Epigenetic Regulation Of Cell Lineage Differentiation In The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$440,983.00
Summary
Exposure of embryos to a range of stresses can increase the predisposition to chronic diseases of adulthood. Stressing embryos at critical stages of development cause errors in reorganization of the nucleus that are required for normal gene expression. These errors are propagated into adulthood. This project will map the normal processes of nuclear reorganization and define how stress to the embryo changes this process, allowing an understanding of the causes of some important chronic diseases.
Epigenetic Reprogramming Within The Pluripotent Lineage Of The Early Embryo
Funder
National Health and Medical Research Council
Funding Amount
$663,050.00
Summary
Cells of the early embryo have the remarkable capacity to form all of the different tissues and organs in the body. This property requires re-organisation of the embryo’s genetic material in a manner analogous to re-booting a computer. This project will define the properties of this rebooting process. This information will allow much better strategies for building spare parts for regenerative medicine and provide the information required to reduce the incidence of inborn defects.
Reappraisal Of The Mechanisms Underlying Implantation Success Or Failure
Funder
National Health and Medical Research Council
Funding Amount
$750,755.00
Summary
Infertility affects 1:6 Australian couples; these seek help. However, for each IVF cycle, there is only ~18.5% chance of a live birth, significantly due to failure of embryo implantation. We discovered nano-vesicles in the uterine cavity, that are released from the womb lining and taken up by the pre-implantation embryo to improve its implantation potential. We will determine how this extracellular environment can enhance implantation success and circumvent/management of infertility.
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
Re-energising The Preimplantation Embryo To Extend Lifetime Health
Funder
National Health and Medical Research Council
Funding Amount
$1,156,936.00
Summary
Diseases of aging are associated with shortening at the ends of chromosomes called telomeres. The length of an individual’s telomeres is established during embryo development, and in situations where embryo development is compromised such as with maternal obesity the normal process of telomere lengthening may not occur. We will determine how such disruptions in embryo telomere lengthening contribute to poor health in adulthood and test ways to restore the natural process.
A BubR1-centred Network For Non-invasively Measuring Human Oocyte Quality
Funder
National Health and Medical Research Council
Funding Amount
$532,207.00
Summary
Oocyte quality is the most important determinant of pregnancy outcome. Selecting the best oocytes for fertility treatments like IVF would therefore greatly improve success rates and reduce costs. We have identified master oocyte regulators and have applied novel digital technology to measure these regulators in a single oocyte. This project will apply this expertise to develop new approaches for evaluating an oocyte’s potential thereby informing its suitability for use in fertility treatment.
Modulation Of Telomere Length And Subtelomeric DNA Methylation In Response To Oxidative Stress In The Male Germ Line; Implications For Tumorigenesis In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$310,684.00
Summary
This research project is designed to elucidate how the quality of a father’s spermatozoa can impact upon the health and wellbeing of his children. We hypothesize that factors, such as infertility, heavy smoking or age create a state of oxidative stress in the testes and that this stress influences the genetic structure of spermatozoa in such a way that the incidence of spontaneous mutations and susceptibility-to-cancer are significantly elevated in the offspring.
Role Of Snail Family Proteins In Male Fertility And Testicular Cancer
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Male fertility requires production of healthy sperm in the testis. This project builds on our discoveries that testicular cells regulate gene activity via the Snail family of proteins during sperm development, and that interruption of their activities reduces fertility in mice and fruitflies. Snail proteins are also active in cancer cells. We propose to study the precise steps in sperm production affected by Snail proteins and how they affect the progression of testicular cancer.
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.
Determing Whether Breast Stem Cells Mediate The Risk Of Developing Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$433,894.00
Summary
Whilst the outcomes for women with breast cancer have improved significantly, the incidence of breast cancer continues to increase. Research needs to focus on prevention now to try to stop the increase. Apart from age, our reproductive behaviour is the largest risk factor for breast cancer. If a woman does not bear children, or has them after 35 years of age, she is at 25-50% increased risk of breast cancer. We would like to determine whether the breast stem cells play a role in this and why.