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
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.
The Mechanism Of Spermatid Differentiation - A Link To Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$506,425.00
Summary
To discover novel regulators of male fertility, we have screened libraries of mutant mice generated by a chemical mutagen. This project aims to define the function of the mutated gene identified in a male-specific infertile mutant mouse line. The mutated gene has been proposed to play a role in regulating cell death and suppress lung tumour formation. Our data may reveal novel options for male infertility treatment and for the development of male contraception and lung cancer biomarkers.
A New Model Of Asthenospermia And A Candidate Gene For Multiple Ciliopathies
Funder
National Health and Medical Research Council
Funding Amount
$629,039.00
Summary
Though the analysis of a unique mouse strain (Mot1) we have identified a previously unknown cause of male infertility and lung disease. We hypothesis that the Mot1 line is a model of human primary cilia dyskinesia and that the Mot1 protein is involved in cilia function. Within this project we will define the consequences of a loss of Mot1 protein function, we will define its binding partners and we will screen for mutations in the corresponding human gene.
Molecular Mechanisms Regulating Spontaneous Onset Of Human Labour
Funder
National Health and Medical Research Council
Funding Amount
$481,156.00
Summary
The single most important complication contributing to poor pregnancy and neonatal outcome is premature birth. If we are to provide the best possible start to life, improve perinatal health and reduce the risk of developing adult disease . A better understanding of labour is requisite to improving health care delivery during pregnancy and outcomes for both mother and baby. This reserach project will investigate the how labour-associated events are reguluated by nuclear proteins.
Molecular Characterization Of Unique Recognition Sites On The Surface Of Human Spermatozoa
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do ....Developing an understanding of the molecular mechanisms that regulate human sperm function is central to the clinical management of male infertility, attempts to develop novel forms of male contraception and strategies for the introduction of transgenes into the male germ line. Defective sperm function is the largest single defined cause of human infertility. Despite the prevalence of this condition we have no idea how most cases of male infertility arise nor, in a vast majority of patients, do we understand which particular aspect of sperm biochemistry is defective. As a consequence we have not been able to develop sensitive biochemical diagnostic tests for the infertile male nor do we have any rational methods of treatment that address the cause of this condition. Similarly no new methods of male fertility regulation have been introduced since vasectomy despite the major advances that have been made in the field of female contraception over the same period of time. Clearly if we are to develop sensitive methods for the diagnosis of defective sperm function, introduce protocols for the treatment and prevention of male infertility and discover novel approaches to male contraception, we must first understand the cellular mechanisms that enable these highly specialized cells to perform their unique function. In this study we shall focus on one of the most important attributes of sperm function the capacity of these cells to recognize the egg. Once the biochemical basis of this fundamental recognition process is understood, it should pave the way for the development of clinical applications that target this signaling system with implications for a range of disciplines including reproductive toxicology, occupational medicine, family planning, infertility and biotechnology.Read moreRead less
Studies Of The Paracrine Role Of Inhibin A/activin A In Ovulation
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enor ....This project aims to study the biochemical processes associated with normal egg maturation and release. Two mouse models will be used. One will involve culturing mouse ovarian tissue and inducing ovulation to study the processes. The other will involve study of gene expression in a mouse ovary around ovulation. The progressive accumulation of knowledge about the processes of ovulation will greatly improve our ability as doctors to manipulate ovulation in clinical practice. This will make an enormous difference to women s health in the following areas: contraception, the possibility of development of new methods of contraception that block egg release without affecting the normal ovarian cycle endocrinology; fertility treatment, better methods of obtaining mature oocytes without subjecting women to high dose gonadotrophin treatment and the accompanying sequelae; improving knowledge of the factors that promote satisfactory oocyte maturation and embryo development so that with improved implantation rates, fewer embryos need be replaced to achieve a pregnancy.Read moreRead less
Cysteine-rich Secretory Protein Regulation Of Ion Channels In Male Fertility And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$474,309.00
Summary
Diagnosis of the precise causes of male infertility and the development of male contraceptives requires improved understanding of sperm function. The Cysteine-Rich Secretory Proteins (CRISPs) are produced in the male reproductive tract where they regulate sperm function. Our project will demonstrate the essential requirement for CRISPs in sperm function and investigate their role in other tissues of the reproductive tract, including the prostate where they may be involved in prostate cancer.