Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less
The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell application ....The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell applications, tissue engineering, tissue repair and regeneration. This project will use zebrafish embryos, new genomic datasets and novel tools to uncover the genetic control of this process, and should have implications in stem cell biology, tissue engineering, repair and regeneration.Read moreRead less
How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
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
How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammali ....How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammalian animals (e.g. pets and endangered species). They are also likely to inform the discipline of stem cell biology in general.Read moreRead less
Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technolo ....Systems analysis of a critical regulatory hub in sex determination. This project seeks to better understand regulatory mechanisms of embryonic development. A key challenge in biology is to understand how genes act in regulatory networks to coordinate the formation of complex organs during embryo development. Although several genes influence embryo sex determination and gonad development, Sox9 has emerged as a master regulator in this system. This project plans to use new systems biology technologies and transgenic mice to identify the suite of Sox9 target genes and partner proteins. Anticipated outcomes include insights into sex determination, stem cell differentiation, and development of many other organ systems that depend on Sox9 function, providing proof-of-concept for high-throughput analysis of molecular control networks in the embryo.Read moreRead less
Modelling stem cell decisions in mouse germ cells. A fundamental problem in biology is how cells transition from pluripotency to lineage commitment. The aim of this project is to study this problem, in vivo, by dissecting the mechanisms active during normal development of primordial germ cells (PGCs, gamete stem cells) in the mouse fetal testis. Using molecular, cellular and whole animal assays three central hypotheses will be addressed regarding genes likely to be important in the process. This ....Modelling stem cell decisions in mouse germ cells. A fundamental problem in biology is how cells transition from pluripotency to lineage commitment. The aim of this project is to study this problem, in vivo, by dissecting the mechanisms active during normal development of primordial germ cells (PGCs, gamete stem cells) in the mouse fetal testis. Using molecular, cellular and whole animal assays three central hypotheses will be addressed regarding genes likely to be important in the process. This research will reveal the molecular nature of bipotential switches in cell identity and will inform some of the most important biological issues of our time, including tissue regeneration, aging and cancer biology.Read moreRead less
Molecular regulation of the mitosis-to-meiosis switch in germ cells. This project will build on our recent major discoveries to study how sperm and oocyte production begins during fetal life. This issue is critical for understanding fertility and infertility in animal species and humans. The answers generated will lay the groundwork for fertility control in humans, pets, pests and endangered animals.
A multi-model approach to characterise conserved regulators of lymphatic vascular development. Lymphatic vessels are important in a number of diseases affecting Australia. There is a significant gap in our basic knowledge of how lymphatic vessels form. This study will characterise key genes that control lymphatic development, providing a base of knowledge contributing to the promotion and maintenance of good health in Australia.
Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.Read moreRead less