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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
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.
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
Anticancer drug development: Enhancing the anticancer activity of mitoxantrone. Many cancer sufferers may benefit from this work if we are able to develop more active derivatives of mitoxantrone, or develop procedures to inhibit the repair of DNA lesions induced by mitoxantrone. This may result in therapies with improved response, reduced drug dosage and/or reduced side-effects. Because this work may result in one or more patents, and possibly commercialisation with Australian (and overseas) pha ....Anticancer drug development: Enhancing the anticancer activity of mitoxantrone. Many cancer sufferers may benefit from this work if we are able to develop more active derivatives of mitoxantrone, or develop procedures to inhibit the repair of DNA lesions induced by mitoxantrone. This may result in therapies with improved response, reduced drug dosage and/or reduced side-effects. Because this work may result in one or more patents, and possibly commercialisation with Australian (and overseas) pharmaceutical companies, there are potential commercial benefits to Australia. The "discovery" aspect of this work may also identify other cellular responses to mitoxantrone (ie specific genes which are re-expressed) and this may also reveal new targets to further enhance the activity of this drug.Read moreRead less
Molecular basis for the synergistic potentiation of anthracycline anticancer agents by formaldehyde-releasing prodrugs. AIMS: The overall aim is to develop a full understanding of the molecular basis for the synergistic activation of Adriamycin (and other anthracycline anticancer agents) by formaldehyde-releasing prodrugs such as AN-9.
SIGNIFICANCE: Because Adriamycin is currently one of the most widely used anticancer agents, and this activity has the potential to be dramatically enhanced by t ....Molecular basis for the synergistic potentiation of anthracycline anticancer agents by formaldehyde-releasing prodrugs. AIMS: The overall aim is to develop a full understanding of the molecular basis for the synergistic activation of Adriamycin (and other anthracycline anticancer agents) by formaldehyde-releasing prodrugs such as AN-9.
SIGNIFICANCE: Because Adriamycin is currently one of the most widely used anticancer agents, and this activity has the potential to be dramatically enhanced by the concurrent use of formaldehyde-releasing prodrugs, a biochemical understanding of these processes will provide the basis to exploit this synergy to provide improved treatment outcomes (eg, lower drug doses,reduced side-effects, improved activity against drug-resistanct tumours etc).
EXPECTED OUTCOMES: The long-term outcome of this project is commercialisation to develop products for clinical use based on this synergy (eg, drug/prodrug combinations) and ultimately the development of tumour-directed therapy to yield a tumour-localised anticancer response.Read moreRead less
The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understoo ....The design of targetable epigenetic modifiers. The project aims to engineer enzymes as valuable tools for understanding gene expression mechanisms and potentially a technology for altering gene expression in plants, animals or humans in a targetable manner. The genetic information encoded in the DNA of all complex organisms has been shown to be augmented by decorations on both DNA and the histone proteins that package DNA. This so-called epigenetic information is important but not well understood. The project plans to design highly specific and targetable enzymes that can interrogate and manipulate epigenetic information in living cells. Understanding the regulation of gene expression and controlling the expression of chosen genes may form a foundation for applications in agriculture, biology and medicine.Read moreRead less