EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cel ....EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cell survival. This project advances basic and applied biology. Its outcomes will be relevant to several research areas and industries, specifically to the propagation of cell cultures that nowadays contributes to the production of a myriad of biotechnical and pharmaceutical commodities.
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Discovery of new metabolic functions in Plasmodium parasites. This research will provide new understanding about the metabolism of parasites, such as those that cause malaria. These parasites have evolved bespoke metabolic networks to survive in diverse host environments including mosquitos and humans. Previous studies have revealed many unique genes and metabolites in these organisms, but their biochemical function is not known. This project will use state-of-the-art metabolomics and proteomics ....Discovery of new metabolic functions in Plasmodium parasites. This research will provide new understanding about the metabolism of parasites, such as those that cause malaria. These parasites have evolved bespoke metabolic networks to survive in diverse host environments including mosquitos and humans. Previous studies have revealed many unique genes and metabolites in these organisms, but their biochemical function is not known. This project will use state-of-the-art metabolomics and proteomics technology to accurately identify novel metabolites produced by the parasites, and discover the enzymes that are responsible for their synthesis. This work will not only advance our understanding of cellular metabolism, but will provide new opportunities for future biotechnology applications.Read moreRead less
Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles o ....Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist with achieving a desired meat quality and yield in beef and other commercially important animals.Read moreRead less
Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pa ....Manipulation of mitochondrial function by Legionella pneumophila. . The intracellular bacterial pathogen Legionella pneumophila co-evolved with eukaryotic hosts and has developed sophisticated mechanisms to manipulate human cell function – mitochondria in particular – by secreting >300 effector proteins through a specialised Type-IV system into the host cell. This research aims to understand the function of effector proteins targeted to mitochondria; delivering important new knowledge in host-pathogen and mitochondrial biology and advanced cell biology tools. With most of the effector proteins yet to be characterised, benefits from the project will be to reveal specifically how these target mitochondria, and more broadly, how bacterial pathogens manipulate organelles for their survival.Read moreRead less
Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quali ....Interrogating the extremes of skeletal muscle plasticity in vertebrates. This project aims to interrogate how muscles adapt to growth and endurance stimuli at different stages of life, relevant to addressing challenges facing the world’s ageing population. Using innovative gene technologies and molecular physiology in zebrafish and mice, this project will answer important, unresolved questions in muscle biology. The project will generate knowledge needed to develop interventions to improve quality of life for older Australians and address the physical realities of an ageing workforce. Benefits extend to enhancing workplace safety and productivity, improving farming efficiencies for livestock and aquaculture industries, and training emerging leaders in the biological sciences.Read moreRead less
How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite prote ....How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite proteins that mediate the uptake of different amino acids into the parasite. The intended outcomes of the project are to provide comprehensive insights into a fundamental aspect of parasite biology, and inform strategies to treat the diseases caused by these parasites by cutting off their nutrient supply.Read moreRead less
Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this ....Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this relates to mice. Expected outcomes and benefits will be a new understanding of which aspects of fat metabolism are most influenced by androgens, and an ability to anticipate potential metabolic impacts of natural or pharmacological fluctuations in androgen levels in humans, laboratory animals and livestock.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
Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundament ....Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundamental insights into how SIK3 in the hypothalamic neurons regulates energy homeostasis. Benefits include improving population health and wellbeing, informing the development of new bio-medical technologies, and expanding the capabilities of Australia’s next generation of researchers.
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