Insulin triggers glucose uptake into fat and muscle tissue, a process that is defective in type 2 diabetes. Insulin does this by triggering a complex cascade of actions once it binds to muscle and fat cells. We will analyse the function of a crucial protein within this cascade. This protein is mutated in humans with severe insulin resistance and our proposed project will dissect how this protein works potentially providing a novel drug target to treat diabetes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput pro ....The role of phosphoinositides in endosomal maturation dynamics. This project aims to investigate the regulation of an intracellular compartment within a cell called endosomes, which plays critical roles in cellular homeostasis, signalling and pathogen entry. New knowledge is expected to be generated in understanding endosome maturation and the signalling events that drive this process using a unique, multidisciplinary approach combining state of the art imaging techniques and high throughput protein analysis. The anticipated outcomes will be to define the molecular steps that govern the membrane-bound machinery on endosomes that directs endosomal maturation. This should provide significant benefits in delineating a process that is linked to almost all aspects of cell life.Read moreRead less
New targets for antiviral therapies. The ability of dangerous viruses to cause lethal disease depends on their capacity to evade the immune system of infected hosts. This project will uncover at the molecular level the strategies used by viruses to disable immune responses; this will identify new ways to treat incurable diseases, by disabling the virus' defences against the immune system.
Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specif ....Phosphoinositide regulation of lysosome reformation during autophagy. This project aims to investigate a new critical step in the autophagy pathway, autophagic lysosome reformation, a fundamental, evolutionarily conserved mechanism for cellular homeostasis. By combining gene function studies with advanced cellular imaging techniques, this project will investigate the dynamic membrane changes that drive this lysosome recycling pathway and how it is regulated by a hierarchical succession of specific enzymes. The expected outcome will be to re-define the archetypical autophagy pathway and characterise novel mechanisms by which it is controlled. This project will reveal new fundamental biological processes, and act as a framework for developing new imaging modalities and tools for studying autophagy.Read moreRead less
Interrogating a novel protein scaffold that coordinates signal transduction and molecular motor function. The inside of a cell is an extremely crowded environment and the precise location of each component is carefully controlled. This project will unravel the protein machinery involved in transporting cargos in cells as they divide and identify new protein targets for the development of next generation anti-cancer drugs.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100046
Funder
Australian Research Council
Funding Amount
$289,381.00
Summary
A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolut ....A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolution. The benefit of this technology is that it will enable scientists in Australia to image, for the first time, the biophysical mechanism by which a protein navigates intracellular architecture to regulate a complex biological function at the single molecule level.Read moreRead less
Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment ....Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment (the cell nucleus).Read moreRead less
Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for i ....Protein Kinase Regulatory Switches: Decision-Making in the Nucleus. This project plans to examine new regulatory mechanisms for an important signalling enzyme in the cell nucleus. It aims to define how this enzyme enters the nucleus, to characterise new modifications that affect its actions, and to establish how a conserved nuclear protein may provide an unexpected regulatory platform to send nucleus-initiated signals back to the cell cytoplasm. This reverse signalling is a novel mechanism for integrating nuclear actions that has the potential to create a signal transduction circuit triggered by environmental or genetic factors. This information is crucial in defining the molecular logic of signalling events that may be ultimately targeted to control cell growth, differentiation and survival.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100037
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
A cellular nano-imaging facility: Probing cellular complexity. Answering the major medical and biotechnology questions of the 21st century will be heavily reliant on the use of advanced imaging techniques. This facility will establish a new and revolutionary microscope which is capable of producing images of living cells in action at high magnification and with the greatest clarity.