The Functional Roles Of ADAMs In The Regulation Of Embryo Implantation.
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate othe ....The initiation of pregnancy in humans and rodents hinges upon the ability of the embryo to attach to the wall of the uterus and invade into the uterine tissue. This process of embryo implantation is tightly regulated and depends on the secretion of enzymes and regulators of these enzymes. A newly identified family of enzymes which might be important in this process is the ADAMs family. These enzymes have the potential to facilitate both cell attachment and cell invasion and also to activate other enzymes and growth factors. Recent studies in our laboratory have shown the ADAMs to be expressed both at the most invasive time of implantation and when invasion is being down-regulated. This project will examine the role of the ADAMs in embryo implantation facilitating attachment and invasion into the uterus by acting enzymatically on the uterine tissue and by activating other enzymes. It will also determine the role of ADAMs in down-regulating invasion potentially by activating a growth factor, TNF-alpha. Knowledge of this process and particularly its regulation is important for the treatment of pregnancy associated diseases that arise from improper implantation. These include infertility, placenta accreta, choriocarcinoma, miscarriage and pre-eclampsia. Furthermore, an understanding of the regulation of implantation will contribute to the treatment of other conditions associated with cell invasion such as cancer metastasis.Read moreRead less
Targeted Disruption Of Lipoxygenase Enzymes To Prevent Oxidative Stress-mediated Pathologies In The Male Germline
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
An estimated 80 million individuals suffer from infertility globally with at least 50% of these cases due to defects in sperm function. Unfortunately, due to a severe lack of knowledge surrounding sperm biology and dysfunction, no successful curative or preventative measures have been established. My project will study why sperm cells die and investigate new ways to limit cellular stress so we can develop new therapeutic strategies to mitigate the growing problems in male reproductive health.
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
Epigenetic Regulation Of Inflammatory Genes In The Fetal Membranes: Role In Term And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$468,534.00
Summary
Preterm birth is the leading cause of death among newborns and the biggest contributor to disability among infants. Here we propose research to define the mechanism that controls the length of pregnancy and is disrupted in preterm birth. Specifically, we will determine what causes the repression of the labour-promoting inflammatory genes in the uterus during pregnancy and what activates them at labour. We will identify new targets for interventions to block or prevent preterm birth.
Male Chlamydia Infections: The Key Role Of Macrophages In Testicular Dissemination And Disrupted Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$868,464.00
Summary
Male partners of couples seeking IVF, who are seropositive for Chlamydia, indicating a prior infection, often have significantly impaired sperm quality (reduced motility, increased DNA damage and abnormal sperm morphology). Our studies will define how Chlamydia are transported to the testis from the penis and how chronic chlamydial infection in the testis disrupts sperm development. We will also develop new antibiotic delivery systems to improve treatment of male chlamydial infections.
Role Of Placental Retroviral Protein Syncytin Carried On Exosomes In Mediating Vulnerability Of Pregnant Women To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$645,145.00
Summary
50% of the women who died due to swine flu were pregnant. This project will examine if factors produced by the placenta make the pregnant woman more susceptible to influenza.
Female Reproductive Health Preservation By Nicotinamide Adenine Dinucleotide (NAD+) And Sirtuin2 (SIRT2)
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Cancer treatment can be severely toxic to women’s eggs. Increasing numbers of women who survive cancer therefore become infertile and prematurely deprived of hormonal support whilst still in their reproductive years. This project will use state-of-the-art techniques to interrogate newly uncovered pathways that can protect eggs from treatment-induced injury thereby greatly improving the quality of life for female cancer survivors.
How The Placental Protein Syncytin Impairs Maternal Immune Responses To Influenza
Funder
National Health and Medical Research Council
Funding Amount
$609,862.00
Summary
Pregnant women are known to be highly susceptible to certain viral infections, especially influenza, which results in severe illness and even death. The reason for this transitory susceptibility are unknown. We have found that a protein, Syncytin, has the ability to impair maternal immune responses to influenza We now will determine how it does this and discover potential interventions to reverse these effects.
Perinatal Stress Leads To Neurosteroid Deficits And Adverse Behavioural Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$1,198,042.00
Summary
This grant will examine the effect of psychosocial stress experienced after birth on the production and regulation of steroid hormones in the brain of newborn animals. The work will investigate how stress changes the levels these brain steroids and sensitivity to them and if these effects are remain into adulthood. The studies will then determine if these changes lead to adolescent behaviour disorders. The effectiveness of steroid therapies in treating these disorders will also be determined.
SISTAQUIT Scale-up In Indigenous Populations In Australia
Funder
National Health and Medical Research Council
Funding Amount
$1,800,000.00
Summary
SISTAQUIT®(Supporting Indigenous Smokers to Assist Quitting) is a research backed training program that provides free, online training in quit smoking methods to health providers. This study aims to expand the SISTAQUIT intervention to all Australian health services that cater to Indigenous women during pregnancy. This research will test numerous methods to implement SISTAQUIT to identify the most effective and economical strategy suitable for roll-out, and build Indigenous workforce capacity.