This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also invest ....This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also investigates how sperm are protected during their development from infection and immunological rejection, achieved in part by a special environment within the tubes in the testis where they grow. It appears that the general mechanisms that the body uses to combat infections are modified within the testis and the way in which this occurs may provide clues that could be applied to prevent the rejection of transplanted organs in general. Some of the substances that control these processes appear to play an important role in the body�s defense against infection. The grant also investigates the processes that are involved in the development of prostate cancer. These changes can occur over many years and the grant will study some substances that appear to be involved. The work will provide new knowledge that may assist in new tests to identify whether a cancer is slow or fast growing, thereby helping each man to decide the most sensible form of treatment. The grant will investigate how a group of proteins, that also are involved in the control of processes discussed above, assist the mother in protecting her baby during pregnancy. The outcomes will assist in the management of disturbances of pregnancy that may put the fetus at risk of survival.Read moreRead less
I am a reproductive biologist working to define key mechanisms for sperm development and function; and by extension the causes of human male infertility.
The Identification Of Male Meiosis Genes Using A New Mouse Line And Human Genome Scans For Gene Copy Number Variations
Funder
National Health and Medical Research Council
Funding Amount
$604,793.00
Summary
Infertility affects 1 in 25 Australian men and meiosis is a key process in male fertility, yet we know very little about the mechanisms that control it. We will use a new point mutant mouse model of meisois failure to identify a novel regulator of male fertility. Further, we hypothesize that changes in gene copy number will lead to meiosis arrest and infertility in some men. Such variations will be assessed through a whole genome scan of a unique set of infertile men.
Cysteine Rich Secretory Proteins (Crisp) Are Ion Channel Regulators With Essential Roles In Male Fertility
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich ....Male infertility affects 1 in 20 Australian men and for the majority of other men, contraception is an issue at some point in their lives. Despite this, relatively little is known about the processes of sperm production and fertilization. As such, there is an urgent need for futher research if we are to hope to develop diagnostics, targeted therapeutics and to take advantage of the growing awareness by pharmaceutical companies of the market for male gamete based contraceptives. The cysteine rich secretory proteins (Crisps) are a group of proteins which show a remarkable bias to the male reproductive tract. All four are incorporated into sperm. Recently published data from us indicates that they have the ability to regulated calcium flow in sperm and as such sperm activity. The aim of the current proposal is to explore the biological relevance of one domain of Crisp proteins using animal models, in vitro sperm tests and through an analysis of ion flux and phosphorylation status under conditions of altered Crisp-1 and -2 content. The data generated from this project will make a significant contribution to the development of novel male gamete based contraceptives for use by either men or women. In addition, through the attainment of a greater understanding of sperm development and function, we will be able to more precisely define types of infertility, thus allowing for the development of more targeted therapies. The development of Crisp agonists or antagonists may also be of value in the treatment of other cilia disorders including primary cilia dykinesia and cystic fibrosis.Read moreRead less
This program will expand research and policy development to overcome androgen misuse (off label testosterone prescribing for invalid indications) and combat androgen ('anabolic steroid') abuse for performance and image enhancement. Beyond expanding ongoing research, it will develop a new focus in developing drugs to accelerate recovery from androgen abuse, thereby preventing relapse during the slow natural recovery period typically lasting 6-18 months or longer
The Sertoli Cell: Master Regulator Of Hormone-induced Spermatogenic Development
Funder
National Health and Medical Research Council
Funding Amount
$563,536.00
Summary
This project will determine the key roles of major hormones (testosterone, follicle-stimulating hormone, Vitamin A) in Sertoli cells, unique highly specialised cells found in the testis that provide essential nutritional and structural support for sperm production. This research will provide new understanding of the biological pathways controlling sperm development, leading to new molecular targets for infertility or cancer treatment or diagnosis, or new contraceptive strategies for men.
ATR-X Syndrome: Role Of ATRX In Testicular Growth And Spermatogenesis
Funder
National Health and Medical Research Council
Funding Amount
$650,881.00
Summary
Infertility is surprisingly common and affects 1 in 20 Australian men. Testosterone and its receptor, the androgen receptor, are well known to be essential for spermatogenesis and fertility. We have identified an important regulator protein (ATRX) of androgen receptor activity and show that loss of function of ATRX in testes of mice leads to spermatogenesis defects. Identifying the molecular action of ATRX will lead to a better understanding of the underlying causes of infertility in men.
Male fertility requires sufficient production of healthy sperm in the testis. This project builds on our discovery that testicular cells communicate via the wnt family of proteins during sperm development, and that interruption of their activities reduces fertility in mice. We propose to use mouse models to study the precise steps in sperm production affected by Wnt signalling and how it works.
Toll-like Receptor And MyD88 Signalling In The Testis
Funder
National Health and Medical Research Council
Funding Amount
$498,411.00
Summary
Infertility affects one in seven couples desiring children. A proportion (5-10%) of the male partners in these couples have immunological reactions against their own sperm. The testes, where sperm are made, and the immune system normally exist in a balanced, beneficial relationship, but sometimes this relationship goes wrong. This can also lead to chronic pain and increased risk of testicular cancer. The project investigates this relationship in order to provide assistance for these men and thei ....Infertility affects one in seven couples desiring children. A proportion (5-10%) of the male partners in these couples have immunological reactions against their own sperm. The testes, where sperm are made, and the immune system normally exist in a balanced, beneficial relationship, but sometimes this relationship goes wrong. This can also lead to chronic pain and increased risk of testicular cancer. The project investigates this relationship in order to provide assistance for these men and their partners.Read moreRead less