Honours Project Book - Faculty of Health Sciences - University of ...

SCHOOL OF PAEDIATRICS AND 

REPRODUCTIVE HEALTH 

2013 

In Paediatrics and Child Health, Reproductive Biology and Regenerative Medicine

Research opportunities for Honours 

students in 2013 

School of Paediatrics and 

Reproductive Health 

Faculty of Health Sciences 

International research leaders in Paediatrics & Child 

Health, Reproductive Biology & Health and 

Regenerative Medicine 

Contents 

Introduction .............................................................................................................................. 3 

Expression of Interest in an Honours Project ......................................................................... 6 

Scholarship Application Form ................................................................................................ 9 

Projects 

Discipline of Obstetrics and Gynaecology........................................................................ 11 

Discipline of Paediatrics ........................................................................................................ 48 

Index........................................................................................................................................ 74 

Last updated 5 November 2012 

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Make a difference 

"The recent Excellence in Research Australia (ERA) 

results have rated the School of Paediatrics and 

Reproductive Health at the highest level (5/5), a feat 

unmatched by any other Paediatrics and 

Reproductive Health Department in Australia. Our 

School is internationally recognised for our research 

in Reproduction, Maternal and Child Health. Our 

graduates are highly sought after and have 

outstanding career opportunities. We invite you to 

take up one of the Honours research opportunities 

outlined in this booklet and join us in making a 

difference." 

Professor Julie Owens, 

Head of School, 

School of Paediatrics and Reproductive Health 

The School of Paediatrics and Reproductive Health invites you to join us for Honours study in 2013. 

Our School and its members have international reputations as research leaders in reproductive biology and 

medicine, maternal, fetal and child health, and reproductive and regenerative medicine. We are recognised for 

our strong links between cutting-edge discoveries in basic research with bridges through to clinical application and 

evaluation in evidence-based medicine. The School’s two Disciplines; Obstetrics & Gynaecology and Paediatrics 

include 300 staff and postgraduate students and over 200 clinical affiliates making our School one of the largest 

and most productive peadiatrics and reproductive health departments in the world. You have the chance to work, 

be educated and graduate from an internationally renowned School to the benefit of your future career. 

The School of Paediatrics and Reproductive Health consists of two disciplines, Paediatrics and Obstetrics and 

Gynaecology. The School hosts and leads one research institute, the Robinson Institute, consisting of four University 

recognised and supported centres and one affiliated University research centre: 

• The Research Centre for Reproductive Health 

• Early Origins of Health and Disease 

Centre for Stem Cell Research 

• The Australian Research Centre for the Health of Women and Babies 

• The affiliated Children’s Research Centre 

Our five major locations are in the Medical School, Women’s and Children’s Hospital, Lyell McEwin Hospital, Royal 

Adelaide Hospital and Robinson Institute on King William Road at North Adelaide. Students can also study with our 

affiliates at these locations and other including the CSIRO and Flinders Medical Centre. 

We are an extremely research-active School, with major project funding from the National Health & Medical 

Research Council, Australian Research Council and the National Institute of Health (US) amongst others. We host 12 

NHMRC Senior Fellows, 2 ARC Future Fellows and numerous Training and Career Development Fellows. Members of 

our School published over 400 peer-reviewed articles in 2011 in the top journals in their fields, including Nature, the 

Cochrane Database of Systemic Reviews, Endocrine Reviews, Journal of Clinical Endocrinology & Metabolism, 

Journal of Paediatrics & Child Health, Lancet, Nature Genetics, New England Journal of Medicine, Obstetrics & 

Gynaecology and Theriogenology. 

This booklet contains information about our Honours course, enrolment and available scholarships, as well as a 

listing of the Honours research projects we are offering for study. Please remember that the research groups within 

the School and its affiliates may also have additional projects available, and often projects can be adapted to suit 

the interests and skills of the student. You should use the outlines in this book as a starting point in developing your 

project with a supervisor. 

We invite you to join us for Honours and develop your career. 

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Eligibility and study options 

Students who have completed an undergraduate degree in a science course, including B Science, B Science 

(Biomedical Science), B Health Science, B Biotechnology, B Agricultural Science, or B Animal Science, or who have 

completed 3 years or more of the MBBS program, are invited to apply for Honours positions within our School. To be 

eligible for Honours, a candidate must have completed the requirements for a Bachelor degree or equivalent to a 

standard that is acceptable to the Faculty for the purposes of admission into the Honours program. For more 

information please visit: 

http://health.adelaide.edu.au/programs/honours/ 

A credit average within relevant subjects is the usual standard expected, but students with a strong interest in a 

particular field and the support of their proposed supervisor/s are also encouraged to apply, and often find their 

Honours year very stimulating and successful. 

Honours students are invited to enrol either full-time (1 year of study), or part-time and study over two/three years. 

The main Honours intake is in February, and students may also commence mid-year. 

Facilities and training opportunities 

Honours students have access to the core facilities of the University and School as required for their specific projects. 

These include state-of-the-art molecular biology and imaging equipment, confocal microscopes, large and small 

animal surgeries and in vivo facilities, cell culture laboratories and an embryology laboratory. Some projects have 

strong clinical components with patient involvement, epidemiological methodologies and genomic linkage. We 

also encourage our Honours students to participate in the School’s workshop series including areas such as 

bioinformatics, new molecular biology techniques and research ethics. Of course, Honours students will also get in 

depth training in their research field and its techniques within their research group throughout their research 

projects. 

Our Honours program 

Our program is designed for you to develop specific knowledge and skills in your chosen research field as well as 

general skills in working independently, critical reasoning, scientific writing and presentation. Our Honours students 

each undertake a full-year research project (or part-time equivalent), with the majority of assessments structured 

around this. In addition, our Honours structured program teaches Honours students the skills they need to succeed in 

research, including experimental design and statistics, research ethics, an understanding of the scientific method, 

good record keeping and laboratory practice, literature searching and bibliographic software and critical 

evaluation of papers during “journal club” tutorial discussions. The overall objective of the program is for students to 

demonstrate a deep understanding and interpretation of their subject area and the ability to clearly and 

thoroughly present the project. 

Aims of the Honours Program 

• To provide mentored training in scientific research methods. 

• To develop skills for independent critical thought and learning. 

• To develop logical reasoning and written and oral presentation skills. 

• To encourage interest in a broad range of child health and reproduction related science. 

One on one contact with the supervisor and other members of the research team is the main method by which 

students gain these skills during Honours. In addition, hands on experience, communication with other members of 

the Honours class, the Honours coordinator, and the School is invaluable. 

Assessment 

The main component of the Honours course is the research project carried out with your supervisor/s. Four points of 

assessment are designed to evaluate and provide feedback on student skills relating to research aptitude, 

knowledge of their field, as well as written and verbal presentation style. 

1. Critical Literature Review (3000 words 15%) 

Students discuss and critically appraise the 10-15 papers most salient to their project. 

2. Examination of Tutorial Course material (2 hours open book 15%, Tutorial Participation 5%) 

Problem/scenario based open book written exam that draws on the issues discussed in the tutorial course. 

3. Thesis (5000 words 50%) 

Demonstrates your ability to undertake scientific research and present your findings as a scientific manuscript. 

4. Final seminar (20 minutes 15% 

Oral presentation of the student research project. 

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Honours graduate career pathways 

Our previous Honours students have gone on to successful careers in a wide range of roles. The skill base that 

Honours gives you is essential for those wanting to undertake postgraduate research training, and valuable across a 

wide range of areas. Approximately half of our students go on to further study, including PhD and postgraduate 

Medicine. Others are now employed as research assistants and officers, journal editors, patent attorneys and 

investment managers. 

Interested? 

The process to undertake Honours within the School of Paediatrics and Reproductive Health involves: 

Browse this booklet to determine a research area or project that interests you. 

Discuss potential projects with Supervisors at our annual Honours Information Session in August or contact 

them directly using the information provided in this booklet. 

If you have any questions about your eligibility, part-time study or other queries, you should contact: 

Dr Kathy Gatford 

Honours Coordinator 

School of Paediarics and Reproductive Health 

Phone: (08) 8313 4158 

Email: kathy.gatford@adelaide.edu.au 

Discuss your intention to apply for the project with the appropriate supervisor and then complete the 

‘Expression of interest in Honours’ form on the following page. 

You will be notified via email of the outcome of your application by the School of Paediatrics and 

Reproductive Health Honours Coordinator following the release of any outstanding results. If your application 

is accepted you will receive an acceptance letter with application to enrol forms. You will be able to enrol 

following once enrolments open (usually late January for Semester 1 or late July for Semester 2). For more 

information regarding the enrolment process contact: 

Faculty of Health Sciences 

Plaza Building, Level 2 

North Terrace Campus 

(08) 8313 5336 

Or visit the Faculty of Health Sciences website: http://www.health.adelaide.edu.au/programs/honours/ 

“The option of undertaking an Honours degree on a full-time (one year) 

or part-time (two year) basis as a medical student is becoming 

increasingly popular. The honours programme is engaging and 

rewarding in gaining thorough 'ground-level' understanding of the 

principles of good clinical research practice. The School of Paediatrics 

and Reproductive Health has been very supportive and flexible with a 

fantastic series of statistics and research tutorials. I would encourage 

those interested in exploring the exciting prospects of honours in the 

School of Paediatrics and Reproductive Health to seek helpful guidance 

from Dr Kathy Gatford as soon as possible” 

Brenton Systermans & Tom Cundy (completed Honours 2010, School of 

Paediatrics and Reproductive Health). 

Tom has since been awarded a $150,000 2011 General Sir John Monash 

scholarship to study for his PhD in robotic surgery. 

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Expression of Interest in an Honours Project 

Personal Details 

Student ID Name 

Address Postcode 

Phone Email 

Alternate contact details (if we need to contact you at a different place/number/ e-mail): 

Dates to use alternate contact details Start date End date 

Address Country 

Telephone Email 

Candidature Details 

Undergraduate degree 

Citizenship (Tick one) 

Australian citizen 

New Zealand citizen 

permanent resident 

I will hold a visa whilst studying honours 

(international students) 

Visa type: ......................................................... 

Start date (Year/Semester) 20 ...... Semester 1 Semester 2 

Enrolment load Full time Part time 

Honours Project Details 

Title 

Discipline (Tick one) Paediatrics Obstetrics & Gynaecology 

Supervision details 

Primary 

Supervisor 

Location 

Email Phone 

Signature Date 

Cosupervisor Email 

ATTACH a copy of your current academic transcript when you return this form. If you have completed 

undergraduate studies at an institution other than the University of Adelaide you will also need to 

provide an official copy of your transcript once your final marks are available. 

DUE DATE: 4 November for first round Semester 1 offers of the following year. 

18 June for mid year offers (Semester 2 of the same year). 

Forms will still be accepted after these dates but will be treated on an ad hoc basis. 

SUBMIT via: Email: sprh.l_and_t@adelaide.edu.au 

In person/ by post to: Honours Coordinator, School of Paediatrics and Reproductive Health 

Level 3, Medical School South, Frome Road, University of Adelaide, Adelaide SA 5005. 

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Honours Scholarships and Support 

Scholarships are available to support full time Honours study in the School of Paediatrics and 

Reproductive Health. Different projects will be eligible for different scholarships, and these 

are indicated by the following symbols next to the project description: 

Robinson Institute .R. 

Discipline of Obstetrics and Gynaecology O&G. 

Eligibility for scholarships 

Applicants must: 

▪ be enrolled in their Honours degree full time. 

▪ be Australian citizens, permanent residents of Australia or hold a suitable Visa 

▪ have completed an undergraduate degree in a relevant area before scholarship 

commencement 

▪ meet the specific requirements for eligibility for specific scholarships (see below) 

Honours scholarship conditions: 

The following conditions apply to all Honours scholarships awarded through our School: 

1. The award of the scholarship is subject to acceptance into an Honours program at 

the University of Adelaide through the School of Paediatrics and Reproductive Health 

and commencement of the project within 12 months of approval. 

2. Awardees may only hold one Honours scholarship funded from within The University of 

Adelaide. 

3. The awardee must complete their Honours degree. Should the awardee withdraw 

from the Honours program the scholarship will be cancelled and all scholarship 

monies are repayable to the sponsor (i.e. Discipline, Robinson Institute, Children’s 

Research Centre or Project supervisor). 

4. You must notify the project sponsor in writing if you: 

a. discontinue your studies 

b. cease to study or cease to be enrolled 

c. change your course of study 

d. change your address 

Selection 

The Scholarships selection committee will review applications, considering the following: 

▪ eligibility criteria 

▪ student Grade Point Average (GPA) 

▪ the strength of the potential Honours project 

▪ endorsement from the potential supervisor 

The selection committee may choose not to award scholarships based on the quality of 

applications. 

Discipline of Obstetrics and Gynaecology Honours Scholarships 

The Discipline of Obstetrics and Gynaecology is offering up to three Honours scholarships, 

each valued at $4000 pa, for Honours students enrolled through our Discipline. These 

scholarships will be awarded to students who have a Disctiction average in their previous 

undergraduate studies. The Discipline of Obstetrics and Gynaecology also provide 

dedicated computers for Honours student use (one computer per two students) to facilitate 

your studies. 

Projects eligible for these scholarships are marked with O&G. 

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Robinson Institute Honours Scholarships 

2011 Jeffrey Robinson Honours 

Scholarship Recipent 

The Jeffrey Robinson Honours Scholarship 

The purpose of The Jeffrey Robinson Honours Scholarship is to attract high quality students to 

the research programs of The Robinson Institute and its constituent centres. Emeritus Professor 

Jeffrey Robinson, born in Northern Ireland, was appointed Professor of Obstetrics and 

Gynaecology at the University of Adelaide in 1986. Under his leadership the University 

developed its outstanding reputation for research into fetal-maternal physiology and 

reproductive medicine and biology. In 2006 he was awarded a Commander of the British 

Empire (CBE) for his services to maternal and fetal heath. Jeffrey continues to be involved in 

research at The Robinson Institute. 

The Robinson Institute will be awarding one Jeffrey Robinson Scholarship to an exceptional 

student. The successful applicant will: 

▪ Undertake a research project within a successful research team 

▪ Receive a tax-free scholarship to the value of $7,000 

▪ Be enrolled in The Robinson Institute Honours Mentoring Program, which provides 

students one-on-one coaching with our leading researchers across areas of 

reproductive health and regenerative medicine. 

Projects eligible for these scholarships are marked with .R. 

The Robinson Institute brings together over 400 

cutting edge researchers in the areas of 

reproductive health, the health of women and 

babies, origins of health of disease and stem cell 

research. 

By focusing on the earliest stages of life, the 

Robinson Institute and its centres are looking at 

preventing disease and promoting health in 

children and adults across generations. The Institute 

bridges the gap between research discoveries and 

medical practice. Many of the Institute's senior 

researchers are leading clinicians in their fields, 

enabling a strong translation of research 

discoveries, with immeasurable benefits, into the 

community. 

As a member of the Robinson Institute you are 

eligible to apply for the Jeffrey Robinson Honours 

Scholarship. The Institute also offers its members the 

opportunity to participate in mentoring and 

professional development programs and gain 

research support, such as assistance in applying for 

awards and external scholarships. 

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Discipline of Obstetrics and Gynaecology 

Scholarship Application Form 

APPLICANT DETAILS 

First name: Surname: Student no: 

Undergraduate Degree: Institution: 

Postal Address: 

Citizenship: (please circle) 

Australian citizen New Zealand citizen Permanent Resident Visa Holder 

Email: Phone: Mobile: 

PROJECT DETAILS 

Proposed Honours Project Title: 

Brief Description: (250 word maximum) 

PRIMARY SUPERVISOR 

Email: Phone: 

Location: 

Signature: Date: 

Co-supervisor: Signature: 

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Scholarship/s being applied for: (Please tick appropriate box/es) 

Robinson Institute .R. 

Discipline of Obstetrics and Gynaecology O&G. 

Please explain how this research project aligns to the Discipline, Robinson Institute or Research Centre 

strategic research objectives. (250 word maximum). 

Declaration 

I declare to the best of my knowledge and belief that the information I have supplied in this application is correct 

and complete. 

I understand that selection for these Honours scholarships is competitive and not all applicants who meet the 

basic eligibility criteria are necessarily awarded scholarships. I have read and understand the conditions of these 

scholarships as outlined in the School of Paediatrics and Reproductive Health ‘Honours Research Opportunities 

booklet’. I recognise that it is my responsibility to provide all necessary documentation and applications with 

incomplete documentation cannot be considered. 

Applicant signature: Date: 

ATTACH to this application: 

1. A cover letter. 

2. Your ‘Expression of interest in Honours’ form and transcript. 

3. A one page current CV. 

DUE DATE: 4 November, 2012. 

SUBMIT via: Email: sprh.l_and_t@adelaide.edu.au 

OR 

In person/ by post to: 

Honours Coordinator 


Level 3, Medical School South, Frome Road 

University of Adelaide, Adelaide SA 5005 

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Discipline of Obstetrics and Gynaecology 

Medical School 

Women’s and Children’s Hospital 

Lyell McEwin Hospital 

Royal Adelaide Hospital 

The Robinson Institute 

“The Discipline of Obstetrics and Gynaecology is a 

leading centre of academic research with an 

international reputation in the areas of maternal-fetal 

physiology, circadian physiology, reproductive 

immunology, embryology, advanced reproductive 

technology, feto-maternal medicine, the fetal origins 

of adult disease, perinatology, placentology, the 

genomics of pregnancy disorders e.g. preterm 

delivery, regenerative medicine and stem cell 

research, pre-eclampsia and cerebral palsy, 

urogynaecology and postmenopausal health . We 

are the largest and most research-active Discipline of 

Obstetrics and Gynaecology in the world and our 

range of interests from basic science through to 

clinical practice creates multiple and successful 

career paths for our graduates.” 

Dr Paul Duggan 

Head of Discipline of Obstetrics and Gynaecology 

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The Australian Research Centre for Health of Women and Babies 

Supervisors (photographs left to right) 

Professor Caroline Crowther 

Professor Jodie Dodd 

Philippa Middleton 

Emeritus Professor Jeffrey Robinson 

Associate Professor Ross Haslam 

Dr Andrew McPhee 

Dr Rosalie Grivell 

Dr Chad Andersen 

Dr Helena Oakey 

Associate Professor Dominic Wilkinson 

Dr Lisa Yelland 

Dr Thach Son Tran 

Professor Alastair MacLennan 

Dr Catherine Gibson 

Dr Michael O’Callaghan 

Dr Lisa Moran 

Dr Yee Khong 

Location: Women’s and Children’s Hospital 

The Australian Research Centre for Health of Women and Babies (ARCH) conducts high quality and timely maternal 

and perinatal research encompassing the spectrum from preconception through pregnancy and childbirth, infancy 

and later life through its six research divisions www.adelaide.edu.au/arch: 

Research Synthesis 

o Through the Research Synthesis Division we conduct, promote and support the preparation and 

updating of high quality systematic reviews of the existing evidence on questions of relevance to 

women and babies in Australia, regionally in South East Asia, and internationally. 

• Clinical Studies and Trials 

o Within the Clinical Studies and Trials Division we focus our research around nine key themes; Preterm 

Birth, Obesity, Diabetes, Maternal and Fetal Medicine, Term Birth, Multiple Pregnancy, Cerebral Palsy, 

Obstetric Medicine and Perinatal Ethics and Decision Making. 

• Translational Research 

o Our Translation Research Health Division focuses on promoting evidence-based practice in women’s 

and babies’ health by the dissemination and implementation of clinical research findings into clinical 

practice. We are achieving this by participating in guideline development, guideline methods and 

conducting implementation studies. 

• Indigenous Maternal and Perinatal Health 

o Through our Indigenous Maternal and Perinatal Health Division we continue to maintain and build our 

collaborations with indigenous organisations, contribute to policy knowledge and endeavour to seek 

collaborative research and evaluation opportunities. 

• Research Networks and Education 

o We continue to provide high profile research opportunities by identifying research gaps and defining 

research questions of major importance in maternal and perinatal health through our Research 

Networks and Education Division. 

• International Maternal and Perinatal Health 

o Within the International Maternal and Perinatal Health Division we have widened our international 

network of collaborators through conducting individual participant data (IPD) meta-analyses. An 

integral component is the formation of an international collaborative group of trialists where 

researchers provide individual data from their trials possibly creating new knowledge not available 

through aggregate meta-analysis. 

12 |

Clinical Studies and Trials 

The Obesity Study Group is focussed on investigating 

whether lifestyle factors can reduce the risks 

associated with obesity in pregnancy. 

1: Assessment of the maternal fatty acid profile 

during pregnancy and relationship to depression, 

anxiety and quality of life during pregnancy and 

post-partum. 

PROJECT: (Clinical) The relationship of depression and 

anxiety with n-3 long-chain polyunsaturated fatty 

acids during pregnancy and post-partum. 

R. O&G. 

Supervisors 

Dr Lisa Moran 


Professor Maria Makrides 

Professor Robert Gibson 

Contact Person 

Lisa Moran 

Phone: 8313 1352 

lisa.moran@adelaide.edu.au 

http://www.adelaide.edu.au/directory/lisa.moran 

Project Background/Aims 

Overweight and obesity are recognised risk factors 

for depression, anxiety and other psychological 

conditions. Although pregnancy is often thought of 

as a time of emotional well-being, longitudinal studies 

have demonstrated that for many women, 

pregnancy is associated with increased levels of 

depression and anxiety, including the onset or 

relapse of major depressive illness. Depression is 

estimated to affect approximately 9% of women in 

the antenatal period, increasing to 16% in the postpartum 

period, although a far greater proportion of 

women commonly report negative mood during over 

the course of their pregnancy. Both obstetric and 

neonatal complications associated with maternal 

depression are well described, with more extreme 

adverse events including suicide and infanticide. The 

relative contribution of factors including diet and 

physical activity to psychological function during 

pregnancy and the post-partum period is unclear. 

Psychological wellbeing may be associated with the 

long-chain n-3 polyunsaturated fatty acids (n-3 LC 

PUFA), specifically the omega-3 fatty acids 

docosahexaenoic acid (DHA) and eicoapentaenoic 

acid (EPA) with some research indicating DHA 

deficiency may be related to depressive symptoms. 

Furthermore, a depletion of maternal plasma DHA 

also occurs during pregnancy and persists following 

birth and higher intake of n-3 LCPUFA from fish and 

seafood during pregnancy are associated with a 

reduced risk of postnatal depressive symptoms. 

However, the effect of maternal overweight and 

obesity on risk of psychological function including 

depression, anxiety and quality of life and the relative 

contribution of dietary factors including n-3 LCPUFA 

has been poorly documented to date. 

Projects available 

1: Assessment of association between n-3 LC PUFA 

from maternal blood, cord blood and dietary 

questionnaires with psychological function 

(depression, anxiety and quality of life) in overweight 

and obese women during pregnancy and the postpartum 

period. 

References 

Jans LA, Giltay EJ, Van der Does AJ. The efficacy of n- 

3 fatty acids DHA and EPA (fish oil) for perinatal 

depression. Br J Nutr 2010; 104:1577–1585. 

Bennett HA, Einarson A, Taddio A, Koren G, Einarson 

TR. Prevalence of depression during pregnancy: 

systematic review. Obstet Gynecol. 2004;103(4):698- 

709. 

2: Assessment of an antenatal lifestyle intervention 

aimed at preventing excessive gestational weight 

gain in overweight and obese women. 

PROJECT (Clinical): The effect of optimising excessive 

gestational weight gain on risk factors for diabetes 

and cardiovascular disease, placental function and 

body composition in mothers and infants. 

R. O&G. 

Supervisors 

Dr Lisa Moran 


Lisa Moran 

Phone: 8313 1352 


http://www.adelaide.edu.au/directory/lisa.moran 


Overweight and obesity are present in over 50% of 

Australian women and are associated with an 

increased risk of obesity-associated metabolic 

diseases such as cardiovascular disease and 

diabetes. Furthermore, maternal obesity and excess 

weight gain during pregnancy are associated with 

worsened maternal health outcomes including 

gestational diabetes, hypertensive conditions and 

pre-eclampsia, infection, thromboembolic events, 

need for induction of labour, caesarean section, 

perinatal death, preterm birth and high birth weight 

and an increased risk of diabetes and cardiovascular 

disease after pregnancy. Infants of mothers who are 

overweight or obese are more likely to be 

macrosomic, require admission to the neonatal 

intensive care unit, be born preterm, have a 

congenital anomaly, and to require treatment for 

jaundice or hypoglycaemia. The effects of maternal 

obesity may also extend to deleterious effects on 

13 |

offspring with regards to adiposity and 

cardiometabolic risk factors. In humans, there is an 

association between infant birth weight and being 

large for gestational age and risk for higher BMI and 

adverse cardiovascular risk profile in childhood. 

Additionally, maternal factors including maternal 

obesity, obesity in pregnancy or high gestational 

weight gain are associated with risk for childhood or 

adult obesity and a worsened cardiovascular risk 

profile in infancy. Optimising weight management 

during pregnancy is therefore crucial for both 

improving maternal and infant pregnancy outcomes 

and for reducing the risk of obesity and obesityassociated 

diseases such as diabetes or 

cardiovascular disease in mothers and children 

during pregnancy and following childbirth. These 

projects relate to a randomised controlled trial 

comparing standard antenatal care with an 

antenatal lifestyle intervention aimed at preventing 

excessive gestational weight gain in overweight and 

obese women (the LIMIT trial). 

Projects available 

1: Assessment of the effect of the LIMIT trial on risk 

factors for diabetes and cardiovascular disease in 

cord blood from infants at birth and maternal risk 

factors for diabetes and cardiovascular disease 

across pregnancy. 

2: Assessment of dietary intake, eating behaviour, 

physical activity and sedentary behaviour in children 

and parents at long-term follow-up (3 years) in LIMIT 

and the relationship with parental and childhood 

obesity. 

3: Evaluate the occurrence of structural inflammatory 

changes within the placenta among women who 

were overweight or obese, and to evaluate the 

effect of increasing body mass index on these 

changes. 

4: Increasing exercise and diet in overweight 

pregnant women: Validation of exercise and dietary 

questionnaire data with markers of cardiometabolic 

function (taken in early pregnancy, 28 weeks 

gestation and 36 weeks gestation). 

5: Effect of an antenatal dietary and lifestyle 

intervention to limit weight gain in pregnancy on 

neonatal growth and development. 

• Evaluation of neonatal body composition at 

birth as measured by birth weight, length 

and head circumference measures, skinfold 

thickness, and bioimpedance data. 

• Correlation of body composition findings 

with neonatal cord blood evaluation 

(glucose, insulin, adiponectin and 

inflammatory cytokines). 

6: Detailed body composition evaluation at 6, and 18 

months of age as measured by weight, length and 

head circumference measures, skin-fold thickness, 

and bioimpedance data. 

7: Correlation of body composition findings with 

epigenetic changes detected by buccal swab. 

References 

Dodd JM, Crowther CA, Robinson JS. Dietary and 

lifestyle interventions to limit weight gain during 

pregnancy for obese or overweight women: a 

systematic review. Acta Obstet Gynecol Scand. 2008 

May 2:1-5. 

Koklu E, Kurtoglu S, Akcakus M, et al. Increased aortic 

intima-media thickness is related to lipid profile in 

newborns with intrauterine growth restriction. 

Hormone research 2006;65(6):269-75. 

Saarelainen H, Valtonen P, Punnonen K, et al. Flow 

mediated vasodilation and circulating 

concentrations of high sensitive C-reactive protein, 

interleukin-6 and tumor necrosis factor-alpha in 

normal pregnancy--The Cardiovascular Risk in Young 

Finns Study. Clin Physiol Funct Imaging 2009;29(5):347- 

52. 

Curry AE, Vogel I, Skogstrand K, et al. Maternal 

plasma cytokines in early- and mid-gestation of 

normal human pregnancy and their association with 

maternal factors. J Reprod Immunol 2008;77(2):152- 

60. 

Hill C, Llewellyn CH, Saxton J et al. Adiposity and 

‘eating in the absence of hunger’ in children. Int J 

Obes 2008, 32:1499-1505. 

PROJECT (CLINICAL): The association between 

maternal obesity and placental histology. 

R. O&G. 

Supervisors 

Prof Jodie Dodd 

Dr Yee Khong 


Jodie Dodd 

Phone: 8161 7619 


Project Background 

Women who are overweight and obese in 

pregnancy are at increased risk of adverse outcomes 

including, hypertensive conditions and preeclampsia, 

gestational diabetes, infection, thromboembolic 

events, need for induction of labour, 

caesarean section and perinatal death. Histological 

examination of the placenta provides important 

information that can be used to interpret clinical 

outcomes of pregnancy and birth. The LIMIT Trial 

recruited women who were overweight and obese in 

pregnancy and collected information about their 

birth outcomes. 

Expected Outcome 

Histological examination of the placentas of a subset 

of women participating in the study may yield 

important information regarding the effect of 

overweight and obesity on pregnancy outcome. 

14 |

Cerebral Palsy Research Group 

The Cerebral Palsy Research group is the world’s 

premier group investigating the interaction of 

genetic and environmental causes of cerebral palsy. 

PROJECT (BASIC): Perinatal Stroke and Cerebral Palsy. 

R. O&G. 

Supervisors/Contact Persons 

Professor Alastair MacLennan 

alastair.maclennan@adelaide.edu.au 

Dr Catherine Gibson 

catherine.s.gibson@adelaide.edu.au 

adelaide.edu.au/directory/catherine.s.gibson 

Dr Michael O’Callaghan 

michael.ocallaghan@adelaide.edu.au 

adelaide.edu.au/directory/michael.ocallaghan 


Cerebral palsy is a developmental disorder affecting 

movement and posture. It is the result of nonprogressive 

brain injury occurring before birth or early 

in life and there is currently no cure. Cerebral palsy 

affects 1 in 500 babies born in Australia with a total of 

33,000 individuals affected in this country alone (1). 

Cerebral palsy presents a burden to the Australian 

economy of $4 billion per annum. The rate of 

diagnosis has not changed in the last 50 years since 

records have been kept. 

Our group’s ongoing research program has provided 

evidence for an association of clotting genes with 

cerebral palsy (2, 3). The aim of this project will be to 

seek clinical details, such as MRI reports and 

evidence of infection for a cohort of patients with 

cerebral palsy. This clinical information will be 

correlated with existing genetic data to help better 

understand the role of thrombosis in cerebral palsy 

causation. 

References 

1. Access Economics. The Economic Impact of 

Cerebral Palsy in Australia in 2007. 2008. 

2. O'Callaghan ME, Maclennan AH, Gibson 

CS, et al. Fetal and Maternal Candidate 

Single Nucleotide Polymorphism 

Associations With Cerebral Palsy: A Case- 

Control Study. Pediatrics 2012:DOI: 

peds.2011-0739 [pii] 10.1542/peds.2011- 

0739. 

3. Gibson CS, MacLennan AH, Hague WM, et 

al. Associations between inherited 

thrombophilias, gestational age, and 

cerebral palsy. Am J Obstet Gynecol 

2005;193:1437. 

Research Synthesis Division 

PROJECT (Clinical): Interventions for improving health 

of women and babies. 

Supervisor 




Dr Rosalie Grivell 



Phone: 8161 7619 

caroline.crowther@adelaide.edu.au 

Project background 

There are many care practices in pregnancy and 

labour care that require a systematic review of the 

literature. 

Expected outcomes 

• publication of a Cochrane review on The 

Cochrane Library 

• a health topic to suit all research interests 

• research skills gained in preparing a 

systematic review 

• research skills gained in preparing umbrella 

reviews around health topic 

• skills in preparing health statements for 

health professionals and consumers. 

Keywords 

Antenatal care, systematic reviews, perinatal health, 

diagnostic test reviews, intervention reviews. 

References 

Tieu J, Crowther CA, Middleton P. Dietary advice in 

pregnancy for preventing gestational diabetes 

mellitus. Cochrane Database Syst Rev. 2008 Apr 

16;(2) Review. 

Rumbold A, Duley L, Crowther CA, Haslam RR. 

Antioxidants for preventing pre-eclampsia. Cochrane 

Database Syst Rev. 2008 Jan 23;(1):CD004227. 

Review. 

McDonald S, Middleton P. Effect of timing of 

umbilical cord clamping of term infants on maternal 

and neonatal outcomes. Cochrane Database of 

Systematic Reviews 2008:2 

Doyle LW, Crowther CA, Middleton P, Marret S, Rouse 

D. Magnesium sulphate for women at risk of preterm 

birth for neuroprotection of the fetus. Cochrane 

Database Syst Rev (to be published Jan 21 2009). 

Translational Health Division 

PROJECT (Clinical): To identify evidence-practice 

gaps in maternity care. 

R. O&G. 

Supervisor 


15 |




Phone: 8161 7619 

caroline.crowther@adelaide.edu.au 


Clinical research results showing treatments to be 

effective are worthless if this information is not then 

used by health care workers to benefit their patients. 

Several projects will by audit techniques identify 

evidence-practice gaps in maternity care and 

Breast Biology and Cancer 

Supervisors 

A/Prof Wendy Ingman 

Dr Danielle Glynn 

explore reasons for these. Audits will be conducted of 

care practices: 

• preconception 

• antenatal period 

Expected outcomes 

Identification of care practices where there is an 

evidence-practice gap, and exploring the reasons 

why. This will lead on to planning intervention studies 

to improve patient care. 

Keywords 

Evidence-practice gap, audit, barrier analysis. 

Location: Medical School and The Queen Elizabeth Hospital (TQEH) 


A/Prof Wendy Ingman 

Phone: 8313 4100 (Medical School) or 8222 6141 (TQEH) 

wendy.ingman@adelaide.edu.au 

Breast cancer is the most prevalent type of cancer among women, with approximately 13,000 new cases 

diagnosed each year in Australia. The aim of our research is to understand the cellular and molecular mechanisms 

that underpin this high incidence of breast cancer. We study how key risk factors, including menstrual cycling and 

breast density, lead to increased susceptibility of the mammary gland to cancer, with specific focus on how these 

risk factors affect the ability of the immune system to protect this unique tissue against carcinogens and other 

cancer initiating factors. The overarching objective of this research is to provide therapies that reduce a woman's 

lifetime risk of developing breast cancer. 

In addition to studies on breast cancer susceptibility, we also conduct mastitis research. Mastitis is a common 

inflammatory disease in lactating women that causes pain, fever, low milk supply and leads many to cease 

breastfeeding. This research explores the cellular mechanisms that lead to inflammation, and investigates potential 

therapies to quickly and effectively stop the symptoms of mastitis. 

PROJECT: (Basic) Cytokine expression in breast 

epithelial cells. 

R. O&G. 


Previous research in our laboratory has shown that 

macrophage phenotype and function in the 

mammary gland fluctuate in response to the 

changing hormone environment during the estrous 

cycle (which is the mouse equivalent to the human 

menstrual cycle). This is significant because the 

number of menstrual cycles a woman experiences in 

her lifetime is an important determinant of breast 

cancer risk. Macrophage function is dependent on 

the types of cytokines the cell is exposed to. This 

project will investigate cytokine production by 

human breast epithelial cells in vitro, in response to 

ovarian hormone stimulation. 

PROJECT: (Basic) Inflammation and mastitis. 

R. O&G. 


Mastitis is a common inflammatory condition that 

affects 15-20% of lactating women in the first 6 

months postpartum. It causes fever, pain, reduced 

milk production and leads many women to cease 

breastfeeding. Although bacterial infection is highly 

associated with mastitis in dairy cows, the link 

between infection and mastitis in women is less clear. 

A family of inflammatory signalling pathways have 

been identified as playing a crucial role in generating 

the symptoms of mastitis. These pathways are known 

to be stimulated by not only bacteria and their by- 

16 |

products, but also naturally occurring molecules 

found in breast milk. This project will utilise a mouse 

model of mastitis developed in our laboratory to 

further characterise the contribution of inflammatory 

signalling pathways and the role of immune cells in 

the pathology and resolution of mastitis. 

17 |

Circadian Physiology Group 


Professor David Kennaway 

Phone: 8313 4090 

david.kennaway@adelaide.edu.au 

Supervisors 

Professor David Kennaway 

Dr Tamara Varcoe 

Location: Medical School North 

It has been known for many years that a wide range of physiological functions change across 24 hours in a 

predictable manner. These daily or circadian rhythms are entrained to the environmental day/night cycle via the 

eyes, the hypothalamus and a suite of clock gene transcription factors. The clock genes are rhythmically expressed 

in a wide range of tissues and organs, including the liver, muscle, adipose tissue, pancreas, mammary glands and 

reproductive tract. This raises the question of the impact of disruption to their expression on health and the 

predisposition to diseases. To this end the Circadian Physiology Group is actively pursuing the role of clock genes 

and proteins in the maintenance of metabolic homeostasis, susceptibility to the development of breast cancer and 

impaired fertility. 

PROJECT: (Basic) Is eating a high fat diet during the 

night harmful to shiftworkers? 

R. O&G. 


There is increasing evidence that abnormal 

rhythmicity may contribute to, as well as result from, 

diabetes and related disorders. Shift work schedules 

disrupt sleep/wake rhythmicity, eating patterns and 

light exposure and as a consequence shift workers 

are at a high risk of becoming obese and developing 

diabetes compared to day workers. This strongly 

suggests that abnormal rhythmicity may be an 

important causal factor in certain diseases. 

Direct 

evidence for this is currently lacking and the nature of 

the underlying mechanisms responsible is unknown. 

We have, however, shown that mutations in clock 

genes that disrupt rhythmicity alter glucose control. 

The aim of this study is to determine the effect of mismatching 

the availability of food and the light dark 

cycle on metabolic homeostasis. 

Mice will be given access to a high fat diet 

exclusively during the light period or during the dark 

period (control) for 4 weeks. The effects on circadian 

rhythms of various organs will be determined, 

together with the effects on metabolic function. 

Expected Outcome 

The continual mis-matching of food availability and 

the light schedule will lead to glucose intolerance 

and insulin resistance. 

What you will gain 

Wider understanding of metabolic control systems, 

analytical skills, including Real time RT-PCR and 

hormone immunoassay. 

Reference 

D. J. Kennaway, J. A. Owens, A. Voultsios, M. J. Boden and T. 

J. Varcoe (2007) Metabolic homeostasis in mice with 

disrupted Clock gene expression in peripheral tissues, 

American Journal of Physiology 293 (4) R1528-R1537 

PROJECT: (Basic) Uterine expression of clock genes 

and clock controlled genes in early pregnancy. 

R. O&G. 


The involvement of daily or circadian rhythmicity in 

reproductive processes has been recognised for over 

30 years and is particularly evident in female rodents. 

Laboratory mice and rats have a precisely timed 

surge in LH on the afternoon of pro-estrus, which 

results in ovulation around 6 hours later and 

copulation and fertilisation within a few hours of the 

ovulation. This rhythmicity is driven by a group of 

neurons in the brain called the suprachiasmatic 

nucleus (SCN). The contemporary view of how the 

SCN generates its endogenous rhythmicity is that a 

set of proteins exerts both positive and negative 

feedback actions on their own gene expression. The 

two key proteins are CLOCK and BMAL1, which form 

heterodimers and bind to an enhancer E-box in the 

promoters of per1 and per2, driving their 

transcription. It is now also clear that peripheral 

tissues including the reproductive tract express a 

wide range of proteins rhythmically and that 

18 |

disruption of either Clock or Bmal1 has a deleterious 

effect on reproduction. 

The aim of this project will be to determine what 

changes occur in early pregnancy in Clock mutant 

mice that lead to the fetal loss often observed in 

these animals. 

Adult Clock ∆ 19 mutant mice and their respective 

control lines will be mated with appropriate control 

males. Uteri will be obtained at 4 hour intervals for 48 

hours, starting on the morning of day 4 after sperm 

detection and processed to measure the expression 

of a range of genes at selected times; 

For example Clock genes: Per1, Per2, Clock & Bmal1; 

Clock controlled genes: Bsg, PAI-1, COX-2, VEGF & 

EG-VEGF. Cytokines: TGFβ, TNFα, IL-10, IL-5, IL-11, IL- 

11R; Growth factors: Leptin, lif, igf-1, igf-2 and igf-bp1; 

Transcription factor: HOXA10 

Expected Outcomes 

This experiment will provide us for the first time with 

information on the role of cellular rhythmicity in the 

peri-implantation period. 

What you will gain 

Wider understanding of early implantation control 

systems, embryology, analytical skills, including Real 

time RT-PCR. 

Reference 

D. J. Kennaway, M. J. Boden and A. Voultsios (2005) 

Reproductive performance in female Clock ∆ 19 mutant 

mice. Reproduction Fertility and Development 16: 801-810 

19 |

Developmental Biology of the Ovary 


Professor Ray Rodgers 

Phone: 8313 3932 

ray.rodgers@adelaide.edu.au 

Supervisors 


Dr Katja Hummitzsch 

Location: Level 2, Medical School North 

The ovary produces eggs and hormones, and these functions are dependent upon growth and development of 

follicles and corpora lutea within the ovary. Control of these processes is externally via hormones, or internally by 

growth factors and extracellular matrix. In particular our laboratory focuses on the role of extracellular matrix in 

regulating ovarian function as this has been poorly studied. We use molecular and cellular biology approaches. This 

area is important as extracellular matrix can be used to regulate ovarian cell function in vitro, as well as aiding in the 

understanding of ovarian diseases including infertility and hormone imbalances. 

Recently we discovered that the follicular basal lamina structure is related to the quality of the oocyte in the follicles 

(1) and we are hunting biomarkers of such follicles with a view to improving success or assisted reproductive 

technologies. We also discovered that a specialized extracellular matrix, focimatrix, is not only developmentally 

regulated in follicles but may be part of the mechanism by which a dominant follicle is selected to ovulate (2). 

Currently we do not understand how one follicle is selected or gains dominance over other follicles as a means of 

controlling ovulation rate, and our discovery could be valuable in unravelling this phenomenon. 

References 

Irving-Rodgers HF, Morris S, Collett RA, Peura TT, Davy M, Thompson JG, Mason HD, Rodgers RJ (2009) Phenotypes of 

the ovarian follicular basal lamina predict developmental competence of oocytes. Human Reprod. 24, 936-944 

Irving-Rodgers HF, Harland ML, Sullivan TR and Rodgers RJ (2009) Studies of granulosa cells maturation in dominant 

and subordinate bovine follicles: Novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol sidechain 

cleavage CYP11A1. Reproduction 137, 825-834. 

Key Words 

Extracellular matrix, ovary, follicle, corpus luteum. 

PROJECT: (Basic) Microarray analysis of the epithelialmesenchymal 

transition (EMT) of granulosa cells. 

R. O&G. 

Supervisors 



The wall of the ovarian follicle is a stratified epithelium 

and at ovulation and after the release of the oocyte, 

the follicle wall remodels completely. At this time the 

follicular basal lamina is degraded, and cells from the 

surrounding stromal thecal layer migrate between 

the epithelial granulosa cells (Fig. 1). The follicle wall 

thus develops into the corpus luteum. This is 

accompanied by a substantial increase in 

progesterone synthesis via a process termed 

luteinisation and the cells derived from the granulosa 

cells are referred to as luteal cells. 

Luteinisation has all the features of an epithelialmesenchymal 

transformation. A key component of 

EMT in vivo is the destruction of the epithelial basal 

lamina (Fig. 2). During this process the epithelial cells 

lose apical-basal polarity and instead develop the 

mesenchymal cell features necessary for migration. 

During embryogenesis and tissue repair or cellular 

reorganization, as well as in the metastasis of 

carcinomas, epithelial cells can undergo a transition 

into mesenchymal cells that is referred to as 

epithelial-mesenchymal transition (EMT) (Fig. 2). 

Studies of EMT have largely been conducted using 

cells from simple epithelia. Importantly, this project 

will study the EMT of the stratified epithelium of the 

ovarian follicle. Techniques used will include 

microarray analysis comparing granulosa cells and 

luteal cells. 

20 |

PROJECT: (Basic) Stem Cells of Ovarian Follicles. 

R. O&G. 

Supervisors 



Our laboratory has shown that a proportion of 

granulosa cells isolated directly from antral follicles 

have a number of stem cell properties. These include 

the ability to divide under anchorage independent 

conditions [2], divide without contact inhibition [1] 

and express telomerase [3]. On this basis we 

proposed the model shown in the above figure [1]. 

It assumes plutipotentiality into at least cumulus cells 

(specialized cells surrounding the oocyte) and mural 

granulosa cells. The pluripotency of granulosa stem 

cells has yet to be demonstrated, however in mice 

expressing a dominant-stable mutant of betacatenin, 

clonally derived granulosa cell tumours 

develop. These can be of granulosa, bone or neural 

phenotype [4], suggesting that tumours of granulosa 

cells are pluripoten. The goals of this project are to 

investigate the pluripotential of granulosa cells. 

PROJECT: (Basic) Thecal stem cells – Real or not? 

R. O&G. 

Supervisors 



In a recent Proceedings of the National Academy of 

Sciences article, ‘thecal stem cells’ [5] were reported 

in new born mice. However in this species follicles 

are still developing at birth. 

Whole ovaries were treated with collagenase and 

from this a heterogeneous mixture of cells was 

cultured and colonies of stem cells were identified in 

anchorage-independent culture. The authors 

identified expression of markers found in thecal cells, 

which in vivo are only expressed in the presence of 

granulosa cells. However they did not examine the 

colonies to see if all cells expressed the markers. 

Therefore it is possible that the colonies were of mixed 

cell type, containing granulosa stem cells and some 

thecal cells. Certainly the colonies bore a sticking 

resemblance to granulosa stem cells [2]. 

References 

Rodgers RJ, Lavranos TC, van Wezel IL, Irving-Rodgers 

HF. Development of the ovarian follicular epithelium. 

Mol Cell Endocrinol 1999; 151: 171-179. 

Lavranos TC, Rodgers HF, Bertoncello I, Rodgers RJ. 

Anchorage-independent culture of bovine granulosa 

cells: the effects of basic fibroblast growth factor and 

dibutyryl cAMP on cell division and differentiation. 

Exp Cell Res 1994; 211: 245-251. 

Lavranos TC, Mathis JM, Latham SE, Kalionis B, Shay 

JW, Rodgers RJ. Evidence for ovarian granulosa stem 

cells: telomerase activity and localization of the 

telomerase ribonucleic acid component in bovine 

ovarian follicles. Biol Reprod 1999; 61: 358-366. 

Boerboom D, White LD, Dalle S, Courty J, Richards JS. 

Dominant-stable beta-catenin expression causes cell 

fate alterations and Wnt signaling antagonist 

expression in a murine granulosa cell tumor model. 

Cancer Res 2006; 66: 1964-1973. 

Honda A, Hirose M, Hara K, Matoba S, Inoue K, Miki H, 

Hiura H, Kanatsu-Shinohara M, Kanai Y, Kono T, 

Shinohara T, Ogura A. Isolation, characterization, and 

in vitro and in vivo differentiation of putative thecal 

stem cells. Proc Natl Acad Sci U S A 2007; 104: 12389- 

12394. 

PROJECT: (Basic) Bioinformatics of Ovarian Follicle 

Development. 

R. O&G. 

Supervisor 


Bioinformatics is a newly emerging area of increasing 

importance in all areas of biology. Currently there 

are insufficient numbers of bioinformaticians to satisfy 

the need to fully exploit the explosion of data 

currently available, much less that to be produced in 

the future. 

Microarrays produce a wealth of data. We have 

conducted over 70 Affymetrix gene expression arrays 

each with over 20,000 probe sets which equates over 

1.5 million pieces of data from our experiments alone. 

We have arrays performed on RNA isolated different 

ovarian compartments (theca layers, granulosa cells, 

cumulus-oocyte complexes) from follicles at different 

stages of health and development, and from cells 

(theca and granulosa) in culture. There are 

numerous computer programs for basic analyses and 

we routinely use Partek and Ingenuity Pathway 

Analysis (IPA) and are currently conducting basic 

analysis of these arrays. We have made novel 

discoveries of follicle development, not hitherto 

apparent by previous hypothesis-driven research. 

Heat Map of gene expression comparing 14 follicles. 

21 |

This project will mine our data in greater detail for 

relationships between in vitro and in vivo data. It will 

compare our data with other data sets available 

publicly or collaboratively from ovaries of other 

species, from other organs and cell types and 

diseases identified by IPA. It will identify unique novel 

markers of cell types and behaviours in follicles. 

Key words 

Bioinformatics, microarray, computer analyses. 

PROJECT: (Basic) Ovarian fetal stroma and PCOS 

(polycystic ovary syndrome). 

R. O&G. 

Supervisors 


Katja Hummitzsch 


Polycystic ovary syndrome (PCOS) is the commonest 

endocrine condition affecting an estimated 5-7% of 

women of reproductive age in Western societies, and 

is a major burden on health costs. It is characterised 

by hyperandrogenaemia and hirsutism, chronic 

anovulation, and polycystic ovaries. Affected 

women are also at increased risk of anovulatory 

infertility, obesity, hyperlipidaemia, type II diabetes 

and possibly cardiovascular disease. 

Its causes are not well understood but it is thought 

that there is both a genetic predisposition and a fetal 

cause. The ovary also has excessive collagen and 

stroma, which in other tissues, is due to increased 

activity of transforming growth factor-β. In a recent 

study (1) we found that fibrillin 3, thought to regulate 

TGFβ activity in tissues and a gene that is familiarly 

linked to PCOS is expressed in fetal ovaries at a 

critical time when follicles are forming and the 

ovarian stroma is expanding. 

This project will examine cultured bovine fetal ovarian 

cells to determine which cells express fibrillin 3 and to 

examine how fibrillin 3 is regulated during gestation. 

This information is the critical next step in 

understanding the causes of PCOS, and hopefully its 

prevention. 

The project will involve primary cell culture from 

ovaries obtained from an abattoir and basic cell and 

molecular biology techniques. 

Reference 

Hatzirodos N, Bayne RA, Irving-Rodgers HF, 

Hummitzsch K, Sabatier L, Lee S, Bonner W, Gibson 

MA, Rainey WR, Carr BR, Mason HD, Reinhardt DP, 

Anderson RA, Rodgers RJ (2011) Linkage of regulators 

of TGFβ activity in the fetal ovary to polycystic ovary 

syndrome. FASEB Journal 25, 2256-2265. 

22 |

Early Development Group 


Dr Mel McDowall 

Phone: 8313 8197 

melanie.mcdowall@adelaide.edu.au 

Supervisors 

Associate Professor Jeremy Thompson 

Dr Robert Gilchrist 

Dr Mel McDowall 

Location: Medical School 

A major focus of our laboratory is the influence of the microenvironment surrounding the oocytes (eggs) and 

embryos on development outcomes, with particular focuses on metabolites (glucose, oxygen) and associated 

pathways and genes (for example Hypoxia Inducible Factor, HIF). The incidence of diet related obesity (such as high 

glucose diets) in Australia is rapidly increasing and is associated with higher susceptibility le to chronic diseases, 

decreased fertility, poor pregnancy outcomes and development of children born from obese mothers. Glucose is 

particularly important for oocyte development and alterations in the level of glucose the oocyte is exposed to prior 

to fertilisation can have a negative impact on the success of embryo development. 

Research performed within our group is relevant to human reproduction, human assisted reproduction and the 

livestock farming industries through a better understanding of the impact of the maternal environment on successful 

fertilisation and early embryonic development. Furthermore, our research aims to enhance the outcomes of both 

human and livestock in vitro embryo production by developing improved culture conditions. 

PROJECT: (Basic) Glucosamine supplementation 

during the peri-conception period and pregnancy 

outcomes. 

R. O&G. 


It is recognised that maternal health during 

pregnancy impacts the pre-natal development and 

long-term health of children. In particular, maternal 

hyperglycaemia (blood glucose levels greater than 

240-300 mg/dl, as a result of type I and II diabetes, 

poor diet and obesity) is related to reduced fertility 

and increased rates of miscarriage and congenital 

abnormalities. 

Recent developments suggest that the brief window 

prior to and during conception (peri-conceptional 

period), coinciding with oocytes (eggs) undergoing 

rapid changes to prepare for fertilisation, is critical for 

successful fertilisation, implantation, pregnancy and 

long-term health. In particular, maternal 

hyperglycaemia is related to compromised oocyte 

development, such as smaller and fewer oocytes 

and reduced ability to successfully develop after 

fertilisation. Hence, the levels of glucose the oocyte is 

exposed to prior to fertilisation can impact the 

establishment of pregnancy and possible the longterm 

health of resulting children. 

Our group has demonstrated that artificially 

stimulating a particular fuel sensing pathway using 

the hyperglycaemia mimetic glucosamine, results in 

poor oocyte and embryo quality. However, the 

mechanisms of how glucosamine is affecting fertility 

are unknown. 

The aim of this project is to characterise the influence 

of glucosamine administration in mice on 

reproductive organs (ovaries, uterus) and pregnancy 

outcomes (fetal development). Techniques include 

animal handling, tissue preparation and staining and 

morphology assessments. 

PROJECT: (Basic) Glucosamine supplementation and 

the oocyte. 

R. O&G. 

Project Backgound 

Glucosamine is a dietary supplement that is 

commonly used to treat joint problems. However, 

glucosamine supplementation during oocyte 

maturation results in poor embryo development postfertilisation 

by mimicking hyperglycaemic conditions. 

The aim of this project is to further investigate the 

mechanisms through which glucosamine 

supplementation is perturbing pig oocyte 

development. Techniques include tissue culture, 

staining and metabolism assays. 

23 |

PROJECT: (Basic) Why is there haemoglobin in 

cumulus cells? 

R. O&G. 


We have recently produced microarrays of mouse 

cumulus cells obtained from naturally ovulated 

cumulus-oocyte complexes (COCs) and in vitro 

matured COCs. A consistent finding is that mRNA for 

haemoglobin is produced by cumulus cells derived 

from in vivo matured COCs at high levels compared 

to in vitro matured COCs. Furthermore, this 

difference has been validated by RT-PCR. 

Haemoglobin production by cumulus cells has never 

previously been reported and is a unique 

observation. This begs the question “Why would 

cumulus cells require the production of 

haemoglobin?” One candidate mechanism involves 

the regulation of cGMP and nitric oxide, both of 

which are known to be involved in the ovulatory 

process. Haemoglobin is a known sequestering 

molecule for nitric oxide, so we have hypothesised 

that cumulus cells derived from in vivo ovulated 

COCs produce haemoglobin in response to the 

ovulatory process and this is lacking during in vitro 

maturation. This project aims to investigate the 

production of haemoglobin and determine its roles 

during follicle ovulation and oocyte maturation. 

Techniques will initially include RT-PCR, 

immunohistochemistry and western blotting. 

References 

Sutton ML, Gilchrist RB and Thompson JG (2003), 

Effects of in vivo and in vitro environments on 

metabolism of the cumulus-oocyte complex and its 

influence on oocyte developmental capacity, Hum 

Reprod Update, 9 (1): 35-48 

Sutton-McDowall ML, Gilchrist RB and 

Thompson JG (2004) Cumulus-expansion and glucose 

utilisation by bovine cumulus-oocyte complexes 

during in vitro maturation: the influence of 

glucosamine and follicle stimulating hormone, 

Reproduction, 128 (3): 313-19 

Sutton-McDowall ML, Mitchell M, Cetica P, 

Dalvit G, Pantaleon M, Lane M, Gilchrist RB and 

Thompson JG (2006) Glucosamine supplementation 

during in vitro maturation inhibits subsequent oocyte 

developmental competence, Biol Reprod, 74: 881-88. 

Schelbach CJ, Kind KL, Lane M and Thompson 

JG (2010) Mechanisms contributing to the reduced 

developmental competence of glucosamineexposed 

mouse oocytes. Reprod Fertil Dev, 22 (5): 

771-9. 

Sutton-McDowall ML, Gilchrist RB and 

Thompson JG (2010) The pivotal role of glucose 

metabolism in determining oocyte developmental 

competence. Reproduction, 139(4):685-95. 

PROJECT: (Basic) Lipid oxidation in cattle/sheep 

oocytes. Unlocking an un-used energy source to 

increase developmental competence during in vitro 

maturation. 

R. O&G. 

Supervisors 

Dr Kylie Dunning 

Dr Melanie McDowall 

A/Prof Jeremy Thompson 


Intra-oocyte ATP levels are correlated with oocyte 

developmental competence post-fertilisation. 

Oocytes have little capacity to produce ATP and are 

dependent on oxidative phosphorylation within 

mitochondria. Cattle, sheep and pig oocytes are 

characterised by significant intracellular stores of 

lipid. It has been calculated that there is enough 

“stored energy” within these lipid stores to drive all 

the necessary ATP production for early development. 

However, when oocytes mature in vitro (or early 

embryos are cultured in vitro), exogenous 

carbohydrates and derivatives are essential for 

further development, suggesting the lipid stores are 

not utilised. Work conducted in the Ovarian Cell 

Biology Group has found that in the mouse, the 

addition of carnitine to oocyte maturation media 

significantly increases lipid metabolism and ATP 

production. Carnitine is a co-factor required for the 

transfer of lipids, in the form of fatty acids, from the 

cytosol, into mitochondria, where they undergoe �oxidation 

and producte ATP. This project will 

investigate the role of carnitine and lipid oxidation 

within cattle/sheep oocyte culture in vitro. Skills 

learnt will include oocyte maturation and embryo 

production in vitro as well as metabolic assays and 

fluorescence microscopy investigating mitochondrial 

function. 

24 |

Early Life Programming of Health and Disease 

Contact Persons 

Professor Julie Owens 

Phone: 8313 4088 

julie.owens@adelaide.edu.au 


Phone: 8313 4158 

kathy.gatford@adelaide.edu.au 

Supervisors 



Professor Claire Roberts 

Dr Miles De Blasio 

Ms Patricia Grant 

Emeritus Professor Jeffrey Robinson 

Our research group is part of the Research Centre for the Early Origins of Health and Disease (EOHaD) and an 

international leader in the investigation of the intergenerational and perinatal origins of metabolic and 

cardiovascular health in postnatal life. We focus on how our health can be profoundly influenced by events in early 

life and possibly in previous generations, including diabetes, obesity and cardiovascular increasing risk of disease. 

Common exposures in early life that affect our later health include placental and fetal growth restriction, maternal 

vitamin supplementation and maternal obesity and diabetes. 

Our aims are to: 

• understand how these exposures interact with the genome and affect the epigenome to determine our later 

health 

• identify interventions to either prevent these conditions that program later health or to overcome or reverse 

such programming. 

Recent key discoveries include: 

• placental restriction 

o inducing diabetes in adult offspring via impaired beta cell function and growth and insulin resistance 

o causing obesity in offspring via altered appetite control 

• altering expression of novel small regulatory RNAs that target and repress expression of multiple mRNAs to 

affect major pathways and funtions 

• maternal folate deficiency or folic acid supplementation in changing the epigenome and physiology of 

offspring. 

Our research strategies include: 

• novel experimental models of common early life exposures in non human species 

• clinical research of human cohorts with exposure to common pregnancy complications 

• in vivo characterisation of insulin action, glucose and lipid control and other physiological functions 

• metabolite and hormone analysis by enzymatic analysis and immunoassay 

• quantitative morphmetric analysis of tissue structures underpinning function 

• molecular analysis of expression of regulatory RNAs and protein coding genes by quantitative PCR, microarray 

and western immunoblotting 

• analysis of epigenetic state of genes by bisulfite treatment of DNA and Sequenom or Pyrosequencing 

• bioinformatics, including pathway analysis of array data of microRNA and mRNA expression. 

We publish in the top discipline specific and general journals, are highly cited and regularly invite to speak at 

leading conferences. Our students publish their work, present at conferences and have gone on to a range of 

careers as researchers, academics, health professionals, in the biotechnology and pharmaceutical industry and 

management. 

25 |

PROJECT: (Basic) Can maternal dietary arginine 

supplementation increase placental function and 

fetal survival at birth? 

R. O&G. 

Supervisors 


Dr Miles De Blasio 


The placenta acts as the lungs, gut and kidneys for 

the growing fetus before birth and influences how 

well it grows, develops and its survival. We have 

shown that increasing maternal dietary intake of the 

amino acid arginine throughout pregnancy may 

increase fetal growth, size at birth and survival. This 

project will investigate the mechanisms underlying 

this improvement, including by increasing production 

of the vasodilator nitric oxide and hence increasing 

placental blood flow, and development of blood 

vessels in the placenta. This may identify a new 

approach to restoring placental functional 

development in women and to enhancing 

reproductive efficiency in the pig industry. 

PROJECT: (Basic) Do small non-coding RNAs mediate 

onset of diabetes and obesity in offspring of obese fat 

fed mothers? 

R. O&G. 

Supervisors 


Dr Karen Kind 



Maternal obesity is common and increasing and 

results in a high birthweight and greater risk of obesity 

and diabetes in offspring later in life. This may be 

partly responsible for the growing epidemic in 

obesity, including in children. Recently, we have 

shown that restricting fetal supply and growth, which 

also leads to diabetes in later life, appears to act in 

part by altering expression of microRNAs (miRs) in key 

functional tissues. A novel and major class of genes 

code for the miRs, which are small RNAs that can 

bind to sites in 3’UTRs of multiple target genes. The 

miRs can regulate many gene mRNA and/or protein 

products in a co-ordinated and powerful fashion. In 

this project we will determine for the first time using 

previously collected samples, if maternal obesity and 

oversupply o f the fetus before birth alters expression 

of microRNAs in the insulin target tissues, skeletal 

muscle and liver and if this relates to altered 

expression of insulin signalling pathways and 

metabolic genes. We will also see if plasma miRs are 

altered and reflect changes in these key tissues 

following maternal obesity. The outcomes will show if 

miRs are a key part of the mechanism by which 

maternal obesity affects metabolic health of 

offspring and if plasma miRs can be used as markers 

of this for future translation into human studies. 

PROJECT: (Basic) Does maternal folic acid 

supplementation alter plasma microRNAs in offspring 

and are these predictive of later metabolic health? 

R. O&G. 

Supervisors 


Dr Karen Kind 


Professor Marie Dziadek 


We have recently shown in rodents that a common 

exposure, maternal folic acid supplementation 

(MFAS), alters metabolic control and insulin action in 

adult offspring. Mandatory food fortification is being 

introduced in Australia as has already occurred 

overseas and will further increase exposure of the 

population before birth. We have shown that MFAS 

acts in part by altering expression of microRNAs 

(miRs) in liver of adult offspring. The miRs can regulate 

many gene mRNA and/or protein products in a coordinated 

and powerful fashion. In this project we will 

determine if MFAS alters plasma concentrations of 

miRs reflecting changed hepatic expression and 

release into blood. If proven, this would identify 

highly accessible potential biomarkers of MFAS 

programming of later diabetes for testing in humans. 

Plasma miRs will be analysed by RTPCR and 

microarray using previously collected samples from 

juvenile as well as adult offspring of obese fat fed 

mothers. 

PROJECT: (Basic) Does maternal obesity alter 

epigenetic state and expression of key regulatory 

and functional genes in offspring? 

R. O&G. 

Supervisors 


Dr Karen Kind 


Professor Marie Dziadek 


Maternal obesity is common and increasing and 

results in a high birthweight and greater risk of obesity 

and diabetes in offspring later in life. This may be 

partly responsible for the growing epidemic in 

obesity, including in children. Maternal obesity 

exposes the developing fetus to high glucose and 

insulin abundance and other metabolic and 

endocrine changes when its epigenetic state is 

changing rapidly. This may alter DNA methylation, a 

major epigenetic mechanism that influences 

expression of genes. Once established, epigenetic 

patterns are heritable through cell division, and can 

26 |

persist long term. There is new evidence in humans 

that maternal obesity can change epigenetic state 

of some genes at birth in the new born, including that 

of PPARCG1A, an important regulator of many 

metabolic genes. This project will test for the first time 

using rodents, if maternal obesity alters epigenetic 

state and expression of PPARCG1A and other 

important genes in key metabolic tissues of offspring 

later in life. DNA methylation in the promoter region 

of PPARCG1A and other genes and their expression 

in liver and skeletal muscle of offspring of obese fat 

fed mothers will be analysed by pyrosequencing 

after DNA bisulfite treatment and by RTPCR. The 

outcomes will show if epigenetic modifications are a 

key part of the mechanism by which maternal 

obesity affects metabolic health of offspring and if 

these can be used as markers of this for future 

translation into human studies. 

PROJECT: (Clinical) 

Is metformin superior to insulin in improving maternal 

and newborn metabolic and cardiovascular risk 

profile in gestational diabetes? 

R. O&G. 

Supervisors 


Dr Bill Hague 


Gestational diabetes is common and increasing in 

prevalence. It is associated with complications for 

the mother and baby and with an increased risk of 

diabetes and associated cardiovascular disease in 

both the mother and the offspring. Modification of 

lifestyle and, if necessary because of maternal 

hyperglycaemia, treatment with insulin injections, 

can improve maternal and infant outcomes at birth. 

Recently, we have shown that oral metformin, which 

improves insulin sensitivity, is similarly effective and 

preferred by women. The aim of this project is to 

measure metabolic, hormonal and other markers of 

diabetes and cardiovascular disease risk in maternal 

blood plasma during and after pregnancy and in 

new born cord blood plasma. These markers will 

include plasma glucose, free fatty acids, triglycerides, 

insulin, C-peptide, leptin, adiponectin and 

inflammatory cytokines. This will provide evidence as 

to the potential efficacy of metformin compared 

with insulin in improving circulating predictors of later 

metabolic and cardiovascular disease in the mother 

and her baby. This will provide the rationale for 

follow-up trials of the long term metabolic outcomes 

for the mother and child. 

PROJECT: (Basic) What are the effects of growth 

hormone on placental development and function? 

R. O&G. 

Supervisors 





Maternal growth hormone treatment can increase 

fetal growth, is being tested as a way to increase size 

at birth in animal industries, and may be a 

therapeutic approach for treating growth-restricted 

pregnancies in humans. Although we have and 

others have shown increased fetal growth in mothers 

given growth hormone injections, we do not know 

the relative importance of maternal metabolic and 

placental responses for increasing fetal growth. In this 

project, we will use archived porcine samples to 

investigate how maternal growth hormone affects 

placental structure and expression of the nutrient 

transporters that determine fetal nutrient supply and 

hence growth, using immunohistology and real-time 

PCR. This may identify a new approach to increasing 

placental functional development in women and in 

animal production, to increase size at birth including 

in growth-restricted pregnancies. This project will be 

jointly supervised by Dr Gatford, Prof Owens and Prof 

Claire Roberts (Placental Biology lab). 

Students undertaking this project are also eligible for 

a Pork CRC Honours scholarship, valued at $10 000 

($5000 stipend plus $5000 operating). 

Application forms (to be completed by you and your 

supervisor and due October 31) are available at 

http://www.porkcrc.com.au/html/education.html. 

References 

M Dziadek. 2005 Genomic imprinting and epigenetic 

programming of fetal development: In: Perinatal 

Programming: Early Life Determinants of Adult Health and 

Disease (Eds DM Hodgson and C Coe). Taylor and Francis 

Medical Books, London. 

Gatford KL, Mohammad SN, Harland ML, De Blasio MJ, 

Fowden AL, Robinson JS, Owens JA (2008) Impaired beta-cell 

function and inadequate compensatory increases in betacell 

mass after intrauterine growth restriction in sheep. 

Endocrinology. 

Oct;149(10):5118-27. 

Quigley SP, Kleemann DO, Walker SK, Speck PA, 

Rudiger SR, Nattrass GS, DeBlasio MJ, Owens JA (2008) Effect 

of variable long-term maternal feed allowance on the 

development of the ovine placenta and fetus. Placenta. 

Jun;29(6):539-48. 

Owens JA, Gatford KL, De Blasio MJ, Edwards LJ, 

McMillen IC, Fowden AL (2007) Restriction of placental 

growth in sheep impairs insulin secretion but not sensitivity 

before birth. J Physiol. 

Nov 1;584(Pt 3):935-49. 

Gatford KL, Boyce JM, Blackmore K, Smits RJ, 

Campbell RG, Owens PC (2004) Long-term, but not shortterm, 

treatment with somatotropin during pregnancy in 

underfed pigs increases the body size of progeny at birth. J 

Anim Sci. Jan;82(1):93-101 

27 |

PROJECT: (Basic) Epigenetic consequences of 

placental restriction and dietary methyl 

supplementation. 

R. O&G. 

Supervisors 


Dr Karen Kind 

Prof Julie Owens 


Poor growth before birth is often caused by poor 

development and function of the placenta, which 

delivers nutrients from the mother to the growing 

fetus. The supply of particular nutrients, including 

methyl donors, is important for chemical 

modifications to DNA, which affect gene 

transcription and can persist into later life. These 

epigenetic changes are thought to contribute to 

long-term increased disease risks, such as diabetes 

and obesity, in the baby who grew poorly before 

birth. We have shown that surgical restriction of 

placental growth and function (PR) produces similar 

long-term outcomes as poor growth before birth in 

humans, including impaired insulin secretion and 

diabetes. As part of a larger NHMRC-funded study, 

we are testing whether feeding the mother extra 

methyl donors in the diet can improve outcomes in 

the growth-restricted lamb. In this study, an Honours 

student will investigate how PR affects circulating 

methyl donors levels in the neonate at birth, and 

whether this can be increased by feeding the mother 

with methyl donors in late pregnancy. We will also 

investigate the effects of PR and methyl donors on 

expression of epigenetically-regulated genes in white 

blood cells and circulating metabolites in plasma 

collected at birth, to assess whether the supply of 

these nutrients in late pregnancy changes epigenetic 

and metabolic state at birth. 

The student will gain skills in animal handling including 

venepuncture, analysis of circulating metabolites 

including radioimmunoassay, measurement of gene 

expression by RT-PCR, data analysis, written and oral 

presentation skills. 

PROJECT: (Basic) Do male and females respond 

differently to restricted growth before birth? 

R. O&G. 

Supervisors 

A/Prof Vicki Clifton 


Dr Karen Kind 



Poor growth before birth is often caused by poor 

development and function of the placenta, which 

delivers nutrients from the mother to the growing 

fetus. Studies in humans, however, suggest that the 

response of male and female fetuses to a poor 

environment differs, so that female fetuses restrict 

their growth and are more likely to survive, while 

males continue to grow, but are then susceptible to 

any worsening of the environment. To test this 

concept, we will investigate the effects of restricted 

growth before birth and fetal sex on gene expression 

at birth in white blood cells collected at birth and in 

placental tissues. We will use our model of placental 

restriction in the sheep for this study, allowing this 

hypothesis to be directly tested in induced growth 

restriction and within a population of similar 

genotype. 


venepuncture, tissue processing, measurement of 

gene expression by array and RT-PCR, data analysis, 

written and oral presentation skills. 

PROJECT: (Basic) Immune function after placental 

restriction and dietary methyl supplementation. 

R. O&G. 

Supervisors 



Dr Karen Kind 



Maternal methyl donor intake during pregnancy has 

been linked to increased incidence of asthma in 

children, suggesting impaired immune responses. 

Little is known about how growth before birth affects 

immune function into later life. As part of a larger 

NHMRC-funded study, we are testing whether 

feeding the mother extra methyl donors in the diet 

can improve metabolic outcomes, particularly for 

insulin action, in the growth-restricted lamb. An 

Honours student will be involved in testing circulating 

immune responses to injection of a stimulus 

(ovalbumin), to assess the effects of growth before 

birth, neonatal growth, and maternal methyl donors 

in late pregnancy, on immune function. We will use 

our model of placental restriction in the sheep for this 

study, allowing this hypothesis to be directly tested in 

induced growth restriction and within a population of 

similar genotype. 


venepuncture, immune challenge, analysis of 

circulating immunoglobulins, data analysis, and 

written and oral presentation skills. 

28 |

PROJECT: (Basic) Behavioural effects of placental 

restriction, neonatal growth and dietary methyl 

supplementation. 

R. O&G. 

Supervisors 

Dr Susan Hazel 

Dr Karen Kind 



Poor growth before birth (IUGR) is associated with 

decreased cognitive function in human children, as 

well as increased risk of metabolic disease in later life. 

These growth-restricted babies also characteristically 

have accelerated neonatal growth rates (neonatal 

catch-up growth). Rapid neonatal catch-up growth 

is independently associated with metabolic disease 

and obesity in later life, but positively predicts 

improved neurological development and survival. 

Using an ovine model of poor growth before birth, 

which produces similar adverse metabolic 

consequences as human IUGR, we wish to test 

whether neonatal interventions that improve insulin 

secretion, but which slow neonatal growth, have any 

impact on behaviour in early postnatal life. The 

Honours student will gain skills in animal handling 

including measures of behaviour and use of 

behavioural analysis software, data analysis, written 

and oral presentation skills. 

29 |

Early Origins of Cancer Supervisors 


Dr Tina Bianco-Miotto 

Phone: 8313 6077 

tina.bianco@adelaide.edu.au 



Location: 

Research Centre for Reproductive Health, Robinson Institute, School of 

Paediatrics and Reproductive Health 

Increasingly, the environment before birth as indicated by foetal growth and birth weight is implicated as a potential 

and influential risk factor for cancer. Thus, high birth weight, reflecting excess nutrition and overgrowth, is associated 

with an increased risk of cancer in many but not all studies. Perturbations of the prenatal environment, such as 

maternal under or overnutrition, malnutrition, obesity or exposure to endocrine disruptors, appear to alter the 

phenotype of offspring long term, affecting their susceptibility to metabolic and cardiovascular disease and other 

conditions, including breast and prostate cancer. High birth weight is also predictive of later obesity, which may 

partly mediate the effects of excess and abnormal nutrition in utero on the risk of cancer. Obesity is increasingly 

implicated in cancer and of concern, maternal obesity and the associated high birth weight are increasingly 

common suggesting the potential for a growing contribution to the burden of disease in future. Our research 

objective is to determine if the early life environment, such as maternal obesity or folic acid supplementation, 

promotes excessive growth before birth and acts on the breast or prostate during development leading to an 

increased susceptibility of the individual to breast or prostate cancer in later life. We are also investigating whether 

epigenetic mechanisms are involved in the developmental origins of cancer. 

PROJECT: (Basic) Is maternal obesity associated with 

an increased risk of prostate or breast cancer in adult 

progeny? 

R. O&G. 


Using a rat model of maternal obesity we will 

investigate whether the male or female progeny of 

mothers on a high fat diet are at an increased risk of 

prostate or breast cancer. The rat prostates or breasts 

from maternal high fat and control diets will be 

examined for histological abnormalities. Key markers 

of cancer development, cell proliferation and 

apoptosis will be assessed by immunohistochemistry 

and real time quantitative PCR. To determine 

whether epigenetic mechanisms are altered 

between the two groups of rats, the expression of 

epigenetic genes will be assessed by QPCR; global 

epigenetic modifications will be assessed by 

immunohistochemistry and high resolution melt 

curves; DNA methylation of key tumour suppressor 

genes and imprinted genes will be assessed by 

methylation specific PCR and pyrosequencing; and 

miRNA expression will also be assessed. A wellcharacterised 

mouse model of prostate or breast 

cancer will also be utilised to determine whether 

maternal obesity alters the time of onset of cancer in 

adult offspring. 

30 |

Gamete and Embryo Biology Laboratory 


Dr Michelle Lane 

Phone: 8313 8176 

michelle.lane@adelaide.edu.au 

PROJECT: (Basic) Making old eggs young. 

R. O&G. 


An increasing number of women seek IVF treatment 

as a result of declining fertility, associated with 

advanced maternal age. However, despite popular 

misconceptions that IVF can cure all infertility, IVF 

cannot cure aged eggs. It is currently this group of 

patients who often do not reach their goal of a baby 

without repeated treatment with its emotional and 

financial toll. Mitochondrial function is the 

powerhouse of the cell and mitochondrial activity 

has been shown to reduce with age resulting in a 

significant reduction in egg and embryo viability. The 

aim of this study is to examine the ability of novel 

mitochondrial nutrients for their ability to rescue 

mitochondrial function in aged eggs and embryos to 

improve pregnancy rates. 

This study will investigate embryo development and 

viability after culture in different media formulations 

of mitochondrial nutrients. Techniques will involve 

general embryology, assessment of metabolism, epi- 

and confocal microscopy, general molecular 

methods such as q-PCR. 

Information from this study will assist in developing 

new media to improve IVF procedures. 

Supervisors 

Dr Michelle Lane 

Dr Deirdre Zander-Fox 

Dr Tod Fullston 

Dr Hassan Bakos 

PROJECT: (Basic) Interaction of male obesity and 

molecular function of human sperm on IVF outcomes. 

R. O&G. 


There is increasing awareness that male obesity has a 

negative impact on sperm quality. Male obesity is 

now known to be associated with reduced success 

rates after IVF treatment as well as increases in 

miscarriage and pregnancy loss. However, the 

mechanism for this impact on pregnancy health is 

largely unknown. The aim of this study is to examine 

the impact of paternal obesity at the time of 

conception on the molecular structure of the sperm 

and how this impacts on fertilization, embryo 

development and pregnancy after IVF treatment. 

This study will investigate sperm motility, count, 

reactive oxygen species, methylation and 

acetylation of sperm in relation to fertilization, sperm 

binding and embryo development. Techniques will 

involve general andrology methods as well as 

immunohistochemistry, epi- and confocal 

microscopy, mitochondrial measurement and cell 

culture. 

31 |

Oocyte Biology Group 



Phone: 8313 8183 

robert.gilchrist@adelaide.edu.au 

Dr David Mottershead 

Phone: 8313 8201 

david.mottershead@adelaide.edu.au 

Supervisors 





The Oocyte Biology Group investigates fundamental physiological aspects of oocyte-granulosa cell interactions in 

an effort to improve understanding of mammalian oocyte biology and to better implement assisted reproductive 

technologies. Ovarian folliculogenesis consists of a series of ordered maturation and differentiation events of both 

the somatic and germ cell components that culminates in ovulation and the production of a mature oocyte that is 

able to support early embryogenesis. The immature oocyte and the follicular granulosa cells are in intimate contact 

and normal growth and development of the oocyte is entirely dependent on this association. Oocyte-secreted 

growth factors have significant effects on the somatic cell compartment of the ovarian follicle. We are actively 

studying two of these proteins, namely growth differentiation factor 9 (GDF9) and bone morphogenetic factor 15 

(BMP15), both of which appear to be essential for mammalian fertility. Our aim is to understand the functioning of 

these proteins and the detailed basis of the somatic/germ cell (oocyte) interactions in the ovary in order to provide 

the optimal environment for early embryonic development. 

PROJECT: (Clinical/Basic) Development of a Novel 

Artificial Reproductive Technology. 

R. O&G. 

Supervisors 




Oocyte In Vitro Maturation (IVM) is an adjunct 

procedure to IVF (in vitro fertilisation) and is a 

platform technology for the treatment of human 

infertility, the generation of embryos for livestock 

biotech and in the generation of stem cells by 

cloning. We have developed a new approach to 

oocyte IVM that dramatically increases embryo yield 

and pregnancy rates. This discovery has significant 

practical and commercial implications (see below). 

Further research is required to understand the basic 

molecular mechanisms in the oocyte and the 

somatic cells associated with the oocyte, which 

underpins this technology and leads to such an 

improvement in oocyte quality. In addition, 

translational research is required to allow the 

generation of an efficacious, robust, and safe 

technique and product that can be used in clinical 

and commercial practice. 

Potential projects include: 

1) Characterisation of the molecular mechanisms 

in cumulus cells and oocytes regulating induced 

oocyte maturation and embryo developmental 

competence 

2) Validating the efficacy and safety of induced 

oocyte IVM to allow rapid translation to 

commercial application and clinical practice. 

We are developing this technology in close 

collaboration with industry and clinical partners. The 

discovery is protected by our patent and we have 

licensed application of this technology in humans to 

a medical device manufacturer. We are conducting 

the first pre-clinical trial of this technology using 

human oocytes in an overseas laboratory. We also 

have an in-house business unit; IVF Vet Solutions 

(ACN), which is set up to capture new intellectual 

property opportunities and to supply our new 

products to the animal embryology sector. Students 

working on these projects will be closely associated 

with these commercial ventures. 

References 

Gilchrist RB and Thompson JG. (2007) Oocyte 

maturation: Emerging concepts and technologies to 

32 |

improve developmental potential in vitro. 

Theriogenology. 67(1):6-15 

Gilchrist RB, Lane M, Thompson JG. (2008) Oocytesecreted 

factors: regulators of cumulus cell function 

and oocyte quality. Human Reproduction Update 

14(2):159-177 

PROJECT: (Basic) Understanding the Functioning of 

Oocyte-derived Growth Factors. 

R. O&G. 

Supervisors 




Oocytes produce proteins of great importance for 

their ability to successfully be fertilized and develop 

into a viable embryo. The transforming growth factor 

β (TGF-β) superfamily of proteins consists of some 40 

members in mammals, many of which are essential 

for normal development and maintenance of the 

adult organism. Growth differentiation factor 9 

(GDF9) and bone morphogenetic factor 15 (BMP15) 

are two members of this family of proteins which are 

produced by oocytes and are critical for female 

fertility. The proteins GDF9 and BMP15 have great 

potential for improving currently used infertility 

treatments, as demonstrated previously by our group 

(see Yeo et al., 2008). In fact Dr. Gilchrist has 

patented this technology and has industry support for 

our research efforts on GDF9/BMP15. To take such 

work to the clinic/industry setting we need well 

characterized, stable preparations of these proteins. 

These and closely related proteins also have great 

potential in the area of stem cell research, both for 

the maintenance of stem cells in a pluripotent state 

as well as for directed differentiation of stem cells 

toward a particular lineage. 

Potential projects include: 

1) Recombinant production and purification of 

various mutants of human GDF9 and BMP15, 

potentially including mutating the proteolytic 

processing site or the phosphorylation / 

glycosylation sites, to determine the impact on 

function of such mutations. 

2) Use of a bacterially expressed recombinant 

GDF/BMP binding protein to create an affinity 

column to purify TGF-β family members from 

physiological fluids, such as follicular fluid or 

seminal plasma. The aim of this project is to 

determine in what forms do the proteins 

GDF9/BMP15 exist in such biological fluids, as 

such information could give insight into the 

mechanisms used in vivo to regulate the 

bioactivity of these proteins. 

Techniques used can include: 

• use of mammalian cell lines for recombinant 

protein production 

• bacterial expression of proteins 

• protein purification, especially affinity 

purification and HPLC/FPLC 

• molecular biology, plasmid preps, PCR, 

transfection of mammalian cells 

• growth factor assays, various types, 

especially transcriptional reporter assays 

References 

Mottershead DG, Ritter LJ, Gilchrist RB. (2012) 

Signalling pathways mediating specific synergistic 

interactions between GDF9 and BMP15. Mol Hum 

Reprod. 18(3):121-8. 

Pulkki MM*, Mottershead DG*, et al. (2012) A 

covalently dimerized recombinant human bone 

morphogenetic protein-15 variant identifies bone 

morphogenetic protein receptor type 1B as a key cell 

surface receptor on ovarian granulosa cells. 

Endocrinology. 153(3):1509-18. 

Pulkki MM, Myllymaa S, et al, Mottershead DG. (2011) 

The bioactivity of human bone morphogenetic 

protein-15 is sensitive to C-terminal modification: 

characterization of the purified untagged processed 

mature region. Mol Cell Endocrinol. 332(1-2):106-15. 

Mottershead DG, Watson AJ. (2009) Oocyte peptides 

as paracrine tools for ovarian stimulation and oocyte 

maturation. Mol Hum Reprod. 15(12):789-94. 

33 |

Placental Development Laboratory 



Phone: 8313 3118 

claire.roberts@adelaide.edu.au 

Location: Medical School North and Lyell McEwin Hospital 

Supervisors 


Dr Denise Furness 

Professor Gus Dekker 

Dr Amada Highet 


Our group’s major current focus in research is on the development of the placenta and the vessels which supply it. A 

number of pathologies of pregnancy, including up to 50% of miscarriages, preeclampsia (hypertension and 

proteinuria in pregnancy), intrauterine growth restriction (IUGR), preterm labour, unexplained stillbirth and placental 

abruption are characterised by an impaired cytotrophoblast invasion and inadequate response of the uterine spiral 

arteries to undergo physiological transformation. Together these conditions affect more than one quarter of 

pregnant women in developed societies. 

We are investigating the cellular and molecular mechanisms underlying the formation of vascular connections 

between the mother and fetus. The uterine arterioles which supply the placenta are invaded by placental 

cytotrophoblast cells and are dramatically remodelled to produce dilated compliant vessels which allow the 12 fold 

increase in blood flow to the uterus which is essential for normal placental, and hence fetal, growth. However, the 

mechanisms by which physiological transformation of these vessels occurs are poorly understood. We are currently 

delineating the cellular and molecular interactions between maternal decidual leukocytes, endothelium and fetal 

trophoblast during the normal transformation of the arterioles which supply the placenta. Our work focuses on the 

role of insulin-like growth factor II (IGF-II) in placental invasion and how a variety of molecules interact with IGF-II in 

early pregnancy. We have discovered that IGF-II is likely to promote invasion by its interaction with a variety of other 

factors that all bind the type 2 IGF receptor (IGF2R) forming a complex. Activation of transforming growth factor 

(TGF)- β1, a cytokine that inhibits invasion, occurs on this complex and so too does the activation of renin, an 

enzyme that takes part in blood pressure control. 

Sufficient understanding of how the placenta invades in early gestation is a pre-requisite to understanding what 

goes wrong in pregnancy complications associated with poor placental invasion and function. Currently the 

treatments we have are symptomatic and are not used until the pregnant woman already has the disease. Our 

animal experiments have shown that treating the pregnant mother in early to mid pregnancy with IGF-II improves 

placental differentiation, transport function and increases fetal weight near term. It is essential that treatment begins 

in early-mid pregnancy to be efficacious. However, who should we treat? We are developing tests to predict which 

women are likely to develop pregnancy complications before symptoms arise. Subsequently, antenatal care could 

be tailored to suit individual women. 

34 |

PROJECT: (Basic) Factors that regulate placental 

trophoblast invasion and angiogenesis. 

R. O&G. 

Supervisor 



Angiogenesis is an essential feature of placental 

morphogenesis. We have shown that a number of 

factors expressed in the placenta promote placental 

trophoblast differentiation and invasion and some of 

these may also be involved in angiogenesis which 

uses common molecules to promote endothelial 

development. The molecular pathway that we have 

discovered regulates placental invasion may or may 

not include a signal transduction pathway from the 

IGF2 receptor complex. This pathway may also 

regulate angiogenesis. This project will utilise several 

human trophoblast and endothelial cell lines to 

demonstrate the molecular pathways involved in 

invasion and angiogenesis. The project will involve 

cell culture, RT-PCR, ELISAs, immuno-histochemistry, 

video image analyses and western blotting. The 

student will gain skills in a variety of experimental 

techniques, as well as data management and 

statistical analyses. 

PROJECT: (Basic) Molecular mechanisms in actions of 

transforming growth factor β1 (TGFβ1) inhibition of 

trophoblast invasion and induction of terminal 

differentiation. 

R. O&G. 

Supervisor 



Although it is known that TGFβ1 inhibits trophoblast 

invasion and likely induces terminal differentiation the 

detailed molecular mechanisms by which this occurs 

are not understood. Trophoblast invasion is an 

important process in early pregnancy that is 

responsible for dramatic re-modelling of the uterine 

vasculature to permit the 12-fold increase in uterine 

blood flow that occurs in normal pregnancy. This 

process is influenced by the low oxygen environment 

in first trimester placenta. In the second half of 

pregnancy placentation is characterised by terminal 

differentiation of trophoblasts with the development 

of a large highly attenuated surface area for 

exchange. This project will explore the molecular 

mechanisms by which TGFβ1 regulates placental 

differentiation and will utilise several human 

trophoblast cell lines and first trimester and term 

human placental samples to demonstrate the 

molecular pathways involved. The project will involve 

cell culture, RT-PCR, ELISAs, immuno-histochemistry, 

video image analyses and western blotting. The 

student will gain skills in a variety of experimental 

techniques, as well as data management and 

statistical analyses. 

PROJECT: (Clinical/basic) Associations between 

genome damage, DNA repair enzyme gene 

polymorphisms and B vitamin status. 

R. O&G. 

Supervisor 


Dr Denise Furness 

Professor Gus Dekker 


We have recently shown that genome damage in 

circulating lymphocytes in mid pregnancy is more 

common in women who subsequently develop 

pregnancy complications in which placental 

insufficiency is a feature. These include preeclampsia, 

pre-term birth and intrauterine growth restriction. This 

project will determine whether genome damage is 

associated with polymorphisms in genes that encode 

DNA repair enzymes and whether severity of 

damage is influenced by B vitamin status and 

circulating homocysteine. If time permits, tunnel 

assays to quantify genome damage in sperm of 

partners of women who develop pregnancy 

complications will be performed and the results 

compared with those from men who father normal 

pregnancies. The student will gain skills in a variety of 

experimental techniques including cytokinesis block 

micronucleus cytome assay, PCR and HRM 

genotyping, as well as data management and 

statistical analyses. The student will interact with 

obstetricians and midwives as well as scientists. 

PROJECT: (Basic) Cytokine gene expression by 

placental trophoblast cells under hypoxic conditions. 

R. O&G. 

Supervisors 


Dr Amanda Highet 


Trophoblast cells form the outer layer of a blastocyst, 

and provide nutrients to the embryo and develop the 

epithelial part of the placenta. They are formed 

during the first stage of pregnancy in a low oxygen 

environment where they invade into the maternal 

decidua and spiral arteries, proliferate, differentiate 

and secrete cytokines. In preeclampsia the 

trophoblast cells fail to adequately invade as 

required to promote materno-placental blood flow. 

The placenta has a local renin-angiotensin system 

from which angiotensin-II and its degradation 

product angiotensin-IV are produced. Angiotensins-II 

and -IV both stimulate the expression of nuclear 

factor-kappaB, a transcription factor which regulates 

gene expression of inflammatory cytokines such as 

35 |

interleukin (IL)-6 which could modify extracellular 

matrix composition, stimulate growth factor secretion 

and promote cell invasion. IL-10 on the other hand is 

an inhibitor of nuclear factor-kappaB and may be an 

important regulator of trophoblast inflammatory 

activity. We have recently shown that polymorphisms 

in the IL-10 and IL-6 genes known to decrease IL-10 

expression and up-regulate IL-6 expression are more 

frequent in babies (and therefore placentas) from 

pregnancies complicated by PE. 

This honours project will use cell culture and real-time 

PCR gene expression assays to show that 1) 

trophoblast cells upregulate expression of the IL-6 

gene and downregulate IL-10 under low oxygen 

conditions and that this is further enhanced in the 

presence of exogenous angiotensin-II and -IV and 2) 

IL-6 gene expression is increased and IL-10 is 

decreased in placenta samples from preeclamptic 

pregnancies compared with normal term placenta. 

This research aims to acquire new knowledge about 

trophoblast cell activity in the low oxygen 

environment by testing our hypothesis that proinflammatory 

cytokines are up-regulated by 

angiotensin-II and -IV under low oxygen conditions. 

Understanding the role of cytokines in hypoxic 

placenta and how they affect trophoblast activity 

could provide insight into the pathways that become 

deregulated in preeclampsia. 

PROJECT: (Basic) Sex differences in placental gene 

expression and the X chromosome. 

R. O&G. 

Supervisors 

Prof Claire Roberts 



We aim to demonstrate for the first time that X 

chromosome genes include many that are important 

in placental development and function and 

maternal adaptation to pregnancy, and that some 

of these escape X inactivation and are therefore 

differentially expressed by the male and female 

placenta. Most research on this to date has been 

conducted in mice which emerging evidence shows 

is unlike the human. Hence we expect our data will 

challenge established dogma. We expect our 

research will explain the different patterns of fetal 

growth observed in males and females before birth. 

This project will utilise our access to human placental 

tissues and skill and knowledge base in placental 

development, fetal growth and epigenetics. This 

project will involve gene expression analyses of X 

chromosome genes as well as epigenetic analysis of 

differentially expressed genes. 

Other associated projects may be negotiated 

36 |

Pregnancy and Development Group 


Associate Professor Vicki Clifton 

Phone: 8313 8321 

vicki.clifton@adelaide.edu.au 

Supervisors (photograph left to right) 

Dr Annette Osei-Kumah 

Dr Michael Stark 

Associate Professor Vicki Clifton 

Dr Nicolette Hodyl 


If you are interested in why males and females are different and if you wonder about how babies survive when they 

deliver preterm or are exposed to a stressful pregnancy then come and work with us. Our group conducts human 

studies on pregnant women and their babies. We are interested in what factors influence the growth of the fetus in 

utero and how in utero events affect the survival of the neonate and their health and development. We find males 

and females are different in how they respond to stress during pregnancy and this difference changes their growth 

and survival. Our work focuses on the mechanisms that confer a difference between male and female babies. 

PROJECT: (Clinical / Basic) 

R. O&G. 

Supervisors 

Dr Nicki Hodyl 

Dr Michael Stark Assoc 



Although neonatal infections affect 50% of infants 

born prior to 32 weeks gestation, the factors that 

contribute to this disturbing statistic are largely 

unknown. 

Current treatment regimes and recent RCTs have 

failed to decrease preterm neonatal infection rates, 

indicating knowledge gaps in our understanding of 

neonatal infection. Evidence supports an intrinsic 

immaturity of the preterm neonatal immune system 

(including deficits in B cell, T cell and innate immune 

function). 

This does not, however, explain sexual dimorphisms in 

the susceptibility to infectious and inflammatory 

conditions in the neonatal period and beyond, with a 

significant male disadvantage. 

Our animal data indicates in-utero events program 

neonatal immunity. We hypothesise that immunecompetence 

in preterm neonates is determined by 

sex, birth weight and timing of exposure to antenatal 

betamethasone as well as products of placental 

inflammation. 

Understanding the developmental profile of the 

human innate immune response may lead to 

interventions that avoid the potential sequelae of 

infections in the preterm neonate. Placenta and cord 

blood will be collected from preterm and term 

deliveries. Cord blood monocytes will be exposed to 

pathogens and cytokines, and intracellular pathway 

activation characterised and related to episodes of 

neonatal infection. 

Projects may include: 

1. Determination of the impact of antenatal steroid 

exposure on innate immune cell signalling pathways 

in the placenta and neonatal immune cells 

2. Identification of sex-specific pathways in placenta 

and / or human vascular endothelial cell lines that 

contribute to aberrant innate immune responses in 

preterm neonates 

PROJECT: (Clinical / Basic) 

R. O&G. 

Supervisors 

Dr Nicki Hodyl 

Dr Michael Stark Assoc 


Improved survival rates following preterm birth have 

not been accompanied by equivalent reduction in 

the incidence of chronic lung disease (CLD), the 

major morbidity associated with prematurity. Despite 

the contribution of perinatal environmental factors in 

its pathogenesis, antenatal interventions have not 

decreased the incidence of CLD, while postnatal 

interventions may be too late to be effective. 

37 |

Perinatal inflammatory cytokine exposure and 

reactive oxygen species (ROS) significantly contribute 

to the pathogenesis of chronic lung disease (CLD). 

Recent attention has focused on novel therapies that 

may modulate inflammatory responses and regulate 

the activation of placental inflammatory pathways 

and the initiation of patho-physiologic processes 

associated with preterm birth. 

These studies will address the role of these modifiable 

pathways in placental inflammatory cytokine and 

ROS production and anti-oxidant defence ex-vivo 

and interrogate sex-specific differences in their 

regulatory function with respect to the pathogenesis 

of CLD. 

Projects may include: 

1. The characterisation placental oxidative stress and 

immune responses to inflammatory stimuli. 

2. Identification of sex-specific pathways that control 

placental anti-inflammatory/anti-oxidant effects in 

placental explant culture and / or human vascular 

endothelial cell lines. 

38 |

Reproductive Biotechnology Group 

Supervisors 

Associate Professor Mark Nottle 

Dr Ivan Vassiliev 



A/Prof Mark Nottle 

Phone: 8313 4087 

mark.nottle@adelaide.edu.au 

The Reproductive Biotechnology group has an international reputation in the general areas of reproductive biology 

and the development of associated technologies for biomedical and agricultural applications. In collaboration with 

a number of university, institute and hospital research groups in Australia as well as overseas, current research is 

focused on developing organ, tissue and cell replacement therapies. 

PROJECT: (Basic) Making embryos for Research. 

R. O&G. 


Our Laboratory uses in vitro produced (IVP) pig 

embryos for much of its research. This uses abattoir 

derived ovaries from which oocytes are removed, 

matured in culture, fertilised and then cultured up to 

six days. While IVP can produce embryos for research 

purposes these are of a lesser quality than those that 

would be found in the reproductive tract. The current 

project aims to improve one or more steps in this 

process so that we can ultimately produce embryos 

of the same quality. Project s are available in this 

general area and will provide students with research 

experience across a range of areas including 

molecular and cell biology and embryology. 

PROJECT: (Basic) Reducing early embryonic loss. 

R. O&G. 


Around 30% of embryos are lost early in pregnancy, 

with the reasons for this unknown. Our Lab is 

examining the hypothesis that the majority of these 

losses are due to differences in oocyte quality as a 

result of changes in nutrition , season, disease etc. In 

particular we are examining how these influence 

oocyte quality and embryo development. Project s 

are available in this general area and will provide 

students with research experience across a range of 

areas including molecular and cell biology and 

embryology. 

PROJECT: (Basic) Saving endangered species. 

R. O&G. 


Somatic cell nuclear transfer or cloning a sit more 

commonly know has been proposed as a way of 

saving endangered species. However this approach 

is limited because not enough oocytes are 

available from endangered females. The use of 

oocytes from another species has been proposed 

as a way of overcoming this shortage. However so 

called interspecies nuclear transfer is still in its 

infancy . The current project aims improve the 

efficiency of interspecies nuclear transfer. 

Projects are available in this general area and will 

provide students with research experience across a 

range of areas including molecular and cell biology 

and embryology 

PROJECT: (Basic) Isolation and characterisation of 

embryonic stem cells. 

R. O&G. 


As human stem cell research advances there is an 

increasing need for a large animal model for 

bridging the gap between mouse studies and 

clinical trials. We have developed a new method for 

isolating ESCs and are using this to develop the pig 

as a large animal model for stem cell research. This 

includes the isolation and characterisation of 

embryonic stem cells from a range of sources 

including parthenogenetic embryos. Project s are 

available in this general area and will provide 

students with research experience in cell biology, 

embryology and stem cells . 

39 |

Reproductive Cancer Research Group 


Dr Carmela Ricciardelli 

Phone: 8313 8255 

carmela.ricciardelli@adelaide.edu.au 

Supervisors 


Associate Professor Martin Oehler 

Dr Darryl Russell 

Dr Alison Elder 


Dr Ricciardelli a Cancer Cell Biologist; joined the Department in April 2005. Dr Ricciardelli was awarded her Ph D in 

1996 (Flinders University) and has undertaken postdoctoral studies in the Department of Surgery, Flinders Medical 

Centre, South Australia (1996-2001) and Dame Roma Mitchell Cancer Research Laboratories, Hanson Institute, South 

Australia (2002-2005). She was awarded a Senior Fellowship with Cancer Council of South Australia (2004-2006). In 

2007 she was the recipient of the Hilda Farmer Fellowship in Faculty of Health Sciences, University of Adelaide which 

has enabled her to build a Reproductive cancer research group in Discipline of Obstetrics and Gynaecology at 

University of Adelaide. Dr Ricciardelli’s current research focuses on further understanding the cross talk between 

cancer cells and the extracellular matrix and mechanisms whereby extracellular matrix proteins promote spread of 

breast, prostate and ovarian cancers. 

PROJECT: (Clinical/basic) Identification of novel 

proteins involved in ovarian cancer spread. 

.R. O&G. 

Supervisors 


Associate Professor Martin Oehler 

Background 

The implantation of cancer cells onto the peritoneal 

surfaces is one of the first crucial steps in ovarian 

cancer metastasis. However it remains unclear which 

factors promote this process. Our recent studies have 

examined the ovarian cancer – peritoneal 

mesothelial cell interaction by means of latest 

proteomics technology. Tumor-mesothelial cell 

interaction have been explored in vitro by coculturing 

human ovarian cancer and peritoneal 

mesothelial cells. This novel strategy may lead to the 

identification of novel proteins likely to be 

mechanistically involved in implantation and 

peritoneal metastasis of ovarian cancer.. Several 

protein bands that are either increased or decreased 

in co-culture experiments with ovarian and 

mesothelial cells have been excised and will be 

identified using MALDI-TOF/TOF mass spectrometry. 

This study will characterise the expression and 

localization of several proteins modulated by ovarian 

cancer cell-peritoneal interactions in human ovarian 

cancer tissues. Proteins whose expression are 

modulated in human ovarian cancer cells compared 

to non-cancer tissues will be further characterised in 

future studies using functional assays (adhesion, 

migration and invasion assays). The identification of 

novel proteins which promote adhesion and invasion 

of ovarian cancer cells to peritoneal cells may serve 

as therapeutic targets to inhibit ovarian cancer 

metastasis. This project will utilise a broad range of 

techniques including tissue culture, motility, adhesion 

and invasion assays. 

Aim 1. Characterise the expression of specific 

proteins modulated by ovarian and peritoneal coculture 

in human ovarian cancer tissues 

Aim 2. Identify novel proteins that modulate ovarian 

cancer cell adhesion, migration and invasion through 

mesothelial cells 

PROJECT: (Basic) Versican as a target to inhibit 

cancer metastasis. 

.R. O&G. 

Supervisors 




There is increasing evidence to suggest that 

extracellular matrix (ECM) components play an 

active role in tumour progression and metastasis. 

Proteoglycans are major components of the ECM 

and have been shown to regulate cell adhesion, cell 

signalling, apoptosis, migration and invasion. 

Increased expression of the chondroitin sulfate (CS) 

proteoglycan, versican in the peritumoral stromal 

matrix is associated with a poor outcome in many 

cancers, including breast and ovarian carcinoma. 

Although there is the accumulating in vivo evidence 

40 |

that versican is pivotal in promoting cancer cell 

metastasis in different cancer types, the means of 

preventing actions of versican in carcinomas have 

not been explored. This study we will evaluate using 

in vitro and in vivo breast cancer models whether 

selective versican inhibition by versican siRNA, in 

addition to drugs known to inhibit versican synthesis; 

genistein, budesonide, formoterol and montelukast, 

can inhibit breast cancer invasive behaviour and 

block breast cancer metastasis. This project will utilise 

a broad range of techniques including using in vitro 

motility, adhesion and invasion assays and an in vivo 

animal model of breast cancer. 

Aim 1. To assess the ability of pharmacological 

agents to inhibit versican synthesis and block invasive 

tumour cell behaviour in vitro 

Aim 2. To determine whether versican synthesis 

inhibitors reduce metastasis in in vivo cancer models 

PROJECT: (Basic) Role of ADAMTS1 and ADAMTS4 

proteases in prostate cancer metastasis. 

.R. O&G. 

Supervisors 




Metastatic spread to the lymph node and bone is 

the most significant cause of relapse and mortality in 

prostate cancer patients. The molecular processes 

which mediate metastasis of cancers to the bone 

have been a strong focus of recent research. The 

Adamts (adamalysin-thrombospondin) proteases are 

a family of metalloproteinases involved in 

extracellular matrix (ECM) processing. Adamts1 and 

Adamts4 are major bone matrix remodelling 

proteases. Substrates include versican a prominant 

stromal matrix component associated with breast 

and prostate tumour progression. A recent report links 

Adamts1 to the bone metastatic gene signature. This 

project will focus on Adamts1 and 4 for which there 

growing evidence of a role in prostate cancer 

progression. This project will utilise a broad range of 

techniques using including immunohistochemistry, 

motility, adhesion and invasion assays and an in vivo 

animal model of prostate cancer. 

Aim 1. To show that Adamts proteases promotes 

invasive migratory behaviour in prostate tumor cell 

lines in vitro. 

Aim 2. To elucidate the association between 

Adamts1 or Adamts4 protein levels and metastatic 

disease in human prostate cancer and an in vivo 

mouse model. 

PROJECT: (Basic) Investigation of a therapeutic target 

for ovarian cancer chemoresistance. 

.R. O&G. 

Supervisors 


Dr Alison Elder 

A/Prof Martin Oehler 


Ovarian cancer is the most lethal gynaecological 

cancer and the development of chemoresistance 

results in significant mortality. Over 80% of patients 

treated via chemotherapy eventually relapse and 

become resistant to chemotherapy. A well 

established cause of chemoresistance involves the 

increased expression of ABC membrane transporter 

proteins, which act to decrease levels of 

chemotherapy drugs within cells. Although effective 

in in vitro studies, clinical trials investigating ABC 

transporter inhibitors have failed to significantly 

improve patient survival, mainly due to focus on only 

a limited number of ABC transporters. Innovative 

treatment strategies to overcome chemoresistance 

are therefore urgently required. Our recent studies 

have linked chemoresistance with the production of 

the extracellular matrix component hyaluronan (HA). 

HA plays an important role in promoting attachment 

of cancer cells to peritoneal cells via interactions with 

the HA receptor, CD44. We have shown that HA can 

increase the expression of ABC transporters in ovarian 

cancer cell lines expressing the HA receptor, CD44, 

and thereby induce resistance to the 

chemotherapeutic drug, carboplatin. This study will 

use samples prospectively collected between 2008 

and 2012 to determine, via ELISA assay, if serum HA 

levels at diagnosis are increased in patients who do 

not respond to first line chemotherapy, and whether 

it is predictive of recurrent or overall survival. Tissue 

sections from serous ovarian carcinoma patients will 

be immunostained with specific antibodies to various 

ABC transporter protein levels to determine whether 

ABC transporter expression correlates with response 

to chemotherapy and impacts on recurrence free 

and overall survival. HA inhibitors will also be used to 

determine whether they are able to significantly 

increase the cytotoxic effect of chemotherapeutic 

drugs on ovarian cancer cells, providing a strong 

rationale for combining HA inhibitors with 

chemotherapy drugs in future clinical studies. This 

project will utilise a broad range of techniques 

including enzymatic assays, immunohistochemistry, 

qPCR and in vitro and in vivo animal models of 

ovarian cancer. 

Aim 1. Identify whether HA levels at diagnosis can 

predict therapeutic response and patient survival. 

Aim 2. Characterise whether ABC transporter 

expression can predict patient outcome. 

Aim 3. Determine whether the combination of HA 

inhibitors with chemotherapy drugs increases survival 

41 |

when compared to treatment with the 

chemotherapeutic drugs alone. 

Publications 

1. Ricciardelli, C., Brooks, J. H., Suwiwat, S., 

Sakko, A. J., Mayne, K., Raymond, W. A., 

Seshadri, R., LeBaron, R. G., and Horsfall, D. 

J. Regulation of stromal versican expression 

by breast cancer cells and importance to 

relapse-free survival in patients with nodenegative 

primary breast cancer. Clin 

Cancer Res, 8: 1054-1060, 2002. 

2. Sakko, A. J., Ricciardelli, C., Mayne, K., 

Suwiwat, S., LeBaron, R. G., Marshall, V. R., 

Tilley, W. D., and Horsfall, D. J. Modulation of 

prostate cancer cell attachment to matrix 

by versican. Cancer Res, 63: 4786-4791, 

2003. 

3. Suwiwat, S., Ricciardelli, C., Tammi, R., 

Tammi, M., Auvinen, P., Kosma, V. M., 

LeBaron, R. G., Raymond, W. A., Tilley, W. D., 

and Horsfall, D. J. Expression of extracellular 

matrix components versican, chondroitin 

sulfate, tenascin, and hyaluronan, and their 

association with disease outcome in nodenegative 

breast cancer. Clin Cancer Res, 

10: 2491-2498, 2004. 

4. Ricciardelli C & Rodgers RJ Matrix of ovarian 

tumours Seminars in Reproductive Medicine 

24:270-82, 2006 

5. Ricciardelli C, Russell D, Ween MP, Mayne K, 

Byers S, VR Marshall Tilley WD and Horsfall 

DJ. Formation of hyaluronan-and versicanrich 

pericellular matrix by prostate cancer 

cells promotes cell motility J Biol Chem: 

282:10814-10825, 2007. 

6. Sakko AJ, Butler MS, Byers S, Reinboth BJ, 

Stahl J, Kench JG, Horvath LG, Sutherland 

RL, Stricker PD, Henshall SM, Marshall VR, 

Tilley WD, Horsfall DJ & Ricciardelli C. 

Immunohistochemical level of unsulfated 

chondroitin disaccharides in the cancer 

stroma is an independent predictor of 

prostate cancer relapse. Cancer 

Biomarkers, Epidemiology & Prevention, 17: 

2488-2497, 2008 

7. Ricciardelli C, Sakko AJ, Stahl J, Tilley WD, 

Marshall VR & Horsfall DJ. Prostatic 

chondroitin sulfate is increased in patients 

with metastatic disease but does not 

predict survival outcome. Prostate 69:761-9, 

2009 

8. Ricciardelli C, Sakko AJ, Ween MP, Russell 

DL & Horsfall DJ. The biological role and 

regulation of versican levels in cancer. 

Cancer and Metastasis Reviews 28:233-45, 

2009 

9. Ricciardelli C & Oehler MK. Diverse 

molecular pathways in ovarian cancer and 

their clinical significance. Maturitas 62:270-5, 

2009 

10. Ween MP, Lokman, NA, Hoffmann P, 

Rodgers RJ, Ricciardelli C* & Oehler MK*. 

Transforming growth factor-beta induced 

protein secreted by peritoneal cells 

increases the metastatic potential of 

ovarian cancer cells. International Journal 

Cancer, 128:1570-84, 2011, * co-directed 

11. Ween MP, Hummitzsch K, Rodgers RJ, 

Oehler MK & Ricciardelli C. Versican 

induces a pro-metastatic ovarian cancer 

cell behavior which can be inhibited by 

small hyaluronan oligosaccharides. Clinical 

and Experimental Metastasis, 28:113-25, 

2011 

12. Ricciardelli C, Frewin KM, Tan IA, Williams 

ED, Opeskin K, Pritchard MA, Ingman WV 

and Russell DL. The Adamts1 protease gene 

is required for mammary tumor growth and 

metastasis. American Journal of Pathology, 

179:3075-85, 2011 

42 |

Reproductive Endocrinology Group 

Supervisors 


Louise Hull 

Phone: 0403 9933312 

louise.hull@adelaide.edu.au 

Dr Louise Hull 

Dr Jonathan McGuane 


PROJECT: (Clinical or clinical/basic) 

.R. O&G. 

Endometriosis 


Endometriosis is another common condition in young 

women and its diagnosis and aetiology is uncertain. 

Dr Hull has pioneered new methods for diagnosis and 

treatment and uses cutting edge technology in her 

research group. Opportunity exists for medical 

students to combine patient interaction with high 

quality laboratory methods in her group. 

43 |

Reproductive Immunology Group 


Professor Sarah Robertson 

Phone: 8313 4094 

sarah.robertson@adelaide.edu.au 

Supervisors 


Dr David Sharkey 

Dr Anne Macpherson 


Dr Kerri Diener 


Sarah Robertson is a NHMRC Senior Research Fellow and Head of the Reproductive Immunology group in the 

Research Centre for Reproductive Health. Her research focus is early pregnancy, particularly the cytokine biology 

and immunology of the uterus and early embryo development. Her team is made up of 6 postdocs and 5 

postgraduate students, who work together to explore the importance of the peri-conceptual immune environment 

in optimal embryo implantation and placental development, and programming fetal development and health after 

birth. 

Research in the Reproductive Immunology group centres on three related themes: 

• The roles of cytokines and leukocytes in the events of embryo development during early pregnancy. 

• The impact of the maternal immune response on success and quality of embryo implantation and reproductive 

outcome. 

• Male seminal fluid signalling in the female reproductive tract and significance for reproductive events and 

immunity to sexually transmitted infection. 

We seek to unravel the immune and cytokine networks of early pregnancy to understand how maternal immune 

tolerance to pregnancy is established, and how failure in this process contributes to infertility, miscarriage and 

pathologies of pregnancy in women. Our work also has applications in animal breeding industries where early 

pregnancy loss is a significant constraint. 

Keywords 

Immunology, cytokines, uterus, embryo, pregnancy 

PROJECT: (Basic) T-Regulatory (Treg) cells and 

activiation of immune tolerance during early 

pregnancy. 

Theme title: Pregnancy immunology 

.R. O&G. 

Supervisor 



To allow embryo implantation and successful 

pregnancy, the maternal immune system must 

become ‘tolerant’ to paternal transplantation 

antigens. Treg cells are now implicated as key cells 

mediating maternal immune tolerance. Discoveries 

in our laboratory show that semen plays an important 

role in establishing functional tolerance to male 

transplantation antigens during early pregnancy. We 

now seek to investigate the role of seminal factors in 

activating and expanding Treg cells in preparation 

for embryo implantation. The aim of this project is to 

investigate in mice the molecular events involved in 

activating Treg cells after mating. In particular the 

importance of seminal plasma TGFbeta and the role 

of male MHC antigens in semen will be investigated. 

The project will employ cytokine null mutant mouse 

models, linked with state-of-the-art digital flow 

cytometry (FACS), and quantitative RT-PCR for the 

44 |

Treg fate-determining transcription factor Foxp3. The 

findings will help us understand the induction phase 

of the maternal immune response permitting 

successful pregnancy, and have broader relevance 

to the transmission of STDs and immune-mediated 

pathologies linked with infertility. 

Keywords 

Immunology / T regulatory cells / pregnancy 

PROJECT: (Clinical/Basic) Novel seminal plasma 

cytokines mediating male-female signalling at 

insemination. 

Theme title: Seminal fluid signalling 

.R. O&G. 

Supervisors 


Dr David Sharkey 


Cytokines present in male seminal plasma play 

essential roles in ‘conditioning’ the female immune 

response for pregnancy, through activating immune 

tolerance to paternal transplantation antigens 

present on the conceptus. The active factors present 

in seminal plasma include members of the TGFβ 

family of cytokines. We have identified some of 

these molecules but the full array of active factors 

and their synergistic interactions remain to be fully 

elucidated. The aim of this project is to identify new 

molecules present in seminal plasma that interact 

with female reproductive tract cells. The project will 

utilize in vitro models of male-female signalling, 

involving human cervical cell lines. Quantitative RT- 

PCR and cytokine immunoassay will be used to 

characterise cervical cell responsiveness to male 

factor regulation. Novel factors will be identified 

using factor-specific neutralising antibodies and 

quantified in an existing bank of human seminal 

plasma samples. We expect the results will provide 

new understanding of the factors mediating seminal 

signalling, and will assist in commercial development 

of novel diagnostic tools for infertility and subfertility in 

men. 

Keywords 

Seminal fluid / female reproductive tract / cytokines 

PROJECT: (Clinical/Basic) Cytokine regulation of 

embryo development. 

Theme title: Embryo development 

.R. O&G. 

Supervisors 


Dr Anne Macpherson 


The cytokine granulocyte-macrophage colonystimulating 

factor (GM-CSF) is produced in the 

oviduct and uterus during early pregnancy where it 

acts as a potent physiological regulator of human 

pre-implantation embryo development. GM-CSF 

added to embryo culture dramatically improves 

viability and developmental competence of human 

IVF embryos. Experiments in mouse and human have 

begun to unravel the mechanisms of action of GM- 

CSF. Microarray transcription profiling studies have 

revealed that in the absence of GM-CSF, apoptosis 

genes and several intracellular stress pathways may 

be activated. The aim of this project is to further 

investigate how GM-CSF acts to promote embryo cell 

survival, by in situ imaging of an array of proteins 

involved in the cellular stress response and in 

regulating the apoptosis cascade. The principal 

techniques will be in vitro embryo culture and 

confocal microscope analysis of immuno-labelled 

embryos, with potential for utilization of anti-sense 

mRNA strategies for investigating the effects of 

perturbing GM-CSF signaling pathways in vitro. The 

experiments are expected to provide new 

information on the molecular pathways by which 

GM-CSF influences optimal embryo development. 

The research will assist in development of improved 

embryo culture processes in human IVF clinics. 

Keywords 

Embryo / cytokines / GM-CSF 

PROJECT: (Basic) TGFβ1 gene dosage effect on 

placental morphogenesis and fetal growth. 

Theme title: Pregnancy immunology 

.R. O&G. 

Supervisors 




Transforming growth factor β1 (TGFβ1) is a key 

cytokine implicated in embryo implantation and 

development of the placenta. Female mice 

homozygous for a null mutation in the TGFβ1 gene 

are almost fully infertile, with impaired ovarian 

function and arrested pre-implantation embryo 

development. In heterozygote breeding pairs, the 

proportion of pups either homozygote or 

heterozygote for the null mutation is substantially 

fewer than the expected Mendelian frequency, 

indicating detrimental effects of reduced TGFβ1 

synthesis in the conceptus. The aim of this project is 

to determine whether the TGFβ1 gene dosage effect 

is mediated through impaired development of the 

placental tissue reflected in reduced capacity to 

support the developing fetus. The project will utilize 

TGFβ1 null mutant mice on immunodeficient and 

immune competent backgrounds. Placental tissue 

45 |

will be analysed by computer-assisted histological 

and morphometric analysis at key milestones in 

development, and quantitative RT-PCR based 

analysis of mRNA expression for placental genes 

implicated in development and function. Fetal tissue 

will be genotyped by diagnostic PCR and growth 

and survival rates of progeny of different genotypes 

will be determined. The potential contribution of 

TGFβ1 in immune-mediated placental dysfunction will 

be analysed by assessing Treg cells, which are 

implicated in maternal immune tolerance of the 

conceptus. The results will provide a better 

understanding of the physiological role of TGFβ1 in 

establishing and maintaining pregnancy, and will 

inform upon the possible contribution of gene 

polymorphisms in TGFβ1, or other environmental 

perturbations in TGFβ1, in infertility and pathologies of 

human pregnancy. 

Keywords 

Placenta / cytokines / TGFβ 

PROJECT: (Basic) Can macrophages aid embryo 

implantation for pregnancy success? 

.R. O&G. 

Supervisor 


Introduction to the laboratory 

To implant and establish the connections that are 

vital for further development, the early embryo must 

attach to and then breech the barrier posed by the 

epithelium of the maternal reproductive tract (Figure 

1). 

Infertility, miscarriage, and other pathologies of 

pregnancy stemming from ‘shallow’ placental 

development are known to have their origins at the 

time of embryo implantation into the uterus. 

However the biological process of embryo 

implantation is not understood. 

While it is clear that precisely regulated changes in a 

wide array of parameters including glycosylated 

proteins are associated with achieving a receptive 

state for embryo implantation (‘window of 

implantation’), how these changes occur remains to 

be clarified. 

Macrophages are particularly prominent amongst 

the large and dynamic population of inflammatory 

cells that traffic through the uterus and are able to 

secrete an array of potent regulatory molecules. 

Figure 1. Epithelial cells stained with lectin in mouse 

uterus (MJJ) 

Their recruitment, differentiation and state of 

activation fluctuate over the course of the oestrous 

cycle and particularly during early pregnancy, under 

the direction of potent local determinants including 

cytokines and chemokines, and components of the 

extracellular matrix (ECM). Amongst these regulators 

of uterine macrophages, our interest has centred on 

the role of seminal fluid, which acts at the time of 

insemination to elicit a rapid and dramatic influx of 

macrophages and other activated inflammatory 

cells into the female reproductive tract (Figure 2). 

The success and quality of pregnancy is 

compromised if macrophage populations are 

disrupted in females by preventing exposure to 

seminal plasma. When the seminal vesicle is 

surgically removed from rodents implantation rates 

are reduced, and fetuses have a high incidence of 

growth retardation secondary to changes in 

placental development. We have postulated that 

the inflammatory cells recruited during the response 

to seminal plasma exposure might impact on uterine 

receptivity, particularly the glycobiology of the 

epithelium associated with pregnancy success. 

The student will develop specialised knowledge of 

the implantation process and early pregnancy. In 

addition, they will develop skills in real-time RT-PCR, 

immunohistochemistry and protein blotting. 

Hypothesis 

1. Successful embryo implantation is dependent on 

communication between uterine macrophages and 

luminal epithelial cells in the uterus during early 

pregnancy. 

2. Morphological and biochemical changes 

associated with epithelial cell receptivity, including 

their adhesive properties are regulated by paracrine 

and juxacrine signals of macrophage origin. 

3. Reduced abundance or altered functional 

phenotype in endometrial macrophages during the 

peri-implantation phase of pregnancy impairs 

embryo implantation and placental morphogenesis, 

with adverse consequences for fetal development 

and health after birth. 

46 |

PROJECT: (Basic) Viral Recognition within the female 

reproductive tract. 

.R. O&G. 

Macrophage 

Supervisor/contact person 

Dr Kerri Diener 

Phone 8313 3376 

kerri.diener@adelaide.edu.au 

est day 1 day 4 day 1 SV- 

Epithelium 


Reproduction in placental mammals represents an 

immunological paradox. This is because the 

ejaculates of males, and indeed the developing 

fetus, contain male-specific antigens which are 

recognised as foreign by the recipient female. Yet, 

the female does not respond destructively, nor is she 

immunologically primed to reject future mating 

events with the same male partner. However, this 

state of immunological tolerance that exists between 

the mother and her mate, and developing fetus, 

should not impinge on her capacity to respond 

appropriately to viral challenges, particularly since 

there is a substantial body of evidence to suggest 

that viral infections can compromise female fertility 

and reproductive outcomes, causing pregnancy 

complications including intrauterine growth restriction 

(IUGR), pre-eclampsia, fetal deformities, preterm 

labour and abortion, as well as postnatal morbidity 

such as cerebral palsy. 

A B C 

Figure 2. Macrophages in the uterus during early pregnancy and the effect of exposure to seminal 

fluid. Immunohistochemistry to detect macrophages is shown at estrus (A), on day 1 (B), and on 

day 4 after mating with a male. The post-mating inflammatory response is ablated on day 1 after 

mating with a male from which the seminal vesicle glands have been surgically removed (D). 

D 

In this project, established mouse models will be used 

to explore these issues, under the premise that it is the 

process of early immune recognition and subsequent 

response to viral challenges by the mother and/or 

the developing fetus which are a major contributing 

factor in causing these induced pathologies. A 

variety of genetically-modified mice made deficient 

for the expression of various early immune 

recognition receptors will be used to determine the 

mechanism behind viral recognition within the 

female reproductive tract. 

Students who have undertaken an honours project in 

the Reproductive Immunology Lab have continued 

on to complete PhDs, or work as research assistants. 

Previous honours students have presented their 

research at local ASMR conferences, and I have 

presented aspects of this work at national and 

international conferences. 

References 

Jones CJ, Aplin JD. Glycosylation at the 

fetomaternal interface: does the glycocode play a 

critical role in implantation? Glycoconj J. 

2009 

Apr;26(3):359-66. Epub 2008 Aug 3. Review. 

Aplin JD, Singh H. Bioinformatics and transcriptomics 

studies of early implantation. 

Ann N Y Acad Sci. 

2008 Apr;1127:116-20. Review 

47 |

Discipline of Paediatrics 

Women’s and Children’s Hospital 

Lyell McEwin Hospital 

Royal Adelaide Hospital 

“The Discipline of Paediatrics is located at the Women's 

and Children's Hospital, and includes the Vaccinology 

and Immunology Research Trials Unit. Honours projects in 

Paediatrics are also supervised by our multiple affiliates 

including members of other hospital departments and 

researchers in the Children's Research Centre. The 

Discipline has a wide range of clinical expertise and a 

strong commitment to clinical service in the Division of 

Paediatric Medicine at the Children, Youth and Women's 

Health Service. Our clinical staff provide services in 

multiple fields, including diabetes, endocrinology, 

gastroenterology, pulmonary medicine, sleep medicine, 

immunology, rheumatology, allergy and child & 

adolescent psychiatry.” 

Professor Jenny Couper 

Head of Discipline of Paediatrics 

48 |

Child Nutrition Research Centre (CNRC) 

Supervisors 

Professor Maria Makrides 

Professor Robert Gibson 

Dr Jo Zhou 

Dr Carmel Collins 

Location: Women’s and Children’s Hospital, Flinders Medical Centre 

and Foodplus Research Centre 

The overall aim of the Child Nutrition Research Centre is to optimise the nutritional intake of mothers and their infants, 

whether the infants are born preterm or at term. The rationale for our research is that improvements in nutritional 

status will optimise the growth, neurological development and immune system of all infants. Reducing susceptibility 

to allergy and associated diseases will have beneficial effects on infant quality of life as well as on whole-of-life 

health care costs. 

PROJECT: (Clinical) Neonatal Nutrition Research 

Priority Setting – partnership with parents and 

clinicians. 

Supervisors/Contact 


Carmel.Collins@health.sa.gov.au 

Prof Maria Makrides 

maria.makrides@adelaide.edu.au 


The aim of the Neonatal Nutrition research priority 

setting partnership is to identify the unanswered 

questions around the nutritional management of 

preterm infants that are important to parents and 

clinicians. The honours project will enable parents 

and clinicians caring for preterm infants to identify 

and prioritise what aspects of nutritional 

management of these vulnerable infants matters to 

them. 

Despite improved survival, preterm infants remain at 

high risk for long-term cognitive and educational 

problems. Their developmental quotient at school 

age is 11 points lower than term born children 

placing an extra burden on health and education 

resources. There is strong evidence that the failure to 

meet the nutritional needs of preterm infants is partly 

to blame for these developmental shortfalls. Setting 

research priorities of importance to those most 

closely involved with the care of preterm infants 

ensures research is grounded in clinical reality and 

addresses the concerns of those closest to these 

infants, the parents. 


Establish research priorities for the nutritional 

management of preterm infants. 

Reference 

Collins CT, Chua MC, Rajadurai VS, McPhee AJ, Miller LN, 

Gibson RA, Makrides M. Higher protein and energy intake 

is associated with increased weight gain in pre-term 

infants. J Paediatr Child Health. 2011 Mar;46(3):96-102. 

PROJECT: (Clinical) Innovative methods to maintain 

large cohorts in long-term studies. 

Supervisors/Contact 


Carmel.Collins@health.sa.gov.au 


maria.makrides@adelaide.edu.au 


The CNRC is conducting follow up studies of women 

and children who participated in large scale dietary 

randomised controlled trials. Incomplete follow-up 

biases the results of a study, for e.g. when 

participants who are ‘lost to follow-up’ are different 

from those who complete follow-up or when there is 

differential dropout rates between study groups. 

Innovative strategies are needed to maintain families 

in the study across the years. 


Determine factors influencing continued 

participation in follow-up studies and develop 

strategies to support long-term involvement. 

49 |

PROJECT: (Basic) Measurement of energy metabolites 

in dried blood spots. 

Supervisors 

Prof Robert Gibson 


http://www.adelaide.edu.au/foodplus/ 

http://www.wchri.com.au/ 



robert.gibson@adelaide.edu.au. 

Please use the subject heading ‘Honours Project’. 


Assessing the nutritional status of preterm infants is of 

vital importance to evaluating their overall health. In 

human trials, blood sample analysis is an integral part 

of assessing physiological and immune function in 

participants. This blood collection is invasive and 

analysis involves using volumes of blood, which are 

not possible to obtain from new born infants. We 

have developed a new system that is based on 

analysis of a single drop of capillary blood collected 

by a finger/heel prick on to a piece of filter paper 

and dried. In this project we will aim to develop and 

validate a method of assessing a range of nutrients 

that are important to good health in dried blood spot 

samples. 

This project will ideally suit an enthusiastic student 

who is interested in learning more about nutrition and 

the development of assays for detecting biomarkers 

for assessing nutrient status. 

Techniques/Skills Learnt: may include 

• Scientific writing & literature review 

• General laboratory techniques 

• Chemical extraction 

• Tandem mass spectrometry 

• High performance liquid chromatography 

Key References 

Jones DP, Park Y, Ziegler TR. Nutritional Metabolomics: 

Progress in Addressing Complexity in Diet and Health. 

Ann Rev Nutr. 2012 Apr 23. [Epub ahead of print] 

Skogstrand et.al. Effects of blood sample handling 

procedure on measurable inflammatory markers in 

plasma, serum, and dried blood spot samples. J Immunol 

Methods 336(2008) 78-84 

PROJECT: (Basic) Influence of maternal diet on the 

concentration of micronutrient elements in breast 

milk. 

Supervisors 

Dr Jo Zhou 







Micronutrients such as iron, zinc and selenium are 

important for many aspects of development, growth 

and metabolism. Breast milk is the sole source of 

dietary micronutrients for exclusively breastfed 

infants. The aim of this study is to examine the 

influence of maternal diet during pregnancy and 

lactation on breast milk elemental micronutrient 

concentrations. 

Techniques/Skills Learnt 


• Dietary intake assessment 

• General laboratory technique 

• Elemental analysis of breast milk with ICPMS 


WHO (2001) Iron deficiency anaemia: assessment, 

prevention and control - A guide for programme 

managers. 

Siimes, et al. Breast milk iron--a declining 

concentration during the course of lactation. Acta 

Paediatr Scand 1979; 68:29 

PROJECT: (Basic) Iodine content of bread after 

mandatory iodine fortification. 

Supervisors 

Dr Jo Zhou 







Iodine is essential for thyroid hormone production, 

which in turn is important for normal growth and 

development. However, iodine deficiency has 

recently re-emerged in Australia. As a result, the 

government introduced mandatory iodine 

fortification by replacement of non-iodised salt with 

iodised salt in commercial bread making as a public 

health measure The aim of the study is to assess 

iodine content of different brands and types of 

breads in the supermarket. 



• General laboratory technique 

• Analysis of iodine content in foods using 

ICPMS 


Food Standards Australia and New Zealand (2008) 

Proposal P1003 Mandatory iodine fortification for 

Australia assessment report. 

Australian Population Health Development Principal 

Committee (APHDPC) (2007) The Prevalence and 

Severity of Iodine Deficiency in Australia. 

50 |

PROJECT: (Basic) Measurement of vitamins A, D and E 

in dried blood spots. 

Supervisors 


Dr Jo Zhou 







Assessing the nutritional status of humans and animals 

is of vital importance to evaluating overall health. In 

both animal and human trials, blood sample analysis 

is an integral part of assessing physiological and 

immune function in participants. This blood collection 

is invasive and analysis involves using volumes of 

blood, which are not possible to obtain from some 

animals and new born infants. We have developed a 

new system that is based on analysis of a single drop 

of capillary blood collected by a finger/heel prick on 

to a piece of filter paper and dried. In this project we 

will aim to develop and validate a method of 

assessing the fat soluble vitamins that are important 

to good health in dried blood spot samples. 






• Scientific writing and literature reviews 

• Basic laboratory techniques 

• Chemical extraction 

• Gas chromatography 

• High performance liquid chromatography 


Santos J, Mendiola JA, Oliveira MB, Ibáñez E, Herrero M. 

Sequential determination of fat- and water-soluble 

vitamins in green leafy vegetables during storage. J 

Chromatogr A. 2012 May 3. [Epub ahead of print] 

Thomas JB, Sharpless KE, Yen JH, Rimmer CA. 

Determination of fat-soluble vitamins and carotenoids in 

standard reference material 3280 

multivitamin/multielement tablets by liquid 

chromatography with absorbance detection. J AOAC 

Int. 2011 May-Jun;94(3):815-22. 

Granado-Lorencio F, Herrero-Barbudo C, Blanco-Navarro 

I, Pérez-Sacristán B. Suitability of ultra-high performance 

liquid chromatography for the determination of fatsoluble 

nutritional status (vitamins A, E, D, and individual 

carotenoids). Anal Bioanal Chem. 2010 Jun;397(3):1389- 

93. Epub 2010 Apr 1. 

PROJECT: (Basic) Measurement of nutrients in breast 

milk. 

Supervisors 


Dr Jo Zhou 







Assessing the nutritional status of humans and animals 

is of vital importance to evaluating overall health. In 

both animal and human studies, assessing the 

nutrient level in breast milk of dams/mothers is vital for 

an understanding of the nutrients that pups/babies 

receive. Currently there is no method to easily 

measure the nutrients in breast milk. We have 

developed a new system that is based on analysis of 

a single drop of breast milk on to a piece of filter 

paper and dried. Sections of the dried milk spot can 

then be analysed by mass spectrometry. In this 

project we will aim to develop and validate a 

method of assessing a range of nutrients that are 

important to good health of infants. 







• Dietary intake assessment 

• General laboratory techniques 

• Analysis of breast milk nutrient levels 

• Mass spectroscopy 


Jones DP, Park Y, Ziegler TR. Nutritional Metabolomics: 

Progress in Addressing Complexity in Diet and Health. 

Ann Rev Nutr. 2012 Apr 23. [Epub ahead of print] 

Mäkelä J, Linderborg K, Niinikoski H, Yang B, Lagström H. 

Breast milk fatty acid composition differs between 

overweight and normal weight women: the STEPS Study. 

Eur J Nutr. 2012 May 26. [Epub ahead of print] 

Hoppu U, Isolauri E, Laakso P, Matomäki J, Laitinen K. 

Probiotics and dietary counselling targeting maternal 

dietary fat intake modifies breast milk fatty acids and 

cytokines. Eur J Nutr. 2012 Mar;51(2):211-9. Epub 2011 

May 31. 

Scholarships Available: Yes * 

* Scholarships are competitive and are awarded 

principally on academic merit. 

51 |

CNS Therapeutics Laboratory, Lysosomal Diseases Research Unit 

Supervisor/Contact Person 

Dr Kim Hemsley 

Phone: 8161 6740 

kim.hemsley@adelaide.edu.au 

Location: SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 

The CNS Therapeutics Lab consists of 2 post-doctoral scientists, 2 scientists and 5 technical officers and 2 Hons 

students and is part of the Lysosomal Diseases Research Unit (LDRU). The LDRU’s research goal is ‘early diagnosis and 

treatment for all lysosomal storage disorders (LSD)’. A large, well-established and multidisciplinary team, the LDRU 

has been extremely successful at both basic science and translating this to successful clinical and commercial 

outcomes. 

LSD are inborn errors of metabolism in which there is a mutation in a gene encoding a lysosomal enzyme, resulting in 

low or no production of that lysosomal enzyme and subsequent accumulation of substrate within cells. Progressive 

neurodegeneration is seen in the majority of LSD and most of these disorders have no treatment at present, so 

affected children often die in their early teens. 

The CNS Therapeutics Lab primarily utilises a mouse model of a neurodegenerative LSD, known as MPS IIIA (1, 2). 

Other disease models are also being established. MPS IIIA is presently untreatable and so we are examining the 

cascade of neuropathological changes that occur within the MPS IIIA brain as a result of the accumulation of 

substrate (3, 4). Gaining a better understanding of how the disorder manifests will permit optimisation of therapies in 

pre-clinical testing and potentially allow us to develop novel therapeutic approaches. Pre-clinical testing is being 

undertaken on the mice including, but not limited to, gene therapy and enzyme replacement therapy (5-8). 

Project: (Basic) Understanding and treating 

neuropathology in murine models of neurodegenerative 

lysosomal storage disorders. 

.R. 


The Honours projects on offer in the lab will examine 

neuropathogenesis, and in some cases, treatment of 

it, using small animal models of lysosomal storage 

disorders that primarily affect the brain. Treatments 

currently being examined in the lab include enzyme 

replacement, gene therapy and a variety of agents 

designed to act as co-therapies. Students involved in 

these studies will gain experience in a variety of 

techniques which may include 

immunohistochemical, histochemical, molecular and 

biochemical assays, small animal handling, surgical 

techniques and behavioural assessments. 

References 

Bhaumik M, Muller VJ, Rozaklis T, Johnson L, Dobrenis 

K, Bhattacharyya R, Wurzelmann S, Finamore P, 

Hopwood JJ, Walkley SU, Stanley P. A mouse model 

for mucopolysaccharidosis type III A (Sanfilippo 

syndrome). Glycobiology. 1999 Dec;9(12):1389-96. 

Crawley AC, Gliddon BL, Auclair D, Brodie SL, Hirte C, 

King BM, Fuller M, Hemsley KM, Hopwood JJ. 

Characterization of a C57BL/6 congenic mouse strain 

of mucopolysaccharidosis type IIIA. Brain Res. 2006 

Aug 9;1104(1):1-17 

Savas PS, Hemsley KM, Hopwood JJ. Intracerebral 

injection of sulfamidase delays neuropathology in 

murine MPS-IIIA. Mol Genet Metab. 2004 

Aug;82(4):273-85. 

Hemsley KM, Beard H, King BM, Hopwood JJ. Effect of 

high dose, repeated intra-CSF injection of 

sulphamidase on neuropathology in MPS IIIA mice. 

Genes Brain Behav. 2008 

Lau AA, Hemsley KM, Meedeniya A, Hopwood JJ. In 

vitro characterization of genetically modified 

embryonic stem cells as a therapy for murine 

mucopolysaccharidosis type IIIA. Mol Genet Metab. 

2004 Feb;81(2):86-95. 

Fraldi A, Hemsley K, Crawley A, Lombardi A, Lau A, 

Sutherland L, Auricchio A, Ballabio A, Hopwood JJ. 

Functional correction of CNS lesions in an MPS-IIIA 

mouse model by intracerebral AAV-mediated 

delivery of sulfamidase and SUMF1 genes. Hum Mol 

Genet. 2007 Nov 15;16(22):2693-702. 

Hemsley KM, King B, Hopwood JJ. Injection of 

recombinant human sulfamidase into the CSF via the 

cerebellomedullary cistern in MPS IIIA mice. Mol 

Genet Metab. 2007 Mar;90(3):313-28 

Hemsley KM, Luck AJ, Crawley AC, Hassiotis S, Beard 

H, King B, Rozek T, Rozaklis T, Fuller M, Hopwood JJ. 

Examination of intravenous and intra-CSF protein 

delivery for treatment of neurological disease. Eur J 

Neurosci. 2009 Mar;29(6):1197-214. 

52 |

Craniofacial Research Group 


Associate Professor Barry Powell 

Phone: 8161 7652 

barry.powell@adelaide.edu.au 

Supervisors 

Associate Professor Barry Powell 

Associate Professor Peter Anderson 

Locations: Women’s and Children’s Hospital, Women’s and Children’s Health 

Research Institute 

Our research involves the study of genes involved in bone growth and craniosynostosis, a developmental disorder 

that affects skull growth and mental development in children (Anderson et al., 2006; Coussens et al., 2007; 2008). Our 

overarching goal is to understand gene actions in skull growth and to use that knowledge to develop novel 

therapeutics to improve treatment of bone disorders in collaboration with clinical colleagues. In the projects 

outlined below you will join a team working at the cutting edge of research, using sophisticated molecular and 

cellular approaches, cell culture and gene knockout animal models to study gene function. Your research could 

impact on the development of adjunctive treatments in the clinical management of craniosynostosis and other 

bone growth disorders and provide new insight into the functions of genes and how bone growth is regulated. 

PROJECT: (Basic) Application of recombinant proteins 

to modify abnormal bone growth. 


We are studying a genetic craniofacial abnormality 

(known as craniosynostosis) that affects skull growth 

by causing premature fusion of the skull plates. The 

only treatment is transcranial surgery, but where bony 

fusion re-occurs surgery is inadequate and novel 

therapies are needed. We have discovered that the 

proteoglycans, glypican 1 and glypican 3 (GPC1 and 

GPC3) regulate activity of the key bone growth 

factor, bone morphogenetic protein 2 (BMP2) in 

cranial cells. 

In this project we will mouse models to test if 

manipulation of BMP2 activity can prevent the reoccurrence 

of bone growth after surgery. This could 

be tested in tissue explants or in vivo. The effects on 

bone fusion, BMP2 activity and markers of bone 

growth can be assessed. 

Outcomes 

This research could lead to the development of novel 

therapeutic approaches to treat abnormal bone 

growth. 

PROJECT: (Basic) How do glypicans and bone 

morphogenetic proteins interact in cranial bone 

growth? 


The proteoglycans, GPC1 and GPC3, act as coreceptors 

for growth factors at the cell surface but 

they can also be released extracellulary to bind 

them. In this project you will investigate how GPC1 

and GPC3 regulate BMP2 in cranial suture cells. 

Building on data that GPC1 and GPC3 interact with 

BMP2 in vitro, this will be tested in vivo in this project. 

We can explore if interaction occurs at the cell 

surface or after the proteins have been released from 

the cell. The fate of GPC-BMP2 complexes can be 

explored. Are they internalised and degraded, or 

recycled? Regions responsible for interaction could 

be mapped using mutant proteins. 

Outcomes 

This research will provide insight into how glypicans 

and BMPs interact and can therefore have impact in 

the broader fields of bone research and 

proteoglycan biology. 

PROJECT: (Basic) What does retinol binding protein do 

in skull growth? 


Retinol binding protein (RBP) is well known as a 

transport protein for retinol in serum and has recently 

been implicated in metabolic syndrome. However, 

our research shows that it may have other 

unexpected functions. We have discovered that RBP 

is expressed by skull bone-forming cells and is 

dramatically down-regulated in the congenital 

condition of craniosynostosis (Coussens et al., 2007) 

suggesting that it has a role in skull bone formation. 

Our recent data analysing RBP and its receptor 

reveal remarkable subcellular locations and 

movement within cells. 

In this project we aim to determine what RBP and its 

receptor do in skull bone-forming cells. 

Outcomes 

This research will provide insight into the function of 

RBP and its receptor in skull bone growth. 

53 |

Techniques that will be used in the projects include 

human cell culture, animal studies, micro-computed 

tomography, gene transfection, real-time RT-PCR, 

luciferase assay, mineralization assay, proliferation 

assay, western blot, immunohistochemistry and 

confocal microscopy. 

References 

Anderson PJ, 

DJ Netherway, P Self and DJ David. 

Scanning electron microscope and Micro CT 

evaluation of cranial sutures in health and disease. 

Journal of Craniofacial Surgery 17, 909-919, 2006. 

Coussens AK, CR Wilkinson, IP Hughes, CP Morris, A 

van Daal, PJ Anderson and BC Powell. 

2007. 

Unravelling the molecular control of calvarial suture 

morphogenesis in children with craniosynostosis. BMC 

Genomics. 8:doi: 10.1186/1471-2164-8-458. 

Coussens AK, CR Wilkinson, IP Hughes, BC Powell, PJ 

Anderson and A van Daal. 2008. Identification of 

genes differentially expressed by prematurely fused 

human sutures using a novel in vivo-in vitro approach. 

Differentiation. 76:531-545. 

Donato R, SA Wood, I Saunders, B Gundsambuu, KY 

Mak, CA Abbott and BC Powell. 

2009. Regulation of 

epithelial apical junctions and barrier function by 

Galpha13, Biochim Biophys Acta - Molecular Cell 

Research 1793, 1228-1235. 

These projects are eligible for the WCHRI Honours 

Scholarship of $2,000. See the website for further 

details and how to apply 

http://www.wchri.com.au/Scholarships.htm. 

54 |

Lysosomal Biology, Lysosomal Diseases Research Unit 


Dr Maria Fuller 

Phone: 8161 6741 

maria.fuller@adelaide.edu.au 

Location: SA Pathology, Women’s and Children’s Hospital 

The Lysosomal Diseases Research Unit is highly regarded by its peers internationally for its seminal scientific 

contributions to the area of lysosomal research. Its research has resulted in FDA approval of first-ever treatments for 

two lysosomal storage disorders. The Unit consists of about 35 research staff and students working on a range of 

projects directed at understanding, improving diagnostic capabilities and treatment for a group of inherited 

metabolic diseases, known as lysosomal storage disorders. The Lysosomal Biology section of the Unit is currently 

investigating the role of the lysosome with respect to lipid metabolism in conditions outside the spectrum of classical 

lysosomal storage disorders, such as diabetes, metabolic syndrome, obesity, and Alzheimer’s and Parkinson’s 

diseases. We utilise state-of-the-art technology, including electrospray ionisation-tandem mass spectrometry, and 

lipid analytical techniques developed in our group. This technology provides a powerful platform to the 

investigation of metabolic disease. In February this year the group acquired a Waters Synapt High Definition mass 

spectrometer – the first one of its kind in Australia – capable of metabolomics, proteomics and MALDI imaging. This 

instrument is unique in offering an additional dimension to the analysis of compounds by using ion mobility 

separation, which allows compounds to be differentiated by size and shape. 

The following projects will give students broad scientific skill in cell models of disease, cell biology and the latest mass 

spectrometry technology in a highly challenging and stimulating academic environment. The student will also have 

ample support from other staff within the group who are experts in the methodology used (pictured above). 

Students will have the opportunity to participate in regular scientific discussions and meetings within the Unit. 

PROJECT: (Basic) Lipid disturbances in Neimann Pick 

C disease. 


Niemann-Pick C (NPC) disease is a hereditary 

cholesterol storage disorder resulting in severe 

neurovisceral pathology for which there is no cure. 

Many of the known risk factors of other diseases such 

as Alzheimer’s disease are also associated with 

cholesterol metabolism. This project proposes a 

“lipidomics” approach to identify the type of lipid 

alterations that occur secondarily to impaired 

cholesterol homeostasis using NPC patient cultured 

skin fibroblasts as a cell model. Sub-cellular 

fractionation techniques will also be employed to 

determine the location of these lipid alterations within 

the cell. The second part of this project will evaluate 

the possibility of normalising these lipid alterations by 

supplementing the culture media with particular fatty 

acids and drugs of lipid metabolism, as a potential 

therapeutic strategy for diseases of cholesterol 

metabolism. 

The overall scientific objective of this project is to 

identify lipid alterations that may be treated with diet 

and/or conventional drugs, providing a treatment for 

many individuals with diseases of cholesterol 

metabolism, including Alzheimer’s and NPC. The 

student will gain experience in cell culture and a 

variety of cell biology techniques including sub- 

cellular fractionation, as well as learning aspects of 

mass spectrometry. 

PROJECT: (Basic) Sphingolipids in diabetes and 

Gaucher disease. 


The membranes of mammalian cells are composed 

of an ordered array of lipids, and in many instances 

chemical or functional changes in these membranes 

are central to the pathogenesis of disease. We have 

shown that membrane lipids are altered in lysosomal 

storage disorders, and recent studies in the 

glycosphingolipid storage disorder, Gaucher disease, 

associate such lipid alterations with insulin resistance. 

It is now obvious that lysosomal storage disorders and 

insulin resistance diabetes share disturbances in 

sphingolipid metabolism, and because sphingolipids 

predominate in membrane rafts, the mechanistic link 

may be mediated by rafts. Rafts are specialised 

membrane microdomains that facilitate interactions 

between the protein and lipid components of 

signalling pathways. This project proposes to 

determine the lipid composition of membrane rafts in 

cell models of Gaucher disease and insulin resistant 

diabetes to unravel common nodes of interactions 

between these two pathogenic mechanisms. For 

effective long term-treatment of these conditions, 

understanding the pathogenic mechanisms will be 

imperative. 

55 |

The student will gain broad experience in cell culture 

with both primary and gene knockdown 

immortalised cell lines. The student will gain 

experience in Western blot analysis, membrane 

microdomain isolation and various aspects of mass 

spectrometry. 

Publications 

Hein LK, Meikle PJ, Hopwood JJ, Fuller M. (2007) 

Secondary sphingolipid accumulation in a cell model 

of Gaucher disease. Mol Genet Metab 92, 336-45. 

Meikle PJ, Whitfield PD, Rozaklis T, Blacklock D, 

Duplock S, Elstein D, Zimran A, Mengel E, Cannell P, 

Hopwood JJ, Fuller M. (2008) Plasma lipids are altered 

in Gaucher disease: Biochemical markers to evaluate 

therapeutic intervention. Blood Cells Mol Dis 40, 420- 

7. 

Meikle PJ, Duplock S, Blacklock D, Whitfield PD, 

Macintosh GL, Hopwood JJ, Fuller M. (2008) Effect of 

lysosomal storage on bis(monoacylglycero) 

phosphate. Biochem J 411, 71-8. 

Fuller M, Rozaklis T, Lovejoy M, Zarrinkalam K, 

Hopwood JJ, Meikle PJ. (2008) Glucosylceramide 

accumulation is not confined to the lysosome in 

fibroblasts from patients with Gaucher disease. Mol 

Genet Metab 93, 437-43. 

Hein LK, Duplock S, Hopwood JJ, Fuller M. (2008) Lipid 

composition of microdomains is altered in a cell 

model of Gaucher disease. J Lipid Res 49, 1725-34. 

56 |

Matrix Biology Unit 


Supervisor/Contact Persons 

Dr Sharon Byers 

Phone: 8161 7093 

sharon.byers@adelaide.edu.au 

Dr Ainslie Derrick-Roberts 

Phone: 8161 6373 

ainslie.derrickroberts@adelaide.edu.au 

Our research interest lies in the regulation of a group of complex carbohydrates called glycosaminoglycans (gags). 

Gags are found in all tissues where they define tissue structure and modify tissue growth through the regulation of 

growth factor activity. They are constantly synthesised and degraded as part of normal development. Defects in 

degradation lead to the mucopolysaccharidosis (MPS) group of inherited metabolic disorders. Our laboratory is 

focused on the characterisation of disease progression and the development of safe and effective therapies for 

MPS children and played a key role in the commercialization of enzyme replacement therapy. The laboratory is 

situated in the department of Genetics and Molecular Pathology, SA Pathology (WCH site). The department is the 

Australasian centre for the diagnosis and treatment of children with MPS. 

The multiple organs systems affected by the accumulation of undegraded gag in MPS presents a challenge to the 

clinical management of affected children. While somatic tissues such as liver and kidney are amenable to 

replacement therapies, the brain and the cartilage component of the musculoskeletal system are untreatable. 

Students will join ongoing projects in one of the following areas:- 

Key Words: 

genetic disease, childhood disorders, therapy, murine models of disease, behavioural tests, bone growth 

PROJECT: (Basic) Targeting CNS pathology in MPS 

disorders. 


CNS pathology that manifests as a severe, 

progressive loss of cognitive function is a major 

symptom of 7 of the 11 MPS types and is currently 

untreatable. The aim of this project is to find a 

minimally invasive approach to treat CNS pathology 

in MPS disorders. Gene therapy replacement of the 

missing gene has shown promising results in mouse 

models (Anson et al., 2011), however has a limited 

effect on the CNS due to the presence of the bloodbrain 

barrier. The aim of this project is to improve 

blood brain barrier transport using a modified 

enzyme to enhance receptor mediated transport 

across the blood-brain barrier. By combining gene 

therapy to increase residual enzyme levels with small 

molecule SDT (Derrick-Roberts et al., 2012) to 

decrease gag levels is another approach to improve 

the outcome of CNS disease in MPS disease also 

under investigation. 

Students undertaking this project will learn 

fundamental research techniques applicable to a 

wide range of research areas. These include small 

animal handling, behavioural testing (eg water maze 

tests), enzyme assay, electrophoresis and 

carbohydrate biochemistry. Equipment to be used 

will include: microscopes, centrifuges, electrophoresis 

equipment, fluorimeter, mass spectrometer and 

laminar flow/biohazard hoods. 

References 

Roberts ALK, Rees MH, Klebe S, Fletcher JM and Byers 

S. (2007): Improvement in behaviour after substrate 

deprivation therapy with rhodamine B in a mouse 

model of MPS IIIA. Molecular Genetics and 

Metabolism, 92: 115-121. 

Anson DS, McIntyre C, Byers S. (2011): Therapies for 

neurological disease in the mucopolysaccharidoses. 

Curr Gene Ther. 11: 132-43. 

Derrick-Roberts ALK, Ly M, Marais W and Byers S. 

(2012). Rhodamine B and 2-acetamido-1,3,6-tri-Oacetyl-4-deoxy-4-fluoro-D-glucopyranose 

(F-GlcNAc) 

inhibit chondroitin/dermatan and keratan sulphate 

synthesis by different mechanisms in bovine 

chondrocytes. Mol. Genet. Metab. 106: 214-20. 

PROJECT: (Basic) Understanding skeletal disease in 

MPS patients. 


Direct injection of enzyme into the joint space 

increases the localized concentration of enzyme 

replacement therapy (ERT) and improves joint 

outcome (Auclair et al 2006, 2007). We have recently 

shown that the same improvement can be achieved 

57 |

y a gene therapy approach to transduce joint cells 

(Byers et al 2009). In this project students will join an 

ongoing project to investigate the efficacy of 

systemic gene therapy alone or in combination with 

intra-articular gene therapy to prevent the 

development of both bone and joint pathology. 

Short stature is a feature of 6 of the 11 MPS disorders 

which leads to problems with mobility. Therapy 

options are limited and ERT available for some MPS 

disorders does not increase bone length in affected 

children even though it has a positive effect on other 

symptoms. This suggests that we need a better 

understanding bone growth and by isolating distinct 

regions of the growth plate responsible for bone 

lengthening we can identify key markers involved in 

long bone growth which can be new targets to 

improve short stature. 

Students undertaking this project will learn 

fundamental research techniques applicable to a 

wide range of research areas. These include small 

animal handling, bone histomorphometric 

techniques, micro CT, laser capture microdissection, 

real-time PCR, electrophoresis and carbohydrate 

biochemistry. Equipment to be used will include: 

microscopes, image analysis equipment, centrifuges, 

electrophoresis equipment, fluorimeter and laminar 

flow/biohazard hoods. 

References 

Macsai CE, Derrick-Roberts AL, et al. (2012): Skeletal 

response to lentiviral mediated gene therapy in a 

mouse model of MPS VII. Mol Genet Metab. 2012 

Jun;106: 202-13 

Byers S, Rothe M, et al. (2009). Lentiviral mediated 

correction of MPS VI cells and gene transfer to 

skeletal tissues. Molecular Genetics and Metabolism, 

97: 102-108. 

Auclair D, Hein LK, et al. (2006): Intra-articular enzyme 

administration for joint disease in feline 

mucopolysaccharidosis VI: Enzyme dose and interval. 

Pediatric Research, 59: 538-542. 

Auclair D, Hopwood JJ, et al. (2007): Intra-articular 

enzyme administration for joint disease in feline 

mucopolysaccharidosis VI: Long-term therapy. 

Molecular Genetics and Metabolism, 91: 352-61. 

58 |

Molecular Immunology 

Cheryl Brown 

Phone: 8161 6729 

cheryl.brown@adelaide.edu.au 

Supervisors/ Contact Persons 

Associate Professor Simon Barry 

Phone: 8161 6562 

simon.barry@adelaide.edu.au 

Tim Sadlon 

Phone: 8161 6729 

timothy.sadlon@adelaide.edu.au 


My lab is interested in how a healthy immune system balances being ready to react by swiftly fighting off 

pathogens, while maintaining tolerance to harmless challenges such as food and body tissues. The cellular immune 

repertoire in humans is broad, but we are focussed on a T cell subset that is shaped along with the immune system 

from birth. These cells are known as regulatory T cells, and they are accepted as the policemen of the immune 

system. There is increasing evidence that in a wide number of disease states including autoimmune diseases such as 

Type 1 diabetes and Multiple Sclerosis, these cells fail to regulate the immune system, and allow inappropriate 

destruction of tissues that are essential for life. In order to understand how this breaks down in disease one must first 

understand what is the basis of a healthy Treg. To do this we are focussed on human cells and we use a number of 

state of the art gene discovery tools such as microarrays to identify and then confirm the key genes in Treg function. 

As Treg play a role in autoimmune disease, cancer and transplantation tolerance, our research findings have a wide 

clinical application. The projects below are from parts of this overall research program. We currently have 11 

members of the research group, which provides lab and academic support for students. 

PROJECT: (Basic or Clinical/basic) Molecular 

identification of Regulatory T cells. 

.R. 


The recent identification of regulatory T cells (Tregs) 

as a key mediator of central and peripheral 

tolerance has led to an increase in our 

understanding of the cellular mechanisms by which 

humans maintains the healthy state. This has been 

confirmed by the identification of a transcription 

factor named FOXP3 in both mouse and human 

Tregs, which is proven to be essential for formation 

and function of the committed T cell subset that has 

regulatory capacity. There is however, very little 

known about the molecular basis of this process. This 

project aims to identify the genes directly regulated 

by FOXP3 and to determine their role in the 

regulatory phenotype. We have used a number of 

direct and indirect molecular approaches such as 

Chromatin Immunoprecipitation and microarray 

analysis to profile genes regulated by FOXP3 (Fig 1), 

and we will validate their role in regulatory function 

by direct assays and by over expression or gene 

ablation studies. 

Fig 1: Comparative microarray analysis of CD4 

CD25+ natural Treg to identify the key genes 

required for function. 

59 |

The candidate genes identified in this approach may 

lead to therapeutic approaches for intervention in 

the function of regulatory cells, and will also have 

application for diagnostic analysis of regulatory cell 

function. Analysis of these and other Tcells from 

disease samples eg IBD (Fig 2) reveals the clinical 

defect in numbers of Treg. 

Fig 2: Comparative analysis of CD4 CD25+ natural Treg 

and Th17 in IBD patients shows a defect in the ratio of 

these cells. 

Techniques/skills/approach 

Molecular biology, RT PCR, microarray data analysis, 

tissue culture lentiviral production, gene silencing and 

over expression, functional assay. 

References 

1. Bresatz S Sadlon T, Millard D, Zola H, Barry SC. 

Purification and characterization of CD4+ CD25+ 

regulatory cells from Cord and peripheral blood. J 

Immunuol Methods 2007;327:53-62 [Epub ahead of 

print]. Impact Factor = 2.5, Journal rank in field 46/114 

2. Zola H, Swart B, Banham A, Barry SC, Beare A, Bensussan 

A, Boumsell L, D Buckley C, Buhring HJ, Clark G, Engel P, 

Fox D, Jin BQ, Macardle PJ, Malavasi F, Mason D, 

Stockinger H, Yang X. CD molecules 2006--human cell 

differentiation molecules. J Immunol Methods 

2007;319(1-2):1-5. Epub 2006 Dec 4. Impact Factor = 2.5, 

Journal rank in field 46/114 

PROJECT: (Basic) Cord Blood Stem cell differentiation 

in to regulatory T cells. 

.R. 


The clinical application of regulatory T cells is 

significantly hampered by the limited cell numbers 

that can be obtained from either cord or adult 

blood. Attempts to expand these purified Treg ex vivo 

have shown some promise, but there is some 

evidence that after extended culture ex vivo these 

cells lose their suppressive capacity. An alternative 

approach is to generate large numbers of T cells de 

novo from stem cells since these cells have the 

capacity to differentiate into all cells of the 

haemopoietic system. We have established an ex 

vivo differentiation assay that can expand cord 

blood stem cells and induce their differentiation 

along the lymphoid pathway using a co-culture 

system giving notch signals via the Notch ligand 

Delta like 1 ( Fig 3). In this system we robustly observe 

5-600 fold expansion of cell numbers and the 

generation of T cell subsets as defined by CD4/CD8 

staining. 

Fig 3. Cord blood stem cells on feeder cells 

showing formation of CD4 CD25+ subsets with 

similar characteristics to natural Treg 


Molecular biology, RT PCR, tissue culture, lentiviral 

production, gene silencing and over expression, 

functional assay with cord blood stem cells. 

References 

1. Hutton JF, Gargett T, Sadlon TJ, Bresatz S, Brown CY, Zola 

H, Shannon MF, D'Andrea RJ, Barry SC: Development of 

CD4 + CD25 + FOXP3 + Regulatory T cells from Cord Blood 

Haemopoietic Progenitor Cells. Journal of Leukocyte 

Biology in press ePub Dec 22 08. Impact Factor = 4.3, 

Journal rank in field 50/156 

PROJECT: (Basic) Lentiviral vectors for gene delivery 

and gene ablation. 

.R. 


Manipulation of primary cells has a key limitation in 

that these cells are refractory to standard 

transfection protocols. Also, since they are often of 

low mitotic index, they are only infected at low 

efficiency by murine retroviruses (RV), as these viruses 

require cell division for integration. The recent 

development of HIV1 based lentivectors (LV) 

provides an attractive option for gene delivery into T 

cell and stem cell populations, as these viruses carry 

the necessary cis elements to facilitate nuclear 

transport and integration in the absence of cell 

division. We have developed a suite of lentiviral 

vectors for stable gene delivery into primary cells 

both for gene therapy and gene discovery 

applications, and more recently for gene ablation 

using RNA interference (Fig 4). This technology relies 

on the expression of a short hairpin RNA structure that 

is complimentary to the gene target, and that is 

processed by cellular machinery to generate an RNA 

oligo that can bind to and target the mRNA for 

destruction. 

60 |

Fig 4. Lentiviral delivery of shRNAi showing abalation of 

FoxP3 expression that is inducible with doxicyclin and is 

reversible. 


Molecular biology, RT PCR, Tissue culture, lentiviral 

production, gene silencing and over expression, 

functional assay, T cell assays. 

References 

1. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, 

Farshid G, Vadas MA, Khew-Goodall Y and Goodall GJ: 

The microRNA-200 family and miR-205 regulate 

epithelial-mesenchymal transition by targeting the Ecadherin 

repressors, ZEB1 and SIP1. Nature Cell Biology 

2008 10 (5)593-601 Impact Factor F = 18.1, [28] J Journal 

rank in field 5/156 

2. Barry SC,Coates PT. Retroviral escape using DC - that's 

what Friends are for. Blood 2007 110(12)3819-3820 

Impact Factor = 10.1, Journal rank in field 2/59 

3. Drabsch Y, Hugo H, Zhang R, Dowhan DH, Miao YR, 

Gewirtz AM, Barry, SC, Ramsay RG and Gonda TJ. 

Mechanism of and Requirement for Estrogen-Regulated 

MYB Expression in Estrogen Receptor-Positive Breast 

Cancer Cells. PNAS 2007;104(34):13762-7. Impact Factor 

= 10.9, Journal rank in field 3/45 

4. Brzezinski M, Yanay O, Waldron L, Barry SC and Osborne 

WRA. G-CSF-lentivirus provided long-term elevated 

neutrophil counts in rats and sequential EPO-lentivirus 

administration produced increased hematocrits in both 

lentivirus treated and naïve rats. J Gene Medicine 

2007;9(7):571-8. Impact Factor = 4.8, Journal rank in 

field 8/75 

5. Barry SC Brezinzki M, Yanay O, Seppen, J Osborne WRA. 

Sustained elevation of neutrophils in rats induced by 

lentivirus-mediated G-CSF delivery. J Gene medicine 

2005;7(12):1510-6. Impact Factor = 4.8, Journal rank in 

field 8/75 

PROJECT: (Basic/clinical basic) Is there a role for 

FOXP3 in Breast Cancer? 

.R. 


There is very recent evidence that FOXP3 may also 

play a role in breast cancer as a new tumour 

suppressor. This means that its expression prevents the 

transformation leading to cancer, and in cells that 

have transformed it is no longer correctly expressed. 

As we have discovered a great many of the genes 

that are directly regulated by FOXP3 in Tregs, it is likely 

that some of these are also required for prevention of 

breast cancer. We have now confirmed that FOXP3 is 

expressed in healthy breast epithelial cells, and are 

testing a number of genes for their role in either the 

loss of normal FOXP3 expression, or the progression to 

cancer. This includes a number of micro RNAs that 

are controlled by FOXP3 (quantitated by RT PCR in 

Fig 5), one of which (mir21) has been confirmed to 

play a role on breast cancer. We aim to demonstrate 

that correction of the FOXP3 expression defect can 

reverse these transformation causing genes and 

restore a healthy state. 

mir7 

mir101 

mir155 

mir19b 

mir21 

mir146a 

0.01 0.10 1.00 10.00 

Log Fold Change in Expression 

BT+Fp3 2 

BT+Fp3 1 

Fig 5: When FOXP3 is over expressed using a lentivirus in 

a breast cancer cell line, we observe increased 

expression of target micro RNAs. 


Molecular biology, RT PCR, microarray data analysis, 

tissue culture, lentiviral production, gene silencing 

and over expression, functional assay in breast 

cancer cells. 

References 

1. Zuo, T., et al., FOXP3 is a novel transcriptional repressor 

for the breast cancer oncogene SKP2. The Journal of 

Clinical Investigation, 2007. 117(12): p. 3765-3773. 

2. Zuo, T., et al., FOXP3 is an x-linked breast cancer 

suppressor gene and an important repressor of the HER- 

2/ErbB2 oncogene. Cell, 2007. 129: p. 1275-1286. 

Collaborators 

Shaun McColl- Micro and Immunol, Adelaide 

Jenny Couper-Diabetes Endocrinology, Adeliade 

Greg Goodall– IMVS, Adelaide 

Tom Gonda – CICR, Brisbane 

Frances Shannon – JCSMR, ANU Canberra 

Heddy Zola – WCHRI, Adelaide 

What happens to Honours students from my lab?: 

2007 Kai Mak: 1st Class Hons. 2yrs as Research 

associate, starting a Ph.D in 2011. 

2008 Tessa Gargett: 1st Class Hons. Awarded the 

Derek Rowley prize for best in year. Currently a 

Research Associate in the Barry lab. 

Steve Pederson: 1st 

class Hons. Awarded APA 

(PhD scholarship) 2yr PhD in the Barry Lab. 

2009 Natasha McInnes: 1st 

class Hons. Awarded 

APA (PhD scholarship) 1yr PhD in the Barry lab. 

Danika Hill: 1st Class Hons, Awarded Derek 

Rowley prize for best in year. Currently a 

Research Associate in the Barry lab. 

Honours students are encouraged to continue on to 

PhD studies in my group. 

61 |

Molecular Neurogenetics 


Dr Cheryl Shoubridge 

Phone: 8161 8105 

cheryl.shoubridge@adelaide.edu.au 

Supervisors 

Dr Cheryl Shoubridge 

Dr Kristie Lee 


Identification of genes and understanding of molecular mechanisms leading to intellectual disabilities, autisms and 

some epilepsies represents a challenge of significant medical importance. Our research seeks to further our 

understanding of human brain function through the identification of genes and characterisation of their naturally 

occurring mutations implicated in various disorders of the brain. The Molecular Neurogenetics laboratory focuses on 

identifying the molecular mechanisms and functional impact of mutations in genes causing X-linked intellectual 

disability (XLID). 

The key areas of research include utilizing primary neuronal cell culture models to investigate the functional impact 

of patient mutations in genes involved in X-linked Intellectual disability, in particular the ARX and IQSEC2 genes. We 

have animal models to investigate functional impact of the two most frequent expanded polyalanine tract 

mutations in the ARX gene. Our ongoing work aims to establish the molecular mechanisms of disease associated 

with a range of expanded polyalanine tract mutations in ARX to begin to understand how these mutations underpin 

the intellectual disability with and without a broad spectrum of associated clinical symptoms in affected patients, 

including epilepsy. We are also interested in more fundamental aspects of ARX biology and are currently 

investigating how phosphorylation may regulate the function of the ARX homeodomain transcription factor. 

Honours students are encouraged to remain with our research team to undertake a Ph.D. 

PROJECT (Basic): Do expanded polyalanine tract 

mutations in ARX disrupt neuronal migration? 


When the function of the Aristaless related 

homeobox gene (ARX) is lost due to severe 

mutations, patients are afflicted with catastrophic 

brain malformations such as smooth brain 

(lissencephaly) or hydrocephaly. Disruptions to 

normal neuronal migration underlie these conditions. 

Understanding the role of ARX in the cell fate and 

migration of neurons during the development of the 

brain remains a key goal. A less severe but more 

common mutation in ARX lead to expanded 

polyalanine tract (polyA expansions) with these 

patients displaying intellectual disability often in 

conjunction with seizures and other clinical features. 

We have mice that model the two most common 

human polyA expansions providing us an excellent 

tool to interrogate the role of ARX in neuronal 

development. The goal of this project would be to 

establish the effect of expanded polyalanine tract 

mutations on neuronal migration. Students would 

generate neurosphere cultures from the embryonic 

brains of wild-type and mutant mice. These 

neurospheres can then be manipulated in culture to 

assess aspects of neuronal migration and establish 

changes in the types and maturity of cells arising 

from the sphere. The findings will be validated in the 

brains of the mutant mice. The research techniques 

the student will be using include small animal 

handling and micro-dissection techniques, 

generation of primary neurospheres in culture, 

immunoflorescent techniques to identify different cell 

types in culture and a broad range of molecular 

techniques including real time PCR, RNA and protein 

extraction and electrophoresis. 

PROJECT (Basic): Understanding the molecular 

pathogenesis of polyalanine expansions in mice 

modelling intellectual disability and epilepsy. 


Intellectual disability (ID) is a disorder whereby 

affected individuals display an intelligent quotient 

≤70. It is estimated that 1-3% population suffer from ID, 

with which mutations in genes at the X chromosome 

account for up to 30% of the cases that have a 

genetic basis. The X chromosome gene Aristaless 

related homeobox gene (ARX) encodes a 

transcription factor that encompasses four 

polyalanine (polyA) tracts, and is one of the most 

frequently mutated ID genes. Mutations leading to 

extended polyalanine tract lengths (polyA 

expansions) are the most common mutations of ARX. 

Human patients with ARX polyA expansions all display 

intellectual disability with varying severity, while some 

also suffer from epilepsy. We have mice that model 

62 |

the two most common human polyA expansions, and 

our research to date has found that polyA mutations 

lead to a loss of ARX protein abundance during 

embryonic development. We are now interested in 

understanding the molecular basis that underlies ARX 

protein reduction, as well as elucidating downstream 

transcription targets that are differentially regulated 

as a result of the polyA expansions. The fundamental 

research techniques the student will be using include 

small animal handling and micro-dissection 

techniques, generation of primary neuronal cell 

culture, a broad range of molecular techniques 

including real time PCR, RNA and protein extraction 

and electrophoresis. 

References 

Shoubridge C, 

Fullston T and Gecz J. ARX spectrum 

disorders; making inroads in to the molecular 

pathology. Human Mutation 31(7) 2010. 

Kitamura, K., Itou, Y., Yanazawa, M., Ohsawa, M., 

Suzuki-Migishima, R., Umeki, Y., Hohjoh, H., 

Yanagawa, Y., Shinba, T., Itoh, M. et al. (2009) Three 

human ARX mutations cause the lissencephaly-like 

and mental retardation with epilepsy-like pleiotropic 

phenotypes in mice. Hum Mol Genet, 18, 3708-24. 

Shoubridge C 

, Tan MH Seiboth G and Gecz J. 

Missense mutations in the homeodomain of ARX 

abolish binding to DNA and cause a loss of 

transcriptional repression activity. Human Molecular 

Genetics, 2012 Apr 1;21(7):1639-47. 

63 |

Nutritional Immunology 


Imme Penttila 

Phone : 8161 7072 

irmeli.penttila@adelaide.edu.au 

Beverly Muhlhausler 

Phone: 8313 0848 

beverly.muhlhausler@adelaide.edu.au 

Supervisors 

A/Prof Imme Penttila 

Dr Beverly Mulhausler 


Location: Women’s and Children’s Health Research 

Institute 

Biomarkers such as cytokines and eicosanoids are potent mediators that can act together and play a critical role in 

inflammation and other disease states. In some clinical trials, blood sample analysis is an integral part of assessing 

physiological and immune function in participants. This blood collection and analysis involves using volumes of 

blood, which are not possible to obtain from new born infants. New born infants however undergo screening 

programs based on analysis of a single sample of capillary blood collected by heel prick between 3 and 14 days of 

age. In this project we will aim to develop and validate a method of assessing cytokines and other markers in dried 

blood spot samples. 

In summary, this project will ideally suit an enthusiastic student who is interested in learning more more about 

nutritional intervention and the development of immuno-based assays for detecting biomarkers from associated 

clinical trials. 

PROJECT: (Basic) Measurement of immune markers in 

dried blood spots by immunoassay. 

WCHRI Scholarship available: 

Contact: 81617443 

Website http://www.wchri.com.au/ 


Biomarkers such as cytokines and eicosanoids are 

potent mediators that can act together and play a 

critical role in inflammation and other disease states. 

In some clinical trials, blood sample analysis is an 

integral part of assessing physiological and immune 

function in participants. This blood collection and 

analysis involves using volumes of blood, which are 

not possible to obtain from new born infants. New 

born infants however undergo screening programs 

based on analysis of a single sample of capillary 

blood collected by heel prick between 3 and 14 

days of age. In this project we will aim to develop 

and validate a method of assessing cytokines and 

other markers in dried blood spot samples. 

In summary, this project will ideally suit an enthusiastic 

student who is interested in learning more about 

nutritional intervention and the development of 

immuno-based assays for detecting biomarkers from 

associated clinical trials. 

Reference 

Skogstrand et.al. Effects of blood sample handling 

procedure on measurable inflammatory markers in 

plasma, serum, and dried blood spot samples. J 

Immunol Methods 336(2008) 78-84 

64 |

Paediatrics and Child Health, Flinders Medical Centre 

Supervisor/Contact Persons 

Dr Dani-Louise Dixon 

Phone: 8204 5494 

dani.dixon@flinders.edu.au 

Prof Kevin Forsyth 

Phone: 8204 5259 

kevin.forsyth@flinders.edu.au 

Major Interests 

• Child Health 

• Strategic planning in health care delivery for children 

• Paediatric Immunology and Paediatric Infectious Diseases 

• Research in the immunopathology of inflammation, particularly viral induced respiratory disease in infants 

• Immunisation 

• Medical Education 

• Curriculum reform in the teaching of Child Health at both undergraduate and postgraduate levels 

• Use of Information Technology in teaching and learning 

PROJECT: (Clinical) Decreasing neutrophil-induced 

lung damage in respiratory syncytial virus (RSV) 

infection: a means to ameliorate infant bronchiolitis. 


Bronchiolitis is the most common severe respiratory 

tract illness in infants and remains a major cause of 

infant hospitalisation as currently there is no 

treatment. Strong evidence suggests that the virus 

which causes bronchiolitis, RSV, induces host immune 

cells (neutrophils) to damage the lung, increasing 

disease severity as well as leading to the 

development of asthma in up to 50% of patients. 

Recently our lab demonstrated the ability of a 

protein, feG, to prevent and treat such lung 

damage. 

We aim to test the therapeutic potential of feG in 

decreasing lung damage caused by RSV, utilising a 

range of techniques which may include in vitro (cell 

culture), animal models, and/or clinical (human) 

aspects. 

The project will be conducted in the Lung Injury 

Laboratory within the discipline of Critical Care 

Medicine. The lab has expertise in fields as diverse as 

immunology, pathology, anatomy, histology, 

physiology, and molecular biology and undertakes 

research that crosses all of these disciplines, in both 

laboratory based and clinical projects. The 

Laboratory has an excellent international reputation 

and an outstanding record of obtaining funding from 

government and non-government sources resulting in 

regular publication in top international journals. 

65 |

Public Health Research Unit 

Supervisors 

Associate Professor Peter Baghurst 

Associate Professor Maree O’Keefe 

Jacqueline Stephens 



Jacqueline Stephens 

Phone: 8161 7790 

jacqueline.stephens@adelaide.edu.au 

The Public Health Research Unit (PHRU) plays a strong support role in the planning and provision of efficient, effective 

and appropriate health services within the Child, Youth and Women’s Health Service. Staff of the PHRU are affiliated 

with the Children’s Research Centre and Healthy Development Adelaide, University of Adelaide. The PHRU aims to 

achieve better health outcomes for consumers and their communities, with a strong focus on epidemiology, social 

epidemiology and public health. 

PROJECT: (Clinical) What influences adolescents to 

decide to have surgical intervention for tonsillitis? 


The removal of tonsils is a very common surgical 

procedure. While most tonsillectomies occur in very 

young children, a considerable number of 

tonsillectomies are also performed in adolescents. 

While the research literature discusses the frequency, 

severity and duration of tonsillitis during the years 

preceding tonsillectomy in adolescents, little is known 

about the adolescent’s role in agreeing to the 

procedure, which is not without significant 

postoperative morbidity. Anecdotal experience has 

shown that adolescents present for consideration of 

tonsillectomy because of the impact it is having on 

their education, sport and social life. A better 

understanding of the motivations for wanting surgical 

intervention, the expectations of the clinical 

encounter, and the experience of surgery may help 

improve our management of this under-studied 

group. 

The research will include interviews with adolescents 

and parents/guardians to gain an understanding of 

what influences the decision to elect for surgical 

intervention for tonsillitis. The study will also aim to 

understand how adolescents assess their tonsillar 

health and how much influence they have in the 

decision to have surgical intervention. 

Training 

The student will be trained in literature reviews, 

interviewing and interview design, recruitment, data 

entry, data analysis and manuscript preparation. 

66 |

Vaccine Safety Research Group 


Dr Mike Gold 

Phone: 8161 7266 

michael.gold@adelaide.edu.au 


Despite the public health benefit of vaccination, concern about the safety of vaccines may be the most important 

issue to affect immunisation coverage and the sustainability of an immunisation program. There is a limited capacity 

to evaluate all aspects of vaccine safety before vaccines are approved for use. This is because the safety 

evaluation of new vaccines takes place during clinical trials, which usually include thousands of healthy subjects 

(which is an adequate number for the purposes of detecting common adverse events), and involves a short period 

of post-vaccination monitoring. Unfortunately, this process does not identify adverse events which are rare, 

delayed, occur with specific vaccine combinations or in a sub-group of children with co-existing disorders. 

Passive surveillance of adverse events following immunisation (AEFI) is used as the primary mechanism for safety 

surveillance following vaccine licensure; however, this also has limitations which include underreporting and the 

inability to establish a casual relationship between immunisation and a specific adverse event. In Australia, other 

mechanisms of surveillance are currently in use; known as enhanced passive surveillance and active sentinel 

surveillance. Given the limitation of resources, it is important to determine the most effective mechanism of 

surveillance for an AEFI. 

The vaccine safety research group is a multi-disciplinary group, funded by the Australian Research Council (ARC) to 

investigate the role of data linkage to assess vaccine safety in Australia. The project involves an investigation of the 

technical feasibility and privacy issues required for data linkage. One of the aims of the project will be to compare 

the effectiveness of surveillance, using data linkage, with other methods of surveillance currently being used in 

Australia. This honours project will assess the performance of three methods of surveillance for three sentinel 

conditions which may occur after immunisation. 

PROJECT: (Clinical/Basic) A comparative analysis of 

the surveillance of intussusceptions, seizures and 

anaphylaxis following immunisation in Australia – 

2007 to 2009. 


Intussusception, seizures, and anaphylaxis are all 

important adverse events for surveillance following 

immunisation. In Australia, health providers are asked 

to report these events to the Adverse Drug Reactions 

Committee (ADRAC) of the Therapeutic Goods 

Administration (TGA). However, these events have 

also been under surveillance using enhanced passive 

surveillance and active sentinel surveillance. The 

Australian Paediatric Surveillance Unit (APSU) 

conducts enhanced passive surveillance by 

requesting monthly AEFI reports from paediatricians. 

Active sentinel surveillance is conducted through a 

Commonwealth initiative known as Paediatric 

Enhanced Disease Surveillance (PAEDS). This scheme 

funds part-time specialist nurses in four tertiary care 

hospitals in Australia (SA, NSW, Vic, and WA) to 

identify children with an AEFI. Detailed clinical data 

and biological samples are collected and additional 

information on risk factor and vaccination history is 

sought from parents. The aim of the project will be to 

evaluate the effectiveness of these three surveillance 

methods by comparing data, which has already 

been collected. The skills required will be an interest 

in one or more of the following areas: public health, 

pharmacovigilance, paediatrics or immunisation. 

The techniques will involve analysis of AEFI reports 

and comparative data analysis. The student will be 

supported by the group who have skills in statistical 

analysis of data, and vaccine safety. 

References 

JML Brotherton, MS Gold, AS Kemp, PB McIntyre, MA 

Burgess, S Campbell-Lloyd, on behalf of the New South Wales 

Health HPV Adverse Events Panel CMAJ. 2008 Sep 

9;179(6):525-33. 

Monitoring vaccine safety: a critical component of 

every immunization programme Brotherton J Gold M. Med J 

Australia 2008: 189(5):243-244 

Human papillomavirus vaccine hypersensitivity 

reactions – a retrospective cohort study in Australia 

Liew WK, Nigel Crawford N, Tang M, Buttery J, Royle J, Gold 

M, Zeigler C, Quinn P, Elia S, Choo S. BMJ 2008: 337;a2642 

Guidelines for collection, analysis and presentation of 

vaccine safety data in pre- and post-licensure clinical 

studies. Bonhoeffer J, Bentsi-Enchill A, Chen RT, Fisher MC, 

Gold MS et al ; The Brighton Collaboration Methods Working 

Group. Vaccine. 2009 Apr 6;27(16):2282-2288. 

Guidelines for collection, analysis and presentation of 

vaccine safety data in surveillance systems. Bonhoeffer J, 

Bentsi-Enchill A, Chen RT, Fisher MC, Gold MS, et al The 

Brighton Collaboration Methods Working Group. Vaccine. 

2009 Apr 6;27(16):2289-2297. Epub 2008 Dec 4 

67 |

Vaccinology and Immunology Research Trials Unit 

Supervisor/Contact Person (Far left) 

Dr Helen Marshall 

Phone: 8161 8115 

helen.marshall@adelaide.edu.au 


The Vaccinology and Immunology Research Trials Unit, is a multidisciplinary immunisation research group at the 

Women’s and Children’s Hospital, affiliated with the University of Adelaide and part of the Children’s Research 

Centre, University of Adelaide. The centre’s membership includes internationally renowned experts in paediatrics, 

immunology and public health. VIRTU’s research program includes clinical trials in investigational vaccines, 

infectious disease epidemiology, social epidemiology, immunology and public health. 

Current research programs include: 

1. Investigational vaccines; meningococcal B vaccine, (pre) pandemic flu vaccines, influenza vaccine, pertussis 

immunisation at birth, Respiratory Syncytial Virus (RSV) and Parainfluenza Virus vaccine (PIV3) 

2. Infectious disease epidemiology; severity of pertussis (whooping cough) infection in hospitalised children, RSV 

epidemiology and severity of disease in hospitalised children, rotavirus vaccine effectiveness 

3. Immunisation of children at special risk; Human Papillomavirus vaccine 

4. Social epidemiology; Pandemic influenza community preparedness, HPV school immunisation program; why 

are girls opting out?, and enhanced surveillance of paediatric conditions of public health importance 

Clinical/Public Health Relevance 

Conducting trials in investigational vaccines provides local Australian data for licensing authorities. Studies of 

investigational vaccines conducted at our centre provide Australian data for regulatory authorities such as the 

Therapeutic Goods Administration (TGA) and Food and Drug Administration, (FDA, US). It is an advantage for both 

vaccine companies and the TGA to have safety and immunogenicity data based on the Australian population 

when licensing of a new vaccine is being considered. Other significant contributions include studies in new 

combination vaccines. This allows a reduction in the number of needles that need to be administered to infants 

and children making vaccination more acceptable (and more cost-effective with less time spent in the clinic) for all 

involved. Many of the new vaccine combinations trialled by our unit are now licensed (or have been filed for 

licensing) for use in Australian children including a combination measles, mumps, rubella, varicella vaccine. Studies 

in vaccine safety identify adverse reactions associated with vaccination and provide data that support changes to 

the vaccination schedule to reduce the adverse effects associated with immunisation. Studies in epidemiology of 

disease provide data used to determine whether development of a vaccine to prevent an infection is feasible and 

guides the scheduling of the vaccine in the National Immunisation Program. Our group also conducts research into 

community attitudes and acceptance of new vaccines to encourage engagement of the community in 

immunisation policy decisions. All studies have resulted in a publication or recent preparation of a manuscript for 

publication. 

PROJECT: (Clinical) Are there differences in severity of 

illness before and after introduction of the infant 

rotavirus vaccination program in children who are 

admitted to hospital with gastroenteritis? 


The introduction of rotavirus vaccination for infants at 

2, 4 and 6 months of age in July 2007 has had a 

significant impact on the number of children 

hospitalised with gastroenteritis in South Australia. 

Recent research from several states in Australia has 

indicated that the reduction in severe rotavirus 

infections is greater than 80% following the 

introduction of the vaccination program. Another 

important question remaining is whether there has 

been any impact on the severity of illness for children 

who still present to hospital with gastroenteritis 

following the introduction of the vaccination 

program. This project aims to review hospitalisations 

occurring in children before and after the 

68 |

introduction of the rotavirus vaccination program 

and to assess severity using two internationally 

recognised severity scoring systems. 

PROJECT: (Clinical) Can presenting symptoms in 

children who present to emergency departments with 

pertussis (whooping cough) infection, predict severity 

of disease? 


Although pertussis immunisation was introduced in 

Australia 50 years ago, initially as a whole cell 

pertussis vaccine and subsequently as an acellular 

vaccine, pertussis remains a poorly controlled 

infection with deaths still occurring in young infants. 

In Australia, the majority of severe pertussis occurs 

under 6 months of age, despite high immunisation 

coverage in children over 6 months of age. 

Unimmunised infants are most likely to develop 

severe disease requiring hospitalisation, frequently 

complicated by apnoea, seizures, encephalopathy 

or death. Approximately 400 infants are hospitalised 

each year in Australia, the majority being < 6 months 

of age. Eighteen deaths due to pertussis occurred in 

Australia during 1993 - 2004, all but two of these 

children were less than 6 months of age. Five deaths 

in infants < 6 months occurred during the current 

2009-2010 epidemic in Australia. 

We have recently developed a severity scoring 

system for pertussis and this project will aim to add 

further data to support our understanding of pertussis 

disease in Australia with a specific aim of establishing 

whether clinical signs and symptoms at presentation 

can predict the likelihood of severe disease requiring 

more intensive management and care. The ability to 

predict which children are likely to require intensive 

care and management early has the potential to 

improve practice and outcomes for vulnerable 

children. 

Training 

The student will be trained in literature reviews, 

human research ethics, data entry and analysis and 

manuscript preparation. 

Recent Publications 

Clarke M, Davidson G, Gold M and Marshall H. 

Decline in Gastroenteritis Admissions in South Australia 

in both vaccinated and unvaccinated children post 

introduction of rotavirus vaccine. Vaccine. 2011 Jun 

24;29(29-30):4663-7. 

Quinn P, Gold M, Royle J, Buttery J, Richmond 

P, McIntyre P, Wood N, Lee SS, Marshall H. 

Recurrence of extensive injection site reactions 

following DTPa or dTpa vaccine in children 4-6 years 

old. Vaccine. 2011 Jun 6;29(25):4230-7. 

Marshall H, Tooher R, Collins J, Mensah F, 

Braunack-Mayer A, Street J, Ryan P. Awareness, 

anxiety, compliance: Community perceptions and 

response to the threat and reality of an influenza 

pandemic. Am J Infection Control. In Press 

Khandaker G, Marshall H, Peadon E, Zurynski Y, 

Burgner D, Buttery J, Gold M, Nissen M, Elliott E, Booy 

R. Congenital and neonatal varicella: Impact of the 

national varicella vaccination program in Australia. 

Arch Dis Child. 2011 May;96(5):453-6. 

Booy R, Richmond P, Nolan T, McVernon J, 

Marshall H, Nissen M, Reynolds G, Ziegler JB, Heron L, 

Lambert S, Caubet M, Mesaros N, Boutriau D. 

Immediate and longer term immunogenicity of a 

single dose of the combined haemophilus influenzae 

type B-Neisseria meningitidis serogroup C-tetanus 

toxoid conjugate vaccine in primed toddlers 12 to 18 

months of age. Pediatr Infect Dis J. 2011 

Apr;30(4):340-2. 

Nolan T, Richmond P, Marshall H, McVernon J, 

Alexander K, Mesaros N, Aris E, Miller J, Poolman J, 

Boutriau D. Immunogenicity and safety of 

vaccination with a combined Haemophilus influenza 

type b - Neiseria meningitidis serogroups C and Y – 

tetanus toxoid candidate vaccine (HibMenCY-TT). 

Pediatr Infect Dis J. 2011 Mar;30(3):190-6. 

Marshall H, Nolan T, Diez-Domingo J, Rombo L, 

Sokal E, Mares J, Casanovas J, Kuriyakose S, Leyssen 

M, J Jacquet. Long-term (5 year) antibody 

persistence following two and three dose regimens of 

a combined hepatitis A and B vaccine in children 

aged 1 – 11 years. Vaccine. 2010 Jun 17;28(27):4411- 

5. 

Nolan T, McVernon J, Skeljo M, Richmond P, 

Wadia U, Lambert S, Nissen M, Marshall H, Booy R, 

Heron L, Hartel G, Lai M, Basser R, Gittleson C, 

Greenberg M. Immunogenicity of a monovalent 2009 

influenza A (H1N1) vaccine in infants and children – a 

randomized trial. Journal of the American Medical 

Association, 2010;303(01):37-46. 

69 |

Respiratory and Sleep Medicine 


Dr David Parsons 

Phone: 8161 7004 

david.parsons@adelaide.edu.au 

Our group is developing an effective treatment and potentially a life-long correction for the airway disease of Cystic 

Fibrosis (CF). This lung disease is the primary cause of worsening health problems in young people with CF, greatly 

affecting their quality of life and is the overwhelming cause of early death. We have been supported by grants from 

the NH&MRC, the USA CF Foundation, CF Australia and South Australian research funding bodies where we use a 

lentivirus-based gene delivery vector to study how to produce safe and effective gene delivery into airway cells. 

We use reporter genes such as LacZ and luciferase, to prepare for studies with the therapeutic gene CFTR. 

Our work has been focussed across three animal models: mice, sheep and marmosets. Our approach especially 

targets airway stem cells in vivo, and in some mouse studies this approach has already produced up to lifetime gene 

expression after a single dose event. The field has lacked a simple way to measure the success in airways and lungs, 

whether for humans or animal models. To overcome that limitation we have developmed new synchrotron X-ray 

imaging techniques with Monash University colleagues. Synchrotron Xrays allow non-invasive viewing of airway 

surfaces in live mice, at resolutions close to that of normal light microscopes. We are also now able to examine 

mouse lung airflows in 3-D. With further development we expect these techniques will create new options for rapid 

and accurate assessment of potential therapies (such as gene-correction) for their effectiveness in improving airway 

health in live and intact animal models. 

Our research is closely connected with the clinical needs of CF children, and most of our studies are carried out at 

the Women’s & Children’s hospital campus in Adelaide. The synchrotron X-ray studies are performed in Japan, and 

in 2010 parallel studies began with the assistance of Monash University collaborators at the new Australian 

Synchrotron in Melbourne. Finally, we have new state-of-the-art research laboratories in 2012! Through the 

enthusiastic initial work of the Cure4CF Foundation Ltd (www.cure4cf.org), and substantial completion funding 

provided by the WCH Foundation, the Alan Scott CF research laboratory is now in place in the Gilbert Building at the 

WCH 

PROJECT (Basic): Airway gene transfer for cystic 

fibrosis: converting fluid-based lentiviral gene vector 

delivery to aerosol delivery. 

.R. 

This study is designed to translate our well established 

and effective protocols for bolus-delivery of the 

lentivirus vector in airway into one that can be 

provided in an aerosol form. Aerosols are considered 

to be the most practical way to deliver lung gene 

therapies in the future. 

Preliminary data from our group indicates that the 

viability of the vector can be largely preserved with 

the incorporation of specific supporting protein 

agents in the viral vector carrier fluid. Using a 

clinically-applicable electronic aerosolisation device 

(Aerogen) the study will be designed to define the 

parameters of vector delivery to maintain viability for 

in-vitro assessment. 

Once those parameters have been defined aerosol 

delivery will be tested in the nasal and lung airways 

of laboratory mice. The outcome sought in this 

Honours year is to define an effective aerosol-based 

delivery using in-vitro methods and apply it in-vivo to 

laboratory mouse airways. 

PROJECT (Basic): Enhancing airway gene transfer for 

cystic fibrosis treatment: effects of agents repurposed 

from current use in clinical care. 

.R. 

Agents used clinically to clear CF airways of mucus 

and cellular debris may be helpful in improving initial 

gene transfer into airway surface epithelial cells, by 

enabling better access by the gene vector to the 

defective epithelial cells lining the affected airways. 

Initial studies will utilise airway-specific cell cultures to 

screen a range of these potentially useful 

compounds, with lead candidates moving to 

preliminary testing using our established gene transfer 

methods in the airways of laboratory mice. 

The outcome desired is to achieve more efficient 

levels of airway gene expression with reporter-genes, 

to improve the future opportunities for development 

of therapeutically active and effective airway gene 

expression using the corrective CFTR gene. 

70 |

Index 

Breast Biology and Cancer, 16 

Child Nutrition Research Centre (CNRC), 49 

Circadian Physiology Group, 18 

CNS Therapeutics Laboratory, Lysosomal Diseases Research Unit, 52 

Craniofacial Research Group, 53 

Developmental Biology of the Ovary, 20 

Early Development Group, 23 

Early Life Programming of Health and Disease, 25 

Early Origins of Cancer, 30 

Gamete and Embryo Biology Laboratory, 31 

Lysosomal Biology, Lysosomal Diseases Research Unit, 55 

Matrix Biology Unit, 57 

Molecular Immunology, 59 

Molecular Neurogenetics, 62 

Nutritional Immunology, 64 

Oocyte Biology Group, 32 

Paediatric Trials Unit, 68 

Paediatrics and Child Health, 65 

Placental Development Laboratory, 34 

Pregnancy and Development Group, 37 

Public Health Research Unit, 66 

Reproductive Biotechnology Group, 39 

Reproductive Cancer Research Group, 40 

Reproductive endocrinology and reproductive medicine group, 43 

Reproductive Immunology Group, 44 

Respiratory and Sleep Medicine, 70 

The Australian Research Centre for Health of Women and Babies, 12 

Vaccine Safety Research Group, 67 

71 |


The University of Adelaide 

Telephone + 61 8 8313 5100 

Facsimile + 61 8313 4099 

Web http://health.adelaide.edu.au/school_paedrepro/honours

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