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
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.
Redox Cycling Of Quinones By Human Spermatozoa: A Potential Strategy For The Dual Regulation Of Fertility And STDs
Funder
National Health and Medical Research Council
Funding Amount
$314,625.00
Summary
The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contrac ....The purpose of this research project is to develop a novel form of contraception that could meet the dual objectives of fertility regulation and prevention of sexually transmitted disease (STD). A particularly novel feature of this proposed spermicide-microbicide is that it has to be activated by spermatozoa i.e the formulation comprises a pro-spermicide that only generates the active principle on contact with sperm. This aspect of the method sets it apart from all other forms of topical contraception because unlike barrier methods and vaginal creams or foams, its use will not be coitus related. Ultimately it is envisaged that the product could be incorporated into a soft pliable vaginal sponge and left in situ until such time as it becomes activated following intercourse. Such a method should be particularly acceptable to young women who are vulnerable to both STDs and unwanted pregnancy as indicated by (a) the relatively high rates of STDs in adolescent girls, particularly in the indigenous community, and (b) the fact that 50% of all recorded pregnancies to Australian women under 19 years of age end in abortion. The method exploits the susceptibility of human spermatozoa and pathogenic organisms responsible for STDs to oxidative stress and, in effect, mimics a naturally occurring cause of male infertility. If successful, this project would produce a female centred method of contraception and STD prevention that would revolutionize reproductive health care for young women worldwide, as well as generating intellectual property of considerable potential value to the nation.Read moreRead less
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
Postviral Wheezing In Childhood: Disregulation Of Airway Tone?
Funder
National Health and Medical Research Council
Funding Amount
$577,040.00
Summary
Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. Ho ....Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. However, many infants who wheeze with viral infections, especially in the first year of life, do not develop allergies in later life, raising the possibility that they did not have the same type of asthma as those whose symptoms persist. This project will study the effects of viral infections on lung function to determine whether particular types of virus can have detrimental effects of lung function lasting for years. We will also examine whether the age at which the infection occurs and the severity of the infection influence the long-term outcome. The project involves studying infants during the recovery phase of respiratory viral infections, older children years after documented infections and experimental animal models that have been infected under controlled conditions. By determining whether respiratory viral infections can have long-term effects on lung function that can mimic asthma, we will advance our understanding of how asthma develops. In addition, specific treatment and preventative strategies could then be developed to prevent these long-term abnormalities, instead of relying on asthma medication (especially inhaled corticosteroids) as is the current practice. Preventative strategies could include encouraging the development of specific vaccines.Read moreRead less
Identification And Characterisation Of Phosphorylation Events Taking Place During Human Sperm Capacitation
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Male infertility affects one in every twenty Australian males and one third of all infertile couples worldwide. The most common cause of human infertility is not a failure to produce sperm, but a failure of these cells to express a normal capacity for fertilization. The cause of this loss of functional competence is unclear. We are going to use our technical expertise in proteomics to characterize the molecular pathways responsible for the defective sperm function seen in infertile patients.
Evolution Of Airway Function And Inflammation In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,447.00
Summary
Our goal is to evaluate if lung function can identify the onset of early lung disease in infants with cystic fibrosis (CF). We aim to evaluate: - Changes in lung function in infants with CF. - Associations between lung function and lung inflammation and infection. - Links between infant lung function and disease severity at 2 years of age. The long term aims are to determine how useful lung function will be in trials of novel treatments for the early treatment of CF.