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Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.
The Long-term Consequences Of Assisted Reproduction On The Growth, Metabolic, Respiratory, Psychological, Immunological And Reproductive Development Of The Offspring.
Funder
National Health and Medical Research Council
Funding Amount
$1,552,096.00
Summary
1 in 25 children are born from IVF treatment - incredibly- to our shame; no data exists as to the long-term health of these children. Presented is a unique opportunity, which would be exceedingly difficult to replicate elsewhere in the world, to determine the long-term consequences of IVF upon the development of the offspring, by comparing their growth, metabolic, respiratory, psychological, immunological and reproductive development to a representative sample of WA children- the Raine cohort.
Understanding Epigenetic Modification During Oogenesis For Novel Treatments Of Female Infertility
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Infertility affects about 10% of Australian women and the success rates of current infertility treatments are low due to our poor knowledge of eggs development. The numbers of obese and older women trying to conceive are increasing; fertility treatments are even less effective for them. I have generated mouse models to elucidate the pathways regulating egg development. I will study for alterations in these pathways in the mouse models which perfectly mimic the obesity and aging in women.
The Negative Transgenerational Impacts Of Paternal Obesity Are Inherited Through Aberrant Methylation And MicroRNA Conetent Of Germ Cells.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
We have shown that obese fathers have reduced sperm function that negatively impacts upon their offspring’s health. But we do not understand the underlying alterations to sperm DNA that cause offspring to inherit poor health from an obese father, and whether these offspring also exhibit the same alterations. My project aims to identify alterations made to sperm DNA and RNA caused by obesity that are inherited by the next generation, ‘programming’ them for poor metabolic and reproductive health.
Insulin Resistance In Polycystic Ovary Syndrome And The Role Of Skeletal Muscle And Adipose Tissue
Funder
National Health and Medical Research Council
Funding Amount
$416,115.00
Summary
11% of women have polycystic ovarian syndrome(PCOS), characterised by insulin resistance, irregular periods and infertility. These women are prone to obesity, diabetes and potentially, heart disease. Treatments include lifestyle modifications +-- medical therapy. Lifestyle is first line, yet the best diet-exercise prescription is unclear. This study will provide insights into the cause of PCOS, will inform on the role of exercise in therapy and may identify targets for future therapies.
The normal processes of development of the embryo require that the information encoded in chromosomes be reprogrammed soon after fertilization. This process is rather fragile and disturbance of the early embryo can upset it. Recent studies for the chief investigator's provide new understanding of the normal processes of reprogramming. The project will explore and validate the implications of these new discoveries and provide a basis for future alleviation of abnormalities to development.
Polycystic ovary syndrome (PCOS) affects 5-10% of women worldwide, yet its origins remain unknown. Androgens are implicated in the development of PCOS, but the decisive, invasive studies needed to confirm and elucidate their roles are not feasible in women. Hence, using our innovative mouse models of androgen resistant female mice, this study will determine the role of androgens in PCOS aiming to better understand, and identify new treatments for this common female reproductive disorder.
Studies Of The Dynamic Changes In The Ovarian Follicular Basal Lamina
Funder
National Health and Medical Research Council
Funding Amount
$305,557.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die during the process of growing to ovulatory size. This project will examine the follicular basal lamina in order to determine its role during follicle growth and development, and when follicles die. This has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
The Role Of FSH And FF-MAS In The Induction Of Meiotic Resumption In The Oocyte
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order ....About one in six couples of reproductive age suffer from reproductive disorders. In a significant proportion of cases, reproductive failure is attributable to a variety of chromosomal and cellular anomalies displayed by the egg, which interfere with the process of fertilization or the capacity of the embryo to grow, implant or develop to term. Because the chances of success of each individual egg are very low, women undergoing IVF therapy are subjected to ovarian stimulation with drugs in order to produce many eggs, thereby increasing the success rate per treatment cycle. But stimulation of ovarian function involves a number of drawbacks including cost of fertility drugs, continued monitoring, discomfort and risk of complications (eg. ovarian hyperstimulation syndrome). It is evident that novel methods for the production of mature eggs in vitro in the absence of ovarian stimulation would mark a breakthrough, making assisted reproduction a more friendly discipline. In general, all IVF patients would benefit from in vitro maturation techniques. In particular, in selected patients (eg. those suffering from polycystic ovary syndrome) the advantages of this method might prove to be invaluable, by achieving production of fully viable eggs under controlled conditions, as opposed to in vivo where oocytes generally fail to acquire full competence, having been subjected to an unfavourable hormonal environment. Unfortunately, attempts to treat IVF patients using eggs matured in vitro has been disappointing so far, with only occasional pregnancies reported over the last decade. Clearly, this is due to lack of knowledge of the fundamental events occurring during egg maturation, as well as the paucity of biological material available for experimentation. So, to make in vitro maturation of eggs a successful fertility treatment we undoubtedly need to achieve a more profound insight into the function of the egg, the first step being to focus our attention upon experimental models.Read moreRead less
Reproductive health critically impacts a woman’s wellbeing, irrespective of her choice to have children. The ovary and its hormones govern physiological events regulating health at puberty, across the menstrual cycle, during the establishment and maintenance of pregnancy, and in parturition, lactation and menopause. The major health burdens concerning ovaries that we are studying include polycystic ovarian syndrome and assisted reproductive technologies used to treat infertility.