Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infer ....Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infertility and how species-specific differences in sperm form are achieved. Such insights may ultimately lead to improved agricultural efficiencies and job creation.Read moreRead less
Maximizing male fertility: the role of CRISP proteins. This project aims to investigate the function of cysteine rich secretory protein (CRISP) family members in fertility. It is expected to generate new knowledge on the role CRISP1 and 4 play in sperm competition in vivo, and thus, evolutionary processes; to define the role seminal plasma CRISPs play in fertility; and identify the mechanism underpinning their biological activities. This will be achieved using a range of innovative, state-of-the ....Maximizing male fertility: the role of CRISP proteins. This project aims to investigate the function of cysteine rich secretory protein (CRISP) family members in fertility. It is expected to generate new knowledge on the role CRISP1 and 4 play in sperm competition in vivo, and thus, evolutionary processes; to define the role seminal plasma CRISPs play in fertility; and identify the mechanism underpinning their biological activities. This will be achieved using a range of innovative, state-of-the-art approaches. Expected outcomes and benefits include an enhanced knowledge of the mechanisms underpinning fertility and infertility, enhanced collaboration and research knowhow, and an evidence base for future applied projects aimed enhancing fertility in agricultural species.Read moreRead less
Improving the efficiency of bovine oocyte maturation in vitro. For the dairy and beef industries, the hundreds of eggs (oocytes) in a high value cow's ovary that fail to produce a pregnancy are a wasted genetic resource. A key technology to unlocking this resource is in vitro maturation of oocytes, but the process is inefficient. One possible cause is that the current approaches to maturing oocytes in vitro do not adequately mimic the natural process in vivo. We will design new systems to matu ....Improving the efficiency of bovine oocyte maturation in vitro. For the dairy and beef industries, the hundreds of eggs (oocytes) in a high value cow's ovary that fail to produce a pregnancy are a wasted genetic resource. A key technology to unlocking this resource is in vitro maturation of oocytes, but the process is inefficient. One possible cause is that the current approaches to maturing oocytes in vitro do not adequately mimic the natural process in vivo. We will design new systems to mature cow oocytes in vitro by altering the chemical composition of maturation medium, thus improving the efficiency of laboratory embryo production and related technologies.Read moreRead less
Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining go ....Dissecting the impact of stress on reproduction: Novel peptide mediates inhibitory effects of stress on female reproduction. This research proposal offers a pioneering opportunity to develop treatments that overcome the negative impact of stress on reproduction. Specifically, knowledge generated in this project will be vital in the development of strategic defences against the impact of stress on reproduction. This project fundamentally addresses Research Priority 2: Promoting and maintaining good health. Given that suppression of reproduction by stress occurs in all mammalian species including humans, domestic animals and wildlife, being able to prevent or overcome stress-induced reproductive dysfunction will generate significant health, social, economic and ecological benefits. Read moreRead less
The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the e ....The impact of environmental toxicants on the fertility of female animals. This study aims to address a problem of national significance; determining the impact of commonly used environmental toxicants (pesticides) on the fertility and health of female animals, both agricultural and native. This project expects to generate new knowledge in the fields of ovarian biology, female fertility and toxicology by using a combination of mouse and marsupial animal models. The expected outcomes include the establishment of interdisciplinary collaborations and provision of world-class training for staff and students in the field of reproductive biology. This project should provide significant benefits, such as improved chemical management in livestock production and the development of marsupial conservation action plans.Read moreRead less
A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims ....A novel microtubule severing protein involved in male germ cell biology. The project aims to better understand the cellular and biochemical mechanisms underlying a key component of male fertility. Microtubules are a fundamental component of all cells. A mechanism that is increasingly recognised as essential for microtubules regulation is severing. It has been discovered that an uncharacterised microtubule severing protein, KATNAL2, has a key role in male germ cell development. This project aims to define the mechanisms underlying KATNAL2 function in the male germ line. It is expected that these data will generate a comprehensive picture of KATNAL2 function and provide foundation data of relevance across multiple species and tissues. In the longer term, it may also reveal a rational strategy for fertility enhancement or suppression.Read moreRead less
Sperm ciliary gating and midpiece formation – a novel player and process. We have identified CCDC112 an essential player in mammalian sperm tail development and male fertility. This project aims to define the role of CCDC112 in 1) the formation of the core to the sperm tail, the axoneme, and 2) the packaging of mitochondria into the midpiece. Within this Discovery Project we will define the mechanism(s) of CCDC112 functions and the consequences of its dysfunction. Insights from this grant will b ....Sperm ciliary gating and midpiece formation – a novel player and process. We have identified CCDC112 an essential player in mammalian sperm tail development and male fertility. This project aims to define the role of CCDC112 in 1) the formation of the core to the sperm tail, the axoneme, and 2) the packaging of mitochondria into the midpiece. Within this Discovery Project we will define the mechanism(s) of CCDC112 functions and the consequences of its dysfunction. Insights from this grant will be of significance to fertility across mammals and may ultimately benefit the selection of highly fertile males within the agricultural sector.Read moreRead less
Battle of the sexes: can surroundings differentially affect male and female mammalian preimplantation embryos. Equality between the sexes is an issue even at conception. The environment surrounding the embryo can bias the development of one sex over another. This project will assist in the understanding of how male and female embryos differ and will improve assisted reproductive technologies for domestic animal breeding programs, endangered animal conservation and human infertility treatment.
Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expect ....Exploring protease inhibitors in placental development and maturation. The placenta is essential for reproduction in many diverse species. This project aims to elucidate fundamental contributions of protease inhibitors and the proteases they target to placental development and maturation. It is expected to generate new knowledge around whether SPINTS play a fundamental role in disparate animals that independently derived a placenta, suggesting convergent genetic evolution. The project is expected to result in disciplinary collaboration, produce novel models, and promote future projects in many species. The project should result in significant benefits toward advancing knowledge in reproductive biology, have economic and commercial benefits, and further enhance Australia's outstanding reputation in the field.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.