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Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less
Roles of the kynurenine pathway in physiological and pathological brain function. This project will aim to study the metabolism of the essential amino acid tryptophan in the brain and its involvement in diseases including multiple sclerosis and brain tumours.
Unraveling the role of N-acetyl-aspartate in normal brain function and disease. The purpose of this project is to define the role of the predominating brain chemical N-acetyl-aspartate for normal nerve cell function and as toxic agent causing neurological illness and severe mental health problems. Findings of this research will enhance the design of novel therapies involving pharmacological and genetic treatment.
A novel family of amino acid transporters in Apicomplexan parasites. Apicomplexan parasites are single celled organisms that are the causative agents of major diseases in livestock and humans. However, the basic biochemistry of these intracellular parasites is poorly understood, and there are limited treatments available for the diseases these parasites cause. The project hypothesis is that a novel family of proteins that are unique to apicomplexan parasites play a key role in the uptake of esse ....A novel family of amino acid transporters in Apicomplexan parasites. Apicomplexan parasites are single celled organisms that are the causative agents of major diseases in livestock and humans. However, the basic biochemistry of these intracellular parasites is poorly understood, and there are limited treatments available for the diseases these parasites cause. The project hypothesis is that a novel family of proteins that are unique to apicomplexan parasites play a key role in the uptake of essential nutrients (amino acids) into these organisms. This project aims to use a combination of genetic, biochemical and physiological methods to understand the function of these proteins, the role(s) that they play in apicomplexan biology, and their importance for parasite survival.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Defining the cellular impacts of protein aggregation in neurodegenerative disease with an aggreomics platform. The brain disease Huntington’s is caused by abnormally shaped proteins that assemble into toxic clusters. This project will design new bioprobes to track how these clusters form and cause damage to cells. This strategy will also provide new opportunities for discovering novel therapeutic targets.
Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Austra ....Improvement of anthracycline chemotherapy by enhancement of apoptotic responses and tumour targeted activation. Improved outcomes for anthracycline anticancer chemotherapy is of clear benefit to the nation. Tumour-localised treatment is expected to lead to improved responses, reduced side-effects and improved quality of life while rational selection of drug combinations is expected to enable treatment of tumours that were previously resistant to anthracyclines. With an aging population in Australia the incidence of cancer is predicted to rise dramatically - improved treatment outcomes and better use of chemotherapeutics will be of obvious national benefit. The development of new tumour-targeted agents is the subject of joint Intellectual Property between Australia and the USA, offering potential economic benefit. Read moreRead less
Tumour localisation and enhancement of anthracycline anticancer activity. The anthracyclines are one of the most widely used anticancer agents today. If the cytotoxicity of these agents can be localised to tumour cells, or their activity improved, then this will result in improved response rates, less side-effects and an improved quality of life for many patients for whom anthracycline treatment is an important part of their therapy. This will result in enormous national/community benefit to an ....Tumour localisation and enhancement of anthracycline anticancer activity. The anthracyclines are one of the most widely used anticancer agents today. If the cytotoxicity of these agents can be localised to tumour cells, or their activity improved, then this will result in improved response rates, less side-effects and an improved quality of life for many patients for whom anthracycline treatment is an important part of their therapy. This will result in enormous national/community benefit to an aging Australian population that is becoming increasingly more prone to cancer. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100985
Funder
Australian Research Council
Funding Amount
$409,574.00
Summary
Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes wit ....Targeted genome editing using engineered CRISPR-Cas endonucleases. This project aims to study the generation of targeted and cell-specific endonucleases. CRISPR-Cas endonucleases have revolutionised the field of genome engineering due to programming simplicity based on a short guide RNA and high cleavage efficiency. This project will combine the use of two technologies in genome engineering and antibody therapeutics to generate new antibody-targeted endonucleases that modify cellular genomes with high efficacy and specificity. This project will provide new and intriguing insights into cellar function, with broad applications in basic research and biotechnology.Read moreRead less