Diversity and Defence: Characterisation of Extremely Variable Defensive Proteins from Sea Urchins. Antibiotic resistance is a global problem. In this project, we will study a new class of potential antibiotics - purpuratins - from sea urchins. Purpuratins are unique when compared to other antimicrobials because of their extreme structural diversity. By investigating that diversity, we will shed new light on biological methods for targeted drug design. This information will be critical to the de ....Diversity and Defence: Characterisation of Extremely Variable Defensive Proteins from Sea Urchins. Antibiotic resistance is a global problem. In this project, we will study a new class of potential antibiotics - purpuratins - from sea urchins. Purpuratins are unique when compared to other antimicrobials because of their extreme structural diversity. By investigating that diversity, we will shed new light on biological methods for targeted drug design. This information will be critical to the development of tailor-made antibiotics that are fine-tuned to kill particular micro-organisms. Our work represents a collaboration between researchers in Australia and the United States. It contributes directly to international scientific co-operation whilst providing high level training for young Australian researchers and students. Read moreRead less
Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryoni ....Molecular control of postnatal heart development. This project aims to improve our understanding of how the heart develops after birth and the molecules that control this process. Recent advances in tissue engineering have opened up opportunities for the generation of synthetic tissues but these studies have also highlighted a fundamental knowledge gap in our understanding of how complex tissues mature to prepare for life as an adult. Much is known about the molecules that control early embryonic development but little is known about the molecules that control maturation after birth. This project aims to build new knowledge that is expected to improve our ability to generate mature heart muscle cells for stem cell applications, tissue repair and regeneration.Read moreRead less
Gamete-specific knockout of Fizzy-Related to examine its meiotic role in oocytes and sperm. Fizzy-Related is a gene that appears to be essential in making an ovulated egg, and it may also have an important role to play in making sperm. A mouse knockout will be generated to examine exactly how it functions; because it affects the egg number remaining in the ovary and egg quality Fizzy-Related may be eventually an important therapeutic target.
Macrophage control of mammalian growth and development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. This project is an international collaboration that 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 animals models and a novel discovery to generate significant new know ....Macrophage control of mammalian growth and development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. This project is an international collaboration that 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 animals models and a novel discovery to generate significant new knowledge that will challenge current concepts of mammalian growth control. The outcomes will enhance Australia's international reputation in the fields of physiology, immunology and developmental biology. 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
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
Unravelling the principles of bilateral brain wiring. This project seeks to investigate the molecular principles of brain wiring in mammals and how small changes can generate complex outcomes. Neurons in the mammalian brain must be precisely wired together for the brain to function correctly. The project aims to identify the molecular and cellular rules governing commissural wiring in the mammalian cortex to determine how the largest fibre tract in the human brain, the corpus callosum, evolved. ....Unravelling the principles of bilateral brain wiring. This project seeks to investigate the molecular principles of brain wiring in mammals and how small changes can generate complex outcomes. Neurons in the mammalian brain must be precisely wired together for the brain to function correctly. The project aims to identify the molecular and cellular rules governing commissural wiring in the mammalian cortex to determine how the largest fibre tract in the human brain, the corpus callosum, evolved. This may have involved modifications in mechanisms affecting axon guidance that differ between placentals and marsupials. The project investigates the regulatory gene networks determining commissural neuron fate, the regulation of axon guidance components, and the influence of surrounding brain tissue on the development of commissural connections.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
FATIGUE IN VERTEBRATE TENDONS: BIOMECHANICAL AND STRUCTURAL CORRELATES OF ONTOGENETIC AND ADAPTIVE CHANGE. Tendons are important vertebrate tissues, but little is known about their mechanical properties under fatigue-loading. Recent research has shown that dramatic differences in fatigue properties occur and that these appear to be linked to the functional roles of tendons. This project uses a variety of approaches to explore how mechanical and structural properties of tendons change during g ....FATIGUE IN VERTEBRATE TENDONS: BIOMECHANICAL AND STRUCTURAL CORRELATES OF ONTOGENETIC AND ADAPTIVE CHANGE. Tendons are important vertebrate tissues, but little is known about their mechanical properties under fatigue-loading. Recent research has shown that dramatic differences in fatigue properties occur and that these appear to be linked to the functional roles of tendons. This project uses a variety of approaches to explore how mechanical and structural properties of tendons change during growth, maturation and adaptation to different loading environments, and the cellular basis of fatigue resistance. An understanding of fatigue properties from cellular to tissue levels has significance in the areas of general biology, materials science and biomedical science.Read moreRead less
Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.Read moreRead less