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Inflammatory Cytokines As Causal Agents In Peri-conception Programming Of Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$604,046.00
Summary
Events at conception set the trajectory of fetal developmental that will determine health of children after birth and in later life. Susceptibility to obesity and metabolic conditions is established at this very early time. This project will define the molecular signals affecting the embryo in the event of maternal or paternal infection, diet and stress. The results will help us devise health advice for intending parents to improve child health and help prevent onset of metabolic disorders.
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
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
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.
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
Chemical principles underpinning a spermostatic-microbiostatic agent capable of preventing pregnancy and the spread of sexually transmitted disease. This project explores the development of a method for simultaneously controlling fertility while preventing the spread of sexually transmitted diseases. A novel aspect of the approach, that will dramatically influence product development, is that the active principles will only be generated on contact with seminal plasma.
Is Calcium part of the mechanism used in glucose signalling in embryogenesis. A vital stage in the development of the embryo is formation of the blastocyst about 4 days after conception. For this to happen the embryo must receive glucose from the mother. We believe that rather being used by the embryo to generate energy, this glucose acts as a signal to switch on the developmental pathway leading to blastocyst formation. Without this signal there is no blastocyst and the pregnancy fails. The pr ....Is Calcium part of the mechanism used in glucose signalling in embryogenesis. A vital stage in the development of the embryo is formation of the blastocyst about 4 days after conception. For this to happen the embryo must receive glucose from the mother. We believe that rather being used by the embryo to generate energy, this glucose acts as a signal to switch on the developmental pathway leading to blastocyst formation. Without this signal there is no blastocyst and the pregnancy fails. The project investigates this signal mechanism. The results will advance understanding of the mechanisms regulating development and in particular link the mother's nutritive status to her fertility during very early pregnancy.Read moreRead less
The control of meiosis in mammalian oocytes. This study will elucidate how the egg undergoes its final steps in preparation for fertilisation and early development. This will produce greater knowledge about how eggs develop, which may reveal new approaches to modulating reproductive capacity.
Development Of Engineered Novel Growth Factors For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$410,439.00
Summary
Infertility comes at an enormous social and financial cost to Australian society. The aim of this proposal is to improve the success rate of an innovative technology that matures eggs in the laboratory and so eliminates the need for the hormones normally used in IVF. To achieve this a newly discovered egg-secreted protein first has to be produced in the laboratory.