Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and en ....Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and enhancing fertility in endangered species. Knowledge of these cellular mechanisms will underpin biotechnology platforms necessary for novel methods of feral animal population control thus contributing at multiple levels to an economically sustainable Australia.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of sy ....Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of synthetic encapsulin-Rubisco carbon-fixing nanoreactors and transform them into leaf chloroplasts to test their impact on plant photosynthesis and growth. Our genetically simpler solution will aid ongoing global efforts to deliver overdue step change improvements in agricultural productivity.Read moreRead less
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.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.
Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu ho ....Detecting stress-induced changes to subcellular copper pools in brain cells. Copper (Cu) plays essential roles in the functioning of brain cells, but the regulation and activity of this metal is poorly understood. This project aims to map sub-cellular Cu pools in brain cells, with particular emphasis on the effects of cellular stresses on these pools. These studies are expected to contribute important new methods for the study of Cu biology, and could provide valuable information about how Cu homeostasis is maintained or perturbed under various stresses. In the future, this work is expected to form the basis of studies of brain Cu pools in neurodegenerative diseases.Read moreRead less
Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. L ....Parasite virulence: the role of activation and suppression of P2X7 receptors. Toxoplasmosis and leishmaniasis pose a threat to the health and well-being of the Australian human and animal populations. Around 6-8 million Australians are infected with Toxoplasma, a parasite that can cause severe problems in immunosuppressed individuals and birth defects and miscarriage in pregnant women with a primary infection. Toxoplasmosis is also the main cause of abortion and stillbirth in Australian sheep. Leishmaniasis, recently found in Australia, is a risk for overseas travellers, livestock and wildlife. This research will provide an understanding of what makes these parasites successful, paving the way for development of novel drugs to combat these chronic diseases.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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Role of Musashi in the regulation of cell cycle proteins. We have identified a protein family that directs cell fate and maintains male fertility. This project will provide new avenues for generation of contraceptives in male animals and to regulate stem cells for production of specialised cell types in biotechnological applications.
How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is funda ....How ribosomal protein loss affects cell fate. This project aims to challenge the dogma that the ribosome behaves only as a ‘‘house-keeper’’. Ribosomal protein (RP) mutations should, and often do, result in reduced cell growth and stunted animal development. Depletion of RPs in Drosophila blood cells impair stem cells and cause massive tissue overgrowth. This suggests RPs are involved in cell fate determination, which this project will research using genetic models. As ribosomal function is fundamental to the development of all living organisms, this work could have wide implications for understanding all biology – from microbes, insects and plants to humans.Read moreRead less