Phosphoinositide 3-kinase Signalling And Skeletal Muscle Mass.
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerat ....Maintenance of skeletal muscle mass is essential for human health and locomotion. In ageing and cancer, loss of muscle mass leads to severe weakness and immobilization causing morbidity and mortality. This grant aims to characterise a novel gene that when deleted in mice leads to significant muscle damage. The molecular pathways within the cell that lead to the observed muscle damage will be investigated and this may provide insights into the pathways that control muscle damage and its regenerationRead moreRead less
Elucidating Crosstalk Between RhoGTPases And Polarity Proteins: The Interface Between Morphology, Immune Function And Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$627,549.00
Summary
Major breakthroughs in cancer and autoimmunity require understanding the molecular basis of by which cell behaviour is controlled. We now know the key molecular players, but still need to determine how they interact within the cell to develop the best treatments and diagnostics. Recent breakthroughs now enable us to “watch” molecular interactions within the cell. We will use these approaches to determine how a key molecular switch is regulated in immune cells and cancer cells.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.
Ciliopathies are an emerging group of syndromes in society that have devastating health effects. Ciliopathy patients exhibit a specturm of disorders including polycystic kidneys, extra digits, retinal degeneration and neural tube defects. INPP5E is a gene that is mutated in patients with a ciliopathy syndrome. These studies will determine the role of INPP5E in ciliopathy disease and may identify INPP5E as a novel treatment target.
The Regulation Of Pleiotropic Responses By Bidentate Motifs Embedded In The Fibroblast Growth Factor Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,336.00
Summary
Cells in our bodies are able to accomplish an impressive array of functions. Diffusible factors (called growth factors) are important in regulating diverse cellular functions. We have identified a new molecular switch inside cells that acts as a master controller of cellular functions. This molecular switch relays information to instruct specific cellular functions. We have shown that these molecular switches are short-circuited in breast cancer promoting cell growth and survival.
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
Molecular Regulation Of The Serine-Threonine Kinase ULK1 In Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Autophagy or self eating is a basic cellular process and can have either beneficial or adverse effects in cancer. It is essential to determine the status of autophagy in patients before considering drugs that block autophagy for therapy. A protein called ULK1 is needed for autophagy and may emerge as a pathological marker for autophagy in cancer as well as a potential drug target. This grant proposal will study ULK1 regulation and will lay the scientific foundation for its medical application.
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