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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
Glucocorticoid receptor-αD1 modulates stress and inflammation . Environmental stressors in mammalian pregnancy often cause inflammation in the mother which has an adverse effect on the fetus and its survival. The current grant aims to examine the mechanism by which stress and inflammation coexist in pregnancy because stress hormones normally exert anti-inflammatory actions. Contrary to convention, a new glucocorticoid receptor (GR), GRalpha D1, is linked to increasing inflammation. Using innova ....Glucocorticoid receptor-αD1 modulates stress and inflammation . Environmental stressors in mammalian pregnancy often cause inflammation in the mother which has an adverse effect on the fetus and its survival. The current grant aims to examine the mechanism by which stress and inflammation coexist in pregnancy because stress hormones normally exert anti-inflammatory actions. Contrary to convention, a new glucocorticoid receptor (GR), GRalpha D1, is linked to increasing inflammation. Using innovative molecular biology approaches, GRalphaD1's function will be examined to provide a deeper understanding of how stress regulates inflammation in animal reproduction. The project aims to enhance interdisciplinary collaborations with expected benefits including a paradigm shift in our knowledge in this field.Read moreRead less
How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) acti .... How are sperm mitochondria eliminated after fertilisation . The fact that mitochondria are inherited exclusively through the maternal germ-line is fundamental feature of sexual reproduction in all but a few organisms. This uni-parental inheritance is thought to prevent genetic conflict between different mitochondrial genomes. The mechanisms controlling uniparental inheritance involve eliminating the sperm mitochondria soon after fertilisation. We will investigate 2 possible mechanisms, (1) active destruction and (2) passive dilution. The results will help explain how heteroplasmy is avoided in order to maintain the fitness of organisms including animals and humans. The results will have long term insights into improving breeding in agriculture and in the prevention of mitochondrial genetic disease.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Understanding why mammalian eggs have so much mitochondrial DNA . During oocyte growth there is massive increase in the replication of mitochondrial DNA so that each ovulated egg has 200,000-400,000 copies of the mitochondrial genome. This mitochondrial compliment will provide the template for all mitochondrial DNA in the subsequent organism. The established role of mitochondria is to provide energy in the form of ATP, but they are also known to be highly adaptive to the metabolic and energetic ....Understanding why mammalian eggs have so much mitochondrial DNA . During oocyte growth there is massive increase in the replication of mitochondrial DNA so that each ovulated egg has 200,000-400,000 copies of the mitochondrial genome. This mitochondrial compliment will provide the template for all mitochondrial DNA in the subsequent organism. The established role of mitochondria is to provide energy in the form of ATP, but they are also known to be highly adaptive to the metabolic and energetic state of the cell. In this project, we will use genetic approaches to decrease the amount of oocyte mitochondrial DNA by 90%. We will examine how this influences mitochondrial organisation, oocyte metabolism and embryo development. This new knowledge will provide insights into animal breeding and human health.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
New insights into female reproductive tract formation and tubulogenesis. Aims: This project aims to improve our understanding of female reproductive tract formation by studying its developmental origins. Most of the female reproductive tract derives from a pair of embryonic tubes called Müllerian ducts, the formation of which is incompletely understood. Significance: Using chicken and mouse models and innovative genetic approaches, the project will undercover novel genes and cellular pathways in ....New insights into female reproductive tract formation and tubulogenesis. Aims: This project aims to improve our understanding of female reproductive tract formation by studying its developmental origins. Most of the female reproductive tract derives from a pair of embryonic tubes called Müllerian ducts, the formation of which is incompletely understood. Significance: Using chicken and mouse models and innovative genetic approaches, the project will undercover novel genes and cellular pathways in Müllerian duct formation. Expected outcomes: This work will enhance knowledge in the biological sciences, in the area of female reproduction and how tubes form in biological systems. Benefits: It will train research scientists, develop collaborations and enhance Australia’s high standing in the field of reproduction.Read moreRead less
A macrophage-centric holistic view of postnatal development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. It is also a time when animals are especially susceptible to infectious disease. This project aims to investigate how cells of the innate immune system called macrophages control somatic growth and development of mature organ function in the early postnatal period. The project aims to build upon investment in new animal models and a no ....A macrophage-centric holistic view of postnatal development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. It is also a time when animals are especially susceptible to infectious disease. This project aims to investigate how cells of the innate immune system called macrophages control somatic growth and development of mature organ function in the early postnatal period. The project aims to build upon investment in new animal models and a novel discovery to generate significant new knowledge that challenges current concepts of mammalian growth control. The outcomes will enhance Australia's international reputation in the fields of physiology, immunology and developmental biology and may translate to improvements in health in animals and humans. 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