Who determines gestation length - mother or fetus? This project will extend our knowledge of a key biological process - pregnancy. Variation of gestation length by 10% is generally deleterious to the offspring, and smaller babies have been shown to be more susceptible to later life diseases. Therefore, extension of the information gained from this project will likely impact researchers in species conservation, pest control, and the livestock industries, as well as human, obstetric care and pract ....Who determines gestation length - mother or fetus? This project will extend our knowledge of a key biological process - pregnancy. Variation of gestation length by 10% is generally deleterious to the offspring, and smaller babies have been shown to be more susceptible to later life diseases. Therefore, extension of the information gained from this project will likely impact researchers in species conservation, pest control, and the livestock industries, as well as human, obstetric care and practice. Specifically, knowledge gained from this project may lead to means of limiting (pest control) as well as enhancing (endangered species) species survival.Read moreRead less
Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success ....Molecular mechanisms for seminal fluid signalling in reproduction. Male seminal fluid regulation of the female reproductive process influences fertility and fecundity in humans and animal species. Infertility and impaired reproductive function is a major economic constraint in livestock industries, and carries a substantial social and public health cost in humans. This research will identify the active signalling molecules in seminal fluid and quantify their importance in reproductive success and health of offspring. The outcomes will inform development of new diagnostic assays for male fertility, and underpin strategic design of novel fertility treatments and products with applications in the human health and animal breeding industries. 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
Extrinsic Control of Mammalian Germ Cell Delineation. Australia is a leader in the recent exciting breakthroughs in reproduction and development, such as cloning and embryonic stem cell propagation, and understanding how germ cells are specified would help us understand the biology underlying specification and developmental potential of all cells. This research will continue to contribute to maintaining Australia's high reputation in advances in reproductive biology. In addition, a greater under ....Extrinsic Control of Mammalian Germ Cell Delineation. Australia is a leader in the recent exciting breakthroughs in reproduction and development, such as cloning and embryonic stem cell propagation, and understanding how germ cells are specified would help us understand the biology underlying specification and developmental potential of all cells. This research will continue to contribute to maintaining Australia's high reputation in advances in reproductive biology. In addition, a greater understanding of marsupial reproduction is a high priority for Australia in the 21st century, with its current unacceptably high rate of mammalian extinctions, for 'we cannot conserve until we comprehend' (Short, 1985).The results therefore are of great potential benefit to society.
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Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge tech ....Shaping the heart in early development - new insights into cellular modelling processes. Heart health is an important contributor to quality of life and longevity. This research will provide new insights into the way hormonal influences early in development shape a healthy heart. The project builds on the application of recently patented, sophisticated cell imaging techniques. Research students and trainees recruited to this project will benefit from their involvement with this leading edge technology. These studies are important in providing a basis for developing optimal management strategies for congenital heart conditions and preterm infants. Improved knowledge of the cardiac effects of fetal and neonatal exposure to steroids (to assist with lung maturation in prematurity or to control maternal asthma) will be gained.Read moreRead less
Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to un ....Mechanistic basis of a reproductive lesion in transforming growth factor beta-1 (TGFb1) null mutant mice. Null mutation in the gene encoding the cytokine transforming growth factor beta-1 (TGFb1) causes infertility in male and female mice. In recent experiments we have found that TGFb1 deficiency is associated with impaired ovarian and testicular steroidogenesis, arrested development of pre-implantation embryos and disrupted mammary gland morphogenesis. The aims of the current project are to unravel the mechanistic basis of the reproductive lesion in TGFb1 null mutant mice and to determine the effect of exogenous systemic delivery of TGFb1 in alleviating this lesion. It is expected that the project will provide new insight into key roles for TGFb1 in governing male and female fertility, and shed light on the prospects for exogenous supplementation of TGFb1 for improving reproductive performance in wild-type animals. This knowledge has potentially important applications in the livestock breeding industry, in devising novel contraceptive vaccine strategies, in the human pharmaceutical industry, and in devising novel contraceptive vaccine strategies.Read moreRead less
Interactions between cells and extracellular matrix in the epithelial-mesenchymal transition of the ovarian follicular stratified epithelium. The lining of many mammalian organs and cavities contain cells that can transform into different cells to bring about organ development or repair but if it goes horribly wrong the cells become metastatic cancers. This project examines the key features of this process especially the roles of matrix that develops around the cells in this process.
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
Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular fun ....Decoding microtubule remodelling in sperm production. All eukaryotic cells possess a dynamic microtubule (MT) cytoskeleton, which requires constant remodelling to satisfy its many essential cellular roles. Emerging data suggests modifications to the MT surface (the tubulin code) may act as instructional signposts for remodelling. This project aims to define a fundamental component of the tubulin code, glutamylation, and define how this directs MT severing. It also aims to define the cellular functions of MT-severing enzyme FIGNL1 and key MT glutamylation enzymes (CCP1, CCP5 and TTLL1). Insights will be generated using sperm production as a model system and will thus inform the mechanisms by which fertile sperm are built, in addition to being relevant to cell biology across eukaryotic species. Read moreRead less
Size matters, but at what cost? Role of male sex hormones in the placenta. This project aims to understand molecular pathways regulated by male sex hormones in the placenta that may contribute to sex-specific fetal growth and survival outcomes in response to reduced oxygen and/or glucose. Through this project, we expect to generate new knowledge of the mechanisms that drive sex-specific placental molecular function using interdisciplinary approaches. The application of this advanced understandin ....Size matters, but at what cost? Role of male sex hormones in the placenta. This project aims to understand molecular pathways regulated by male sex hormones in the placenta that may contribute to sex-specific fetal growth and survival outcomes in response to reduced oxygen and/or glucose. Through this project, we expect to generate new knowledge of the mechanisms that drive sex-specific placental molecular function using interdisciplinary approaches. The application of this advanced understanding of the sex-specific regulation of placental molecular function and fetal growth may be targeted in future studies to improve fetal growth outcomes in placental mammals such as livestock, domestic pets, and humans.Read moreRead less