The Role Of Growth Differentiation Factor 9 (GDF9) In Human Fertility
Funder
National Health and Medical Research Council
Funding Amount
$568,811.00
Summary
IVF comes at a substantial financial burden to the Australia health system through Medicare. There is mounting evidence to suggest that egg quality is the key limiting factor in female fertility. The aim of this proposal is to produce a key egg-secreted protein which is critical for the ability of the egg to be fertilized and to develop a diagnostic assay to measure egg quality to improve the treatment of infertility.
Activation Of GDF9 Regulates Human Folliculogenesis
Funder
National Health and Medical Research Council
Funding Amount
$531,690.00
Summary
GDF9 is a key regulator of fertility in female mammals, as it controls the process of folliculogenesis. In this grant, we will demonstrate the importance of GDF9 in human folliculogenesis, determine the mechanisms that activate GDF9 and show why aberrant GDF9 activation leads to ovarian disorders. Collectively, the outcomes of this proposal will increase our understanding of the fundamental mechanisms that regulate ovarian folliculogenesis and provide new avenues to manipulate this process.
Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
RNA Binding Protein Musashi: Role In Folliculogenesis And Oocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$419,223.00
Summary
Women in Australian have opted for social and economic reasons to delay both marriage and childbirth. Both infertility and congenital abnormality is associated with advancing maternal age as the ovarian pool of oocytes declines in number and quality. In this project we aim to gain an understanding of the molecular mechanisms underpinning healthy oocyte development. Insights gained have the potential to alleviate miscarriage, infertility and congenital abnormalities in Australian families.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.
Reducing The Burden Of Breast Cancer Through Precision Prevention, Targeted Treatment And Enhanced Survivorship
Funder
National Health and Medical Research Council
Funding Amount
$1,491,192.00
Summary
Breast cancer affects 1 in 8 Australian women. Of all the cancers, breast cancer results in the largest number of years of healthy life lost from death and illness. My research will reduce this unacceptable burden of breast cancer for women and their families. Spanning prevention, through treatment to survivorship, it will facilitate reduced breast cancer incidence, more effective treatments and enhanced understanding of the effects of new treatments on ovarian function and fertility.
Xenobiotics - Oxidative Stress In The Mammalian Ovary
Funder
National Health and Medical Research Council
Funding Amount
$377,922.00
Summary
Synthetic chemicals called xenobiotics in the environment are capable of interfering with female fertility. Xenobiotics can trigger oocyte depletion of the ovary and infertility. Exhaustion of the oocyte population results in the menopause, loss of ovarian hormones and profoundly affects female health through increasing susceptibility to heart and bone disease. This research will characterise xenobiotic effects on the ovary and will lead to significant advances in reproductive healthcare.
Regulation Of Haematopoietic Stem Cells Through Histone Modifications
Funder
National Health and Medical Research Council
Funding Amount
$797,014.00
Summary
The genetic material is packaged in the cell nucleus with histone proteins. Modifications of histones determine if a particular area of the genome is active or repressed. We are investigating a family of histone modifying proteins, the MYST proteins. Mutations in these proteins cause intellectual disability and blood cancer. In this project we examine the role of MYST2 in blood stem cells. Knowledge gained may become the basis for the development of drugs for the treatment of cancer.
OVARIAN CANCER METASTASIS: Unraveling The Biology Of The Plasminogen Activation Cascade
Funder
National Health and Medical Research Council
Funding Amount
$169,875.00
Summary
Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of t ....Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of the biology of ovarian cancer metastasis may lead to new therapies designed to control these processes - as such this would be a major inroad into our fight against this cancer. The aim of this novel research project is to unravel the role that one cell surface system (the plasminogen (Plg) activation cascade) plays in determining the ability of ovarian cancer cells to metastasise and regulate new tumour blood vessel formation. This study addresses the paradoxical observations that this cascade can simultaneously facilitate cancer metastasis whilst concomitantly stopping new blood vessel formation in tumours. Using a number of advanced molecular cell biology methods, the hypothesis we will test is that the capacity of ovarian cancer to metastasise is determined by differential processing of plasminogen subsequent to cell-surface Plg binding. This results in a delicate balance between the generation of cell surface proteases and the release of protein fragments capable of stopping tumour blood vessel growth. Our group is well-equipped to address this hypothesis since we have already shown that: (1) Plg binding and activation is required for cancer cell invasion; (2) Plg binding and activation is elevated on malignant compared to benign cancers (3) Plg unfolds after it binds to cell surfaces or recombinant receptors; and, (4) Plg is easily fragmented to products that inhibit new blood vessel formation after binding to some cancer cells.Read moreRead less