Discovery Early Career Researcher Award - Grant ID: DE120101242
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Regulation of germ cell number and quality by Fizzy-related protein. Females have a limited supply of eggs in their ovaries and it appears that the Fizzy-related gene (FZR1) is important in making sure this full complement is gained. By using novel mouse knockouts of the FZR1 gene, the project will determine how this protein functions at the earliest stages of egg development.
Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and ....Reverse chemical proteomics: harnessing yeast display for drug discovery. This project aims to develop a technique that can rapidly identify the cellular protein targets of biologically active natural products. This project expects to provide fundamental biological and chemical insights into Australia's unique biodiversity that will facilitate the development of new therapeutic agents and agrochemicals based on leads provided by Nature. Expected outcomes of this project include an optimised and validated platform technology for accelerating drug discovery and development. This should substantially reduce the costs associated with fighting human and animal diseases, leading to improved health, productivity and quality of life.Read moreRead less
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will ....Molecular mechanisms determining the lipid composition of synapses. Synapses between neurons play a key role in all functions of the nervous system including learning and memory. They are mostly composed of the unique combination of proteins and lipids, which function together to enable neurotransmission. While the molecular mechanisms determining the protein composition of synapses are well characterised, the mechanisms defining the lipid composition of synapses remain unknown. The project will use advanced techniques of neuroscience and lipid research to determine the mechanisms of lipid transport and retention at synapses. The project is expected to generate new knowledge about the fundamental mechanisms of brain function, which will be useful for developing new therapeutics enhancing the brain power.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
Understanding the chemical components that influence the flavour and quality of milk under different pasture management systems. The project will preserve and substantially increase the penetration of Australian milk into the Asian import market for dairy products, which stands at $2.1 billion annually, and is expected to grow at 6.6%per annum over the next 5 years. This outcome can potentially counteract the decline in dairy farm numbers in northern NSW, attract new suppliers to the region, an ....Understanding the chemical components that influence the flavour and quality of milk under different pasture management systems. The project will preserve and substantially increase the penetration of Australian milk into the Asian import market for dairy products, which stands at $2.1 billion annually, and is expected to grow at 6.6%per annum over the next 5 years. This outcome can potentially counteract the decline in dairy farm numbers in northern NSW, attract new suppliers to the region, and stimulate rural community growth and prosperity.Read moreRead less
How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less
The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increa ....The role of the transcription factor Runx2 during mammary gland development and lactation. This proposal will further our understanding of mammary gland development and lactation and the mechanisms controlling mammary cell fate decisions such as differentiation. Regulation of cell fate lies at the core of most aspects of cell biology from normal development to dysfunction such as cancer. The knowledge gleamed from this project also has the potential to make economic gains for Australia by increasing the profitability and ensuring the sustainability of both the dairy and meat industries. Better understanding of the mechanisms controlling mammary epithelial cell differentiation should enable augmentation of lactation such as increasing milk protein content, using marker assisted selection (of targets such as Runx2) in cattle.Read moreRead less
Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve f ....Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve function. This may lead to new therapies to combat cardiovascular disease and enable ageing Australians to maintain productive and independent lifestyles.Read moreRead less
Elucidation of the signalling pathways during fertilization in mammals. This grant sets out to understand how the union of the sperm and egg at fertilization generates a viable embryo: this is a fundamental event in biology. We aim to understand the basic signalling pathways from the sperm which allow the egg to become an embryo and are known to influence embryo quality. They are therefore important in our understanding of what constitutes a healthy early start to life. Australia also has econom ....Elucidation of the signalling pathways during fertilization in mammals. This grant sets out to understand how the union of the sperm and egg at fertilization generates a viable embryo: this is a fundamental event in biology. We aim to understand the basic signalling pathways from the sperm which allow the egg to become an embryo and are known to influence embryo quality. They are therefore important in our understanding of what constitutes a healthy early start to life. Australia also has economic interests in understanding the reproductive process in aiding breeding programs for commercially important livestock and endangered species and contraception programs for pest populations. Read moreRead less