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2015 CHANNEL 7 CHILDREN’S RESEARCH FOUNDATION ANNUAL REPORT WWW.CRF.ORG.AU 1

CONTENTS Contents ................................................................................................................................ 1

About the Foundation ........................................................................................................... 2

Patron ................................................................................................................................... 2

Board of Directors 2015 ........................................................................................................ 3

Research Committee 2015 .................................................................................................... 4

Executive Summary ............................................................................................................... 5

Research Committee Report ................................................................................................. 6

Table 1 – Research Project Grants Commencing in 2015 ............................................... 7

Table 2 – Institutions Receiving Grants In 2015 ............................................................ 13

Table 3 – Annual Grants History* (1977/78 – 2015 incl) .............................................. 13

Table 4 – Independent Referees for the 2015 Grant Round ......................................... 14

Financial Report 2014-2015 ................................................................................................ 16

Notes to the Financial Statements for the Year Ended 30 June 2015 ........................... 20

Statement by the Board of Directors ............................................................................ 27

Report by the Board of Directors ........................................................................................ 28

Independent Audit Report .................................................................................................. 29


ABOUT THE FOUNDATION The Channel 7 Children's Research Foundation of South Australia Incorporated (CRF) was established in 1976 by television station Channel 7 Adelaide (then Channel 10) with the proceeds from a Telethon Appeal.

The purpose of the Foundation is to encourage and advance investigation into the cause, prevention, diagnosis and treatment of any condition which may affect the general health, education or welfare of children, and the promotion and funding of health, educational or social research.

The Foundation supports research undertaken by universities, research institutes, health services and other organisations in South Australia or the Northern Territory in all relevant branches of science.

Funding for research projects is granted annually on the recommendation of an independent Research Committee. The maximum funding per grant is $75,000 for research in the fields of Medicine, Education, Dentistry, Nursing and Midwifery, Social Sciences, Environment, Mental Health and Allied Health Professions.

PATRON The Patron of the Foundation is the Governor of South Australia, His Excellency the Honourable Hieu Van Le AO.


BOARD OF DIRECTORS 2015

Mr D Earl FCPA FCIS JP – CHAIRPERSON (Representative of Channel 7 Adelaide)

Mr L Frankham FCPA GAICD JP – DEPUTY CHAIRPERSON (Representative of Channel 7 Adelaide)

Mr S Smith BA(Acc) GradDipBusAdmin FCPA JP (Representative of Channel 7 Adelaide)

Ms L Rayner (Representative of Channel 7 Adelaide)

Mr S Woolley (Representative of Channel 7 Adelaide)

Professor M Kidd AM MBBS MD DCCH DipRACOG FRACGP FACHI FAFPM (Hon) FHKCFP (Hon) FRNZCGP (Hon) FCGPSL (Hon) MAICD (Representative of Flinders University)

Mr G de Cure BA(IS)(Hons) (Representative of Novita Children’s Services)

Professor S Robertson PhD (Representative of The University of Adelaide)

Professor P Buckley PhD BPharm (Representative of the University of South Australia)

Adjunct Associate Professor N Dwyer MBL (Representative of Women’s and Children’s Health Network)

Emeritus Professor C Matthews AO MD FRANZCOG CREI (Co-opted by the Board)

Mr G Rappensberg RN BMgmt AFCHSE MAICD – EXECUTIVE DIRECTOR

Mr M Belperio BA(Acc) ACPA – TREASURER


RESEARCH COMMITTEE 2015

Emeritus Professor C Matthews AO MD FRANZCOG CREI – CHAIRPERSON (Nominee of the Board)

Mr D Earl FCPA FCIS JP (Representative of the Board)

Professor K Forsyth MB ChB MD PhD FRACP FRCPA (Representative of Flinders University)

Associate Professor R Robker PhD (Representative of the University of Adelaide)

Dr J Fereday RN, RM, DipAppSc(Nsg), MEd(Mgt), PhD (Representative of Women's and Children's Health Network)

Professor C Xian BAgSc (Guangzhou) MSci PhD (Representative of the University of South Australia)

Professor J Beilby MBBS, MD, MPH, FRACGP (Co-opted by the Board)


EXECUTIVE SUMMARY We are pleased to present the 39th Annual Report of the Channel 7 Children’s Research Foundation, for the year ending 30 June 2015.

Since 1976, the Foundation’s grants program for research in South Australia and the Northern Territory has provided valuable support to both established and early career researchers, funding grants to a maximum amount of $75,000 per annum, or $35,000 per grant for Early Career Researchers.

In the competitive environment, the importance of the Foundation’s grants program cannot be underestimated and we also acknowledge that the program assists researchers to establish their credentials and thus improve their chances of obtaining future NHMRC funding.

The Foundation supported a total of 18 projects in 2015, to the value of $1,123,000. (Refer Table 1)

Partnerships As always, we thank Channel 7 for its ongoing support of the Foundation. Our partnership with Healthy Development Adelaide (HDA) commenced in 2007 and we are proud to continue to support the HDA, through sponsoring the Channel 7 Children’s Research Foundation PhD (top-up) Scholarships. These scholarships are available for domestic and international students researching in the area of Healthy Development.

The South Australian chapter of the Australian Society for Medical Research (ASMR) again hosted the annual ASMR SA Medical Research Week in Adelaide, a highlight of which was the Gala Dinner. The Foundation was very pleased to be a major supporter of this event.

Finance The Foundation is well placed to continue its objectives of promoting health, educational or social research, and encouraging and advancing investigation into the cause, prevention, diagnosis and treatment of any condition that may affect the general health, education or welfare of children. The financial result for the 2014-15 financial year shows a net surplus of $2,037,366 for the financial year ended 30 June 2015, compared to $1,734,905 in the 2013-14 financial year.

The increased surplus result for 2014-2015 compared to 2013-14 was due to higher dividend and franking credit income compared to the 2013-14 financial year. This was a direct result of the off market buybacks conducted by Rio Tinto and Telstra during 2014-15.

Total expenditure for the year was $ 1,332,400 compared to $1,340,290 in 2013-2014. The major expenditure for the year was the payment of research grants of $1,149,904.

Total assets of the Foundation at 30 June were $37,583,690; an increase of $1,625,481 on the previous year. The increase was due principally to the increase in the value of the


Foundation’s investment portfolio by $1,592,791 at 30 June 2015, compared to 30 June 2014.

In conclusion, we acknowledge the commitment and expertise of the Board and Finance Committee, and of the Research Committee led by Emeritus Professor Colin Matthews AO, and extend our appreciation for their prudent management and support of the work of the Foundation. Mr Dennis Earl Mr Glenn Rappensberg CHAIRPERSON EXECUTIVE DIRECTOR

RESEARCH COMMITTEE REPORT The Channel 7 Children’s Research Foundation supports research into the health of children and young people by providing funding for research projects, on an annual basis, through a competitive grants process.

Grants are available to universities, medical research institutions and hospitals in South Australia and the Northern Territory. (Refer Table 1 for details)

The institutions which received funding in 2015 were Flinders University, Menzies School of Health Research, the South Australian Health and Medical Research Institute (SAHMRI), The University of Adelaide and the University of South Australia. (Refer Table 2 for details)

The Foundation supported a total of 18 projects in 2015, to the value of $1,123,000. The Research Committee reviewed 125 Expressions of Interest for 2015 funding, of which 35 were shortlisted to progress to the grant application stage.

The maximum funding of $75,000 was awarded to seven researchers.

The Foundation is proud to encourage and nurture emerging researchers and was pleased to support four Early Career researchers, with grants to the maximum of $35,000.

To date, the Foundation has allocated funding to a total of $22,906,365 (Refer Table 3 for details)

As always, I acknowledge and express my appreciation for our colleagues in the research community, both within Australia and internationally, who are willing to contribute by being independent referees, providing peer review reports on the grant applications. As experts in their fields, their additional insight is very valuable and helps to ensure the Foundation supports the highest standard of research. (Refer Table 4 for details)

I also acknowledge and thank my colleagues on the Research Committee, who are to be commended for their contribution to the process. It is a great pleasure to work with them in advancing the work of the Foundation, ensuring the continuation of research towards improving the lives of children.

Emeritus Professor Colin Matthews AO CHAIRPERSON, RESEARCH COMMITTEE


TABLE 1 – RESEARCH PROJECT GRANTS COMMENCING IN 2015

The Channel 7 Children’s Research Foundation supports research into the health of children and young people by providing funding for research projects, on an annual basis. In 2015, the Foundation allocated $1,123,000 to 18 projects.

Grant funding details and the researchers’ summaries are presented as follows:

FLINDERS UNIVERSITY

Professor Jamie Craig $74,800 Improving genetic diagnosis and reproductive options for families with congenital, and developmental glaucoma Glaucoma in infants is a rare but devastating condition. Without treatment, elevated eye pressure leads to the expanding eyes with total blindness. Most cases need multiple surgical procedures and general anesthetics. The cause of infantile and childhood glaucoma is almost entirely genetic, but in most cases the causative gene is unknown. Parents usually seek an accurate understanding of the risk to subsequent children, and options for prevention. This project aims to define a greater proportion of the genetic risk for pediatric glaucoma, and to make improved testing available for families.

MENZIES SCHOOL OF HEALTH RESEARCH

Dr Erin Price $74,900 What are the important targets for prevention of Haemophilus influenzae lung infection? Preventable paediatric disease caused by infection with the nontypeable Haemophilus influenzae (NTHi) bacterium is a major yet under-recognised health burden. NTHi infection can lead to bronchiectasis, a severe and irreversible lung condition that disproportionately affects Aboriginal children in the Northern Territory, with 1 in every 68 suffering from this disease. It has lifelong consequences including premature death in the 3rd-4th decade of life. A vaccine that is effective across all NTHi strains is urgently needed to reduce the burden of this preventable disease in Aboriginal children.

Dr Tonia Woodberry $75,000 Understanding dendritic cell dysfunction in children with malaria Malaria, a disease caused by Plasmodium parasites affects ~450 million people each year with 0.6 million deaths, most in children less than 5 years old. Vaccine development is a key goal for malaria elimination. Vaccine responsiveness relies on functional dendritic cells (DC). However, we have identified that adults with malaria have dysfunctional DC, meaning vaccines may not work. We here will examine DC in children with malaria to determine if they are functional. The data will tell us whether parasite clearance is required before administration of childhood vaccines.


SOUTH AUSTRALIAN HEALTH & MEDICAL RESEARCH INSTITUTE

Dr Susan Heatley $75,000 Developing a robust screening tool to identify Children with high risk "Ph-like" Acute Lymphoblastic Leukaemia (ALL) that will lead to improved outcomes through the use of targeted therapies. High risk relapsed B-ALL remains the leading cause of non-traumatic death in children and young adults, with ~20% of patients dying from this disease. Novel chromosomal changes resulting in the formation of new proteins have recently been identified in a significant number of cases. Importantly, drugs that target these proteins are in use for other diseases and are safe. Rapid, accurate screening tests to identify these genetic lesions will greatly enhance the clinical application of anti-leukaemic drugs which are highly likely to improve the low cure rates in children with high risk ALL.

THE UNIVERSITY OF ADELAIDE

Miss Zuleeza Ahmad $35,000 (Early Career) Investigation of a novel protein tyrosine phosphatase in Streptococcus pneumoniae Streptococcus pneumoniae causes 25% of all preventable deaths in children under the age of five. This equates to more than 1.2 million deaths annually. A putative protein tyrosine phosphatase (designated PTPa) has recently been identified as a virulence factor in the pneumococcus, as is the case in many other bacterial pathogens. This project will focus on uncovering the reasons for this effect, in an effort to investigate the role of PTPa in pneumococcal pathogenesis. As issues of vaccine ineffectiveness and antibiotic resistance prevail, PTPa may present a novel drug target.

Associate Professor Vicki Clifton $66,300 Intergenerational impact of maternal asthma on cardiovascular risk in offspring Asthma (12% adults) and cardiovascular disease (19% adults) are two non-communicable chronic diseases that are major health, social and economic burdens in our society. The major questions related to chronic disease are how to prevent them and in the absence of prevention, how to manage them clinically. We will identify how maternal asthma, asthma exacerbations and corticosteroid treatment during pregnancy affects cardiovascular risk in offspring. This study will provide us with important information on whether asthma control during pregnancy improves childhood cardiovascular health.


Professor Jenny Couper $59,500 Can the glucagon-like peptide-1 agonist, exenatide, improve blood glucose control in young people with cystic fibrosis related diabetes? Cystic fibrosis is a severe genetic disorder affecting the lungs, liver and pancreas of children. Life expectancy has improved greatly; however, with this comes the development of cystic fibrosis related diabetes. Diabetes is associated with worsening nutrition and lung function, and increased mortality. We have shown that blood glucose control in teenagers with CF is improved by slowing gastric emptying and increasing incretin hormone secretion. Exenatide is an incretin-like medication and we wish to investigate whether this can improve blood glucose control as a more effective strategy.

Professor Stan Gronthos $75,000 Identification of TWIST-1 regulated microRNAs which control cranial bone development in children. Saethren-Chotzen Syndrome (SCS) is a disorder associated with craniosynostosis, leading to abnormal head shape, asymmetrical facial features and increased pressure on the growing brain in infants. One cause of SCS is a mutation in the TWIST-1 gene, involved in mesodermal development. MicroRNA (miRNA) have emerged as important regulators of bone development. The identification of Twist-1 regulated miRNAs and their gene targets during cranial development and SCS will help identify novel molecular pathways for exploiting in new therapeutic strategies.

Dr Luke Grzeskowiak $35,000 (Early Career) CODDLED: A Double-Blind Randomised Controlled Trial Comparing Two Domperidone Doses on Duration and Exclusivity of Breastfeeding in Mothers of Term Infants Experiencing Lactation Difficulties The presence of lactation difficulties is one of the most commonly reported reasons for discontinuation of breastfeeding. Within South Australia alone, it is estimated that >1,000 mothers are given domperidone each year to improve breast milk supply. This is despite limited evidence to guide its optimal use. Improving existing evidence on domperidone is of major public health importance as expected improvements in breastfeeding outcomes will provide immense immediate and long-term benefits towards infant growth and development.


Dr Nicolette Hodyl $58,600 Regulating inflammation in the preterm neonate: the contribution of microRNAs Seventy percent of the neonatal deaths due to infection occur in preterm infants. This is due in part to a functionally immature innate immune system. Inflammation is central to combating infection, but its dysregulation leads to pathology. MicroRNAs (miRs) critically regulate inflammation in adults yet the contribution of miRs to the dysregulated preterm innate immunity is unknown. We will characterise the role of miRs in regulating preterm innate immunity, providing a target for future interventions.

Dr Nicolette Hodyl $49,200 Cord blood miRNA expression profiles and childhood cognitive outcomes following preterm birth Poor neurodevelopment is a major adverse outcome of prematurity, reflected by reduced cognitive performance in school-aged children, and poorer health and socioeconomic status later in life. Recent data associates placental microRNAs with neonatal neurodevelopmental indices yet links to child outcomes are unknown. Using our cord blood biobank with matched cognitive assessments at 5 years of age, we will determine cord blood microRNA profiles that predict poor cognitive development in children born preterm. This will lead to targeted, cost effective interventions to improve future outcomes.

Dr James Hughes $75,000 Phenotypic analysis and pharmacological rescue of a novel genetic mouse model for childhood focal epilepsy. Epilepsy is a common and debilitating disorder. In 2013 we showed that mutations in DEPDC5, a key inhibitor of mTORC1 signalling, are a major cause of Focal Epilepsy (FE) in children. We have recently generated a Depdc5 KO mouse model of FE and have preliminary data showing deregulation of mTORC1 signalling. The goal of this proposal is to fully characterise the neuronal phenotype of these mice using biochemical and behavioural analyses. We will also test the exciting possibility that mTORC1 inhibitors rescue the Depdc5 KO phenotype, which has obvious implications for FE treatment.


Dr Lachlan Jolly $75,000 Identifying pathological mechanisms underlying intellectual disability An estimated 2-3% of children suffer from intellectual disability and in Australia it costs in excess of $14.7 billion/annum. In up to 80% of the affected children, the cause remains unidentified. We have however identified genetic mutations in multiple genes that are common to a single 'quality control' pathway in cells that do cause intellectual disability. We now seek to understand when and where this pathway is required during brain development as a prerequisite to peruse design and testing of treatment strategies aimed at improving the affected children's quality of life.

UNIVERSITY OF SOUTH AUSTRALIA

Professor Gregory Goodall $75,000 miR-200 and its targets as inhibitors of neuroblastoma growth and metastasis Neuroblastoma almost exclusively strikes infants and children, is the third most common type of childhood cancer and the leading cause of cancer deaths of children under 5 accounting for 15% of all pediatric cancer deaths. Aggressive neuroblastoma has not seen a major change in the survival rate in the last ten years. Metastasis is the main cause of death for these children, so finding ways to combat metastasis is a priority. We are examining the potential for a microRNA and its targets to be exploited therapeutically to combat growth, invasion and metastasis in neuroblastoma.

Associate Professor John Hayball $74,700 Modulating Fc receptor signalling to treat and prevent peanut allergy Peanut allergy prevalence in Australian children has risen to 3% in recent years. Despite the risk of potentially fatal reactions, there is currently no method available in routine clinical practice for treating peanut allergies. We have established a robust murine peanut-induced anaphylaxis model that will be used to test an immunotherapic approach which aims to selectively inhibit the production of peanut allergen-specific antibodies and decreases the risk of anaphylaxis during the desensitization process. This type of immunotherapy could have broad application in treating allergic diseases.


Dr Melanie Ramiasa $35,000 (Early Career) Point of care device for early diagnosis and prognosis of paediatric kidney diseases - a non-invasive alternative to renal biopsy The prevalence of chronic Kidney Disease (KD) in children is reported to be around 40 per million children of the world population. Australia is no exception with more than 1200 children developing end stage kidney failure or hefty kidney illnesses such as nephrotic syndrome each year. Children suffering kidney failure require life-long dialysis treatments or transplantation. Early detection can delay or even prevent kidney failure. Yet, current strategies to diagnose the early stage of KD rely on blood analysis and invasive biopsies, thus more accurate non-invasive tests for KD are needed.

Dr Yu-Wen Su $35,000 (Early Career) Accelerating bone healing by locally delivering osteogenic and angiogenic factor neurotrophin-3 (NT-3) About 50% children experience a bone fracture. Whilst most fractures can heal, delayed/impaired healing remains a key challenge as it causes substantial morbidity, time off school, and healthcare burden. More work is needed to find ways to promote bone healing. Our pilot work shows dramatic induction of NT-3 & receptor TrkC in healing rat tibia, and it induces the major osteogenic factor BMP2 and angiogenic factor VEGF (both critical for bone repair). This work addresses if NT-3 local delivery accelerates bone healing, and could lead to a novel approach for overcoming impaired healing.

Professor Shudong Wang $75,000 Discovery of CDK6 inhibitors for treatment of childhood medulloblastoma Medulloblastoma (MB) is the most common malignant brain tumor of childhood, accounting for up to 30% of central nervous system tumors in children. Current therapies are associated with poor survival rate and significant long-term side effects. Cyclin-dependent kinase 6 (CDK6) is highly activated in MB patients and is associated with the adverse prognosis. Inhibiting CDK6 activity can stop MB tumour cells to proliferate leading to cancer cells death. This project aims to develop first-in-class CDK6 inhibitors which will have significant impact on developing new treatment for childhood MB cancer.


TABLE 2 – INSTITUTIONS RECEIVING GRANTS IN 2015

RECIPIENT 2015 NUMBER OF GRANTS

TOTAL $

Flinders University 1 74,800 7% Menzies School of Health Research 2 149,900 13% SAHMRI 1 75,000 7% The University of Adelaide 9 528,600 47% University of South Australia 5 294,700 26% TOTAL 18 1,123,000 100%

TABLE 2 - *ALLOCATED – NOT DISBURSED

TABLE 3 – ANNUAL GRANTS HISTORY* (1977/78 – 2015 INCL)

FUNDING YEAR #

PROJECTS FUNDED

FUNDING ALLOCATED

$

AVERAGE GRANT

$ 1977/78 - 1986/87 222 2,326,250 1987/88 - 1996/97 198 4,178,615 1997/98 - 2004-05 171 5,320,300

2006 33 978,000 29,636 2007 32 893,000 27,906 2008 24 939,000 39,125 2009 31 1,200,000 38,709 2010 23 1,163,000 50,565 2011 22 1,138,200 51,736 2012 21 1,253,000 59,666 2013 20 1,180,000 59,000 2014 19 1,214,000 63,894 2015 18 1,123,000 62,388 Total 834 22,906,365

TABLE 3 - *ALLOCATED – NOT DISBURSED


TABLE 4 – INDEPENDENT REFEREES FOR THE 2015 GRANT ROUND

The Channel 7 Children’s Research Foundation thanks the following members of the international research community, as well as those who wish to remain anonymous, for sharing their expertise and providing independent referee reports on the grant applications.

Dr Judith Boswell Dr Andrew Moore

Dr Chris Brebner Professor Anthony Moorman

Professor Anthony Catto-Smith Associate Professor Timothy Moss

Dr Gianpiero Cavalleri Professor Victor Nossar

Dr Maurizio Costabile Professor Marco Oggioni

Professor Andrew Day Associate Professor Geraldine O'Neill

Dr Michaela Denti Dr Michael Piper

Dr Peter Farlie Professor Sarah Robertson

Associate Professor Brian Gabrieli Emeritus Professor Ian Roberts-Thomson

Dr Kathryn Gatford Dr Alison Russell

Professor Paul Goldwater Dr Zarqa Saif

Professor Georges Grau Dr Catherine Satzke

Dr Uta Griesenbach Professor Mark Schembri

Professor Hans Griesser Dr John Schenken

Associate Professor Michele Grimbaldeston Dr Kate Seib

Professor Prue Hart Associate Professor Michael Stark

Dr Joachim Heinrich Assistant Professor David Teachey

Dr Pravin Hissaria Assistant Professor Carlos Tirado

Associate Professor Bernard Hughes Associate Professor Maria Torcia

Associate Professor Charlene Kahler Professor Grant Townsend

Dr Marcel Kool Dr Stephen Tristam

Associate Professor Martha Lappas Dr Andrea Vincent

Associate Professor Helen Liley Dr Fabien Vincent

Professor Christopher B Little Professor Mark Walker

Associate Professor Peta Macardle Dr Paul Webster

Associate Professor Helen Marshall Associate Professor Hong Zhou

Professor Peter McIntyre Dr David Ziegler


FINANCIAL REPORT 2014-2015

STATEMENT OF FINANCIAL POSITION AS AT 30 JUNE 2015


STATEMENT OF PROFIT OR LOSS & OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED 30 JUNE 2015


STATEMENT OF PROFIT OR LOSS & OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED 30 JUNE 2015 (CONT’D)

STATEMENT OF CHANGES IN EQUITY FOR THE YEAR ENDED 30 JUNE 2015


STATEMENT OF CASH FLOWS FOR THE YEAR ENDED 30 JUNE 2015


NOTES TO THE FINANCIAL STATEMENTS FOR THE YEAR ENDED 30

JUNE 2015


NOTES T O T HE F INA NCIA L STATEME NTS FOR T HE YEAR ENDED 30 JU NE 2015 (CONT’D)


NOTES T O T HE F INA NCIA L STATEME NTS FOR T HE YEAR ENDED 30 JU NE 2015

(CONT’D)


STATEMENT BY THE BOARD OF DIRECTORS


REPORT BY THE BOARD OF DIRECTORS


INDEPENDENT AUDIT REPORT


AUDITOR’S INDEPENDENCE DECLARATION

Auditors

KPMG

151 Pirie Street, Adelaide SA 5000

Bankers

ANZ

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Investors

Macquarie Private Wealth

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Solicitors

Finlaysons

81 Flinders Street, Adelaide SA 5000

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