immediate Prof Ben Mol’s research has shown that their Canadian collaborators next plan to for small babies of women with non- evaluate these drug candidates in primate and life-long risks to severe hypertensive disorder at 34-37 models of preterm labour, to determine weeks gestation, there is a significantly whether fetal injury can be mitigated. the infant’s health and increased risk of neonatal respiratory We discovered that increased extraction distress syndrome. Ben’s results of oxygen from blood by the brain predicts survival as the brain demonstrate that routine immediate early neonatal brain injury. A/Prof Michael and organs are not fully delivery in these women is not justified Stark showed this increased risk can and expectant monitoring should be by lowered by early blood transfusion in developed. considered for pregnant women with late those very preterm infants with the highest preterm hypertensive disorders. extraction, potentially protecting against serious brain injury in the first hours of life. Antenatal Corticosteroid Guidelines We demonstrated that Toll-Like Receptor To improve outcomes for babies born 4 (TLR4) is critical for the pathway Prof Caroline Crowther and A/Prof Philippa preterm and to ultimately predict and controlling on-time labour in mice. Prof Middleton were part of a bi-national, prevent premature birth, the Robinson Sarah Robertson and Hanah Wahid multidisciplinary development panel that Research Institute is: believe this provides a new direction for prepared the Australian and New Zealand >> Uncovering how factors such as targeting drugs to prevent preterm birth Clinical Practice Guidelines for Antenatal infection, stress and immune responses in humans. Corticosteroids given to women prior to interact in some women to trigger early birth to improve fetal, infant, child and labour and birth adult health. >> Developing predictive tests to identify These guidelines identify research early in pregnancy which women are at priorities and provide clinical practice increased risk for preterm birth recommendations for administration of >> Identifying and evaluating preventative antenatal corticosteroids to women at risk drugs and treatments for mothers of preterm birth, women having an elective assessed to be at risk caesarean section at term and women with diabetes during pregnancy.

Annual Report 2015 13 RESEARCH PRIORITIES Maximising brain developmental potential

14 Robinson Research Institute We demonstrated that daily variations in the levels of the stress hormone cortisol The development of the brain and nervous influence brain plasticity and learning. Prof Michael Ridding’s findings will expand system is fundamental to how we function opportunities to improve learning and memory in impaired populations. throughout life. Children born preterm often We identified THOC2 and mRNA export pathway as a crucial component of experience problems in neurodevelopment, normal brain function. Prof Jozef Gecz which impacts their ability to contribute to and Dr Raman Sharma found that variants in THOC2 cause syndromic intellectual society and affects career, earning potential, disability. We demonstrated the safety of metformin and physical and psychological health. Others exposure in utero, since treatment did not cause any difference at two years of have genetic conditions that impair normal age in the neurocognitive development. Prof Bill Hague’s research reinforces intellectual function. the safety of prescribing this useful drug in the management of women with gestational diabetes. To further our limited understanding clinical geneticists, paediatricians and We determined that cerebral palsy has a of genetic and environmental drivers neurologists. New technologies of genome genetic origin in at least 14% of cases, of neurodevelopment, the Robinson sequencing have been applied to these but likely more. E/Prof Alastair MacLennan Research Institute is: cases. Once a disease gene and DNA and Prof Jozef Gecz’s findings suggest cerebral palsy can be considered as a >> Investigating the physiology that or protein variant are identified, further neurodevelopmental disorder, with genes is responsible for changes in cell and molecular biology evidence is at least party to blame. neurodevelopment for preterm babies, generated to provide a basis for reporting and determining whether changes new findings to clinicians and families. We highlighted the importance of term are due to being born early, or growth birth in perinatal care. Prof John Lynch restriction during pregnancy Preterm birth research impact showed that children born at 40–41 The research findings from Dr Julia weeks gestation have the lowest risk of >> Understanding how adverse Pitcher’s research team demonstrates developmental vulnerability at school entry. environments during pregnancy subtle but significant neurophysiological and events in early life affect brain We determined that extra dosages of changes in brain function in adolescents development the protein coding gene STAG2 and its born mildly preterm or early term. These resultant cohesion complex could be >> Developing interventions to counter results have contributed notably to the detrimental to normal brain development. neurodevelopmental changes through increasing international recognition by Prof Jozef Gecz and Dr Raman Sharma’s improving the strength of neuron clinicians and educational experts that this findings showed extra STAG2 can lead connections in the brain and improving very large group of children are vulnerable to intellectual disability with behavioural environmental learning settings for to increased health, educational and problems. children behavioural difficulties into adulthood. We showed for the first time that the >> Gaining a better understanding of how For example, her group’s findings are brain’s motor inhibitory interneurons are socioeconomic disadvantage effects informing the current debate regarding functioning at adult levels before 10 years cognitive and motor abilities the relative risks of elective inductions of age in term-born children. Dr Julia and caesarian sections prior to 37 weeks >> Identifying genetic causes of Pitcher’s team also showed that young gestation for non-medical reasons. neurodevelopmental disease children have enhanced activity in their excitatory interneurons. This new evidence Translational Impact Advances in 2015 contradicts previously held dogma that young children have enhanced We demonstrated that cortisol rhythms neuroplasticity due to reduced inhibition, Identifying genetic causes of are important for cognitive performance and presents possible new therapeutic neurodevelopmental diseases and can be influenced by variants in the targets for helping children with delayed Prof Jozef Gecz’s Neurogenetics research glucocorticoid receptor. Dr Nicolette Hodyl’s motor development. group has worked to identify more than findings will be important for future studies 100 neurodevelopmental disease genes. attempting to identify effective methods to We identified submicroscopic changes Since more than 50% of children with improve cognitive performance following to the structure of the X-chromosome a neurodevelopmental disease have no an adverse early life environment. harbouring genes, that when in excess cause intellectual disability and accurate diagnosis, this information has We demonstrated that a higher quality behavioural disturbances. A/Prof Cheryl helped many families in Australia and relationship with carers in childcare is Shoubridge’s discovery expands our overseas to find precise diagnosis and important in reducing developmental gaps. understanding of the genetic origins of plan for a healthy family. Prof John Lynch’s findings indicate that neurodevelopmental disorders. Jozef’s research team is focusing on improved relationships will help to reduce more unexplained cases in collaboration developmental gaps between children with local, national and international from low and high-income families.

Annual Report 2015 15 RESEARCH PRIORITIES Preventing and reversing childhood obesity

16 Robinson Research Institute We discovered that obesity in both parents at conception is more detrimental Approximately 56% of women, 70% of men to fetal development than when one parent is obese. A/Prof Rebecca Robker and 23% of children in Australia are overweight and Prof Michelle Lane’s research provides new information about how obesity- or obese. Children born to overweight or induced alterations to the gametes influence obesity risk for the offspring. obese parents are at increased risk of obesity We established the Obesity in Pregnancy throughout life. Research and Translation Alliance with collaborators in Australia and the United Kingdom. Prof Jodie Dodd and Prof Julie Owens lead this group that seeks a To reduce the incidence of obesity and Advances in 2015 global approach to addressing obesity in tackle its intergenerational transmission, pregnancy research, and translate findings We showed that maternal obesity the Robinson Research Institute is: into improved clinical practice. at commencement of pregnancy is >> Developing interventions for pregnant associated with a four-fold increase We discovered that intermittent fasting is women who are overweight or obese in the risk of the child experiencing an as effective as traditional weight loss diets to improve pregnancy health and the accelerating growth trajectory in early to reduce risk markers of type 2 diabetes health of the baby - through large childhood. Dr Lynne Giles’ findings add and poor cardiovascular health. A/Prof Leonie randomised controlled trials to the growing body of evidence linking Heilbronn showed fasting is better than >> Identifying key dietary, metabolic and obesity in parents with childhood obesity. dieting at improving cardiovascular health other factors in obese mothers that are markers in women with metabolic syndrome. We demonstrated that maternal body size related to poor health in their children prior to pregnancy is positively associated We demonstrated that obesity at conception >> Uncovering why maternal and paternal with child insulin resistance at 9-10 years. results in the embryo accumulating obesity can each lead to an increased Prof Michael Davies, Prof Vivenne Moore perturbations from both the egg and risk of poor metabolic health and and Oana Maftei’s findings provide evidence the sperm, leading to irregular placental obesity in their children of the link between maternal obesity and gene expression, altered fetal growth and >> Developing tools to match women to the development of diabetes in children. reduced fetal liver mitochondrial DNA copy numbers. Prof Michelle Lane and the most appropriate and cost-effective We showed that lifestyle advice in Dr Nicole McPherson stress that healthy form of intervention to limit gestational pregnancy for overweight and obese weight at conception is important for both weight gain, especially in disadvantaged women reduces the likelihood of giving men and women. and Indigenous women birth to a heavy baby. Prof Jodie Dodd >> Developing guidelines and tools for and colleagues have developed clinical We demonstrated that female obesity improving clinical care of pregnant approaches that deliver health benefits before conception imparts a legacy of women who are overweight or obese without increasing the cost of health care. mitochondrial loss in offspring. A/Prof Rebecca Robker’s research showed that loss is reversible during the final stages of oocyte development and maturation.

Annual Report 2015 17 RESEARCH PRIORITIES Discovering causes and cures for reproductive cancers

18 Robinson Research Institute Translational Impact Advances in 2015 Breast and prostate We demonstrated that immune cells and Ovarian cancer diagnosis inflammatory mediators are altered in cancers are the most Despite improvements in surgery and new breast tissue with high mammographic developments in chemotherapy, ovarian density. A/Prof Wendy Ingman suggests prevalent forms of cancer mortality rates have not improved that increased susceptibility of high- substantially over the last two decades. density breast tissue leading to cancer is cancer with 1 in 9 The poor prognosis results from late associated with inflammation. diagnosis and limited treatment options We discovered that interacting proteins after recurrence. Important approaches Australians diagnosed annexin A2 and S100A10 are independent to improve survival rates include early predictors of serous ovarian cancer each year; and this is diagnosis. This requires the identification outcome. Prof Martin Oehler and Dr of specific biomarkers, and devising more Carmela Ricciardelli’s findings offer novel increasing. effective molecularly targeted therapies for prognostic biomarkers to aid patient advanced stage disease. management and potential therapies. Prof Martin Oehler and Dr Carmela We demonstrated that cancers synthesize To understand and cure reproductive Ricciardelli’s work investigating specific extracellular matrix structures. cancers the Robinson Research interactions between ovarian cancer These modulate cancer cell behaviour, Institute is: and the mesothelium (a layer of cells promote growth of the tumour and surrounding abdominal organs) have >> Identifying the common features of the inflammatory response to cancer, identified a protein, annexin A2, that reproductive organs which contribute to stimulating development of new blood plays a major role in ovarian cancer cancer susceptibility in these tissues vessels to fuel tumour growth. invasion. Annexin A2 is highly expressed >> Understanding the functions of sex A/Prof Darryl Russell is investigating in 90% of serous ovarian cancers and hormone responsive tissues and how how the extracellular matrix structure actively involved in the process of ovarian their frequent changes compromise remodeling capacity of cancers can cancer metastasis. Additionally, they the immune system, leading to be targeted to block invasive cancer have demonstrated that up-regulation cancer development development and relapse. of annexin A2 within the tumour is >> Uncovering how diet, lifestyle and reflected in a systemic ~2.0-fold increase environmental factors encourage of annexin A2 in the plasma of patients (or discourage) reproductive cancer with early stage serous ovarian cancer. development Plasma annexin A2 levels in combination >> Developing new treatment options with CA125 significantly improves the to prevent cancer-related disability sensitivity and specificity of detecting and death early stage serous ovarian cancer. These findings hold considerable promise for using annexin A2 as both a therapeutic target and diagnostic marker and improving ovarian cancer survival.

Cytokeratin 5 immunostaining in an ovarian cancer tissue. Dr Carmela Ricciardelli

Annual Report 2015 19 RESEARCH PRIORITIES Investigating early life origins of allergies and developing interventions

improve short and long-term outcomes for the fetus and offspring by improving Allergies affect hundreds of millions of children maternal asthma control. worldwide and there is no cure. Asthma, rhinitis, Advances in 2015 eczema, dermatitis, food allergies and anaphylaxis We showed that the plasticity of T cell development in neonates provides a are on the increase – now 20% of Australians window of opportunity to ‘re-program’ the immune system against allergy suffer from at least one allergy. development and other inflammatory disorders. Prof Antonio Ferrante’s discovery suggests this occurs through an To progress allergy and immunity >> Educating the community about how epigenetic/nutrient control. research the Robinson Research to safely manage allergies and asthma We discovered that restricted growth Institute is: during pregnancy before birth protects against allergy. Dr >> Identifying environmental factors and Kathy Gatford, Prof Julie Owens and events that occur during pregnancy that Translational Impact collaborators are now investigating increase susceptibility to allergy in the underlying mechanisms in order to childhood Controlling maternal asthma translate this finding to improve the health of the community. >> Identifying the genetic and epigenetic In a national collaborative study, Dr changes that occur in the placenta Kathy Gatford, A/Prof Vicki Clifton, Amy We demonstrated that laboratory that program immune function in early Wooldridge and collaborators at Monash responses to whole egg powder and raw childhood and increase susceptibility University developed a pre-clinical model egg were similar in blood from allergic to allergy of maternal asthma in pregnancy, which children. A/Prof Michael Gold’s results will >> Identifying biomarkers that predict the will help improve maternal asthma control make it easier and safer to test for egg risk of allergy in childhood in pregnancy and minimise the long-term allergy in the future. >> Developing effective interventions health risks associated with being born to for allergy prevention either during a mother with poorly controlled asthma. pregnancy or after birth Their results show that exposure to the >> Uncovering the causes of food allergies environment of allergy during pregnancy and developing interventions to prevent impairs fetal development, independent and treat these allergies of genetic effects. The group seeks to

20 Robinson Research Institute Annual Report 2015 21 RESEARCH PRIORITIES Tackling life-threatening infectious diseases

22 Robinson Research Institute >> Uncovering how and why some health potentially life-threatening infections, conditions, such as pregnancy, obesity influenza and pertussis as a result. Protecting children and immune compromise, impact on vaccine effectiveness Advances in 2015 and adolescents from >> Educating the community on the importance of vaccinations and We investigated reports from several serious infectious incorporating community views and countries that changes in circulating values into immunisation policy Bordetella Pertussis genotypes may diseases is a national affect disease severity in children. A/Prof Helen Marshall and Michelle Clarke’s priority to secure the Translational Impact study showed that there was no relationship between pertussis genotype future health of the Immunisation clinic and level of disease severity in children Associate Professor Helen Marshall’s hospitalised with infection, providing nation. research team identified two key reassurance that current pertussis groups who miss out on life-saving immunisation programs are adequate to immunisations, pregnant women control severe pertussis disease. and children with underlying medical We identified diverse reasons as to To eliminate life-threatening conditions conditions. To target two groups at why some Australian children are in children the Robinson Research highest risk of complications and death not adequately immunised including; Institute is: from infections such as influenza, being from a large family, living with a the Adelaide Immunisation Centre of >> Combatting life threatening infections sole parent, being a mobile-family and such as meningococcal and Excellence was established within the having difficulty accessing immunisation pneumococcal disease by optimising Women’s and Children’s Hospital. providers, rather than due to anti- infectious disease prevention The challenge is to improve immunisation vaccination beliefs. Only 9.3% of infants uptake and protection for these at-risk are incompletely immunised in Australia >> Improving the effectiveness of vaccine and of these only 16% had mothers who programs for pregnant women to groups, initially focusing on pregnant disagreed with immunisation. A/Prof increase protection for both pregnant women. The midwife-led immunisation Helen Marshall and Prof John Lynch’s women and their babies against program has resulted in pregnant women evaluation showed that barriers to serious infections such as influenza and increasing uptake of the pertussis vaccine immunisation are diverse and not usually whooping cough (whooping cough) from 20% to 82% and an increase in uptake of influenza due to disagreement with immunisation, >> Testing new and current vaccines for vaccine from 30% to 75%. The majority of suggesting a need for tailored babies, children, adolescents and pregnant women attending the Women’s interventions alongside policy decisions pregnant women to ensure they are and Children’s Hospital and their newborn such as the No Jab, No Pay policy, to safe and effective babies are now protected against improve immunisation protection.

Annual Report 2015 23 RESEARCH PRIORITIES Pioneering interventions to improve the health of children

24 Robinson Research Institute pharmaceutical company in treating Many serious physical and mental disorders depression in adolescents is ineffective and linked to suicidal and self-harming affecting adults have their origins in childhood. To behaviours. prevent the development of disease and disability, They believe regulatory research authorities should mandate that all data interventions need to be administered in early life, and protocols from clinical trials world- wide are accessible, to prevent any be safe and as targeted as possible. misrepresentation of industry-funded studies from occurring in the future.

Biomarker translation As part of a biomarker discovery program To tackle childhood genetic, more likely to experience poorer health, jointly funded by the CRC for Biomarker neurodevelopmental, metabolic education and development outcomes translation and the NHMRC, A/Prof Simon and immunological conditions, the measured across government systems Barry has developed a novel biomarker Robinson Research Institute is: spanning hospital, community-based of immune cell subsets PI16, also named >> Uncovering the causes of these care, education and welfare. CD364. Becton Dickinson now licenses childhood conditions through discovery This unique partnership provided evidence this biomarker for sale on the international research, large-scale clinical trials and that is being used to support early market. The antibody is being tested for cohort studies intervention to prevent these children diagnostic utility in a number of diseases including type 1 diabetes, IBD and >> Developing effective treatments and proceeding on negative life trajectories infertility, and is a new tool to advance interventions to prevent disorders that will affect their later life opportunities. research into regulatory T lymphocytes in progressing from early life to adulthood Genetic diagnosis for primary laboratories around the world. >> Running unique e-health delivery trials immunodeficiency diseases to provide healthcare services and Cell Therapy Manufacturing Led by Prof Antonio Ferrante, the parenting support Paediatric Immunopathology Research In 2014 a new $63 million CRC for and SA Pathology Service Department Cell Therapy Manufacturing was jointly Translational Impact at the Women’s and Children’s Hospital established with the University of South is a leader in developmental and genetic Australia, with A/Prof Simon Barry leading Child Health and Development immunology and now offers genetic the T cell therapy program. This CRC aims to develop novel cell manufacturing Over the past 18 months the BetterStart diagnosis for primary immunodeficiency devices and protocols aimed at increasing Child Health and Development group diseases (PID) for over 40 genes. the availability and reducing the cost of led by Prof John Lynch, has been Their work allows paediatric cell therapy. collaborating with the SA Department immunologists to achieve a definitive of Premier and Cabinet (SADPC) on diagnosis of PID for patients and assists New cell therapy projects underway child health and development projects in managing transplantation, as well as include: utilising the Early Childhood Data Project. carrier testing and prenatal diagnosis. >> Developing methods to expand This project contains information on Their service has substantially reduced the clinically relevant T cell populations, 280,000 South Australian children turnaround time of testing and provides including regulatory T cells, for born from 1999 onwards, collected by genetic diagnosis of PID from ’s treatment of autoimmune disease and government agencies, and covers more Royal Children’s Hospital, and other transplantation. This involves novel than 13 different data sources by linking Australian state clinics. Their service has methods for human T cell expansion education, child protection, health, and extended to recently developed assays using functionalised scaffolds that welfare services information. of T cell Receptor Excision Circles and facilitate human T cell expansion for As an example, BetterStart has worked Multiplex Ligation-dependent Probe cGMP manufacture. collaboratively with the SADPC on Amplification assays. These together with >> Developing cancer immunotherapy developing a profile of boys who are Sanger sequencing gives the group a products with a novel target for emotionally vulnerable and disadvantaged powerful diagnostic investigation activity of immunodeletion using chimeric antigen at school entry, to understand how the international standing. receptor (CAR-T) technology. This government can intervene to prevent technology arms T cells with tumour adverse consequences of developmental Restoring Study 329 specific targeting and killing capacity, disadvantage. Results showed that Prof Jon Jureidini and Dr Melissa Raven which is showing great clinical promise boys who were emotionally vulnerable demonstrated that a psychiatric drug for on target long term cancer therapy. and disadvantaged at school entry were claimed to be safe and effective by a

Annual Report 2015 25 Advances in 2015 We discovered the importance of salt intake and exercise in blood vessel health We attended the TEDDY consortium in the in diabetic children. Prof Jenny Couper will US to address type 1 diabetes. Prof Jenny distribute this knowledge to improve clinical Couper’s team was invited to align their work care for thousands of affected children. to global efforts aiming to prevent type 1 We confirmed that particle clearance can diabetes. be measured in large animal airways at We identified that neurosteroid allopregnanolone the Australian Synchrotron. A/Prof David deficiency is the likely basis for a form of Parsons, Dr Martin Donnelley and Maged female-only epilepsy, intellectual disability Awadalla showed that measured rates match and autism. Prof Jozef Gecz’s discovery previous human and sheep measurements. indicates this is due to mutations in the We utilised new generation exome PCDH19 gene, shedding light on a new sequencing to show that 14% of cases of pathway causing the condition. cerebral palsy are likely due to causative We discovered that there are more airway single gene mutations and up to 31% are stem cells present in cystic fibrosis mice clinically relevant copy number variations. compared to normal mice, and that this may E/Prof Alastair MacLennan’s findings provide be age dependent. A/Prof David Parsons, a new focus for research into the causes of Dr Nigel Farrow, Dr Patricia Cmielewski and cerebral palsy. Dr Martin Donnelley’s findings will be useful We completed studies uncovering how the for targeting stem cell therapies for cystic stomach functions in type 1 diabetes and fibrosis. the affect on blood glucose levels. This work We developed a new platform to improve from Prof Jenny Couper’s group will lead islet cell transplantation utilising spatial to improved strategies for diet and lifestyle control of 3D printing. Prof Toby Coates’ management. technology may offer alternate sites for We showed that inflammatory markers transplantation with the ability to monitor IFNγ and TNFα are increased in children graft function and rejection in situ or by with mild sleep disordered breathing. Prof routine biopsy. Declan Kennedy and Anna Kontos found We generated a mouse model for PCDH19- the increase in inflammation is associated epilepsy. Prof Paul Thomas and Daniel with increased blood flow velocity in the Pederick’s analysis of this model has provided ascending aorta. unique insight in the pathobiology of this We trialled the eMums program, a pilot relative common form of genetic epilepsy, program providing new parents with an identifying new targets for intervention. online service and forum to connect with We confirmed that it is possible to nurses and other parents. Prof Michael differentiate embryonic stem cells to insulin Sawyer’s program provides parents with producing cells. Prof Mark Nottle and Dr access to reliable and reputable information Ivan Vassiliev developed a relatively simpler that can provide guidance and information protocol compared with those already from their homes. published, increasing the practical utility of this approach in diabetes medicine. We discovered that blood flow velocity in the brachial artery was increased in children with mild sleep disordered breathing compared to control children. Prof Declan Kennedy and Anna Kontos’ findings provide new insight into the causes of sleep disordered breathing.

26 Robinson Research Institute Pioneering interventions to improve the health of children

Annual Report 2015 27 Funding Highlights

During 2015 the Robinson Research Institute successfully attracted funding from major bodies to continue to support our research. A selection of highlights are listed below.

NHMRC $796,979 to Prof David Kennaway ARC Impact of disrupted sleep and rhythms during Prof Sarah Robertson awarded $433,100 for Centres for Research Excellence pregnancy on the mother and her offspring her project: Male to female sperm signaling – commencing in 2015 $683,622 to A/Prof Cheryl Shoubridge a new role for sperm in reproduction? $2.5 million to Prof Jennifer Couper Improving the phenotypic severity of Prof Jennifer Couper, Prof Jodie Dodd intellectual disability and seizures caused by Channel 7 Children’s Research and Dr Lynne Giles awarded a CRE for the expanded polyalanine tract mutations in the Foundation Protection of Pancreatic Beta Cells ARX homeobox transcription factor RRI members were awarded 12 project $2.5 million to Prof Helena Teede grants commencing in 2015/2016 totaling Targeted Call awarded in 2015 Prof Helena Teede (Monash University more than $700,000. This includes $75,000 CIA) together with RRI members Prof Prof Jozef Gecz and team (led by Prof to Prof Michael Sawyer for his project: A Robert Norman, Prof Michael Davies, Prof Kathryn North and Prof Andrew Sinclair) randomised controlled trial evaluating the Ray Rodgers, Dr Lisa Moran and Dr Alice awarded $25 million effectiveness of a nurse-moderated group- Rumbold awarded a CRE for Evaluation, Prof Kathryn North and Prof Andrew Sinclair based internet support program for mothers Management and Health Care Needs of (Murdoch Children’s Research Institute) who comorbid mild to moderate depression Polycystic Ovary Syndrome and Related together with 47 partner organisations and parenting problems. Health Implications including Prof Jozef Gecz, awarded a Targeted Call for Research into Preparing Diabetes Australia Centres for Research Excellence Australia for the Genomics Revolution in A/Prof Rebecca Robker awarded $60,000 awarded in 2015 Health Care for her project: Is mitochondrial dysfunction in IVF blastocysts responsible for impaired $2.5 million to Prof John Lynch Adelaide Research and Innovation Prof John Lynch, Prof Michael Sawyer, Prof glucose metabolism in offspring? Prof Claire Roberts, Prof Martin Oehler, Ben Mol, Prof Claire Roberts, Prof Gus Dek- A/Prof Jeremy Thompson and colleagues ker and A/Prof Naomi Dwyer awarded a CRE National Institute for awarded $153,800 for three projects: for EMPOWER: Health Systems, Adversity Health Research Validating algorithms that predict risk for and Child Well Being Prof Ben Mol is a Chief Investigator on pregnancy complications; Evaluating the use three UK projects totaling £3,100,000 Project Grants commencing in 2015 of Annexin A2 as a novel diagnostic marker to investigate: Genetic and early life $585,276 to Prof Sarah Robertson for serous ovarian cancer; and Freeze drying determinants of childhood obesity; Accuracy Inflammatory cytokines as causal agents in embryo production media for cattle in vitro of clinical characteristics, biochemical peri-conception programming of offspring health embryo production. and ultrasound markers in the prediction of preeclampsia; and A double blind $397,077 to Prof Michelle Lane Metabolic Allan and Joyce Ballantyne and molecular basis of embryo signaling placebo controlled trial of a combination Medical and Surgical Education and of methotrexate and gefitinib versus Project Grants awarded in 2015 Research Trust methotrexate alone as a treatment for $1.3 million to E/Prof Alastair MacLennan A/Prof Louise Hull awarded $198,000 for ectopic pregnancy. Genetic pathways to cerebral palsy two projects: Regulation of macrophages in endometriosis; and Alterations in Ovarian Cancer Research Foundation $920,972 to Prof Sarah Robertson macrophage activation status facilitates Priming the maternal immune response to Prof Oehler Martin awarded $189,000 for two endometriotic lesion development. resist inflammatory disorders of pregnancy projects: Blood proteomic signatures of ovarian cancer; and Funding of a study nurseand $814,272 to A/Prof David Parsons research assistant for biospecimen collection. Identifying the role of airway stem cells in maintaining lentiviral mediated gene expression for cystic fibrosis lung disease

28 Robinson Research Institute PCDH19 Alliance Women’s and Children’s Hospital Prof Jozef Gecz and Prof Paul Thomas Foundation were awarded $100,000 for two projects: In RRI members were awarded 12 project vivo investigation of the cellular interference grants commencing in 2015/2016 totaling model using unique PCDH19 mouse more than $710,000. This included $68,000 Front row: Danielle Edwards, Alexandra models and brain tissue from a PCDH19- to Dr Cheryl Brown for her project: PI16- Hendry, Megan Penno, back row: Leanne GCE affected female; and Female Epilepsy CD26 interaction: a new mechanism for Hornibrook, Rebecca Thomson, Chris Hope, Meredith Krieg, Alison Gwiazdzinski and (PCDH19-FE). immune tolerance in humans? Jenny Couper

JDRF / Helmsley Charitable Trust

Prof Jennifer Couper awarded $8 million from a partnership between the Juvenile Diabetes Research Foundation and Helmsley Charitable Trust to further the Environmental Determinants of Islet Autoimmunity study.

Annual Report 2015 29 Professor Ben Mol

National Health and Medical Research Council Prof Ben Mol was the highest ranked Practitioner Fellow recipient

30 Robinson Research Institute Fellowships and Awards

ARC Lloyd Cox Fellowship Healthy Development Adelaide (HDA) Prof Michael Davies, Dr Nicolette Hodyl, Dr Sam Buckberry, Dr Angela Gialamas, Ms Commencing in 2015 Prof David Kennaway, Dr Julia Pitcher, Dr Macarena Gonzalez, Dr Jessica Laurence, Ms Carmela Ricciardelli, A/Prof Michael Ridding Emer Van Ryswyk, Ms Siew Wong and Ms ARC Future Fellow and A/Prof Darryl Russell Amy Wooldridge awarded HDA Travel Grants Associate Professor Megan Warin MS McLeod Research Fellowship International Federation of Awarded in 2015 Dr Nicolette Hodyl Placenta Associations Discovery Early Career Research Award Women’s and Children’s Health Dr Sam Buckberry and Ms Petra Verburg Dr Lachlan Jolly Network Clinical Fellowship awarded YW Loke New Investigator Dr Priya Augustine Travel Awards National Council of Technological and NHMRC Scientific Development Awards and Prizes Dr David Gonzalez awarded CNPq Commencing in 2015 Androgen Excess and PCOS Society Productivity Research Fellow Senior Research Fellowship Prof Rob Norman awarded the Inaugural Nutrition Society of Australia A/Prof Jeremy Thompson Ricardo Azziz Distinguished Researcher Ms Mansi Dassingh awarded a Travel Grant Senior Practitioner Fellowship Award Science Excellence Awards Prof Jodie Dodd and Prof Ben Mol Australian Academy of Health Prof Michelle Lane was a finalist for the Career Development Fellowship and Medical Sciences South Australian Scientist of the Year A/Prof Helen Marshall Prof Jozef Gecz, Prof John Lynch, Prof Society for Reproductive Biology (SRB) Robert Norman and Prof Sarah Robertson Early Career Fellowship Prof David Kennaway awarded Life Member, were inducted into the Academy. A/Prof Philippa Middleton Prof Claire Roberts, A/Prof Mark Nottle and CJ Martin Biomedical Early Career Australian and New Zealand Placental A/Prof Darryl Russell awarded Fellow of Research Fellowship Research Association (ANZPRA) SRB, Dr Melanie McDowall, Ms Siew Wong Dr Alison Care Dr Prabha Andraweera awarded an ANZPRA and collaborators awarded Publication of Travel Award Peter Doherty Biomedical Early the Year, Dr Linda Wu awarded Mid-Career Career Research Fellowship Australian Sleep Association Poster Award and Ms Ella Green awarded Dr Prabha Andraweera, Dr Nicole Ms Anna Kontos awarded a Travel Award David Healy New Investigator Award McPherson and Dr Ann-Maree Vallence Australian Society for Medical Society for the Study of Reproduction Research (ASMR) Dr Melanie McDowall awarded the Awarded 2015 Ms Helana Shehadeh awarded the Best International Award for Best Abstract from Research Fellowship Presentation and Ms Cassandra Carbone Australia and New Zealand A/Prof Darryl Russell and Prof Ray Rodgers awarded Best Honours Poster at the ASMR The Society for Maternal-Fetal Medicine NHMRC-ARC Dementia Annual Scientific Meeting Prof Ben Mol received the Distinguished Research Development Fellowship Endocrine Society of Australia Lecture award Dr Sam Buckberry and Dr Mitchell Goldsworthy Dr Lisa Moran awarded the Mid-Career The University of Adelaide Award and Ms Amy Garett awarded the Early Prof Robert Norman awarded an Honorary Career Researcher Travel Award Other Fellowships Doctor of Medicine Freemasons Foundation (awarded 2015) Prof Jodie Dodd, Prof Michelle Lane, Prof Mr Adrian Kaczmarek awarded the Trevor Claire Roberts, Prof Ray Rodgers, A/Prof Barbara Kidman Women’s Fellowship Prescott Memorial Scholarship and Ms Mark Nottle and A/Prof Jeremy Thompson Dr Melanie McDowall and Dr Melissa Dania Ruminski-Smith awarded an Honours awarded Lloyd Cox Strategic Research Whitrow Scholarship Excellence Awards Inaugural Lin Huddleston Ovarian Frontiers in Reproduction Dr Nicolette Hodyl and Dr Lisa Moran Cancer Research Fellowship Ms Macarena Gonzalzes awarded the awarded the Vice-Chancellor’s Early Career Dr Carmela Ricciardelli Marine Biology Laboratory Summer Award for Women’s Research Excellence Scholarship Ms Emer Van Ryswyk awarded the Deans Commendations for Doctoral Thesis Excellence

Annual Report 2015 31 Ms Amy Garrett awarded the Australian Postgraduate Award Dr Amy Keir awarded the Robert Seamark Scholarship Dr Catherine Chittleborough awarded Dr Hannah Innovation and Excellence in Teaching. Prof John Lynch awarded Postgraduate Brown Teacher of the Year Dr Hannah Brown Prof Paul Thomas awarded Excellence awarded the Young in Teaching Investigator of the Ms Michelle Clarke awarded Florey Medical Year Award plus the Research Foundation Postgraduate prize People’s Choice Award Ms Siew Wong awarded DR Stranks Travelling Fellowship A/Prof Lisa Smithers awarded Best Publication by a Mid-Career Researcher Dr Amanda Highet awarded Llewellin and Margaret Davey Travel Award Thomson Reuters Prof John Lynch acknowledged as World High Cite Scientist

ARC Financials $1,286,178 Donations and philanthropic foundations $233,971

Govt & public sector $1,269,130

NHMRC Industry $7,682,421 $4,703,539

32 Robinson Research Institute Key collaborations

SA Hospitals SA Fertility clinics HDA runs a suite of events each year to create opportunities for communication, The Robinson Research Institute is firmly Robinson Research Institute members networking and multidisciplinary research embedded within South Australia’s public have a key presence in clinical practice collaborations, supports the next generation health system. Institute members occupy a and research development at two leading of researchers with top-up PhD scholarships physical presence and conduct collaborative fertility clinics in Adelaide: Repromed and funded by the Channel 7 Children’s Research research projects in the state’s key hospitals: Fertility SA. The Institute’s research findings Foundation and travel grants. Women’s and Children’s Hospital, Lyell McEwin and new treatment options are translated Hospital, Queen Elizabeth Hospital, Modbury into practice, ensuring greater choices for Hospital and the Royal Adelaide Hospital. couples seeking fertility assistance. Your Fertility The unique and diverse affiliations we enjoy The Your Fertility partnership works to in these hospitals ensure our scientists Women’s and Children’s address the gap in community knowledge and clinicians are integrated within South and understanding about modifiable factors Australia’s medical practice, are able to Health Research Alliance that affect fertility, targeting its messages translate research findings into practice, play (WCHRA) to Australian women and men aged 25-35 a role in shaping effective health policy and Through the WCHRA Alliance, the Institute years. By sharing the latest scientific and access clinical materials as appropriate. builds allegiance with the Women’s medical information, Your Fertility aims to and Children’s Hospital, Women’s and empower people to make informed and Jean Hailes Foundation for Children’s Hospital Foundation, Women’s timely decisions regarding their reproductive and Children’s Health Research Institute, health. Women’s Health Women’s and Children’s Health Network, The Robinson Research Institute is a proud The Institute collaborates with the Jean Hailes SA Pathology, South Australian Health partner in Your Fertility, along with the Victorian Foundation for Women’s Health through and Medical Research Institute, and other Assisted Reproductive Treatment Authority the National Alliance on Polycystic Ovarian research groups at the Women’s and (VARTA), Jean Hailes for Women’s Health Syndrome (PCOS). This unique initiative brings Children’s Hospital site. This alliance seeks and Andrology Australia.The Institute made together multidisciplinary clinicians, women to foster research excellence in the area important contributions to the with PCOS, researchers and government of women’s and children’s health in South 2015 program and its major activities, including: representatives, and has developed a vision Australia, translate research findings into to improve the lives of Australian women policy, practice and delivery, establish a Fertility Week with PCOS through education, research and highly visible focus for funding, ensure Fertility Week is a national campaign evidence-based health care. sufficient research infrastructure needs are promoting fertility awareness. In 2015 the met, and communicate the benefits of health campaign focused on promoting behaviour investment to the wider community. change messages around the effects Institute for Photonics and of weight on fertility and reproductive Advanced Sensing Healthy Development outcomes. The Fertility Coalition shared The Institute for Photonics and Advanced fertility messages across social media which Sensing, along with partners Macquarie Adelaide reached over 2.6 million Australians. University and the Royal Melbourne Institute The Institute is a major founding partner In conjunction, Professor Sarah Robertson of Technology, were successful in receiving of Healthy Development Adelaide (HDA). presented her research on Parenting begins a $23,000,000 ARC-funded Centre of HDA promotes, facilitates and enables before conception, exploring the effects Excellence for Nanoscale BioPhotonics grant, multidisciplinary research that advances of lifestyle and environmental factors on headquartered at the University of Adelaide. the understanding of healthy development, reproductive outcomes at the annual Louis RRI Institute research leader A/Prof Jeremy and ensures the physical, psychological Waller Lecture hosted by VARTA. Thompson is a group leader on this 7-year and social health of infants, children and project and collaborates with physicists adolescents are met. Personalised fertility tool and chemists, alongside other biologists, to Established in 2004 as an initiative of the In collaboration with VARTA, the RRI is develop new technologies based on sensing University of Adelaide, HDA plays a key role leading the development of a fertility and biological activity with light to advance in South Australia, linking research, service pre-conception health web-tool to feature on reproductive health research and practice. delivery and policy development, and is the Your Fertility website. This interactive tool currently led by Institute research leaders is designed to raise community awareness Prof Claire Roberts and Prof Michael Sawyer. of the key factors that impact fertility in men and women.

Annual Report 2015 33 South Australian Health and Presentations and speaker Medical Research Institute invitations (SAHMRI) In 2015 Robinson Research Institute The Robinson Research Institute connects members were invited to share their research with SAHMRI to develop collaborative at more than 120 presentations. Of these partnerships in research relevant to the more than 50 were plenary and key-note Healthy Mothers, Babies and Children talks at international meetings, disseminating research theme, and other SAHMRI themes. discoveries and advances to peers and partners around the world.

International Visitor Spotlight

Dr Erin Greaves Professor David Olson Petra Verburg Edinburgh, UK Edmonton, Canada Groningen, The Netherlands

Dr Erin Greaves is a Professor David Petra Verburg is Principal Investigator Olson is a Professor a Medical Doctor and and Medical of Obstetrics currently undertaking Research Council and Gynecology, her PhD in a joint Career Development Pediatrics and program with the Research Fellow at Physiology and the University of the Medical Research University of Alberta, Groningen and the Council Centre for Edmonton. Robinson Research Reproductive Health, David’s career Institute. University of Edinburgh, Scotland. and research programs have been Petra’s research focus is on pregnancy Erin is an expert in endometrial function dedicated to improving maternal-child complications, including pre-eclampsia, and dysfunction, specifically focusing health. His expertise in preterm labour gestational diabetes mellitus, preterm on endometriosis; sharing research and his international collaborations in the birth and small for gestational age. She is interests with Professor Sarah Robertson development of new risk assessment tools exploring sexual dimorphism and seasonality and Dr Louise Hull regarding the role of and interventions (therapies, drugs) to of pregnancy complications, and working macrophages in the endometrium and predict and delay preterm birth has led to on multiple clinical trials including the STOP endometriosis. Upon learning of their a 10+ year collaboration with Professor study (early pregnancy prediction of women common research interests in 2014, Erin Sarah Robertson. at increased risk of pregnancy complications) planned a visit to the Robinson Research In 2015 David visited the Robinson Research and the COFFEE Clinic (post-pregnancy Institute in 2015 to strengthen relationships Institute to progress preclinical studies cardiovascular follow up for women after a for future collaborations with the aim of testing new drugs for preterm birth in the pregnancy complication). progressing endometriosis research. Erin Reproductive Immunology Laboratory. The Petra first travelled to Australia in 2013 to was awarded prestigious travel awards from RRI mouse models for preterm labour are undertake a 6-month research elective at the both the Society for Endocrinology and the first rate and have allowed David, Sarah Pregnancy Outcome Unit of SA Health, with Royal Society to fund her visit to Adelaide. and their collaborators to rapidly evaluate Professors Gus Dekker and Claire Roberts During her postdoctoral training with the efficacy of drugs developed in Montreal, and Dr Wendy Scheil. Upon completing her Professor Philippa Saunders in Edinburgh, with the aim of progressing to clinical elective she returned to The Netherlands, Erin developed a novel mouse model of development for human use. decided to continue working in research, endometriosis. Erin trained RRI researchers David has strived to find a solution to and this led to her joint PhD. In 2015 Petra how to use this model, which they are now preterm birth for most of his career and returned to Australia and managed the clinical using to further their research. Additionally, realised that the best chance of succeeding side of the STOP study. Additionally she Erin was able to use a specific transgenic is through bringing together teams of experts progressed her own research looking at mouse while in Australia that allows from around the world to work collaboratively maternal haemodynamics in pregnancy. conditional depletion of macrophages to on a solution. Also while visiting the RRI, Petra plans to return to Australia in 2016 to address specific questions that form part of David progressed new collaborative grant continue her collaborative research projects, her current fellowship. Erin plans to return applications involving researchers from ultimately seeking to prevent pregnancy to Australia for a longer trip in the future to Adelaide, Perth, Melbourne, Edmonton, complications and cardiovascular disease continue her collaborations with the Institute. Montreal, Seattle and China. after pregnancy, and build bridges between research in Australia and Europe.

34 Robinson Research Institute Universities

Robinson Research Institute members collaborate with universities and research institutes around the globe to maximise efforts to answer major research questions. Some of our important collaborations are listed below:

AUSTRALIA IRELAND UNITED KINGDOM

>> ANZAC Research Institute >> University College Cork >> Barts and the London School >> Flinders University of Medicine and Dentistry ITALY >> Garvan Institute of Medical Research >> Bristol University >> Hudson Institute of Medical Research >> Universita Cattolica >> King’s College London >> Mater Medical Research Institute >> University of Sassari >> National Institute for Medical Research >> Menzies School of Health Research >> The University of Edinburgh JAPAN >> Monash University >> The University of Nottingham >> SAHMRI >> Osaka University >> University College London >> The Florey Institute >> University of Glasgow THE NETHERLANDS >> The University of Newcastle >> >> The University of South Australia >> Radboud University >> University of Southampton >> The University of Western Australia >> Rotterdam University >> University of Westminster >> University of New South Wales >> University of Groningen UNITED STATES OF AMERICA >> Victoria University >> Utrecht University >> Baylor College of Medicine CANADA NEW ZEALAND >> Benaroya Research Institute >> McGill University >> The University of Auckland >> Harvard Pilgrim Health Care >> University of Alberta >> University of Otago >> Louisiana State University >> University of Montreal >> National Institutes of Health SPAIN >> University of California CHINA >> University of Madrid >> University of North Carolina at Chapel Hill >> Peking University >> University of Washington SOUTH AFRICA >> Shanghai Jiao Tong University >> University of Witwatersrand VIETNAM >> Zhejiang University >> Vietnam National University SWITZERLAND GERMANY >> ETH Zurich >> Goethe University >> University of Lausanne >> Limes-Institut-Bonn >> School of Life Sciences

Annual Report 2015 35 Institute Engagement

Research Events Involvement in research events provides members the opportunity to network with peers, share research discoveries, learn about recent advances and build existing and new collaborations to address important health issues. Events in 2015 include:

RRI Symposium The Institute’s largest internal event brings members together for a day of collaboration and networking. Members have the opportunity to present their work and learn about the research of their colleagues. A focus in 2015 was interdisciplinary research and new and emerging research areas. Professor Claire Robert’s Placental Development Group Geoffrey Thorburn Visiting at the RRI Symposium Ethically Acceptable Fertility Care Lecture Series results,network and foster collaborations with The RRI and SAHMRI co-hosted the forum Together with PSANZ and the IMPACT like-minded peers from around the world. Ethically acceptable fertility care: what is is Network, the Institute hosted the 2015 event and how do we do it? Presenters included on the topic The impact of clinical trials in preterm birth: prevention, treatment and Annual Genetics Society of RRI members Dr Michelle Lane, Prof Ben Australasia Mol and Prof Vivienne Moore. outcomes. Prof Ben Mol was one of three invited speakers on the program. The RRI sponsored the Celebrating Genetics New Frontiers for a in Adelaide conference, convened by Healthy Start to Life RRI member Prof Frank Grutzner. This Sponsorships conference attracted over 200 national The RRI hosted the second New Frontiers and international genetics researchers. RRI thinktank conference, which bought together To support members in their career growth research leaders and students were well researchers spanning the healthy start topic, and to increase brand awareness, the RRI represented in talks, invited plenary speakers both internal and external to the RRI. This strategically sponsored the following events and poster presentations. unique conference stimulates new interactions in 2015: and offers a forum for big picture thinking. SRB INSPIRE Series For the 10th year in a row the RRI sponsored The INSPIRE Series luncheon, provides the Society for Reproductive Biology at its annual the opportunity for the Institute’s early joint meeting with the Endocrine Society of career researchers to network with and Australia. The Institute sponsored the Robinson learn from the Institute’s Emeritus Faculty. Research Institute Mid-Career Award. Prof Grant Sutherland AC talked about his ANZPRA transformational work in the Human Genome Project to provide the first sequence of The RRI was the principal sponsor of the human chromosome 16. Australian and New Zealand Placental Research Satellite Meeting Placenta: Bench OPRATA Symposium to bedside. Hosted by the RRI, this event ASMR The Obesity in Pregnancy Research and allowed members to share research findings Sponsorship of the ASMR Annual Scientific Translation Alliance is a group of internationally with national and international peers in the Meeting provides the opportunity to support renowned researchers in the field of obesity field of placental research. the Institute’s early career researchers in pregnancy, led by Prof Jodie Dodd and and students in career development. The IFPA Prof Julie Owens. Hosted at the Institute, the Institute sponsored the Robinson Research 2015 event addressed the current research More than 300 placenta researchers attended Institute prize for the best presentation in agenda and controversies in the field, the annual IFPA meeting. Sponsorship provided the field of reproduction, pregnancy or and encouraged collaboration to translate the RRI with a strong profile at this international child health, which was awarded to RRI research into high quality clinical care. event and enabled researchers to disseminate member Helana Shehadeh.

36 Robinson Research Institute Prof Ross Andrews, Mr Iann Homer, A/Prof Mike Gold, Prof Peter McIntyre, A/Prof Naomi Dwyer, A/Prof Helen Marshall, Dr Stephen SA Vaccinology Update Christley and Prof Sarah Robertson The RRI teamed up with SA Health, the Women’s and Children’s Hospital and SAHMRI to host the second SA Vaccinology Update. This full day event for immunisation providers, doctors and researchers featured 16 presenters who discussed the latest developments in immunisation research, centres and programs.

Community Events Robinson Research Institute members regularly present at public events to inform the local community about ways to improve health for intending parents and families. Events in 2015 include:

Peri-conception planning to protect pregnancy and infant health Co-hosted by the RRI and Healthy Development Adelaide. Attendees heard from Prof Claire Roberts, A/Prof Rebecca Robker, Dr Susan Evans and Prof Ben Mol

Lloyd Cox Memorial Lecture The Institute’s flagship annual public lecture was presented by Laureate Prof John Aitken, Pro-Vice Chancellor of the University of Newcastle on the topic The Janus faces of human fertility – how commercial interests, in Melbourne, this annual lecture is hosted Mol - Treat, Trial and Transform: Towards a education and pollution are shaping the by the Victorian Assisted Reproductive globally self-learning and wholly evidence- future of our species. Treatment Authority. informed health; and Dr Michelle Lane - Stem Cells: Extracting the facts. Louis Waller Lecture Research Tuesdays Prof Sarah Robertson presented the Hosted by the University of Adelaide, Louis Waller public forum on the topic Institute members presented at two Parenting begins before conception. Held Research Tuesdays events in 2015; Prof Ben

Annual Report 2015 37 Dr Jessica Grieger being Media Impact interviewed about her research.

The Robinson Research Institute’s research discoveries are actively publicised in the media and on social media to better inform the community about reproduction and fertility, pregnancy and child health issues.

In 2015 the Institute disseminated 24 media uterus, and protects embryos from stress, releases, reaching more than 3.5 billion making them stronger and more robust in people. Our top performing stories included: the days following conception. Associate Media circulation Professor Louise Hull is utilising this new Cerebral Palsy – it can be in treatment in clinical trials. Fertility SA is Online your genes leading the first Australian BlastGen clinical It has long been believed that cerebral trial. 3,293,771,517 palsy occurs when a child experiences a lack of oxygen during pregnancy or at Antidepressant misrepresented as Press birth. However, Emeritus Professor Alastair safe for adolescents MacLennan and collaborators found at least Professor Jon Jureidini led a team of 8,343,311 14% of cerebral palsy cases likely have an international researchers to re-examine underlying genetic cause. Published in the Study 329, a 14-year old randomised TV Nature Journal, Molecular Psychiatry. controlled trial that evaluated the efficacy and safety of the drug paroxetine as a treatment 6,360,800 First screening test for common for depression in adolescents. Their results pregnancy complications showed that paroxetine is actually ineffective Radio Professor Claire Roberts has developed the and is associated with serious side effects. world’s first pregnancy screening test to Published in BMJ. 2,595,100 predict a woman’s risk of developing one or more of the four most common pregnancy Breakthrough in treating poor complications; preeclampsia, preterm birth, quality eggs intrauterine growth restriction and gestational Dr Hannah Brown discovered a key To stay up-to-date with our diabetes. Commercial development component missing in poor-quality eggs latest research discoveries, is supported by Adelaide Research & is haemoglobin. Together with Associate follow the Institute: Innovation. Professor Jeremy Thompson, she found that adding haemoglobin to damaged or stressed facebook.com/RobsInstitute IVF invention bringing new hope oocytes can improve developmental to families potential, increasing the chances of conception. twitter.com/RobsInstitute The new IVF treatment BlastGen, contains Dr Hannah Brown received the 2015 Young the signalling molecule GM-CSF. This Investigator Award for this research. youtube.com/RobinsonInstitute bioactive agent is found naturally in the

38 Robinson Research Institute Annual Report 2015 39 Comparative Reproductive Biology of Mammals Professor Bill Breed Comparative morphology of gametes and their interaction at fertilisation in Australian mammals

Australia’s unique mammalian fauna has a In 2015 our research focused on the effects Group Members southern Gondwanan origin, the marsupials, of variation in post-copulatory sexual Research Leader: Bill Breed and a northern Asian origin, the native selection on sperm form and the resultant Senior Lecturer: Eleanor Peirce rodents. Our work focuses on the evolution morphological differences that occur. We PhD Candidates: Liberty Olds, Karleah and morphology of the sperm and eggs, and found that species with relatively large Trengove and Harsha Wechalekar their interaction at fertilisation in selected testes mass produce far more uniform and Research Assistant: Chris Leigh species from both of these groups of mammals. streamlined spermatozoa than those with small relative testes mass where the highly Honours Students: Alison Pullen and Hanna We use various light and electron Maclennan microscopical methods to determine the polymorphic sperm populations show some Affiliate Member: Natasha Speight gamete morphology. By plotting the data on similarities to those in humans. a molecular phylogenetic tree we can then Our next step is to test our predictions that External Collaborators: Chris Dickman (University of Sydney), Kris Helgen (National gain insight into the polarity of the evolution the differences in sperm morphology we Museum of Natural History), Stefan Lupold of gamete form. We have found marked observed across species relate to differences (University of Zurich), Richard Oko (Queen’s interspecies differences in the relative in sperm behaviour and fertilisation success. University) and Kevin Rowe (Museum Victoria) testes mass, together with quantitative This work helps us to understand the and qualitative differences in the sperm evolutionary origins of reproductive behaviour produced. From this data we can predict the and function, and has relevance to devising effects of sexual selection on sperm form new strategies for regulating fertility in various across the species. species.

Obesity and Metabolism Professor Frank Grützner Defining genetic and epigenetic mechanisms that contribute to human diseases through comparison with other mammalian species

The comparison of genes, genomes and monotremes provides the opportunity Group Members epigenetic mechanisms in different species to identify the role of key genes involved Research Leader: Frank Grützner has provided many fundamental insights in stomach function and metabolism in Visiting Research Fellow: Dan Kortschak into how genes function in humans, how humans, and may lead to the identification Lecturer: Tasman Daish they evolved, and how they contribute of new therapeutic targets for metabolic to diseases. Studying genes in species diseases such as diabetes. PhD Candidates: Aaron Casey, Reuben Jacob, David Stevens, Deborah Toldo-Flores, Nicole distantly related to humans has helped in In 2015 we continued to investigate the Williams and Megan Wright the development of novel drugs including role of genes in the piRNA pathway in the Honours Student: Cyan Sylvester treatment for type 2 diabetes. ovary and ovarian cancer. We embarked RRI Collaborators: Stefan Hiendleder, Martin The Comparative Genome Biology group new research to investigate if the interaction Oehler, Carmela Ricciardelli and Darryl Russell study gene evolution in mammalian species of genes in the nucleus changes in ovarian External Collaborators: Peter Donnelly (Oxford distantly related to humans. Monotremes cancer when compared to normal cells. University), Briony Forbes (Flinders University), in particular (platypus and echidna) have Additionally, we published research Henrik Kaessman (University of Lausanne), an extraordinary sex chromosome system demonstrating that in monotremes, sex James Turner (Medical Research Council that can reveal novel genes and pathways chromosomes are not silenced at male London) and Wesley Warren (University of involved in sex determination in humans. meiosis. This is a significant finding as it Washington) Monotremes experienced radical changes shows that silencing mechanisms evolved to their stomach anatomy and physiology, later in mammalian evolution with the accompanied by significant loss or change emergence of the sex chromosomes in in genes involved in digestion. Studying therian mammals.

40 Robinson Research Institute Obesity and Metabolism Associate Professor Leonie Heilbronn Understanding and overcoming the metabolic risks associated with obesity and IVF

Overweight and obesity is rising globally, and obesity in human health, with a Group Members increasing the risk for many chronic diseases particular interest in the long-term health Research Leader: Leonie Heilbronn including type 2 diabetes. Concurrently, consequences of IVF. Postdoctoral Researcher: Miaoxin Chen and the number of children conceived by In The group recently completed an intervention Amy Hutchinson Vitro Fertilisaton (IVF) is increasing, and trial in 90 women examining the metabolic Research Assistants: Nicole Isaacs and now totals more than five million across the benefits of alternate day fasting diets. Briohny Johnston world. Accumulating evidence suggests that They demonstrated that these diets are PhD Candidates: Thomas Butler and Bo Liu children born via IVF have altered health as effective as traditional weight loss diets Rob Norman and Rebecca profiles compared to their non-IVF peers. RRI Collaborators: in improving health, and they are currently Robker This includes increased fatness, raised blood looking at the molecular mechanisms pressure, increased fasting blood glucose External Collaborators: Siobhan Banks underlying these improvements. Additionally, (University of South Australia), Grant Brinkwork and triglycerides, and lower flow mediated the group are expanding their recent (CSIRO), Alison Coates (University of South blood vessel dilation. In animal models, adult work examining impacts of IVF on the Australia), Michelle Keske (Menzies), Manny mice conceived by IVF also show increased embryo, and examining for markers of liver Noakes (CSIRO), Dorit Samocha-Bonet (Garvan body fat and fasting insulin, increased Institute), Charmaine Tam (University of Sydney) metabolism in IVF offspring. and Gary Wittert (University of Adelaide) systolic blood pressure, and impaired In collaboration with A/Prof Robker, we plan glucose tolerance. to extend our IVF work to understand the The Obesity and Metabolism group seeks mechanisms underlying metabolic health to provide new data regarding the long- risk in IVF offspring, and to find new ways to term health consequences of over-nutrition mitigate the risk for future generations.

Endometriosis Associate Professor Louise Hull Understanding the biological basis of endometriosis to develop diagnostic tools and therapies for clinical practice

Endometriosis affects approximately 10% endometriosis, identifying several promising Group Members of women, causing pelvic pain and often methods for non-invasive identification, Research Leader: Louise Hull infertility. Surgery is required to diagnose for including MRI and scanning for deep Specialist Surgeon: Susan Evans endometriosis and medical therapies treat infiltrating endometriosis, however further Clinical Lecturer: Vicki Nisenblat the symptoms rather than the causes of the trials are required to confirm accuracy. PhD Candidate: Kavita Panir disease. Increasing our understanding of the In 2015, we completed a clinical trial of biology of this debilitating condition will lead Elagolix, which is an oral GnRH antagonist RRI Collaborators: Hannah Brown, Ben to improved diagnostic tools and a wider Mol, Robert Norman, Sarah Robertson, in association with Abbvie. We anticipate Rebecca Robker, John Schjenken and Jeremy range of therapies to help women suffering the results and the opportunity to utilise this Thompson from endometriosis. medication clinically in 2016 or 2017. External Collaborator: Chris Print The Endometriosis group have identified In 2016 the group aims to establish (The University of Auckland) and evaluated microRNAs as a blood based microRNA deficient mouse models of diagnostic for endometriosis. Mouse models endometriosis including a syngeneic of endometriosis have been established menstrual mouse model of endometriosis, to evaluate environmental factors such as and progress a study determining the the contribution of seminal plasma to the effectiveness of several endometriosis endometriotic disease process, and the imaging modalities. A key ambition is to effect of deletion of specific genes such as establish a national cohort to determine TGFβ on endometriotic lesion development. the impact of endometriosis on health The group have also completed a and wellbeing. Cochrane Review of diagnostic methods for

Annual Report 2015 41 Breast Biology and Cancer Associate Professor Wendy Ingman Exploring how the immune system in the breast affects cancer and mastitis susceptibility

Breast cancer is the most common type of The Breast Biology and Cancer group works Group Members cancer in Australian women, affecting 1 in 8 closely with surgeons and oncologists at Research Leader: Wendy Ingman before the age of 85. While breast cancer The Queen Elizabeth Hospital to understand Postdoctoral Researchers: Pallave Dasari, treatment has improved, little progress has how hormones and immune cells affect Danielle Glynn and Eleanor Need been made towards reducing the incidence breast function. The group seeks to better Research Nurse: Kathryn Mildren of this disease. understand the biological mechanisms that Research Officer: Leigh Hodson Also common in women is lactation underpin breast cancer risk factors, including PhD Candidates: Siti Noordin and Sally Sun mastitis; an inflammatory breast disease menstrual cycling, pregnancy and mammo- that affects 1 in 4 breastfeeding women. graphic density, to aid in the prevention and Masters Student: Vahid Atashgaran The disease causes localised pain and is early detection of breast cancer. Honours Student: Maddison Archer frequently accompanied by the rapid onset A key focus in 2015 was understanding how RRI Collaborators: Simon Barry and Sarah of systemic symptoms including fever, immune cells and inflammatory factors affect Robertson muscle aches, and fatigue. The challenges breast density. Breast density is an important External Collaborators: Lisa Amir (LaTrobe posed by this disease often lead women risk factor in the development of breast cancer, University), Kara Britt (Peter MacCallum to cease breastfeeding, leaving their however little is known about the biological Institute), Andreas Evdokiou and Mark infants at increased risk of respiratory and mechanisms that cause highly dense tissue Hutchinson (University of Adelaide), Fiona Pixley (University of Western Australia), Tim Price gastrointestinal diseases as babies, and a to be at increased risk. We demonstrated (Queen Elizabeth Hospital), Rik Thompson number of non-communicable diseases such that immune cells are altered in highly dense (University of Queensland) and David Walsh as heart disease and diabetes as adults. breast tissue, which may predispose the (Queen Elizabeth Hospital) breast to increased risk of cancer.

Gamete and Embryo Biology Dr Michelle Lane Understanding the impact of environmental insults to gametes on developmental trajectory of the embryo, and disease development in offspring

We now understand that modifications to Our research program principally focuses Group Members the molecular constituency of either the on how obesity and sub-fertility impact the Research Leader: Michelle Lane egg or sperm not only impact the viability metabolic health and epigenetic marks in Research Fellows: Nicole McPherson and Tod of the resultant embryo, but also program gametes and embryos that alter the growth Fullston growth in utero which may influence disease and development of subsequent offspring. Postdoctoral Fellow: Francesca Bell risk in adulthood. Obesity and various In 2015, we demonstrated in animal models Research Assistant: Lauren Sandeman lifestyle factors have been shown to change that females with overweight fathers had molecular marks in gametes, and it is PhD Candidates: Alexander Penn and alterations to genes in the ovarian cells Helena Shehadeh estimated that the youth of today will be (associated with reduced fertility), and the first generation to live shorter lives than Honours Students: Cassandra Carbone, amplified metabolic disturbances when Rachael Collett and Dania Ruminski-Smith their parents. Understanding the pathways exposed to high-fat diets as adults. Affiliate Member: Deirdre Zander-Fox of transmission of parental environmental We completed a systematic review insults to the next generation is essential for demonstrating that obese men are more RRI Collaborators: Julie Owens, Sarah Robertson and Rebecca Robker developing strategies to intervene. likely to be sub-fertile and their partners The Gamete and Embryo Biology Group is experience more miscarriages. We also External Collaborators: John Aitken (University uncovering the functional pathways in the showed that when both parents were obese of Newcastle), Rob McLachlan (PHMRI), Moira O’Bryan (Monash University) and Gary Wittert transmission of parental health cues to the there is an additive negative impact on (University of Adelaide) next generation, and seeks to identify the embryo development and offspring health. characteristics of “good” eggs and sperm.

42 Robinson Research Institute Evidence Based Women’s Health Care Professor Ben Mol Evaluation of the effectiveness of health care for women and implementation of best practice

Much medical practice around the world PROMPT (investigating the effectiveness Group Members is conducted without the certainty that the of pessaries for preterm birth), STRIDER Research Leader: Ben Mol interventions are beneficial to the patient and (interventions for prenatal growth Research Fellows: Sean O’Leary, Clarabelle will not cause harm. Many such interventions resetriction), COPOP (seeking to develop Pham, and Tamara Varcoe are commonplace and have been conducted core outcome sets for research in preterm Clinical Researcher: Suzette Coat for years or even decades, with limited birth) and iHOPE (improving understanding Visiting Research Fellow: Rui Wang questioning as to the effectiveness of of preeclampsia). These studies are treatments. coordinated through the Global Obstetrics RRI Collaborators: Caroline Crowther, Michael Davies, Bill Hague, Jodie Dodd, Gus Dekker, Network chaired by Ben, and include The Evidence Based Women’s Health Care Louise Hull, John Lynch, Michelle Lane, Helen group believes all medical interventions perinatal research centres in the US, UK, Marshall, Vivienne Moore, Rob Norman, Martin require an underlying knowledge base Canada, Australia, New Zealand, Brazil Oehler, Julie Owens, Claire Roberts, Sarah demonstrating treatments are expected to and China. Robertson, Michael Stark and Jeremy Thompson do more good than harm. In 2016 the group plans to propose a model External Collaborators: Siladitya Bhattacharya of shared savings for SA health and the (University of Aberdeen), Arri Coomarasamy The group aims to provide insight to the (University of Birmingham), Tony Duan (Shanghai effectiveness of all medical interventions in hospitals for the treatment of miscarriage, Tongji University), Bill Grobham (Northwestern reproductive health, ideally through large screening for gestational diabetes, University), Justus Hofmeyr (University of international collaborations in randomised prevention of first caesareans and iatrogenic Witwatersrand), Rodolfo Pacagnella (University preterm labour. of Capinas), Shakila Thangaratinam (Blizard clinical trials. Institute), Homan Tuong (Vietnam National During 2015 Ben co-established large University), Xiaoke Wu (Heilongjang University of international research projects including; Chinese Medicine) and the Dutch Consortium for Research in Women’s Health

Reproductive Endocrine and Medicine Professor Rob Norman AO Improving outcomes in fertility treatments, polycystic ovary syndrome and related conditions

Approximately 1 in 10 couples will methods to diagnose PCOS with a particular many overseas groups, especially in Beijing experience infertility and more than 1 in focus on ultrasound, antimullerian hormone, and Shandong. 10 women suffer from Polycystic Ovary androgens and menstrual abnormalities. Group Members Syndrome (PCOS), which is the most In 2015 we commenced the NHMRC Centre Research Leader: Rob Norman common condition of female reproduction. of Excellence in PCOS with collaborators Environmental impacts such as poor from across Australia as part of a five-year Postdoctoral Research Fellow: Lisa Moran nutrition, obesity, pollutants and stress grant. Additionally, we completed the largest Research Fellows: Tania Chechurova and Vicki significantly influence reproductive potential, international study on hGH in IVF for poor Nisenblat and fertility treatments are being increasingly responders, finding that there was no benefit RRI Collaborators: Leonie Heilbronn, Louise utilised by patients at earlier stages than in of this expensive treatment on women seeking Hull, Neil Johnson, Ben Mol, Rebecca Robker and Ray Rodgers the past. PCOS is on the rise, and sufferers a higher pregnancy rate on IVF. We also may experience associated sequela such completed a study of ovulation induction using External Collaborators: Bart Fauser (University of Ultrect), David Handelsman as metabolic syndrome, diabetes and clomiphene, letrozole and FSH, demonstrating cardiovascular disease. (ANZAC Institute), Rodger Hart (University of high success rate of these treatments. Western Australia), Joop Lavern (Rottersdam The Reproductive Endocrine and Medicine Our focus in 2016 will be to look at the University), Lois Salamonsen (Hudson Institute), Group seeks to optimise the health of role of AMH in the diagnosis of polycystic Qiao Jie (Beijing), Chen Zhi-Jiang (Shanghai the mother and father prior to pregnancy and Shangdong) and Helena Teede (Monash ovary morphology in collaboration with an University). based on the best available biological, international team. We will also expand our psychological and physiological evidence, international PCOS research links with and are committed to reviewing the best

Annual Report 2015 43  Reproductive Biotechnology Associate Professor Mark Nottle Development of organ, tissue and cell replacement therapies

The demand for organ transplantation has The group seeks to develop new Group Members rapidly increased around the world over the biotechnologies to address this global Research Leader: Mark Nottle last ten years. This is due to the improved problem. As part of this research they are Research Fellows: Thai Chen and Ivan Vassilev success of transplant procedures and developing the pig as a large animal model Research Assistant: Stephen McIlfatrick the increased incidence of organ failures. for human stem cell research. In 2015 the However, donations have not kept up with group demonstrated that porcine embryonic RRI Collaborators: Toby Coates, Stefan Hiendleder, Michelle Lane, David Parsons and these increased requirements and there is a stem cells have the ability to differentiate Paul Thomas global shortage of human organ, tissue and to multiple cell types, including insulin- Peter Cowan cell donors. producing cells, using a relatively simple External Collaborators: (St Vincents Hospital), Emmanuele Cozzie The Reproductive Biotechnology group is protocol when compared to those already (University of Padau), Wayne Hawthorne working alongside a number of interstate and published. The group aims to continue this (Westmead Millennium Institute), Nam Kim overseas collaborators examining methods research to characterise these and other cell (Chungbuk University), Andrew Lew (WEHI), types in a pig model. Philip O’Connell (Westmead Millennium to overcome what is one of medical sciences Institute), Simon Robson (Harvard Medical greatest challenges. This multidisciplinary School) and John Paul Soulilou (Universite effort is recognised as the leading research de Nantes) of its kind in the world.

Reproductive Cancer Professor Martin Oehler and Dr Carmela Ricciardelli Identification of novel biomarkers and therapeutic targets for ovarian cancer

Ovarian cancer is a devastating disease finding that interacting proteins annexin A2 Group Members and the leading cause of death from and S100A10 are independent predictors Research Leaders: Martin Oehler and gynaecological malignancies. It affects of serous ovarian cancer outcome. Annexin Carmela Ricciardelli approximately 1 in 90 women in Australia A2 and S100A10 are novel prognostic Postdoctoral Researcher: Noor Lokman and over 70% of patients present with biomarkers that can be utilised to aid patient Research Assistants: Anita Oehler, Carmen advanced disease. Despite improvements management, and could offer opportunities Pyragius and Anne Macpherson in surgery and new developments in for new molecular targeted therapies to RRI Collaborators: Frank Grutzner, Ray chemotherapy, ovarian cancer mortality rates improve outcome. We identified that the Rodgers and Darryl Russell have not changed dramatically over the last cytoskeletal protein, keratin 5, is linked to External Collaborators: Peter Hoffmann decade. Significant improvement in ovarian chemotherapy resistance and progression. (University of Adelaide), Andrew Ruszkiewicz cancer survival will require the development Developing strategies to target keratin 5 (SA Pathology), Andrew Stephens (Prince of ovarian cancer biomarkers for early may prevent recurrence and chemotherapy Henry’s Institute of Medical Research) and detection and more effective molecularly resistance in serous ovarian cancer. Florian Weiland (University of Adelaide) targeted therapeutics. In 2016 we will determine whether protein The Reproductive Cancer group seeks biomarkers and autoantibodies recently to understand the mechanisms involved identified in plasma could be used as a in ovarian cancer spread, resistance to diagnostic test for serous ovarian cancer in chemotherapy and the identification of novel independent cohorts. We will also assess biomarkers for detection. whether hyaluronan inhibitors are effective In 2015 the group continued to uncover the at reversing chemo-resistance using in vivo role of the annexin A2 in cancer progression, models of ovarian cancer.

44 Robinson Research Institute Reproductive Immunology Professor Sarah Robertson Understanding how the immune system impacts reproductive capability and disorders of pregnancy

In pregnancy, the female immune system In 2015 we made substantial progress Group Members recognises the fetus as foreign and special in understanding molecular pathways by Research Leader: Sarah Robertson adaptation is required to prevent rejection. which the immune response contributes to Research Fellow: Kerrilyn Diener An active state of immunological tolerance pregnancy and offspring health, including Senior Postdoctoral Researchers: Lachlan must be established to allow embryo demonstrating that the male partner makes Moldenhauer and David Sharkey implantation and development. Many an important contribution to the peri- Postdoctoral Researchers: Peck Chin and common reproductive and pregnancy conception environment. We are expanding John Schjenken disorders - including unexplained infertility, our studies to explore how both sperm and Dexter Chan, Ella Green, recurrent miscarriage, preeclampsia and seminal plasma factors interact with cells PhD Candidates: Tom Kieffer, Kavita Panir, Hanan Wahid and preterm birth - have their origins in immune in the female reproductive tract of women, Bihong Zhang and inflammatory disturbances that impact regulating gene expression to impact Research Officer: Camilla Dorian placental development and leave the fetus pathways that control uterine receptivity to vulnerable to immune and inflammatory attack. embryo implantation. RRI Collaborators: Simon Barry, Louise Hull, Wendy Ingman, Rebecca Robker and Jeremy The Reproductive Immunology group Additionally, we investigated new drug Thompson explores the mechanisms through which the compounds for tackling preterm birth. By External Collaborators: Sylvain Chemtob female immune system becomes activated suppressing the pro-inflammatory pathway (University of Montreal), Mark Hutchinson at the time of conception to confer tolerance activated by infection or by sterile insults, (University of Adelaide), David Olson (University before embryo implantation. We focus on small molecules that block Toll-like receptor 4, of Alberta) and Kenner Rice (National Institute of Health,) events at conception that elicit a sequence and/or peptide antagonists of IL-1 signaling, of events to stimulate the generation are showing great promise in inhibiting the steps regulatory T cells (Treg cells). Treg cells are that would otherwise lead to premature birth. anti-inflammatory and protect the implanting embryo and developing placenta.

Ovarian Cell Biology Associate Professor Rebecca Robker Discovering the biological mechanisms that drive ovulation and embryo development

A good egg at the right time is required to and dietary mouse models of obesity, we fetal development. Most importantly, we produce a healthy new baby. Yet, rapidly have shown that the detrimental effects of discovered a class of compounds that when changing environments and lifestyles are obesity on female reproduction and embryo administered to obese female mice, prevent challenging this highly sensitive biology development commence with dramatic the mitochondrial changes in oocytes. with profound implications for fertility alterations in oocyte quality. Group Members and the health of offspring. For instance, We found that cumulus-oocyte-complexes Research Leader: Rebecca Robker approximately 60% of Australian women are of obese mice contain high levels of lipid overweight or obese, and this is associated and mitochondrial dysfunction, and in Postdoctoral Researcher: Linda Wu with anovulation and Polycystic Ovarian collaboration with Fertility SA, verified PhD Candidates: Miaoxin Chen, Macarena Syndrome, reduced pregnancy rates, and similar changes in obese women. Our Bermudez Gonzalez and Siew Wong increased risk of obesity for their children. most recent studies in mice now show RRI Collaborators: Leonie Heilbronn, Michelle The Ovarian Cell Biology group is that obesity-induced mitochondrial Lane, Robert Norman, Darryl Russell and Jeremy Thompson investigating the biological mechanisms by disturbance in oocytes persist into offspring which ovarian cells endow the oocyte with tissues, a finding with major implications External Collaborators: Michael Barry (Fertility SA), John Carroll (Monash University), Mark the capacity to form an embryo and then for understanding the transgenerational Febbraio (Garvan Institute), Jon Hennebold trigger its timely release. This information is transmission of obesity. Collaborating (Oregon National Primate Research Center), essential for understanding the foundations with the Gamete Biology Group, we also Justin St John (Hudson Institute), Ryan Rose of reproduction and the earliest stages documented that when both parents are (Fertility SA) and Kirsty Walters (ANZAC Institute) of embryogenesis. Using both genetic obese, there are even greater shifts in

Annual Report 2015 45 Ovarian Developmental Biology Professor Ray Rodgers Understanding how the ovary produces oocytes and hormones, what can go wrong and why

Reproductive health significantly impacts functions of the ovary including growth of the Group Members a woman’s wellbeing throughout her life, follicle and hormone production, and if these Research Leader: Ray Rodgers irrespective of her choice to have children. cells do not function properly infertility and Postdoctoral Researcher: Katja Hummitzch In addition to producing eggs, the ovary’s hormone imbalances can result. Research Assistants: Wendy Bonner and hormones govern cyclical changes regulating In 2015 with collaborators, we made Nicholas Hatzirodos somatic and psychological health at important discoveries about how key PhD Candidates: Katrina Copping and Monica puberty, across the menstrual cycle, during enzymes in the synthesis of androgens Hartanti pregnancy, and in parturition, lactation and and estrogen are regulated and cexert their Honours Student: Nicole Bastian menopause. Very common disorders of the function in cells. This was with both purified ovary such as polycystic ovary syndrome RRI Collaborators: Michelle Lane, Sarah enzymes, and ovary and adrenals cells in Robertson and Darryl Russell affect up to 18% of women of reproductive culture. Additionally in collaboration we External Collaborators: Richard Anderson age, and some women experience failure completed our examination of ovaries at of the ovary, premature menopause, and (University of Edinburgh), Ross Bathgate the Australian Synchrotron, and identified (Howard Florey Institute), Hugh Harris ovarian cancers. which cells in the ovary accumulated trace (University of Adelaide), Phil Knight (University The Ovarian Developmental Biology group elements such as selenium, zinc, copper of Reading), Lisa Martin (Monash University), studies the cell biology of the ovary to and iron. We are now identifying the roles Viv Perry (University of Nottingham), Dieter Reinhardt (McGill Institute) and Dagmar Wilhelm understand how the ovary functions and of selenium and copper in the ovary, and (Monash University) to discover what can go wrong in disease. their impact on the ability of cells to produce Ovarian cells carry out many of the unique estrogen and progesterone.

Ovarian and Reproductive Cancer Cell Biology Associate Professor Darryl Russell Defining the molecular mechanisms of hormone control of ovarian folluculogenesis

Ovarian follicles coordinate input from the >> Apply our experience in hormone Group Members maternal system and oocyte secreted factors controlled morphogenic processes Research Leader: Darryl Russell to guide oocyte maturation. This interaction to understand the mechanisms of Postdoctoral Researcher: Kylie Dunning impacts the endocrine health of women and reproductive organ cancer incidence Senior Scientist: Jill Muhling ultimately the lifelong health of offspring. and metastasis PhD Candidates: Adrian Kaczmarek and Javier The Ovarian and Reproductive Cancer Cell In 2015 we characterised novel aspects of Rodriguez Baena Biology group is focused on understanding the molecular control of oocyte development Research Officer: Laura Watson the unified mechanisms by which hormone and ovarian function. We demonstrated that signals and tissue structure determine the a range of environment and lifestyle stressors RRI Collaborators: Simon Barry, Frank Grutzner, Michelle Lane, Carmela Ricciardelli, health and function of ovaries. The group influence ovarian somatic cell function and Claire Roberts, Sarah Robertson, Rebecca seeks to harness this knowledge to improve in turn impact oocyte and embryo health. Robker and Jeremy Thompson reproductive health and advance treatments The mechanisms by which stressed oocytes External Collaborators: Juan Carlos for infertility and cancer. signal to somatic cells and the response Rodriguez-Maneque (University of Grenada), We aim to: intended to prevent damage, which can Robert Gilchrist (University of New South Wales) lead to infertility or poor fetal developmental and John Sandy (Rush University) >> Understand the fundamental mechanisms outcomes, continue to be investigated. by which hormones and tissue These stress response mechanisms are morphogenesis control ovarian function important in the initiation and progression of >> Harness this knowledge to improve cancers of reproductive organs. reproductive health and advance treatments that directly address the causes of infertility and endocrine dysfunction

46 Robinson Research Institute Neural Development Professor Paul Thomas Generation and analysis of mouse models for epilepsy and intellectual disability

Neurological disorders are amongst the genetic control of brain development and Group Members most common condition in children. The the biological basis of mental retardation and Research Leader: Paul Thomas Neural Development Group seeks to epilepsy. They have also established a unique Postdoctoral Research Fellow: James Hughes uncover the genetic causes of neurological mouse model of sex reversal in which Research Assistants: Sandie Piltz and disorders with a particular interest in epilepsy chromosomally female mice develop as Melissa White and intellectual disability, which affect males. These mice are providing exciting PhD Candidates: Dale McAnich approximately 3% of the population. new insights into the evolution and molecular Masters Student: Louise Robertson Using mouse models and stem cells, the mechanism of sex determination in mammals. group seeks to understand the disease In 2016 the group will continue to expand Honours Students: Daniel Pederick mechanism that underpins these debilitating their expertise in genome editing, and will RRI Collaborator: Jozef Gecz conditions. Using CRISPR/CAS9 genome analyse existing mouse models of epilepsy External Collaborator: Robin Lovell-Badge editing, the group established novel mouse and intellectual disability to investigate disease (Francis Crick Institute) models for neurological disease genes, mechanisms and explore new therapies. which are providing unique insights into the

Early Development Associate Professor Jeremy Thompson Understanding altered metabolic states within oocytes and embryos, and epigenetic mechanisms controlling growth

Accompanying fertilisation are dynamic From the application of new fluorophores, Research Assistant: Tiffany Cheow, Wan Xian molecular and biochemical processes that we are mapping the metabolic heterogeneity Kang and Annie Whitty significantly impact subsequent embryonic between individual blastomeres of embryos, Manager, IVF Vet Solutions: Marie Anastasi and fetal development, as well as adult revealing that whole embryo metabolic PhD Candidate: Hanna McLennan health. The newly fertilised egg is extremely analysis often masks the variability Technical Officer: Anwar Fatohi sensitive to the microenvironment within between individual blastomeres. We the maternal reproductive tract, and this is extended our collaboration with RMIT and Honours Students: Thao Dinh, Megan Lim, Mitchell Ross and Emma Tregoweth reflected in the resetting of its epigenetic enhanced capabilities for autofluorescence code. If the metabolic microenvironment methodology and analysis, with promising RRI Collaborators: Michael Davies, Michelle Lane, Mark Nottle, Sarah Robertson, Rebecca surrounding the oocyte and embryo is data examining novel biomarkers of oocyte Robker and Darryl Russell altered as a result of IVF, diet or lifestyle and early embryo developmental competence, External Collaborators: Andrew Abell factors, this will influence the epigenetic with exciting commercial prospects. (University of Adelaide), Michael Barry (Fertility mechanisms that ultimately control the Continued efforts in defining histone SA), Jose Buratini (Universidade Estadual growth rate and development potential of the modifications within oocyte and early embryo Paulista), Pabio Certica (University of Beunos resulting fetus. Aires), Michel DeVos (Vrije Universiteit Brussell), chromatin has revealed major perturbations David Gardiner (), Brant The Early Development group seeks to associated with not only hyperglycemic Gibson (RMIT), Robert Gilchrist (University of explain how environmental stress impacts conditions but also standard conditions New South Wales), Ewa Goldys (Macquarie early development, to produce new tools to encountered within IVF. University), Hayley McGrice (University of Adelaide), Jen Kelly (SARDI), David Mottershead measure the changes, and to successfully Group Members (Mottasis Review), Nicki Packer (Macquarie develop interventions to reduce the impact. University), Ryan Rose (Fertility SA), Johan Research Leader: Jeremy Thompson In 2015 our work within the ARC Centre Smitz (Vrije Universiteit Brussell), Yvonne Stokes (University of Adelaide), Alan Tilbrook (SARDI) of Excellence for Nanoscale BioPhotonics Postdoctoral Researchers: Hannah Brown and Melanie McDowall and Simon Walton (Australian Reproductive focused on transferring new technologies Technologies) into the early embryo development field. Senior Research Officer and Laboratory Manager: Lesley Ritter

Annual Report 2015 47 Health of Women and Babies Professor Caroline Crowther and Associate Professor Philippa Middleton Improving the care of women and babies through evidence-based clinical practice.

The Health of Women and Babies group >> STRIDER NZAus Sildenafil Therapy In Group Members seeks to improve health care to benefit Dismal Prognosis Early-Onset Intrauterine Research Leaders: Caroline Crowther and women and babies by: Growth Restriction Philippa Middleton >> Answering questions of major importance >> My Baby’s Movements Trial maternal Research Fellows: Emily Bain and Shanshan Han in the field of maternal and perinatal health awareness of fetal movements to prevent Research Officers: Melissa Ewens and >> Generating research evidence of the stillbirth Thach Tran highest quality >> A*STEROID Australian antenatal study Research Assistants: Caroline Holst, Michaela Jarrett and Kaye Robinson >> Ensuring research findings are to evaluate the role of intramuscular incorporated into health care practice dexamethasone versus betamethasone Senior Clinical Trials Manager: Pat Ashwood prior to preterm birth to increase survival PhD Candidates: Angela Brown, Emer Heatley The multidisciplinary research team has free of childhood neurosensory disability and Zohra Lassi strong local, national and international collaborations in maternal and perinatal >> IDEAL Investigation of dietary advice for Data Management Team: Vincent Ball and Sasha Zhang research, with strategic commitment to women with borderline gestational diabetes Mary Paleologos, research, education and training. This >> BAC Looking at planned vaginal birth vs Administrative Assistants: and Jacqueline Smith ensures high quality and timely maternal and planned elective repeat caesarean for perinatal research is conducted, evaluated women at term with a single previous and translated into clinical practice and caesarean section health policy. >> PROGRESS Progesterone after previous In 2015 the group continued to coordinate, preterm birth for the prevention of neonatal collaborate and conduct follow up for major respiratory distress syndrome randomised clinical trials and studies including: >> WISH Working to improve survival and >> MAGENTA Administering magnesium health for babies born very preterm – an sulphate at 30 to 34 weeks gestational Australian and New Zealand translational age for fetal neuroprotection health project

48 Robinson Research Institute Health of Pregnant Mothers and Babies Professor Jodie Dodd Ensuring health outcomes improve for pregnant women and their babies

In 2013, the WHO estimated that 423 million In 2015 we established OPRATA (Obesity Data Managers: Vincent Ball and Sasha Zhang children were overweight or obese, stating in Pregnancy Research and Translation Research Assistants: Lauren Cates, Tiffany childhood obesity as one of the most serious Alliance) with collaborators in Australia and Cornish, Ashlee Fairclough, Louise Fraser, public health challenges of the 21st century. the United Kingdom. This group seeks to Caroline Holst, Lavern Kannieappan, Erin Keen, To date, public health strategies focusing develop a collaborative and harmonised Anita Lo, Ellen Lyrtzis and Caroline Sheppard on decreasing energy intake and increasing approach towards addressing research PhD Candidate: Rachel Earl, Cecelia O’Brien, energy output have not been effective. As such, questions on the obesity in pregnancy Casey Nottage and Tulika Sundernathan a focus on the early life origins of overweight research agenda, and translating new Masters Student: Sarah Cash and obesity before birth has emerged. Dietary research findings into clinical practice. Administrative Assistant: Jacqueline Smith and lifestyle modifications, as well as pharma- RRI Collaborators: Jennifer Couper, Lynne cological interventions are being investigated Group Members Giles, Vivienne Moore, Robert Norman, Julie for their capacity to alter the intrauterine Research Leader: Jodie Dodd Owens, Jeffrey Robinson and Ian Symonds environment and reduce the risk of childhood Co-Research Leader: Rosalie Grivell Collaborators: Matt Gillman (Harvard obesity and cardiovascular disease. Clinical Researchers: Chad Andersen, Cecelia Pilgrim Health Care), Mark Kilby (Birmingham O’Brien, Ross Haslam and Andy McPhee Women’s Hospital), John Kingdom (Mt In particular the Health of Pregnant Mothers Sinai Hospital), Berthold Koletzko (Ludwig- and Babies group focus on the short and long- Clinical Trials Manager: Andrea Deussen Maximillans University Munich), Debbie term effects of improved nutrition and physical Postdoctoral Researcher: Lisa Moran Lawlor (Bristol University), Fionnuala McAuliffe activity for women planning pregnancy, (University College Dublin), Lucilla Poston Senior Statistician: Lisa Yelland (King’s College London), Phil Robinson pregnant women and their children. They Statistician: Jennie Louise (Women’s and Children’s Hospital), Greg seek to positively influence the health of Ryan (Mt Sinai Hospital), Wendy Scheil (South mothers and their babies through developing Research Dieticians: Courtney Cramp, Shan Australian Pregnancy Outcome Unit), Shakila Han and Stephanie Zrim effective interventions, including diet and Thangaratinam (Queen Mary’s University lifestyle changes for women and the use of Research Midwife: Meredith Kelsey London) and Rory Windrim (Mt Sinai Hospital) metformin for women who are overweight or Research Coordinator: Angela Newman Affiliate Members: Maria Makrides, Jonathan Karnon and Prash Sanders obese in pregnancy, and follow women and their children to assess longer-term health.

Obstetric Medicine Professor Bill Hague Improving outcomes for pregnant women with medical complications

Over 10% of pregnant women experience of post natal intervention in women with Group Members medical complications. Complications may gestational diabetes to prevent or delay Research Leader: Bill Hague predate pregnancy, or develop during or after the onset of type 2 diabetes; and began Research Coordinator: Suzette Coat pregnancy, with some cases threatening the planning for the new TOBOGM trial with PhD Candidate: Mansi Dass Singh lives of both mother and baby. While early interstate collaborators, to assess the identification and appropriate therapy is value of testing for gestational diabetes in RRI Collaborators: Jennifer Couper, Jodie Dodd, Ben Mol, Julie Owens and Julia Pitcher vital, the research base for some therapeutic women at their first pregnancy appointment. decisions is limited with insufficient evidence Additionally, we are continuing efforts to External Collaborators: Hanneke de Vries (Free University Hospital), Michael Fenech to support interventions. progress in collaboration the PITCHES trial of (CSIRO), Anand Hardikar (University of Sydney), The Obstetric Medicine Group seeks to treatment in women with the pregnancy liver Laura Magee (University of British Colombia), develop and evaluate interventions for two disease obstetric cholestasis. Marc Rodger (University of Ottawa), Janet major medical disorders of pregnancy; Finally, our follow-up data from the MiG trial Rowan (Auckland Hospital), David Simmons (University of Western Sydney), Mark Walker gestational diabetes and preeclampsia. cohort points to no differences at 2 years in the and Shi-Wu Wen (University of Ottawa) and In 2015 our group completed recruitment neurocognitive development of those exposed Catherine Williamson (King’s College London) for the large international FACT trial of folic to metformin in utero, reinforcing the safety acid supplementation in the prevention of of prescribing this useful drug in the manage- preeclampsia; completed the Australian ment of women with gestational diabetes. MAGDA trial nested within a cohort study

Annual Report 2015 49 Epigenetics and Genetics Professor Stefan Hiendleder Understanding epigenetic and genetic mechanisms and programming in prenatal development to optimise outcomes

Prenatal growth trajectory and birth weight In 2015 we used an animal model to Group Members are strongly associated with developmental determine drivers of sex-specific fetal Research Leader: Stefan Hiendleder capacity and health throughout life. We now overgrowth that manifests at birth and Postdoctoral Researchers: Sadeesh Money know that prenatal growth and weight at impacts future development. We found and Dana Thomsen birth are determined not only by nucleotide that non-mendelian polar over-dominance PhD Candidates: Consuelo Estrella, Entesar sequence of genes, but also by epigenetic effects, ie molecular and phenotypic patterns Shuaib and Amanda Camp mechanisms such as imprinting, which in offspring that depend on inheritance of RRI Collaborators: Kathy Gatford, Frank regulate gene expression and phenotype maternal or paternal parental alleles, drive Grutzner, David Kennaway, Karen Kind, Mark at a higher level. Additionally, interactions the observed effects from mid-gestation Nottle, Julie Owens, and Claire Roberts between classical mendelian genetic, onwards. Our observation of polar over- External Collaborators: Axel Janke (Goethe non-mendelian genetic, and epigenetic dominance in imprinted gene expression, an University), Daniela Bebbere and Sergio Ledda mechanisms and factors shape prenatal important driver of fetal growth, is consistent (University of Sassari), Susanne Ulbrich (ETH development and phenotype at birth in a with polar over-dominance effects on Zurich) and Eckhard Wolf (LMU & Gene Center Munich) sex-specific manner. placental and umbilical cord phenotype. The Epigenetics and Genetics group focuses Our current work is focused on collaborative on dissection of the complex molecular bioinformatic analyses of gene and miRNA genetic architecture of prenatal growth networks in key tissues that control placental trajectory and birth weight. We uncover novel and fetal phenotype. This information epigenetic and genetic effects on prenatal will provide deeper insight into the non- growth and their interactions with environmental mendelian molecular architecture of birth factors. This allows us to identify risk factors weight phenotype. and to develop intervention strategies for optimal outcomes at birth.

Cerebral Palsy Emeritus Professor Alastair MacLennan Uncovering the genetic causes of cerebral palsy via new generation sequencing technologies

Cerebral palsy is a neurodevelopmental During 2015 our cerebral palsy family whole sequencing are likely to increase the disability affecting posture and movement DNA biobank was greatly enlarged with discovery of genetic variants contributing control for 1 in every 500 children. This recruitment in SA, NSW and Qld. Using to cerebral palsy which may allow early disability greatly affects quality of life exome sequencing we have demonstrated diagnosis and genetic interventions. for those affected and their families. Its that DNA mutations are plausibly causing prevalence has not changed during the at least 14% and up to 45% of cerebral Group Members past 50 years and costs Australia billions of palsy, much higher than the 1-2% previously Research Leader: Alastair MacLennan dollars per year. described in the literature. Results from our Senior Genetic Scientist: Jozef Gecz Using their unique cerebral palsy family DNA studies were published in the high impact Genetic Scientist: Mark Corbett journal Molecular Psychiatry and in the biobank and clinical database, The Australian Statistician: Stephen Bent American Journal of Obstetrics & Gynecology. Collaborative Cerebral Palsy Research group Research Officers: Clare Van Eyk and Kelly Harper is performing new generation sequencing Additionally, detailed in silico and animal Project Officer: Jessica Broadbent on families with a cerebral palsy child to function studies commenced in our high determine genetic causes of the disorder. priority cerebral palsy candidate genes. Research Assistant: Bryan Haines Candidate genes undergo validation in For 2016 onwards, we have a second large External Collaborators: Mathew Bainbridge function studies to ascertain whether these cohort of cerebral palsy families ready for (Baylor College), Daniel Geschwind (UCSF), Richard Gibbs (Baylor College), Eric Hoffman genes disrupt motor function. exome and whole genome sequencing and (National Institute of Health) and Michael Kruer gene function studies. Further identification (University of Arizona) of contributing copy number variations and

50 Robinson Research Institute Placental Development Professor Claire Roberts and Professor Gus Dekker Developing screening tests for women in early pregnancy to alleviate major complications of pregnancy

The four main complications of pregnancy by which fetal sex impacts pregnancy outcome; Visiting Scientist: Gabriela Leghi - preeclampsia, preterm birth, intrauterine and how micronutrients impact placental Research Assistants: Dylan McCullough and growth restriction and gestational diabetes development and function in vivo and in vitro. Zimin Zhuang - affect 1 in 4 first pregnancies and are life In 2015 we filed a provisional patent Research Midwives: Julia Dalton and threatening to the mother and/or baby in application for our algorithms that predict Samantha Pahl up to 6% of pregnancies. Globally more a first-time mother’s risk of pregnancy PhD Candidates: Sam Buckberry, Sultana than 300,000 women die each year from complications early in her pregnancy. Khoda, Alison Leviton, Ben Mayne, Dee McCormack and Rebecca Wilson complications of pregnancy and childbirth, We identified molecular pathways in the with 99% of these in developing nations. placenta that are perturbed in pregnancy Visiting PhD Student: Petra Verburg Additionally, there are 15 million preterm complications and demonstrated important Technical Officer: Caitilin McCullough births annually and this is considered the effects of gene environment interactions on Honours Students: Alexandra Samantha greatest factor contributing to the 6 million placental differentiation and function, and fetal children who die before their 5th birthday. RRI Collaborators: Kathy Gatford, Stefan growth. Our research program in human Hiendleder, John Lynch, Helen Marshall, Ben There are currently no screening tools pregnancy and mouse models is revealing Mol and Michael Sawyer, in clinical practice to identify pregnant novel molecular mechanisms by which maternal External Collaborators: Louise Kenny women at risk, largely because of a poor micronutrient status impacts placental and (University College Cork), Lucilla Poston understanding of the pathogenesis of fetal development and function. (Kings College London), Jimmy Walker pregnancy complications and the complex (Leeds University), Jenny Myers (University of inter-relationships in causal factors. Group Members Manchester) and Lesley McCowan (University of Auckland) The Placental Development group have Research Leaders: Claire Roberts and Gus Dekker established pregnancy cohort databases Research Fellow: Tina Bianco-Miotto and biobanks, and ex vivo, in vitro and animal Postdoctoral Researchers: Prabha models to investigate: the molecular profile of Andrawera, Jessica Grieger, Amanda Highet, the placenta across gestation at the genome Tanja Jankovic-Karasoulos, Jessica Laurence, and epigenome levels; molecular mechanisms Shalem Leemaqz and Dale McAninch

Annual Report 2015 51 Life Course and Intergenerational Health (LIGHT) Professor Michael Davies and Professor Vivienne Moore Uncovering how inequalities in the health of women and children arise though integrated social and biological pathways, and identifying opportunities for change

Early life is the foundation for future health We also undertake epidemiological, Group Members and life potential. Growth and development anthropological and other narrative research Research Leaders: Michael Davies and of the child, both before birth and after, are to understand how to improve the health of Vivienne Moore intimately linked to the health and well being disadvantaged women. Research Fellows: Alice Rumbold and of the mother. In turn, a woman’s health is In 2015 we showed that sleep disturbances Megan Warin influenced by her current family circumstances, were almost twice as common in women ARC Future Fellow: Lynne Giles her own life experiences, and her health with polycystic ovary syndrome. Assessment Senior Postdoctoral Researcher: Wendy inheritance from previous generations. and management of sleep problems in March, Melissa Whitrow and Tanya Zivkovic The LIGHT group seeks to understand the these women would improve quality of Statisticians: Chris Davies, Suzanne Edwards interplay of social and biological factors life and could forestall deterioration in and Kristyn Willson that influence health over the life course. cardio-metabolic health over time. We CIS Facility Coordinator: Stephanie Champion A major focus is how chronic diseases contributed to work to understand the low Research Coordinator: Kendall Smith and their risk factors are transmitted from rate of testing for fetal anomalies among PhD Candidate: Renae Fernandez parents to the next generation and how we pregnant Aboriginal women. Impediments could intervene to improve this situation. We to organising testing were identified, but the RRI Collaborators: Jodie Dodd, Michelle Lane, investigate this in cohort studies, looking most important recommendation was for the Ben Mol, Julie Owens and Darryl Russell at the developmental origins of congenital test and related counseling to be undertaken External Collaborators: Kurt Barnhart malformations, reproductive disorders, type by Aboriginal health practitioners. (University of Pennsylvania), Siladitya Bhattacharya (University of Aberdeen), Bianca 2 diabetes and cardiovascular disease. de Stavola (London School of Hygiene and Tropical Medicine), Dmitry Kissin (Centers for Disease Control and Prevention), Jennifer Marino (University of Melbourne) and Stanley Ulijaszek (University of Oxford)

Perinatal Health and Child Development Dr Nicolette Hodyl Understanding the impact of early life adversity on child development

Poor cognitive development and poor mental In 2015 we explored how cortisol diurnal Group Members health can lead to lifelong dysfunction in social, rhythms influence cognitive function, and Research Leader: Nicolette Hodyl emotional, academic, employment and physical how this can be affected by different variants Research Assistant: Tara Crawford health domains. Problems often arise following in the gene that encodes the cortisol receptor. PhD Candidates: Natalie Aboustate, Rebecca exposure to adverse early life environments, This is important, as early life adversity is well Collins and Amy Keir resulting in an intergenerational problem; known to reprogram the physiological systems Masters Student: Kathryn Martinello biologically and socially inherited social, that influence daily cortisol rhythms. This may economic and physical health issues. be a mechanism by which early life adversity Honours Students: Nathan Beu, Amy Garrett, influences cognitive function. Additionally, we Sophie Richards, Sophia Xin Sui and Nicollette The Perinatal Health and Child Development Thornton group aims to increase our understanding ran our first Nursery Research Day in the Women’s and Children’s Hospital, which seeked RRI Collaborators: Chad Andersen, Julia of how early adversity becomes biologically Pitcher, Michael Ridding, Claire Roberts and embedded in our systems to influence to up-skill clinical staff in the nursery in research Michael Stark practice. Ultimately, this will increase the neurodevelopment, and to identify ways to External Collaborators: Angela Clow (University circumnavigate the detrimental effects on research capacity of the neonatal intensive care of Westminster), Bernd Froessler (Lyell McEwin child growth and development. We integrate unit so high quality research can be performed Hospital), Andrew Lawrence (SA Pathology), clinical, epidemiological and basic science to improve the clinical care of sick babies. Oliver Schubert (Royal Adelaide Hospital), Ashleigh Smith (University of South Australia) strategies to understand the biology of early In 2016 we plan to assess cord biomarkers and David Torpy (Royal Adelaide Hospital). life adversity and explore mechanisms that that can be used with clinical features to drive poor outcomes. predict poor neurodevelopmental outcomes, through retrospective and prospective studies.

52 Robinson Research Institute Early Origins of Health and Disease Professor Julie Owens and Dr Kathryn Gatford Understanding the mechanisms underlying the early origins of health and disease and testing interventions

The early environment - before and shortly (IUGR). We aim to understand whether Group Members after birth - influences an individual’s risk individuals with growth restriction before Research Leaders: Julie Owens and of developing major non-communicable birth experience the same improvements Kathryn Gatford diseases including diabetes, cardiovascular in glucose control and insulin sensitivity as Emeritus Professor: Jeffrey Robinson disease, impaired neurological function and normal individuals when they undertake PhD Candidates: Vincent Chu, Patricia Grant, allergy. Importantly, the effects of adverse regular moderate exercise. So far we have Himawan Harryanto, Dane Horton, Damien prenatal exposures are not always permanent demonstrated adverse effects of IUGR on Hunter, Wee-Ching Kong, Ezani Mohamed or irreversible, opening the way for interventions learning and memory, which are ameliorated Jamil, Siti Sulaiman, Tulika Sundernathan, Hong in early life to improve outcomes. by the extent of postnatal catch-up growth, Liu and Amy Wooldridge Honours Student: Manpreet Kaur The Early Origins of Health and Disease suggesting interventions to promote catch group seeks to optimise the life-long health up could improve outcomes. RRI Collaborators: Jodie Dodd, Stefan of the next generation by understanding how In 2016 we will continue to evaluate adult Hiendleder, Julia Pitcher and Claire Roberts early life exposures cause long-term changes outcomes of exercise training in progeny Key collaborators: Robert Bischof and in health. The goal is to develop interventions from normal or growth-restricted pregnancies, Jane Black (Monash University), Vicki Clifton (Mater Medical Research Institute), Karen during pregnancy or in early postnatal including effects on insulin signalling to control Kind (University of Adelaide), Debbie Lawlor, life to improve health and reduce risks of glucose levels. We are also collaborating to Glenn McConell (Victoria University), Margaret non-communicable disease in the next identify mechanisms and interventions to Morris (University of NSW), Tim Moss (Hudson generation. We are also interested in defining improve metabolic and neurodevelopmental Institute), Beverly Muhlhausler (University of Adelaide), Caroline Relton (Newcastle the developmental stages at which such outcomes after other common perinatal University) and Rebecca Simmons (University of intervention strategies are most effective. exposures, including shift work during Pennsylvania) In 2015 we evaluated the metabolic and pregnancy, maternal overweight and obesity, other benefits of exercise training in later preterm birth and maternal asthma. life, after intrauterine growth restriction

Genetic Epidemiology Professor Lyle Palmer Investigating the epidemiology and genetic epidemiology of the origins of health and disease

The burden of disease in pregnancy, birth informatic and clinical disciplines to better Register regarding a South-Australian node and childhood is increasing, both clinically understand and treat important diseases. that would seek to enroll all multiple live and economically. In order to disentangle In 2015 we published in a number of high births occurring in South Australia. the complex genetic and environmental impact journals detailing our ongoing Group Members determinants of key phenotypes in genetic and epidemiological investigations Research Leader: Lyle Palmer early life and childhood, large-scale and into: adult body size and shape; adult BMI comprehensive cohort resources are required. and insulin biology; BMI across childhood; RRI Collaborators: Michael Davies, Ben Mol, Vivienne Moore and Claire Roberts The Genetic Epidemiology group seeks to educational attainment and depression; understand the genetic and environmental melanoma; obstructive sleep apnea; and the determinants of complex disorders such effects of neighborhood ‘green space’ on as preterm birth, pre-eclampsia, growth in cardiovascular outcomes. utero, and development over childhood (ie Additionally, we continued constructing a growth, lung function and blood pressure population-based genomics resource based trajectory). Our focus is on applying upon linked health data available on all live multidisciplinary approaches using combined births in South Australia. Discussions have statistical, epidemiological, genetic, molecular, also been initiated with the Australian Twins

Annual Report 2015 53 Neuromotor Plasticity and Development (NeuroPAD) Associate Professor Michael Ridding and Dr Julia Pitcher Investigating how early life events affect the development of the human brain and its ability to learn and remember, and to recover from injury or illness

Experiences throughout life constantly The NeuroPAD group aims to understand Group Members shape and rewire the brain. This occurs how experiences and injuries alter human Research Leaders: Michael Ridding and through changing the strength of existing brain motor and cognitive function Julia Pitcher neural connections and developing new throughout the lifespan, and to develop Research Fellow: Mitchell Goldsworthy connections, and is known as neuroplasticity. effective therapies and interventions to Postdoctoral Researchers: Richard Harris, Neuroplasticity underlies our ability to ameliorate the negative consequences. Brenton Hordacre and Luke Schneider learn and remember new skills, to forget During 2015 NeuroPAD continued research Paediatric Neurologist: Nicholas Smith information, and to recover from injuries to on two major projects; examining changes Rebecca Collins and the brain. While this ability is life-long, the PhD Candidates: in brain plasticity following ischemic stroke, Sam Darvishi brain is at its most plastic in fetal life and and uncovering whether preterm birth Research Assistant: Sophie Ballinger early childhood. This facilitates the rapid is associated with impairments in brain Honours Students: Ishita Lath, Sophie learning of our early development, but it also plasticity and function. Additionally, Dr makes the brain more vulnerable to adverse Richards, Robert Sadler, Sophia Sui and Mitchell Goldsworthy conducted a study to Nicollette Thornton experiences and injury in early life. During explore the possible usefulness of several this time the brain is less able to adapt RRI Collaborators: Nicolette Hodyl and neurophysiological markers for detecting Michael Stark appropriately to experiences and reduces the early cognitive impairment. ability to recover from injury in later life. Collaborators: Angela Clow and John Rothwell

Neonatal Medicine Associate Professor Michael Stark Ensuring life-long health for newborns born preterm

Events, illnesses and treatments in the neonatal brain injury, transfusion medicine, Emelia approach, and expand research newborn period can have a profound and and optimising neurodevelopmental outcome capacity with new medical, nursing and long-term effect on growth, development following preterm birth. In 2015 research allied health led research projects being and life-long health. Integrating clinical and highlights included international recognition established at the Women’s and Children’s basic science research projects is critical to of the groups early neonatal brain injury Hospital. advancing our understanding of the major and cerebral oxygen kinetics research; morbidities that complicate preterm birth, and continuation of a unique randomised control Group Members to form the basis of novel interventions to trial of washed red blood cell transfusion in Research Leader: Michael Stark improve outcomes for babies born too soon. very preterm neonates to prevent significant Clinical Partners: Chad Andersen, Ross Haslam and Andrew McPhee The Neonatal Medicine group integrates neonatal morbidity; and the entrenchment basic and clinical research to inform best of the Reggio Emeilia philosophy within the PhD Candidates: Natalie Aboustate and Amy Keir practice in the care of preterm newborns. Neonatal Intensive Care Unit. The group operates in a family-centred In 2016 the group will increase input from RRI Collaborators: Jodie Dodd, Nicolette Hodyl, Ben Mol and Claire Roberts philosophy towards the care of the newborn consumers and related stakeholders in infant, which has fast-tracked improvements setting research objectives; progress key in day-to-day care. international collaborative projects focusing The group operates within four research on evidence based transfusion practice themes: neonatal nutrition, oxygen in the neonatal population; develop new physiology with a particular focus on research partnerships focusing on the Reggio

54 Robinson Research Institute A/Prof Michael Stark in the Neonatal Intensive Care Unit

Annual Report 2015 55 Molecular Immunology Associate Professor Simon Barry Understanding the molecular basis for immune tolerance

How does a healthy immune system balance The group is investigating the molecular Group Members a swift response to fight off pathogens, with mechanisms that switch genes on and off Research Leader: Simon Barry maintaining tolerance to harmless challenges to control T cell function, and are focused Postdoctoral Research Fellows: Veronika such as food, normal body tissues, and the on a master switch gene named FOXP3, Bandara, Cheryl Brown, Christopher Hope and fertilised egg in pregnancy? A rare but vital which orchestrates the function of Treg Timothy Sadlon subset of immune cells known as regulatory cells. A key step has been identifying all of Research Assistants: Arunesh Mohandas and T cells (Tregs) is believed to play a critical the regions of the genome that FOXP3 can Batjargal Gundsambuu role. Tregs are essential for immune tolerance, bind to, and therefore potentially regulate. Technical Officer: Sylvia Nobbs and defects are implicated in autoimmune In order to understand how mutations alter PhD Candidates: Kristen Malatesta and disorders, cancer and other diseases. immune tolerance we have developed a new Vincent Wong technology that is able to map interactions at The Molecular Immunology group seeks to Honours Student: Ying Ying Wong characterise Tregs under normal conditions, long distances that form as a result of DNA Affiliate Member: Stephen Pederson with a view to understand what goes wrong looping. This will identify the gene targets of RRI Collaborators: Jennifer Couper, Wendy with these cells in immunological disorders. point mutations associated with disease, by Ingman, Sarah Robertson and Darryl Russell Using state of the art molecular biology, mapping them to the regions of the genome the group investigates the genes involved that they interact with. External Collaborators: Marc Beyer (LIMES), Dan Campbell and Thomas Duhen (Benorya), in immune function in Tregs, and aims to Greg Goodall (Centre for Cancer Biology), Randall understand how key genes are regulated to Grose (SAHMRI), Giovanna Lombardi (King’s control normal function. College London), Kellie MacDonald (QIMR), Joachim Schultze (LIMES), Raymond Steptoe (Diamantia Institute), Tim Tree (King’s College London) and Kathryn Wood (Oxford University)

Transplantation Professor Toby Coates Generation of novel beta cell replacement therapy to treat type 1 diabetes

Type 1 diabetes is a major cause of morbidity with collaborators. This is a potentially Group Members and mortality in young Australians. It is exciting infinite source of beta cells for Research Leader: Toby Coates caused by autoimmune destruction of transplantation and the treatment of type-1 Principal Medical Scientist: Christopher the pancreatic beta cells, the only insulin diabetes. Defined differentiation protocols Drogemuller secreting cell type in the body. have been developed and the resulting Senior Medical Scientist: Svjetlana Kireta cells characterised for their insulin-secretion The Transplantation group performs clinical Senior Postdoctoral Researchers: Darling capacity. The group also continued to islet cell transplantation as a part of South Rojas-Canales and Plinio Hurtado work on novel means to alter the immune Australia’s only Nationally Funded Centre for Jodie Nitschke and system and protect pancreatic beta cells by Senior Scientists: Islet Cell Transplantation. This is currently the Danielle Penko only treatment option for type 1 diabetes with exploring the IGF-II pathway and transducing pancreatic beta cells with programmed death Clinical Researchers: Rob Carroll, Shilpa hypoglycemic unawareness. In the laboratory Jesudason and Chen Au Peh we investigate new sources of insulin-secreting ligand-2 (PDL-2), a T cell death ligand which Technical Officer: Julie Johnston tissue for transplantation as well as novel deletes both allo-reactive and auto reactive T PhD Candidates: Ernesto Hurtado Perez, Bron ways to protect transplanted pancreatic cells. Additionally we successfully 3D printed Lett, Sebastian Stead and Kisha Sivanathan beta cells from destruction by the immune human islets (with EPC) in a supporting system. This involves 3D printing, material ink structure to enhance islet function and RRI Collaborator: Mark Nottle science and use of specialized endothelial survival following transplantation. We hope External Collaborators: Shane Grey (Garvan progenitor cells (EPC) and T regulatory cells. through this work to deliver novel treatments Institute of Medical Research) and Claudine for children and adults affected by this Bonder (University of South Australia) During 2015 we generated insulin-secreting increasingly common disease. tissue from porcine embryonic stem cells

56 Robinson Research Institute Diabetes Professor Jennifer Couper Preventing type 1 diabetes and its complications

The incidence of type 1 diabetes in childhood collaborations. This builds upon the NHMRC/ Research Officer: Roger Gent has increased worldwide, doubling in Australia JDRF Centre of Research Excellence for the Research Nurses: Sarah Beresford, and over the last 20 years; suggesting the modern Protection of Pancreatic Beta Cells. We were Meredith Krieg changing environment plays a role in type 1 invited by the TEDDY consortium in US to PhD Candidates: Jemma Anderson, Jessica diabetes. The specific environmental factors attend their closed meeting to best align our Phillips, Priya Augustine that contribute to and protect against type work to global efforts aimed at preventing Masters Student: Myf Geyer 1 diabetes are unknown, although it is likely type 1 diabetes. Additionally, we discovered RRI Collaborators: Simon Barry, Jodie Dodd that exposures in pregnancy and very early the importance of salt intake and exercise in and Lynne Giles life are critical. Children with type 1 diabetes blood vessel health in children with diabetes; External Collaborators: Fergus Cameron have an increased lifetime risk of heart, completed studies uncovering how the (Royal Children’s Hospital), Peter Colman kidney, and eye disease due to damage to stomach functions in type 1 diabetes and (RHM), Maria Craig (University of Sydney), their blood vessels. the affect on blood glucose control; and Elizabeth Davis (Telethon Kid’s Institute), David presented the results of the first randomised Dunger (University of Cambridge), Josephine The Diabetes group conducts clinical and Forbes (University of Queensland), Kim laboratory research focusing on: controlled trial of the blood vessel benefits Donaghue (University of Sydney), Len Harrison of the medication metformin in adolescents >> Environmental exposures that drive diabetes (WEHI), Michael Horowitz (Royal Adelaide with type 1 diabetes. Hospital), Tim Jones (Telethon Kid’s Institute), >> Immune regulatory function Tony Papenfuss (WEHI), Joe Petrosino (Baylor College), Bill Rawlinson (University of New >> The protection of blood vessel health in Group Members Research Leader: Jennifer Couper South Wales), Chris Raynar (Royal Adelaide children and adolescents Hospital), Richard Sinnott (University of In 2015 the ENDIA pregnancy to birth cohort Clinical Partner: Alexia Pena Melbourne), Peter Vuillermin (Deakin University) received $8 million from JDRF Australia and Centre of Research Excellence Project and John Wentworth (WEHI) the Helmsley Charitable Trust to expand Manager: Megan Penno recruitment and data acquisition across ENDIA Study Project Manager: Rebecca Australia, and to develop international Thomson

Annual Report 2015 57 Developmental & Genetic Immunology Professor Antonio Ferrante Cellular signalling pathways in childhood allergy and inflammatory disorders

Children afflicted with autoimmune and In 2015 our group focused on allergy Group Members inflammatory diseases experience life-long development in children. The results suggest Research Leader: Antonio Ferrante pain and disability. A powerful approach that the protein kinase C (PKC)zeta isozyme Principal Scientists: Charles Hii and Nick Gorgani in the prevention and management of regulates T cell development from an Clinical Researchers: Tatjana Banovic and inflammatory reactions is to target the immature Th2 lymphocyte cytokine profile Jovanka King intercellular and intracellular communication to a mature Th1 profile. Importantly, PKC Postdoctoral Researcher: Alex Quach signals that dictate aggressive cellular zeta levels in cord blood are increased by behavior in the tissues of patients with omega 3 fatty acid supplementation, most PhD Candidates: Usma Munawara, Marwah Basin Khlah and David Shields disorders such as allergy, juvenile arthritis, likely through an epigenetic action. Thus diabetes and cystic fibrosis. The key the immaturity of the PKCzeta expression RRI Collaborators: Jennifer Couper, Jozef pathways involved remain obscure, in neonates ensures phenotypic plasticity Gecz and Declan Kennedy which limits advancements in therapeutic during early immune development. These External Collaborators: Catherine Abbott developments and applications. findings could lead to devising nutrient (Flinders University), Paul Anderson (University of South Australia), Peter Hofmann (University of The Developmental and Genetic Immunology supplementations for the prevention of Adelaide), Suresh Mahaligam (Griffith University), group aims to identify signaling molecules allergy in childhood. Howard Morris (University of South Australia), that regulate immune cellular functions in Our next steps are to extend this research Susan Prescott (University of Western Australia), Susanna Proudman (SA Health) and Kanchana inflammation. We seek to categorise the into the epigenetic control of immature T Usuwanthim (Naresuan University) interactive network between the intercellular cell in neonates in relation to functional signaling inflammatory mediators, their receptors phenotypes relevant to allergic and and the intracellular signaling pathways, autoimmune- inflammatory diseases. which control the initiation, manifestation and resolution of the inflammatory disease.

Human cortical neural stem cells. Claire Homan & Prof Jozef Gecz

58 Robinson Research Institute  Neurogenetics Professor Jozef Gecz Investigating the genetics and biology of human neurological disorders

Intellectual disability, epilepsy, autism and neurodevelopmental disorders listed above. Group Members cerebral palsy are among the most frequent In intellectual disabilities, they identified and Research Leader: Jozef Gecz developmental disabilities, together affecting functionally characterised multiple novel genes Postdoctoral Fellow: Lachlan Jolly 4% of children. Over the last decade major and mutations, namely mRNA export complex Research Officer: Mark Corbett, Duyan Pham advances have occurred in the understanding and THOC2, cohesin complex and STAG2, and Raman Sharma of the genetic architecture of these disorders, histone modifications KDM5C or RNA Clinical Researcher: Bregje van Bon with thousands of novel genes and tens of modification by FTSJ1. In epilepsies they thousands of mutations identified. Translating proposed a fundamentally new hypothesis of Research Assistants: Renee Carroll, Alison Gardner, Brett Johnson, Marie Shaw and Annie genetic variation to the understanding of action of neurosteroids on GABA receptors Sun the biology, cell and molecular pathways in early infantile epileptic encephalopathy involved in these disorders is crucial for due to mutations in the PCDH19 gene. This PhD Candidates: Deepti Domingo, Claire Homan and Stanley Tan improved diagnosis, management and research led to a Phase II clinical trial that is treatment of these conditions. currently underway looking at ganaxolone RRI Collaborators: Alastair MacLennan, Cheryl Shoubridge and Paul Thomas The Neurogenetics group seeks to identify supplementation in PCDH19 EIEE. External Collaborators: Sam Berkovic and interpret novel genetic variations The group’s focus over the next year is to (University of Melbourne), Evan Elchler associated with paediatric neurological implement high quality functional assays (Washington University), Dan Geschwind disorders, intellectual disability, epilepsy, to define the effects of genetic variation (University of California, Los Angeles), Vera autism and cerebral palsy. on function of numerous genes involved in Kelscheuer (Max Planck Institute), Ingrid Scheffer (University of Melbourne) and Miles In 2015 the group made several major normal neuronal development. Wilkinson (University of California, San Diego) discoveries across all domains of the

 Allergy and Vaccine Safety Associate Professor Michael Gold Michael leads two research groups in the areas of allergy and vaccine safety

Prevention and management of analysed, and will provide an evidence base time surveillance system for all vaccines in all food allergy and allergic disease for feeding guidelines for infants and mothers ages. These findings will inform a number of both nationally and internationally. current TGA surveillance activities. In westernised and developed countries there is an evolving epidemic of allergic Improving monitoring of Group Members disease that primarily affects children vaccine safety Research Leader: Michael Gold under 5 years of age. Recent studies have Research Coordinator: Gabriella Lincoln shown that one in ten Australian children When a new vaccine or seasonal flu vaccine aged 12 months have an egg allergy - the is licensed for use, safety information about Research Officer: Alexis Wheeler highest documented rate in the world. The potential rare reactions is incomplete. The Research Nurses: Christine Health and Mary Allergy group’s goal is to understand the current system of surveillance for these Walker immunological mechanisms associated events lacks the capability to detect these PhD Candidate: Karen Best, Katherine with the prevention and management of reactions in a timely way. The Vaccine Safety Duszynski and Merryn Netting group aims to address the current deficiencies food allergy, and to understand the role of RRI Collaborators: John Lynch and Helen early-life egg exposure in the development of in surveillance by exploring health provider Marshall reporting, active sentinel surveillance and tolerance to egg. External Collaborators: Katie Allen (MCRI), e-Health, including data linkage. During 2015 multiple trials progressed Annette Braunack-Mayer (University of Adelaide), Maria Makrides (SAHMRI), Nicole looking at early versus late introduction Current projects by this group seek to link data from the Australian Childhood Pratt (University of South Australia), Susan of egg into an infant’s diet, the possible Prescott (Telethon Kid’s Institute), Patrick Quinn therapeutic benefits of heat-treated egg, and Immunisation Register with the National (WCHN) and Mimi Tang (MCRI) fish oil supplementation in pregnancy. These Death Index and state-based morbidity data, studies have now completed, are being and have developed an SMS-based real

Annual Report 2015 59 Critical and Ethical Mental Health Professor Jon Jureidini Promoting safe, effective and ethical research and practice in mental health

Misinformation about mental health The Critical and Ethical Mental Health to children and adolescents, adverse and mental disorders misleads health research group conducts research events, and de-prescribing for older people. professionals, the media, the public, and (particularly critical appraisal and meta- Additionally, we continued our work on governments, jeopardising the rational research), teaching, and advocacy in mental citation distortion/misrepresentation, social allocation of billions of dollars of taxpayers’ health, to promote safer, more effective, and determinants of mental health and suicide, money every year. more ethical research, policy and practice in and ethical issues related to protection of There is clear evidence that: mental health. participants in clinical trials. In 2015 our main focus was the re-analysis >> Psychiatric research has been biased Group Members of an infamous randomised controlled trial and misrepresented by pharmaceutical Research Leader: Jon Jureidini industry funding of antidepressants in adolescents (GSK’s Study 329), undertaken as part of the RIAT Research Fellow: Anne Tonkin >> Additional biases and misrepresentations (restoring invisible and abandoned trials) Postdoctoral Researcher: Melissa Raven have been used to support a range of project. With our collaborators, we found Elia Abi-Jaoude vested interests External Collaborators: that paroxetine and imipramine are not safe (University of Toronto), David Healy and Joanna >> Social determinants of mental health have for the treatment of major depression in Le Noury (Bangor University), Barbara Mintzes (University of Sydney), John Nardo (Emory been neglected in favour of biological adolescents, with the previous published factors and individual characteristics University), Patrick Russell (Royal Adelaide report misrepresenting the findings. Hospital) and Catalin Tufanaru (University of >> The voices of people who live with mental We commenced collaborative research on Adelaide) illness have been marginalised antipsychotics, focusing on: prescribing

Sleep Disorders Professor Declan Kennedy Understanding the morbidity of sleep disorders and their effect on child development

Sleep disordered breathing in children is During 2015 our team had three main Project Manager: Anna Kontos common, with as many as 10% of children objectives; to assess cardiovascular, Manager Sleep Disorders Unit, WCH: reported to snore on a regular basis. The autonomic nervous system and inflammatory Yvonne Pamula severity of sleep disordered breathing ranges response in young children awaiting PhD Candidates: Jessica Carlson-Jones and from primary snoring, to the more severe adenotonsillectomy; post operative Benlee Yap obstructive sleep apnea and a reduction neurocognitive evaluation of those children Technical Officers: Alex Chatburn, Scott in blood oxygen levels and increase in who had previously been assessed and Coussens, Tyler Grummett, Pauli Pignata, Tony carbon dioxide profile. Even relatively mild treated with adenotonsillectomy; and to Pignata and Kate Sutherland condition has significant daytime effects on continue to recruit participants into a multicentre Administrative Assistant: Kostas Kontos neurocognitive domains and behaviour. study looking at the efficacy of adenoton- Honours Student: Charmaine O’Reilly sillectomy treatment for sleep disordered The Sleep Disorders group seeks to RRI Collaborators: Jennifer Couper and understand the impact of poor sleep on breathing in young preschool children. Antonio Ferrante the health of the developing child. Our Group Members External Collaborators: Mathias Baumert multidisciplinary team of researchers primarily (University of Adelaide), Roger Gent (Women’s Research Leader: Declan Kennedy focuses on the effects of sleep disordered and Children’s Hospital), Quenten Schwarz breathing on neurocognition, cardiovascular Co-Research Leaders: Kurt Lushington and (University of South Australia) and Scott James Martin Willoughby (University of Adelaide) development, and immune, metabolic and nervous system function. Research Affiliates: Mark Kolher and David Wabnitz

60 Robinson Research Institute BetterStart Professor John Lynch Providing children with the best start in life

Health and developmental gaps appear early and development, particularly among lower Group Members in life, with significant variability between socio-economic communities. Research Leader: John Lynch children. To provide all children with the best Our research in 2015 spanned data linkage Postdoctoral Researchers: Angela Gialamas, start to life, early intervention is crucial to studies of perinatal factors and learning Rhiannon Pilkington, Alyssa Sawyer and Lisa improve health and developmental trajectory, outcomes, the importance of quality childcare, Smithers especially for disadvantaged children. the role of self-regulatory abilities on academic Statistician: Murthy Mittinty The Better Start Child Health and achievement, comparing contrasting study Senior Lecturer: Catherine Chittleborough Development group aims to understand how designs to improve causal inference, and the Affiliates: Amelia Maika and Anna Pearce genetic, social and environmental factors prediction of poor child development from RRI Collaborators: Gus Dekker, Nicki Hodyl, interact to enhance children’s physical, routinely collected perinatal data. Ben Mol, Claire Roberts and Michael Sawyer mental, social and emotional health, and their In 2016 we will commence work on our External Collaborators: Aluiso Barros cognitive ability and academic achievement. newly funded NHMRC Centre of Research (University of Pelotas), Deborah Cobb-Clark Our focus is on interventional epidemiology Excellence; EMPOWER: Health systems, (University of Sydney), George Davey Smith and spanning health and development from the adversity and child well-being. This CRE will Neil Davies (University of Bristol), Pernille Due (Danish National Public Health Institute), Steve perinatal period into adolescence. We focus spearhead development of several pragmatic Guthridge (Northern Territory Government), on assembling evidence for a diverse range randomised controlled trials, and will build Louise Jorm (University of NSW), Catherine of interventions related to perinatal health, even greater capacity in data linkage and Law (Institute of Child Health), Stefi Schurer parenting, childcare, diet, self-regulation routine cost effective evaluation of health (University of Sydney) and Sven Silburn and cognitive ability to improve child health care and education services for children. (Menzies Institute)

Vaccines and Infectious Diseases Associate Professor Helen Marshall Improving immunisation strategies to optimise protection for babies, children and pregnant women against serious infectious diseases

Infections such as whooping cough, We found strong support for immunisation Research Nurses: Chris Heath (Senior), Louise meningococcal disease and influenza still programs for pregnant women, but found Goodchild, Jane Tuckerman and Mary Walker cause death and disability in young infants. lower uptake of vaccines in pregnant women PhD Candidate: Bing Wang During the last whooping cough epidemic with English as a second language. We used RRI Collaborators: Simon Barry, Gus Dekker, 10 babies died from the whooping cough these findings to implement interventions Jodie Dodd, Mike Gold, John Lynch, Andy infection (pertussis) with most of these such as midwife delivered pertussis and McPhee, Ben Mol and Claire Roberts babies under 4 months of age. influenza immunizations, and have translated External Collaborators: Ross Andrews (Charles Darwin University) Hossein Afzali The Vaccines and Infectious Disease group brochures about vaccines in pregnancy. Translation of our research findings has and Annettee Braunack-Mayer (University aims to improve protection and outcomes of Adelaide), Helen Bedford (UCL Institute for children from serious infections. Our assisted in improving uptake for the pertussis of Health, UK), Jim Buttery (University of research combines studies of the burden vaccine from 20% to 82% at the Women’s Melbourne), Margie Danchin (Murdoch of disease from serious infections such and Children’s Hospital. Children’s Research Institute), Katherine Edwards (Vanderbilt University), Stephen as meningococcal disease, influenza and Group Members Lambert (Queensland Children’s Medical pertussis, clinical trials of new vaccines to Research Leader: Helen Marshall Research Institute), David Lynn (SAHMRI), prevent these infections, and evaluation of Kristine Macartney and Peter McIntyre community acceptance of immunisation Clinical Researchers: Sue Evans and Suja (University of Sydney), Terry Nolan (University Mathew of Melbourne), Amy Pollard (Oxford University), programs to inform policy and practice. Postdoctoral Researcher: Joanne Collins and Julie Ratcliffe (Flinders University), Peter In 2015 with our interstate collaborators we Adriana Parrella Richmond (University of Western Australia), showed that immunising infants in the first Geraint Rogers (SAHMRI), Matthew Snape Research Managers: Michelle Clarke and few days of life against whooping cough is (Oxford University), Rebecca Tooher (University Susan Lee of Adelaide), Steve Wesselingh (SAHMRI), safe and likely to give good protection at a Research Coordinators: Mark McMillan, Nicholas Wood (University of Sydney) and time infants are most vulnerable to infection. Kathryn Riley and Jane Tidswell Gregory Zimet (Indiana University)

Annual Report 2015 61 Cystic Fibrosis Associate Professor David Parsons Development of gene and cell therapies, and novel outcome measures for cystic fibrosis airway disease

Cystic fibrosis is a relatively common During 2015 the group completed studies Research Assistants: Maged Awadalla and chronic and early-fatal genetic disease. It demonstrating that stem cell compartments Nathan Rout-Pitt is autosomal recessive and occurs when in cystic fibrosis and normal mice are PhD Candidates: Ryan Green and two faulty copies of a gene known as different, and treatment can be targeted Harsha Padmanabhan CFTR are inherited, one from each parent. with the group’s unique gene vector delivery Honours Student: Alexandra McCarron In many sufferers it reduces lifespan to method. The group developed a cell therapy Administrative Assistants: Bernadette Boog young adulthood, mostly through its steady research stream involving isolation and gene and Paula Mitchell destruction of the lungs and failure of other correction of these stem cells, and tested RRI Collaborators: Simon Barry, Jill Muhling, organ systems. the use of CFTR competent human amnion Mark Nottle and Paul Thomas The Cystic Fibrosis group aims to develop epithelial cells as a potential cell therapy External Collaborators: Ivan Bertoncello an effective genetic therapy to prevent or for CF. Additionally, the synchrotron studies (Melbourne University), Ric Boucher (University cure cystic fibrosis airway disease. Research using a combined airway surface liquid of North Carolina), Andrea Fouras (Monash depth and mucociliary clearance assessment University), Albert Juhasz (University of SA), activities are focused on achieving effective Tim Kuchel (SAHMRI), Ivan Lee (University of lentiviral CFTR vector gene delivery and technique continued, and proof-of-principle SA), Maria Limberis (University of Pennsylvania), transduction of airway stem cells in situ large animal tissue imaging studies at the Jonathan McQualter (University of Melbourne), to enable extended gene expression. Australian Synchrotron occurred. Kaye Morgan (Monash University), Karen Siu (Monash University), Euan Smith (University of The effectiveness of pharmaceutical and Group Members SA), Rob Tarran (University of North Carolina), genetic therapies for cystic fibrosis is hard Research Leader: David Parsons Kentaro Uesugi (JSDTI), Naoto Yagi (JASRI) and to quantify, so the group is also developing Roger Yazbek (Flinders University) rapid and accurate outcome measures for the Postdoctoral Research Fellow: Martin Donnelley assessment of the effects of novel therapies. Postdoctoral Researchers: Patricia Cmielewski, Nigel Farrow and Chantelle McIntyre

Research and Evaluation Professor Michael Sawyer Developing and evaluating new population-level interventions for the health and wellbeing of mothers and children

Optimal physical and mental health Australia to develop and evaluate new Group Members is important for strong and resilient population-level interventions that have the Research Leader: Michael Sawyer communities. Unfortunately many mothers potential to improve the health and wellbeing PhD Candidates: Amy Kaim and Sara Pfeiffer and children experience sub-optimal of the community. The effectiveness of Research Assistants: Olivia Carger, Christine health and wellbeing; 13% of new mothers interventions is assessed in clinical trials Mpundu-Kaambwa, Jacqueline Peters and experience significant symptoms of conducted as part of routine service delivery Christy Reece depression, while at any single point in time in the community child health service. Project Officer: Jennifer Clark 14% of children and adolescents experience In 2015 Michael and colleagues trialled the John Lynch, Ben Mol and mental health problems. What is concerning RRI Collaborators: eMums program, a new intervention that Claire Roberts is the repeated finding that only a minority combines the skills of community nurses and of those experiencing problems receive help the Internet to reach large numbers of from professional services. There is a strong mothers. The effectiveness of this intervention requirement to develop new cost-effective was evaluated through a pragmatic preference interventions that will improve the health and randomised controlled trial conducted within wellbeing of mothers and their children in the the community child health service in South general community. Australia. The final follow-up assessments for The Child and Adolescent Mental Health the trial were completed in late 2015 and the group works closely with clinical staff in the analysis of results and further development community child health service in South will occur in 2016.

62 Robinson Research Institute Molecular Neurogenetics Associate Professor Cheryl Shoubridge Assessing molecular targets for therapeutic interventions in X-linked intellectual disabilities

Approximately 1 in 50 people worldwide seizures. We identified submicroscopic Group Members suffer from intellectual disability, and the changes to the structure of the Research Leader: Cheryl Shoubridge cost to Australia is estimated at $14 billion X-chromosome harbouring genes, that Postdoctoral Researchers: Matilda Jackson annually. Intellectual disability is described as when in excess cause intellectual disability and Kristie Lee significantly impaired cognitive functioning, and behavioural disturbances. We utilised PhD Candidate: Tessa Mattiske coupled with a deficit in adaptive behaviour next generation sequencing techniques to Research Officer: Susan Hinze with onset before age 18. In many cases, investigate changes to gene expression in therapies to prevent or ameliorate the the developing brain of mouse modes of Research Assistant: Ching Moey consequences of these genetic disorders are genetic mutations, and identified networks Honours Student: Olivia Dearsley not yet available. or pathways of genes that may contribute as RRI Collaborators: Jozef Gecz and Claire Roberts early triggers. The Molecular Neurogenetics group seeks External Collaborators: Gaelle Friocourt to understand the molecular mechanisms In 2016 we will undertake an exciting new (INSERM), Nigel Jones (University of and impact of naturally occurring mutations direction for our research by establishing a Melbourne), Jeffrey Noebels (Baylor College of Medicine) and Terance O’Brien (University of in genes causing intellectual disability and genome-wide molecular and corresponding Melbourne) seizures, with the aim of developing effective cellular basis of improvements in outcomes therapies to improve the quality of life for for mice with mutations in the ARX gene, patients and their families. following treatment with neurosteroids at In 2015 we continued to identify genetic early stages after birth. contributors to intellectual disability and

Annual Report 2015 63 Rebecca Wilson, Tara Crawford, Amy Garrett and Alexandra McCarron

Fostering Research Excellence

To continue to be a world-leader in the areas of reproduction, pregnancy and child health research, the Institute invests in people, networks and facilities.

Core Facilities The Institute’s core facilities enhance research capability, and deliver more efficient, cost effective and productive research.

Adelaide Research Assay Bioinformatics Facility Biostatistics Facility Facility (ARAF) Dr Jimmy Breen Dr Nancy Briggs Professor David Kennaway Bioinformatics The Biostatistics Facility The Adelaide Research enhances the Institute’s provides expert advice Assay Facility provides capability in next- in research design, specialised, high- generation sequencing statistical analysis throughput and and systems biology and presentation of high-sensitivity assays approaches to basic data. This service of physiologically science and clinical complements important analytes for research investigating researcher expertise academic researchers human and animal reproduction and through the provision of effective statistical and commercial customers Australia-wide. development. Strategies to design and analysis that delivers clear and precise ARAF provide services and consultation analyse transcriptome, deep-sequencing, answers to their questions. for specialised measurements of analytes genome and proteome data sets are In 2016, biostatistics will continue to be in human or animal biological fluids or cell a powerful approach to generating afforded to research leaders to improve the culture / tissue extracts. These cover broad fundamental knowledge on systems and likelihood of securing future NHMRC grants research areas including but not limited to processes in biology and disease. and to provide general research design advice endocrinology, neuroscience, physiology, Bioinformatic methods allows researchers for continuing and new research projects. immunology, pathology and cancer. to follow a complementary path in their In 2015 the facility analysed plasma and research that promotes exploratory analysis saliva samples for 4 groups in the RRI, and hypothesis generation, as well as University of Adelaide researchers at focused analysis of previously identified Roseworthy, and groups at SARDI, UniSA, targets of interest. This can provide stronger and Flinders, Melbourne, Monash and and more clinically applicable results from Sydney Universities. a research program, and yield publication, funding, and patent outcome improvement.

64 Robinson Research Institute Dr Tod Fullston

Career Development Fellowship This fellowship funds the salary of an ‘Emerging Star’ early-career researcher for one year, supporting career development to enable competitiveness for an NHMRC Career Development Fellowship or similar. In 2015 the fellowship was awarded to Dr Tod Fullston, and will progress his research investigating how paternal obesity contributes to developmental programming, impairing the metabolic and reproductive health of two generations of offspring.

Cohort and Intergenerational Gene Silencing and SA Genome Editing Facility (SAGE) Studies Facility (CIS) Expression Facility (GSEx) Professor Paul Thomas Professors Jodie Dodd and Julie Owens Dr Jill Muhling The SA Genome The Gene Silencing Editing Facility uses and Expression cutting edge genome Facility provides gene editing technology to manipulation services to generate mutant mice Australian researchers for a wide range of in a fully equipped applications. Utilising PC2 laboratory. The new CRISPR/Cas9 facility offers custom system technology, the facility offer a number The Cohort and Intergenerational Studies production of lentiviral, AAV and retroviral of services including generation of custom Facility underpins the strategic utilisation vectors, and stock viruses for purchase by knock out, point mutation and tagged alleles. of unique Adelaide generated longitudinal the microlitre. In addition, customers can SAGE’s services are highly accessible studies - both cohorts and randomised access CRISPR, non-viral vector and other offering a significantly reduced cost and fast controlled trials - established before or at birth, cell and molecular biology services. turnaround compared to traditional ES cell or in childhood. CIS and its resources enhance In 2015, GSEx increased production and has methods - providing researchers an edge collaborations, support novel interrogations now produced over 150 viral vectors since when applying for grants and publishing in of accrued data and enable pooling of studies. the core was established. These viruses have high impact journals. This will advance research to address been used to infect immortal cell lines and Since operations began in 2014, 13 mutant complex challenges in reproductive and primary cell cultures. GSEx demonstrated lines have been produced with another paediatric health, now and into the future. the effectiveness of both lentivirus and AAV seven projects underway. In 2016 SAGE CIS aims to align, maintain and enhance in mouse cumulus oocyte complexes and aims to grow its understanding of CRISPR/ cohorts, databases and related resources, cancer cell lines in rodents and humans. Cas9 and its variants, as well as expanding stimulate research that addresses prioritised Additionally, the facility demonstrated services on offer to include production of complex challenges in reproductive and robust reporter expression following human conditional alleles. paediatric health, and increase participation in T-cell infection. national and international consortia. This will lead to increased publications in high quality journals and international invitations to present findings, thereby ensuring wide dissemination of findings to an international audience.

Annual Report 2015 65 RRI Postdoctoral Fellow in Global Health For the first time in 2015, the Institute partnered with the University of Adelaide’s Faculty of Professions to offer a fellowship for research specifically focusing on global health problems and solutions. The inaugural fellowship was awarded to Zohra Lassi to progress her research on the early life origins of non-communicable diseases, focusing on developing countries in the Asia-Pacific region.

Investing in People and High Impact Paper Funding Pr of Stephen Tong, University of Melbourne. Publishing in high impact journals is a Building Capacity Host: Professor Ben Mol leading factor in research success and RRI delivers a suite of programs and career development. This program provides Dr Thomas Ohnesorg, Murdoch Children’s scholarships to build knowledge, expertise financial support to enable the publication Research Institute. and leadership skills in our members. In of research findings into prestigious journals Host: Prof Ray Rodgers 2015 our investment in building research that attract an international, interdisciplinary capability included the following: A/Pr of Laura Parry, University of Melbourne. audience. It provides heightened credibility Host: Prof Claire Roberts and esteem to our research achievements. Investment for Success Dr Kirsty Walters, ANZAC Research In 2015 eight members received funding for Institute, University of Sydney. This program aims to increase the Institute’s their high impact publications. Host: A/Prof Rebecca Robker NHMRC funding by developing highly A/Pr of Vicky Flenady, competitive (but as yet unfunded) project High Performance Researcher grant applications, into more competitive Mater Medical Research Institute, University applications for the 2016 round submission. Facilitated by an external specialist, this of Queensland. new program seeks to up-skill researchers As a seed funding program it serves Host: Prof Ben Mol by providing them with the tools required to to enable proof-of-concept studies, Dr Andrew Pask, University of Melbourne. forge a successful career in research. This experiments or analysis, to ensure rapid Host: A/Prof Jeremy Thompson and Dr is achieved through a series of professional publication of a pivotal paper or increase Hannah Brown development workshops, and external scientific quality, significance and innovation. support for the Institute’s early and mid Dr Christopher Slape, Monash Institute of 2015 recipients: career researchers. Medical Research. >> A/Prof Simon Barry Host: Dr Hannah Brown >> Prof Michael Davies Visiting Speakers Dr Douglas Gibson, The Queen’s Medical Research Institute, University of Edinburgh, UK. >> Prof Jodie Dodd The Visiting Speakers Program supports Host: Prof Sarah Robertson >> Prof Antonio Ferrante external research leaders to visit the Institute, and encourages collaboration between A/Pr of Hannah Landecker, Institute for >> Prof Julie Owens Institutions, providing insight and new Society and Genetics, UCLA, USA. >> A/Prof Rebecca Robker perspectives on our research priorities. Host: Dr Megan Warin >> A/Prof Jeremy Thompson In 2015 the following visitors were supported Dr Amanda Sferruzzi-Perri, Dr Jenna Haverfield, Centre de Recherche University of Cambridge, UK. du Centre Hospitalier de l’Université de Host: Prof Claire Roberts and Prof Sarah Montréal, Canada. Robertson RRI Host: A/Prof Darryl Russell & Dr Hannah Dr Patrick Western, Monash Institute of Brown Medical Research. Host: Prof Sarah Robertson

66 Robinson Research Institute Cassandra Carbone Jeffrey Robinson Honours Scholarship

In 2015, the Institute awarded the Jeffrey “My plan now is to finish my medical degree, Robinson Honours Scholarship to Cassandra and then complete my PhD in this same Carbone. group. Long term I’m interested in pursuing Cassandra’s interest in fertility led her to a career in obstetrics and fertility medicine.” major in reproductive health during her Cassandra was honoured and humbled to undergraduate degree. During this time, receive a scholarship named after one of her her passion for helping women to achieve role models, a healthy pregnancy and baby increased, “The scholarship allowed me to completely and she went on to undertake an Honours dedicate my time to my degree without degree in Dr Michelle Lane’s Gamete and having to manage part-time work. I have Embryo Biology group on the project since been accepted into a medical school “I was really excited Metabolic and molecular determinants of where a portfolio was required, and I strongly embryo viability. believe this scholarship was an influential by the results from Currently it is difficult to select the best single factor in me being selected.” embryo to transfer to women undergoing As an ambitious young female in the early my Honours year. I assisted reproduction. To address this, stages of a career in research, Cassandra believe this research will Cassandra’s project investigated novel non- felt privileged to undertake her research invasive approaches for embryo selection. within the Robinson Research Institute. Specifically, she assessed metabolic markers ultimately help women “One of my favourite aspects of my honours of embryo metabolism in order to determine year was having the opportunity to listen to if results were a reflection on the embryo’s (particularly those and learn from inspiring female researchers health and chromosomal status. leaving pregnancy until such as Dr Michelle Lane, Dr Deirdre Zander- Cassandra’s results were promising, Fox, Prof Sarah Robertson and Prof Clare later) to conceive and demonstrating that reactive oxygen species Roberts (just to name a few). I too hope to (ROS) production and trends in glucose uptake follow and become a leader in my research go on to give birth to appeared to be promising measures of embryo field in the future.” viability. Further research will continue to healthy babies.” refine her measures and techniques. Cassandra was supervised by Dr Michelle Lane, Dr Deirdre Zander-Fox and Dr Tod Fullston.

Annual Report 2015 67 Innovation Seed Funding This pilot program supports early and mid-career researchers to collaborate across research groups and themes and to explore novel research questions. Its goal is to harness and progress these ideas towards competitive, fundable research that addresses significant knowledge gaps. This program supported seven projects in 2015, bringing together 20 researchers. The following highlights the story and progress of one of the funded projects:

Dr Alice Rumbold Life Course and Intergenerational Health group

Dr Alice Rumbold teamed up with Dr Lisa Moran, Prof Michael Davies and Prof Vivienne Moore to initiate the project Exploring the relationship between maternal characteristics and major birth defects. Congenital anomalies, including anatomical malformations and chromosomal abnormalities, occur in up to 5% of babies born in Australia, and are the leading cause of fetal and neonatal death. Of those who survive, there are often life-long consequences, including impaired health and wellbeing of the child, significant health and educational costs, and severe impact on the families involved. This project will investigate the extent to which maternal factors such as age, diabetes and hypertension in pregnancy are contributing to these anomalies, with the long-term aim of developing targeted screening and education for affected women of reproductive age. The project will harness Dr Rumbold’s skills in quantifying risk factors for adverse perinatal outcomes, together with Dr Moran’s understanding of the mechanisms underlying poor cardiometabolic health in pregnancy, Professor Davies’ knowledge of the aetiology of birth defects and Professor Moore’s advanced analytical expertise including examination of rare outcomes to delineate the risk factors associated with specific classes of birth defects.

Exchange Program Prof Didier Dewailly, Endocrine, Mentoring Program Gynaecology and Reproductive Medicine, The Exchange Program seeks to build Lille University Hospital, France. Each year the Institute runs a year-long collaborations with international researchers mentoring program, matching senior RRI Host: Prof Rob Norman - to expand the international profile of the researchers with early or mid-career Institute - with the aim of increasing research Hosts to Robinson Research researchers. This program seeks to capacity and facilitating access to international Institute Members strengthen networks, build relationships, funding, databases and expertise. Prof Joachim Schultze and develop career pathways and enhance In 2015 five visitations were supported, Dr Marc Beyer, Life and Medical Sciences resumes, providing mutual benefit for building links with research groups from Institute, University of Bonn, Germany. both the mentee and mentor. In 2015 ten France, Germany, UK, and USA. RRI Visitor: A/Prof Simon Barry pairs were established, who met regularly throughout the year to address personalised Visitors to the Robinson Dr Dmitry Kissin, Centre for Disease Control career progression. Research Institute and Prevention, US. Prof William Grobman, Clinical RRI Visitor: Prof Michael Davies Effectiveness Research in Women’s Health, A/Prof Andrew Pollard, Oxford Vaccine North Western University, US. Group, University of Oxford, UK. RRI Host: Prof Ben Mol RRI Visitor: A/Prof Helen Marshall

68 Robinson Research Institute Travel Grants Supporting researchers to travel so they can present and share their research findings at national and international conferences and meetings is essential for career development and building a strong track record. Attendance at key conferences enables important networking with peers, and the opportunity to develop future collaborations. In 2015 the Institute awarded $25,000 to 34 early and mid-career researchers and students who participated in 27 conferences in Australia and around the world. Researchers are encouraged to submit a brief story about their travel – here’s what Macarena had to say:

Macarena Bermudez Gonzalez 2015 Frontiers in Reproduction Symposium Massachusetts, USA

Macarena from the I also learnt and practised a wide range of Ovarian Cell Biology techniques in other areas of reproductive group attended the 2015 Frontiers in biology, using different (and sometimes Reproduction Symposium, and presented exotic) animal models. her work: Improving oocyte quality and embryo development by inducing heat shock Who did you meet and what plans How was the experience of value to you? were made? proteins in an overweight mouse model. I am very grateful to the Robinson Research I had the fortune of meeting many excellent Institute, Healthy Development Adelaide, What was a highlight of your travel? researchers, it would be difficult to pick just The University of Adelaide and The Marine a few. The direction team became close I was one of 20 students from around Biological Laboratory for their support of my mentors to all the students, and I learnt a the world selected to participate in the attendance to this workshop. The experience great deal from each of them, especially 2015 Frontiers In Reproduction Research benefited me immensely, both personally and Rafael Fissore with whom I share similar Workshop. Held before the symposium, this professionally. I made many new contacts interests in oocyte biology. Having the workshop ran for 6 weeks and provided that I hope to collaborate with in the future, opportunity to meet people like Gloria Perez, intensive research training in the reproductive and acquired new skills during the 6-week Paula Stein, Carmen Williams, Dolores Lamb sciences field. workshop. I am now more confident in my and many more who are successful female I was able to refine my skills in many research, and my ability to present and leaders in their fields was inspirational and commonly used laboratory techniques, advocate for my research. which I hadn’t used since my undergraduate encouraging. In addition, I have maintained degree, and to adapt some of the techniques a close relationship with my fellow students, that I currently use to the latest technology. as each of us were willing to collaborate with and support each other.

Annual Report 2015 69 Advisory Board

Prof Jock Findlay AO (Chair) Prof Mike Brooks Prof Alastair Burt

A/Prof Naomi Dwyer Dr Susan Evans Prof Julie Owens

Prof Sarah Robertson Prof Andrew Zannettino

70 Robinson Research Institute Executive Committee

Prof Sarah Robertson A/Prof Simon Barry Prof Jenny Couper Prof Jodie Dodd (Chair)

Marcus Goddard Kate Irving A/Prof Helen Marshall Prof Julie Owens

Prof Claire Roberts A/Prof Rebecca Robker Prof Ray Rodgers A/Prof Darryl Russell

A/Prof Michael Stark

Annual Report 2015 71 Member list

Thank you to all of the Institute’s members who have contributed to another successful year.

Members Brown, Angela Cornish, Tiffany Ferrante, Antonio Haslam, Ross Johnston, Julie Aboustate, Natalie Brown, Cheryl Couper, Jennifer Ferres, Kathrine Hatzirodos, Nicholas Jolly, Lachlan Anastasi, Marie Buckberry, Sam Coussens, Scott Fraser, Louise Heath, Christine Jureidini, Jon Anderson, Jemma Butler, Thomas Cramp, Courtney Fullston, Tod Heilbronn, Leonie Kaczmarek, Adrian Andersen, Chad Camp, Amanda Crawford, Tara Gardner, Alison Hiendleder, Stefan Kaim, Amy Andraweera, Prabha Carbone, Cassandra Crowther, Caroline Garrett, Amy Highet, Amanda Kannieappan, Archer, Maddison Carger, Olivia Cyan, Sylvester Gatford, Kathyrn Hii, Charles Lavern Ashwood, Pat Carroll, Renee Daish, Tasman Gecz, Jozef Hinze, Susan Kaur, Manpreet Atashagaran, Vahid Carroll, Rob Dalton, Julia Gent, Roger Hodson, Leigh Keen, Erin Augustine, Priya Casey, Aaron Darvishi, Sam Geyer, Myf Hodyl, Nicolette Keir, Amy Awadalla, Maged Cash, Sarah Dasari, Pallave Gialamas, Angela Holst, Caroline Kelsey, Meredith Bain, Emily Cates, Lauren Davies, Chris Giles, Lynne Homan, Claire Kennaway, David Ball, Vincent Champion, Davies, Michael Glynn, Danielle Hope, Christopher Kennedy, Declan Ballinger, Sophie Stephanie Dearsley, Oliver Gold, Michael Hordacre, Brenton Khoda, Sultana Bandara, Veronika Chan, Hon Yeung Dekker, Gus Goldsworthy, Horton, Dane Kieffer, Tom (Dexter) Banovic, Tatjana Deussen, Andrea Mitchell Hughes, James King, Jovanka Chatburn, Alex Barry, Simon Diener, Kerri Goodchild, Louise Hull, Louise Kireta, Svjetlana Chechurova, Tania Basin Khalah, Dinh, Thao Gorgani, Nick Hummitzsch, Katja Kohler, Mark Chen, Miaoxin Marwah Dodd, Jodie Grant, Patricia Hunter, Damien Kong, Wee-Ching Chen, Thai Bastian, Nicole Domingo, Deepti Green, Ryan Hurtado, Plinio Kontos, Anna Cheow, Yuen Tan Bell, Francesca Donnelley, Martin Green, Ella Hurtado Perez, Kontos, Kostas (Tiffany) Bent, Stephen Dorian, Camilla Grieg, Meredith Ernesto Kortschak, Dan Chin, Peck (Loretta) Beresford, Sarah Drogemuller, Grieger, Jessica Hutchinson, Amy Krieg, Meredith Chittleborough, Bermudez Gonzalez, Christopher Grivell, Rosalie Ingman, Wendy Kuo, Gabriel Catherine Macarena Dunning, Kylie Grummett, Tyler Isaacs, Nicole Lane, Michelle Chu, Wing Hong Best, Karen (Vincent) Duszynski, Katherine Grutzner, Frank Jackson, Matilda Lassi, Zohra Beu, Nathan Clark, Jennifer Earl, Rachel Grzeskowiak, Luke Jacob, Reuben Lath, Ishita Bianco-Miotto, Tina Clarke, Michelle Edwards, Suzanne Gundsambuu, Jamil, Ezani Laurence, Jessica Bonder, Claudine Batjargal Mohamed Cmielewski, Patricia Estralla, Consuelo Lee, Kristie Bonner, Wendy Hague, William Jankovic- Coat, Suzette Evans, Susan Lee, Su-san Boog, Bernadette Haines, Bryan Karasoulos, Tanja Coates, Toby Evans, Sue Leemaqz, Shalem Braunack-Mayer, Han, Shan Jarrett, Michaela Collett, Rachael Ewens, Melissa Leghi, Gabriela Annette Harper, Kelly Jesudason, Shilpa Collins, Rebecca Fairclough, Ashlee Leigh, Chris Breed, William Harris, Richard Johan, Zaihed Collins, Joanne Farrow, Nigel Lett, Bron Broadbent, Jessica Harryanto, Himawan Johnson, Brett Copping, Katrina Fatohi, Anwar Leviton, Alison Brown, Hannah Hartanti, Monica Johnston, Briohny Corbett, Mark Fernandez, Renae Lim, Megan

72 Robinson Research Institute Lincoln, Gabriella Muhling, Jill Pullaniparambil Smith, Jacki Willson, Kristyn Clinical Partners Liu, Hong Munawara, Usma Mohandas, Arunesh Smith, Kendall Wilson, Rebecca Andersen, Chad Liu, Bo Need, Eleanor Pyragius, Carmen Smith, Nicholas Woenig, Joshua Boros, Christina Lo, Anita Netting, Merryn Quach, Alex Smithers, Lisa Wong, Ying Ying Duggan, Paul Lokman, Noor Newman, Angela Radesic, Bruno Stark, Michael Wong, Vincent Froessler, Bernd Louise, Jennie Nicole, Williams Raven, Melissa Stevens, David Wong, Siew Grivell, Rosalie Lushington, Kurt Nisenblat, Vicki Reece, Christy Sui, Sophia Xin Wooldridge, Amy Haslam, Ross Lynch, John Nitschke, Jodie Ricciardelli, Carmela Sulaiman, Siti Wright, Megan McPhee, Andrew Lyrtzis, Ellen Nobbs, Sylvia Richards, Sophie Sun, Sally Wu, Linda Pena, Alexia MacLennan, Alastair Noordin, Siti Ridding, Michael Sun, Annie Yelland, Lisa Smith, Nicholas Macpherson, Anne Norman, Rob Riley, Kathryn Sundernathan, Tulika Zhang, Sasha Symonds, Ian Maika, Amelia Nottle, Mark Ritter, Lesley Sutherland, Kate Zhang, Bihong Teague, Warwick Malatesta, Kristen O’Reily, Charmaine Roberts, Claire Tan, Stanley Zhuang, Zimin Wilkinson, Chris March, Wendy Oehler, Anita Robertson, Louise Thomas, Paul Zivkovic, Tanya Robertson, Sarah RRI Professional Marshall, Helen Oehler, Martin Thompson, Jeremy Zrim, Stephanie Staff Martin, James Olds, Liberty Robinson, Jeffrey Thomsen, Dana Affiliate Craig, Imogen Martinello, Kathryn Robinson, Kaye Owens, Julie Thomson, Rebecca Members Eley, Sarah Mathew, Suja Robker, Rebecca Padmanabhan, Thornton, Nicollette Avery, Jodie Goddard, Marcus Mattiske, Tessa Harsha Rodgers, Raymond Tidswell, Jane Barnett, Christopher Hooper, Mairead Mayne, Benjamin Pahl, Samantha Rodriguez Baena, Toldo-Flores, Barry, Michael Irving, Kate Paleologos, Mary Javier Deborah McAninch, Dale Bertoncello, Ivan Rojas-Canales, Spencer, Laura McCarron, Palmer, Lyle Tonkin, Anne Darling Clifton, Vicki Trueman, Cathy Alexandra Pamula, Yvonne Tran, Thach Ross, Mitchell Clow, Angela McCormack, Panir, Kavita Tregoweth, Emma Rout-Pitt, Nathan Froessler, Bernd Catherine (Dee) Parrella, Adriana Trengove, Karleah Rumbold, Alice Gilchrist, Robert McCullough, Dylan Parsons, David Tuck, Astrud Ruminski-Smith, Johnson, Neil McCullough, Caitlin Pearce, Anna Tuckerman, Jane Dania Karnon, Jonathan McDowall, Melanie Pederick, Daniel Van Eyk, Clare Russell, Darryl Maika, Amelia McGuane, Jonathan Pederson, Stephen Van Ryswyk, Emer Sadler, Robert Makrides, Maria McIlfatrick, Stephen Peh, Chen Varcoe, Tamara Sadlon, Timothy Moran, Lisa McIntyre, Chantelle Peirce, Eleanor Vassilev, Ivan Samantha, Mottershead, David McLennan, Hanna Pena, Alexia Verburg, Petra Alexandra Newman, Morgan McMillan, Mark Penko, Daniella Wabnitz, David Sandemann, Lauren Omari, Taher McPhee, Andrew Penn, Alexander Wahid, Hanan Sawyer, Alyssa Pearce, Anna McPherson, Nicole Penno, Megan Walker, Mary Sawyer, Michael Pederson, Stephen Middleton, Philippa Perano, Shiree Wan Xian, Kang Schjenken, John Pilkington, Rhiannon Mildren, Kathryn Peters, Jacqueline Wang, Zhao Schneider, Luke Rothwell, John Mitchell, Paula Pfeiffer, Sara Wang, Rui Sharkey, David Russo, Ray Mittinty, Murthy Pham, Clarabelle Wang, Bing Sharma, Raman Sanders, Moey, Ching Pham, Duyen Shaw, Marie Warin, Megan Prashanthan Mol, Ben Phillips, Jessica Shehadeh, Helana Watson, Katherine Thompson, Suzanna Moldenhauer, Pignata, Silvia Sheppard, Caroline Watson, Laura Tufanaru, Catalin Lachlan Pignata, Pauli Shields, David Wechalekar, Harsha Whitehead, Clare Money, Sadeesh Pignata, Tony Shoubridge, Cheryl Wheeler, Alexis Wilkinson, Dominic Moore, Vivienne Pilkington, Rhiannon Shuaib, Entesar White, Melissa Xafis, Vicki Moran, Lisa Piltz, Sandie Singh, Mansi Whitrow, Melissa Zander-Fox, Deirdre Mpundu-Kaambwa, Pitcher, Julia Whitty, Annie Christine Sivanathan, Kisha Zhou, Jo

This list aims to be as comprehensive as possible and any omissions are unintentional.

Annual Report 2015 73 Publications

1. Aarts, J. W. M., Nieboer, T. E., Johnson, N., 10. Andraweera, P. H., Dekker, G. A., 20. Beckmann, K., Lynch, J., Hiller, J., Farshid, Tavender, E., Garry, R., Mol, B. W. J., & Jayasekara, R. W., Dissanayake, V. H. W., G., Duffy, S., & Roder, D. (2015). Estimating Kluivers, K. B. (2015). Surgical approach to & Roberts, C. T. (2015). The obesity-related over-diagnosis of breast cancer (Authors’ hysterectomy for benign gynaecological disease. FTO gene variant associates with the risk Reply). International Journal of Cancer, 136(10). Cochrane Database of Systematic Reviews (8). of recurrent miscarriage. Acta Obstetricia et Beckmann, K. R., Lynch, J. W., Hiller, J. Gynecologica Scandinavica, 94(7), 722-726. 21. 2. Abheiden, C. N. H., Van Hoorn, M. E., E., Farshid, G., Houssami, N., Duffy, S. W., Hague, W. M., Kostense, P. J., van Pampus, 11. Andraweera, P. H., Gatford, K. L., Dekker, & Roder, D. M. (2015). A novel case-control M. G., & de Vries, J. I. P. (2015). Does low- G. A., Leemaqz, S., Russell, D., Thompson, design to estimate the extent of over-diagnosis molecular-weight heparin influence fetal growth S. D., McCowan, L., Roberts, C. T. (2015). of breast cancer due to organised population- and uterine and umbilical arterial flow-velocities Insulin family polymorphisms in pregnancies based mammography screening. International in women with a history of early-onset utero- complicated by small for gestational age infants. Journal of Cancer, 136(6), 1411-1421. placental insufficiency and an inheritable Molecular Human Reproduction, 21(9), 745-752. 22. Beesley, V. L., Rowlands, I. J., Hayes, S. thrombophilia? Secondary RCT results. BJOG: 12. Anuradha, S., Donovan, P. J., Webb, P. M., C., Janda, M., O’Rourke, P., Marquart, L., An International Journal of Obstetrics and Brand, A. H., Goh, J., Friedlander, M., Oehler, Quinn, M. A., Spurdle, A. B., Obermair, A., Gynaecology, OnlinePubl(5), 1-9. M. K., Quinn, M., Steer, C. & Jordan, S. J. (2015). Brand, A., Oehler, M. K., Leung, Y., McQuire, 3. Ahmed, S., Makrides, M., Sim, N., McPhee, Variations in adjuvant chemotherapy and survival L. & Webb, P. M. (2015). Incidence, risk factors A., Quinlivan, J., Gibson, R., & Umberger, W. in women with epithelial ovarian cancer - a and estimates of a woman’s risk of developing (2015). Analysis of hospital cost outcome of population-based study. Acta Oncologica (2), 1-8. secondary lower limb lymphedema and DHA-rich fish-oil supplementation in pregnancy: lymphedema-specific supportive care needs 13. Arenas-Hernandez, M., Sanchez-Rodriguez, evidence from a randomized controlled trial. in women treated for endometrial cancer. E. N., Mial, T. N., Robertson, S. A., & Gomez- Prostaglandins, Leukotrienes and Essential Gynecologic Oncology, 136(1), 87-93. Lopez, N. (2015). Isolation of leukocytes from Fatty Acids, 102-103(C), 5-11. the murine tissues at the maternal-fetal interface. 23. Beesley, V. L., Rowlands, I. J., Hayes, S. C., 4. Aloia, A. L., Abraham, A. M., Bonder, C. S., Journal of Visualized Experiments, 2015 (99). Janda, M., O’Rourke, P., Marquart, L., Quinn, Pitson, S. M., & Carr, J. M. (2015). Dengue M. A., Spurdle, A. B., Obermair, A., Brand, A., 14. Arentz, G., Weiland, F., Oehler, M. K., & Virus-Induced Inflammation of the Endothelium Oehler, M. K., Leung, Y., McQuire, L. & Webb, Hoffmann, P. (2015). State of the art of 2D and the Potential Roles of Sphingosine Kinase-1 P. M. (2015). Incidence, risk factors, and DIGE. Proteomics - Clinical Applications, 9(3-4), and MicroRNAs. Mediators of Inflammation estimates of a woman’s risk for developing 277-288. secondary lower limb lymphedema and 5. Aloia, A. L., Eyre, N. S., Black, S., Bent, S. J., 15. Avery, J. C., Braunack-Mayer, A., Duggan, lymphedema-specific supportive care needs Gaeguta, A., Guo, Z., Narayana, S. K., Chase, P., Taylor, A., & Stocks, N. (2015). ‘It’s our lot’: in women treated for endometrial cancer. R., Locarnini, S., Carr, J. M., Howe, J. A. & how resilience influences the experience of Obstetrical and Gynecological Survey, 70(3), Beard, M. R. (2015). Generation of a chimeric depression in women with urinary incontinence. 176-177. hepatitis C replicon encoding a genotype-6a Health Sociology Review, 24(1), 94-108. NS3 protease and assessment of boceprevir 24. Bell, L. K., Edwards, S., & Grieger, J. A. (SCH503034) sensitivity and drug-associated 16. Baetu, I., Burns, N. R., Urry, K., Barbante, (2015). The relationship between dietary patterns mutations. Antiviral therapy, 20(3), 271-280. G. G., & Pitcher, J. B. (2015). Commonly- and metabolic health in a representative sample occurring polymorphisms in the COMT, DRD1 of adult Australians. Nutrients, 7(8), 6491-6505. 6. Alvarez, G., Casiro, S., Gutnisky, C., Dalvit, and DRD2 genes influence different aspects G. C., Sutton-McDowall, M. L., Thompson, 25. Bensdorp, A. J., Tjon-Kon-Fat, R. I., of motor sequence learning in humans. J. G., & Cetica, P. D. (2015). Implications of Bossuyt, P. M. M., Koks, C. A. M., Oosterhuis, Neurobiology of Learning and Memory, 125(C), Glycolytic and Pentose Phosphate Pathways G. J. E., Hoek, A., Mol., B. W., van Wely, M. et 176-188. on the oxidative status and active mitochondria al. (2015). Prevention of multiple pregnancies in of the porcine oocyte during in vitro maturation. 17. Bain, E., Bubner, T., Ashwood, P., Van couples with unexplained or mild male subfertility: Theriogenology, Online Publ, 1-35. Ryswyk, E., Simmonds, L., Reid, S., Middleton, randomised controlled trial of in vitro fertilisation P. & Crowther, C. A. (2015). Barriers and with single embryo transfer or in vitro fertilisation 7. Alves, E., Fielder, A., Ghabriel, N., Sawyer, enablers to implementing antenatal magnesium in modified natural cycle compared with M., & Buisman-Pijlman, F. T. A. (2015). Early sulphate for fetal neuroprotection guidelines: a intrauterine insemination with controlled ovarian social environment affects the endogenous study using the theoretical domains framework. hyperstimulation. BMJ, 350(Jan), g7714-7771. oxytocin system: a review and future directions. BMC Pregnancy and Childbirth, 15(1), 171-176. Frontiers in Endocrinology, 6(MAR), 31-36. 26. Bernardes, T. P., Mol, B. W., Ravelli, A. 18. Baumert, M., Pamula, Y., Kohler, M., Martin, C., van den Berg, P. P., Stolk, R. P., & Groen, 8. Andersen, C. C., Karayil, S. M., Hodyl, N. A., J., Kennedy, D., Nalivaiko, E., & Immanuel, S. H. (2015). [46-OR]: Early and late onset & Stark, M. J. (2015). Early red cell transfusion A. (2015). Effect of respiration on heartbeat- preeclampsia versus small for gestational age favourably alters cerebral oxygen extraction in evoked potentials during sleep in children with risks in subsequent pregnancies. Pregnancy very preterm newborns. Archives of Disease in sleep-disordered breathing. Sleep Medicine, Hypertension, 5(1), 24. Childhood: Fetal and Neonatal Edition, 100(5), 16(5), 665-667. F433-F435. 27. Bersten, D. C., Sullivan, A. E., Li, D., 19. Beckmann, K., Duffy, S. W., Lynch, J., Hiller, J., Bhakti, V., Bent, S. J., & Whitelaw, M. L. 9. Andersen, C. C., Keir, A. K., Kirpalani, H., Farshid, G., & Roder, D. (2015). Estimates of (2015). Inducible and reversible lentiviral & Stark, M. (2015). Anaemia in the premature over-diagnosis of breast cancer due to population- and recombination mediated cassette infant and red blood cell transfusion: new based mammography screening in South exchange (RMCE) systems for controlling approaches to an age-old problem. Current Australia after adjustment for lead time effects. gene expression. PLoS One, 10(3), Treatment Options in Pediatrics, 1(3), 191-201. Journal of medical screening, 22(3), 127-135. e0116320-e0116373.

74 Robinson Research Institute 28. Bhutta, Z. A., & Lassi, Z. S. (2015). 40. Breijer, M. C., & Mol, B. W. J. (2016). 49. Burgess, T., Braunack-Mayer, A., Tooher, Preconception care and nutrition interventions Transvaginal ultrasound measurement of the R., Collins, J., O’Keefe, M., Skinner, R., Watson, in low- and middle-income countries. Nestle endometrium remains the first line test for M., Ashmeade, H., Proeve, C. & Marshall, H. Nutrition Institute Workshop Series, 80, 15-26. investigating postmenopausal bleeding but (2015). Optimizing intersectoral collaboration integration of patient characteristics into testing between health and education: the Health 29. Bloomfield, .F H., Crowther, C. A., Harding, may further improve diagnostic algorithms. Bridges study. Journal of Public Health. J. E., Conlon, C. A., Jiang, Y., & Cormack, B. BJOG: An International Journal of Obstetrics 50. Burke, M. T., Morais, C., Oliver, K. A., E. (2015). The ProVIDe study: the impact of and Gynaecology, 123(3), 447. protein intravenous nutrition on development Lambie, D. L. J., Gobe, G. C., Carroll, R. in extremely low birthweight babies. BMC 41. Breijer, M. C., Van Hanegem, N., Visser, P., Staatz, C. E., Sinnya, S., Soyer, H. P., Pediatrics, 15(1), 100-107. N. C. M., Verheijen, R. H. M., Mol, B. W. J., Winterford, C., Haass, N. K., Campbell, S. B. Pijnenborg, J. M. A., Timmermans, A. et al. & Isbel, N. M. (2015). Expression of Bcl-xL and 30. Borg, S. A., Tonkin, A., Kleinig, T., & Waters, (2015). Does probability guided hysteroscopy Mcl-1 in the nonmelanoma skin cancers of M. (2015). Unusual presentation of Epstein- reduce costs in women investigated for renal transplant recipients. American Journal of Barr virus encephalitis in an older patient with postmenopausal bleeding? Scientific World Clinical Pathology, 143(4), 514-526. a dramatic clinical response to intravenous Journal, 2015, 605312. immunoglobulin. Internal Medicine Journal, 51. Calvert, J. K., Helbig, K. J., Dimasi, D., 45(8), 879-881. 42. Broekhuijsen, K., Bernardes, T., van Baaren, Cockshell, M., Beard, M. R., Pitson, S. M., G. J., Tajik, P., Novikova, N., Thangaratinam, Bonder, C. S. & Carr, J. M. (2015). Dengue 31. Bosco, M. D., Drogemuller, C., Zalewski, P., S., Boers, K., Koopmans, C. M., Wallace, K., virus infection of primary endothelial cells & Coates, P. T. (2015). Zinc transporters in the Shennan, A. H., Langenveld, J., Green, H., van induces innate immune responses, changes endocrine pancreas. In M. S. Islam (Ed.), Islets den Berg, P. P., Bol, B. W. & Franssen, M. T. in endothelial cells function and is restricted of Langerhans (Second Edition) (Vol. 2, pp. (2015). Relevance of individual participant data by interferon-stimulated responses. Journal 511-527). Netherlands: Springer. meta-analysis for studies in obstetrics: delivery of interferon & cytokine research: the official 32. Bosteels, J., Weyers, S., Kasius, J., versus expectant monitoring for hypertensive journal of the International Society for Interferon Broekmans, F. J., Mol, B. W. J., & D’Hooghe, disorders of pregnancy. European Journal of and Cytokine Research, 35(8), 654-665. Obstetrics & Gynecology and Reproductive T. M. (2015). Anti-adhesion therapy following 52. Campbell, J. M., Lane, M., Owens, J. A., & Biology, 191(C), 80-83. operative hysteroscopy for treatment of female Bakos, H. W. (2015). Paternal obesity negatively subfertility. Cochrane Database of Systematic 43. Broekhuijsen, K., Van Baaren, G. J., Van affects male fertility and assisted reproduction Reviews (11). Pampus, M. G., Ganzevoort, W., Sikkema, outcomes: a systematic review and meta-analysis. 33. Boterhoven de Haan, K. L., Hafekost, J., J. M., Woiski, M. D., Mol, B. W., Langenveld, Reproductive BioMedicine Online, 31(5), 593-604. J. et al (2015). Immediate delivery versus Lawrence, D., Sawyer, M. G., & Zubrick, S. R. 53. Carpi, G., Walter, K. S., Bent, S. J., Hoen, expectant monitoring for hypertensive (2015). Reliability and validity of a short version A. G., Diuk-Wasser, M., & Caccone, A. (2015). disorders of pregnancy between 34 and 37 of the general functioning subscale of the Whole genome capture of vector-borne pathogens weeks of gestation (HYPITAT-II): an open- McMaster Family Assessment Device. Family from mixed DNA samples: a case study of Borrelia label, randomised controlled trial. The Lancet, Process, 54(1), 116-123. burgdorferi. BMC Genomics, 16(1), 431-434. 385(9986), 2492-2501. 34. Braakhekke, M., Kamphuis, E. I., Mol, F., 54. Carroll, R., & Coates, P. T. (2015). Does 44. Broekhuijsen, K., Van Baaren, G. J., Van Norman, R. J., Bhattacharya, S., Van Der Veen, rituximab help in HLA desensitization for kidney Pampus, M. G., Ganzevoort, W., Sikkema, F., & Mol, B. W. J. (2015). Effectiveness and transplantation? Kidney International, 87(2), J. M., Woiski, M. D., Mol, B. W., Langenveld, safety as outcome measures in reproductive 277-279. medicine. Human Reproduction, 30(10), 2249- J. et al. (2015). Immediate delivery versus 2251. expectant monitoring for hypertensive disorders 55. Carter, D. A., Sendziuk, P., Eliott, J. A., & of pregnancy between 34 and 37 weeks Braunack-Mayer, A. (2015). Why is pain still under- 35. Bradnam, L. V., Graetz, L. J., McDonnell, M. of gestation (HYPITAT-II): An open-label, treated in the emergency department? Two new N., & Ridding, M. C. (2015). Anodal transcranial randomised controlled trial. Obstetrical and hypotheses. Bioethics, OnlinePubl(3), 1-8. direct current stimulation to the cerebellum Gynecological Survey, 70(10), 605-607. improves handwriting and cyclic drawing 56. Casey, A. E., Daish, T. J., & Grutzner, F. kinematics in focal hand dystonia. Frontiers in 45. Brookes, E., Laurent, B., Õunap, K., Carroll, (2015). Identification and characterisation of Human Neuroscience, 9(May), 281-289. R., Moeschler, J. 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