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.
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.
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 Male Partner Contribution To Pregnancy Immune Tolerance Deficit In Women
Funder
National Health and Medical Research Council
Funding Amount
$1,462,925.00
Summary
A complication-free pregnancy and birth of a healthy infant depends on adequate preparation of the mother's immune system to tolerate the 'foreign' fetus, Both the mother and the father contribute to establishing optimal immune tolerance. This project will determine the links between specific agents in male seminal fluid and the female immune response, and will make progress towards new diagnostic tests and treatment options for unexplained subfertility and gestational disorders.
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.
A Media Formulation To Improve Implantation Rates And Pregnancy Outcome Following ART
Funder
National Health and Medical Research Council
Funding Amount
$304,380.00
Summary
Since women are delaying childbearing, ART is increasingly required. 2-3% of births in Australia follow ART. Only 15-40% of embryo transfers in assisted reproduction (ART) result in ongoing pregnancies. The poor success rate is due to the fact that the embryo culture media bear no resemblance to the maternal environment in which they grow normally. The new culture media to be validated in this proposal includes factors that are critical for embryo implantation and will improve ART success.
Role Of HtrA And RseP, Stress Response Proteases, In Development And Persistence Of Chlamydia Trachomatis Infections
Funder
National Health and Medical Research Council
Funding Amount
$389,984.00
Summary
This project will research the most commonly reported bacterial sexually transmitted infection Chlamydia trachomatis. Bacterial proteins which could play a role in chronic infections of humans will be investigated. Proteins will be biologically examined to determine their role during disease. This may identify proteins which could be used for diagnostic and therapeutic tools to prevent chronic Chlamydia infection (which can result in infertility and other serious conditions).
Periconceptual Foundations For A Healthy Start To Life.
Funder
National Health and Medical Research Council
Funding Amount
$11,022,802.00
Summary
Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions i ....Preconception and early pregnancy is a critical time for a women's health and that of her future child. New research suggests that a woman's genetic potential, her lifestyle and the physical and socioeconomic environment in which she lives, and her biological and social relationship with her male partner, all impact on the long term health of her baby. Abnormal events around the time of conception and in early pregnancy can predispose a newborn to later occurrence, in adult life, of conditions including heart disease, diabetes, obesity and stroke. These adverse events originate in the way that eggs and sperm develop, the uterus is prepared for implantation, the attachment of the early embryo to the lining of the uterus and subsequent growth of the placenta. This Program will study the early life events that promote or limit development of a baby's true potential for successful and healthy life. A better understanding of how lifestyle and environment interact with genes and biology to facilitate optimal growth of the fetus will underpin new preventative measures and therapeutic treatments for infertility, miscarriage and other reproductive disorders. The knowledge gained will inform health policy and clinical practise to improve reproductive health in all Australian women and promote healthy development in all Australian children. The team of researchers is a world-class group of clinicians, scientists and epidemiologists who have made major contributions to our understanding of this area. This team will interface with clinics and hospitals that engage with women prior to and during pregnancy, while having the influence to alter clinical and health practices as well as public health policies. The team will utilize the latest, most technologically advanced laboratory methods and clinical skills, including gene profiling, imaging of early pregnancy, randomised clinical trials and access to the best epidemiological and statistical assessments.Read moreRead less
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