Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will ....A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will be information on the mechanics of curdlan production that will complement that emerging from our molecular biological and biochemical studies. These will have implications for understanding bacterial polysaccharide production in general and may have a commercial outcome in enhanced curdlan production.Read moreRead less
Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of ....Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of pollen is a novel type of gene that encodes a small RNA molecule but no protein. Knowledge gained by studying the self-incompatibility genes will help us to understand how plant cells recognise each other, and may allow us to manipulate seed (and hence crop) production.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347970
Funder
Australian Research Council
Funding Amount
$186,000.00
Summary
Integrated Bio-nano-fabrication Facility. The project proposes the upgrade of a joint facility for the probing, fabrication and operation of hybrid bio-nano-devices. The facility will enhance the proposers' capabilities in the area of the fundamental and prototype-type research on biomolecular/cellular devices. The ultimate goal of these projects is to thrust Australian science in the era when the essential functions of cells can be replicated and controlled on devices that are smaller than livi ....Integrated Bio-nano-fabrication Facility. The project proposes the upgrade of a joint facility for the probing, fabrication and operation of hybrid bio-nano-devices. The facility will enhance the proposers' capabilities in the area of the fundamental and prototype-type research on biomolecular/cellular devices. The ultimate goal of these projects is to thrust Australian science in the era when the essential functions of cells can be replicated and controlled on devices that are smaller than living cells. The proposed facility has a modular structure consisting of additional nano-positioning, confocal microscope and zeta potential modules built on the existent laser tweezers/scissors, picoliter pipette and Atomic Force Microscope modules.Read moreRead less
Injectable scaffolds for treatments of neurological disorders. Cell replacement therapies offer potentially effective treatments for a host of neurological disorders but a major obstacle confronting their development is to ensure appropriate connections are formed within the brain. This proposal aims to utilize injectable biodegradable polymers, to demonstrate the feasibility of assisting neural cells and stem cells to bridge glial scars or significant distances in the brain and repair damaged n ....Injectable scaffolds for treatments of neurological disorders. Cell replacement therapies offer potentially effective treatments for a host of neurological disorders but a major obstacle confronting their development is to ensure appropriate connections are formed within the brain. This proposal aims to utilize injectable biodegradable polymers, to demonstrate the feasibility of assisting neural cells and stem cells to bridge glial scars or significant distances in the brain and repair damaged neural pathways. This proposal will focus on naturally occurring polysaccharides, which will act as "scaffolds" for the growing neurones. The role the scaffolds play in regulating neurite extension will be investigated in vitro and in vivo.Read moreRead less
Manipulating nano-fibres to control nerve regeneration. Diseases of the brain and mind are the most common diseases in the western world; being even more prevalent than cardiac or malignant disease. With Australia's aging demographic, diseases of the brain and mind will continue to impact on our productivity in the workplace, our quality of life, and the ability of the medicare and private health care systems to keep up with the ever-increasing demand for older Australians.
The research prop ....Manipulating nano-fibres to control nerve regeneration. Diseases of the brain and mind are the most common diseases in the western world; being even more prevalent than cardiac or malignant disease. With Australia's aging demographic, diseases of the brain and mind will continue to impact on our productivity in the workplace, our quality of life, and the ability of the medicare and private health care systems to keep up with the ever-increasing demand for older Australians.
The research proposed here will enable us to find solutions to this serious problem by building on Australia's strong track record in nanotechnology and biotechnology research, and help towards new and effective treatments.
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The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases ....The regulation of signalling molecules in Saccharomyces Cerevisiae by inositol polyphosphate 5-phosphatases. Phosphoinositide signalling molecules regulate the actin cytoskeleton, secretion, vesicular trafficking and cell growth and death. We have identified, cloned and characterised a family of signal terminating enzymes called inositol polyphosphate 5-phosphatases (5-phosphatases) that regulate phosphoinositide signalling molecules. We have cloned and characterised four distinct 5-phosphatases in the yeast Saccharomyces Cerevisiae and demonstrated by both deletion and overexpression studies that these enzymes regulate the actin cytoskeleton, endocytosis and secretion. This research proposal aims to investigate the signalling complexes the 5-phosphatases form with specific actin binding and or regulatory proteins, investigate the complex interactions of phosphoinositide lipid phosphatases and the roles they play in regulating secretion from the endoplasmic reticulum and finally characterize a novel 5-phosphatase that we have recently identified. Collectively the outcome of these studies will provide novel information about the functionallly significant signalling pathways regulated by this important enzyme family.Read moreRead less