Discovery Early Career Researcher Award - Grant ID: DE120101550
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Understanding multidrug resistance: identifying the molecular basis of substrate and inhibitor transport by P-glycoprotein. Chemotherapy resistance causes 90 per cent of cancer deaths and is commonly triggered by the increased activity of P-glycoprotein, which controls the cellular clearance of drugs. This project will determine how P-glycoprotein recognises and transports drugs, essential knowledge for the design of anticancer agents that can stop chemotherapy resistance.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100043
Funder
Australian Research Council
Funding Amount
$389,000.00
Summary
Rapid Molecular (Bio)material Imaging by Infrared and Raman Microscopies. This project aims to undertake fast probe-free biochemical/chemical imaging of heterogeneity within cells and materials surfaces with new infrared and Raman imaging. It will generate new fundamental knowledge on: cell heterogeneity and dynamic processes; technologies for optimising cell printing; understanding toxicity of microplastics; and protocols for measuring materials of technological relevance. Expected outcomes inc ....Rapid Molecular (Bio)material Imaging by Infrared and Raman Microscopies. This project aims to undertake fast probe-free biochemical/chemical imaging of heterogeneity within cells and materials surfaces with new infrared and Raman imaging. It will generate new fundamental knowledge on: cell heterogeneity and dynamic processes; technologies for optimising cell printing; understanding toxicity of microplastics; and protocols for measuring materials of technological relevance. Expected outcomes include: interdisciplinary collaborations in new protocols for in-vitro drug development; cell printing technologies; environmental impacts of microplastics; and materials design. Expected benefits include innovative approaches to early stage drug design; improved environmental controls and advances in innovative materials.Read moreRead less
Caged lanthanides for use in photo-dynamic therapy and near infra-red imaging. The early detection and effective treatment of cancer are two critical factors which determine survivability. This project will provide improved drugs for photo-dynamic therapy and develop emissive probes for near infra-red imaging to allow better discrimination between healthy and diseased tissue and improve subsequent treatment.
Micro-dissection of clathrins role in mitosis via chemical biology probes. This project aims to contribute to understanding the molecular mechanisms of the role of a key protein, clathrin, in cell division. In doing so it expects to reveal new approaches to stop uncontrolled cell division and proliferation, the hallmarks of cancer. The outcomes could in the long term inform breakthroughs in cancer treatment, significant enhancements in life quality and a reduction in cancer death rates.
Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as l ....Novel platinum(IV) complexes that are targeted to and trapped by tumours and tumour cells. Platinum complexes continue to be a mainstay in the treatment of solid tumours and their combination with molecularly targeted agents selected for the type of tumour and the mutations identified is expected to lead to continued growth in their use. However, their toxicity remains a major impediment to their use and effectiveness and therefore, this project aims to develop less toxic analogues that are as least as effective as current drugs. This project will combine recent developments in stabilisation and cellular trapping of platinum(IV) pro-drugs with a range of strategies designed to limit activation of these pro-drugs to the tumour environment.Read moreRead less
Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechani ....Molecular mechanisms for copper trafficking across membranes. Copper is a trace metal that is essential for all forms of life, however it is toxic in excess. Tightly controlled protein-based metalloregulatory systems are responsible for copper uptake and homeostasis in all cells. Components of these systems are integral membrane transport proteins, which include the Ctr proteins that are solely responsible for copper uptake into eukaryotic cells. This project aims to define the molecular mechanisms by which the Ctr proteins transport copper across eukaryotic cell membranes, by solving their three-dimensional structures by X-ray crystallography.Read moreRead less
Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected ....Biologically inert probes to unravel nutrient directed cellular processing . In this project we will develop novel compounds that can act as probes of the pathways present in cells for the uptake of nutrients and other essential molecules and show how to generate new agents for identifying and targeting specific populations of cells. The project will generate new tools for understanding biological processes including cell transport and processing. The insights gained from this work are expected to help guide the development of new agents for selectively delivering imaging and biologically active agents to cells.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC200100052
Funder
Australian Research Council
Funding Amount
$4,789,838.00
Summary
ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide signifi ....ARC Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery. This Centre aims to train industry-ready, world class graduates in cryo-electron microscopy of membrane proteins. The Centre’s graduates and research results would enable tomorrow’s industrial expansion in structure-enhanced drug design. Expected outcomes are world-first structural biology knowledge and techniques, and the entrepreneurial and technical skills desired by industry. This should provide significant benefits including advancing Australian biotechnological capacity and improved linkages with major pharmaceutical partners. It should also provide a substantive competitive advantage to nascent Australian biotechnology companies that also links into new National investment into drug discovery and development infrastructure.Read moreRead less
Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit ....Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit it for our own benefit is needed. This project aims to anticipate evolution by simulating it in the laboratory, allowing for the best preparation for change. New pesticides will be designed to combat insecticide resistance based upon the molecular structure of an insect CBE. This project aims to exploit these newly evolved enzymes to create biosensors and decontamination agents.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100293
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a l ....Cracking the phosphoinositide code. This project seeks to determine how protein interactions with membrane lipids regulate recruitment to cellular organelles, providing new insight into the complex pathways of cellular homeostasis. Controlling the distribution of proteins within cells is critical for cell signalling and membrane trafficking. This is orchestrated by the interaction of specific protein modules with lipids on the surface of different organelles. The phox homology (PX) domain is a lipid-binding module found in numerous proteins essential for normal cell trafficking and homeostasis, and perturbed in many conditions including immune dysfunction and cancer. This project plans to investigate molecular determinants of PX-lipid association, generating knowledge about protein-membrane interactions required for cellular function. These insights may underpin future drug design.Read moreRead less