Apoptosis And Stem/Progenitor Cells In The Development And Treatment Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$21,809,604.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks. The first is excessive cell survival. To combat this, we are developing drugs with commercial partners that directly activate the cell's death machinery. The second hallmark is inexorable proliferation, akin to that of stem cells, which can generate entire tissues, as we showed for the breast. ‘Rogue’ stem-like cells may initiate certain cancers. We hope to advance cancer therapy by identifying such cells and drugs that kill them.
Osteosarcoma is the most common tumour of bone. Recent success in targeting immune checkpoint blockers such as Programmed death-1 (PD-1) in genomically complex tumours suggests that osteosarcomas may be amenable to such strategies. We will characterise the role of the PD-1 pathway in osteosarcoma development and growth. Using preclinical mouse models we will investigate the biology of the PD-1 pathway and study its potential as a therapeutic target in advanced and resectable osteosarcoma.
Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
Enhancing Peripheral Clearance Of Beta Amyloid As A Treatment For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$548,681.00
Summary
Amyloid-beta (abeta) accumulation in the brain is a key step in the development of Alzheimer's disease, with potential therapies focusing on its clearance. Compounds that bind abeta in blood have been shown to alter brain abeta levels. We will assess the efficacy of a novel abeta-binding peptide to promote peripheral clearance of brain-derived abeta in a mouse model of AD. Such a drug would be effective in sporadic AD, where the efflux transport, clearance and degradation systems are defective.
Discovery Early Career Researcher Award - Grant ID: DE240100449
Funder
Australian Research Council
Funding Amount
$426,600.00
Summary
Diversity Oriented Clicking - Streamlined Synthesis of Molecular Frameworks. Innovation in synthetic chemistry drives the discovery of new life-changing drugs, agrochemicals and functional materials. This project aims to use a novel chemical concept, termed Diversity Oriented Clicking, for new sustainable and streamlined synthetic transformations. The new chemical processes are expected to deliver improved economy, efficiency and precision in the synthesis of bioactive molecules and functional m ....Diversity Oriented Clicking - Streamlined Synthesis of Molecular Frameworks. Innovation in synthetic chemistry drives the discovery of new life-changing drugs, agrochemicals and functional materials. This project aims to use a novel chemical concept, termed Diversity Oriented Clicking, for new sustainable and streamlined synthetic transformations. The new chemical processes are expected to deliver improved economy, efficiency and precision in the synthesis of bioactive molecules and functional materials that are inaccessible or challenging to prepare with existing technologies. The conceptual and practical outcomes of this project are expected to benefit both academia and industry as the synthetic routes to diverse complex molecules can be greatly streamlined, and reducing chemical waste and required purification.Read moreRead less
Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other pote ....Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other potentially valuable compounds. In addition to providing unprecedented insight into the ecology and biosynthesis of this enigmatic toxin, the data generated will enable improved management of seafood safety and provide a foundation for the future development of novel neuroactive compounds.Read moreRead less
Mid-Career Industry Fellowships - Grant ID: IM230100154
Funder
Australian Research Council
Funding Amount
$1,049,904.00
Summary
Fungi Power: Designer Fungal Cell Factories for Advanced Biomanufacturing. This project aims to build an advanced biomanufacturing platform based on filamentous fungi in collaboration with industry. Using synthetic biology, the project expects to engineer superior fungal host strains customisable to the needs of the industry and to address their technological gaps. The expected outcomes include the development of cost-efficient and sustainable fungal-based bioprocesses for the companies to produ ....Fungi Power: Designer Fungal Cell Factories for Advanced Biomanufacturing. This project aims to build an advanced biomanufacturing platform based on filamentous fungi in collaboration with industry. Using synthetic biology, the project expects to engineer superior fungal host strains customisable to the needs of the industry and to address their technological gaps. The expected outcomes include the development of cost-efficient and sustainable fungal-based bioprocesses for the companies to produce products, such as fine chemicals, pharmaceutical actives and food ingredients. The project would provide significant benefits by enabling existing and emerging companies' commercial successes and competitiveness in global markets, creating new jobs and resulting in the growth of the bio-economy in Australia.Read moreRead less
Towards the sustainable discovery and development of new antibiotics. This project aims to define how to access silent biosynthetic genes within microbial genome to facilitate access to new chemical diversity hidden within microbial genomes. Using interdisciplinary approaches in genome mining and metabolomics technologies, the project expects to inspire and enable the future design of more effective antibiotics. Expected outcomes from this program include define new microbial defence molecules, ....Towards the sustainable discovery and development of new antibiotics. This project aims to define how to access silent biosynthetic genes within microbial genome to facilitate access to new chemical diversity hidden within microbial genomes. Using interdisciplinary approaches in genome mining and metabolomics technologies, the project expects to inspire and enable the future design of more effective antibiotics. Expected outcomes from this program include define new microbial defence molecules, to meet future demands in agrochemical and environmental sciences. It will also train future scientists and develop international collaborations. This should provide significant benefit, including a higher-quality workforce for research and innovation, positioning Australia at the forefront of drug discovery. Read moreRead less