Is SPINT1 a key regulator of placental development? . The placenta is an essential organ required for reproduction in placental species. This project aims to elucidate the fundamental biology of SPINT1 in placental development. It will generate new knowledge about whether the spatial and temporal expression of SPINT1 is conserved across several species; cow, sheep, lizard, mouse and human. It will also define the molecular mechanisms by which SPINT1 directs formation, maturation and expansion o ....Is SPINT1 a key regulator of placental development? . The placenta is an essential organ required for reproduction in placental species. This project aims to elucidate the fundamental biology of SPINT1 in placental development. It will generate new knowledge about whether the spatial and temporal expression of SPINT1 is conserved across several species; cow, sheep, lizard, mouse and human. It will also define the molecular mechanisms by which SPINT1 directs formation, maturation and expansion of the placental exchange interface which is critical for offspring survival.
The project will increase understanding of placental development, enhance collaboration and research knowhow, and promote future applied projects in all species that reproduce via placental support.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
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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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
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
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
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
Discovery Early Career Researcher Award - Grant ID: DE210100103
Funder
Australian Research Council
Funding Amount
$459,674.00
Summary
Fortifying animal and plant germ cells against proteotoxic stress. Cellular stress is responsible for widespread inefficiencies in plant and animal reproduction. Using high resolution proteomics and cryo-electron microscopy, this project aims to investigate how plant and animal germ cells respond to environmental stresses that are known to disrupt fertility, and assess two novel strategies to decrease the sensitivity of cells to stress. This project is expected to generate new global knowledge i ....Fortifying animal and plant germ cells against proteotoxic stress. Cellular stress is responsible for widespread inefficiencies in plant and animal reproduction. Using high resolution proteomics and cryo-electron microscopy, this project aims to investigate how plant and animal germ cells respond to environmental stresses that are known to disrupt fertility, and assess two novel strategies to decrease the sensitivity of cells to stress. This project is expected to generate new global knowledge in the area of fertility regulation with the potential to improve the tolerance of crop species to heat stress, prevent economic losses and help to secure future food production. Further, this project has the intended benefit of improving the fertility of animal species that suffer from stress-induced infertility.
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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