Development Of BRET Detection Systems: Tools For Functional Proteomics And Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
The internal structure of articular cartilage is critical to its biomechanical function. Cartilage is one of the most intricate and difficult tissues to examine in-vivo. Maintenance of its functional characteristics depends heavily of the internal microstructure of the tissue, while conventional arthroscopy can only give a view of the surface and provides no information on the internal structure. Biopsy examination can also destroy the integrity of the tissue, making it impossible to concurrentl ....The internal structure of articular cartilage is critical to its biomechanical function. Cartilage is one of the most intricate and difficult tissues to examine in-vivo. Maintenance of its functional characteristics depends heavily of the internal microstructure of the tissue, while conventional arthroscopy can only give a view of the surface and provides no information on the internal structure. Biopsy examination can also destroy the integrity of the tissue, making it impossible to concurrently examine the structure and function of the tissue. The structure-function relationship is thus critical to the study and the advancement of clinical treatment techniques for cartilage disorders. Osteoarthritis is characterized by severe disruption to the cartilage matrix. The emergence of autologous chondrocyte implant (ACI) therapy as a method for repairing cartilage defects has further increased interest in clinical techniques for the examination of cartilage structure and function. The development of confocal microscopy facilitates internal examination of loaded tissue for the first time, enabling direct examination of the association between structure and function of the tissue. A prototype confocal arthroscope has been developed to facilitate clinical examination of cartilage structure. This, in turn, allows the functional characteristics of the tissue to be deduced. Cartilage exhibits little intrinsic repair making biopsies undesirable. Thus, with respect to cartilage in particular, the developed technologies promise to enable examination to a level of detail which was previously impossible. The current prototype arthroscope has demonstrated the feasibility of a genuine clinical instrument. This grant application seeks funds to conduct initial clinical trials in order to gain sufficient practical feedback to enable design and construction of a clinically ready system.Read moreRead less
Development Of Resonance Energy Transfer Technologies To Detect GPCR Heterodimer Complexes In Living Cells
Funder
National Health and Medical Research Council
Funding Amount
$205,555.00
Summary
G-protein coupled receptors are proteins at the surface of most cells in the body. They bind to drugs, transmitting signals into cells that change what cells are doing. Recent research indicates that different types of these proteins can interact with each other and when one of these protein combinations binds a drug, it acts differently to when the proteins act separately. The aim of our project is to find out which protein combinations exist and to find drugs that bind to them specifically.
Understanding Selective Drug Signaling At G Protein-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$362,206.00
Summary
The maintenance of optimum health and function living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific reciever protein at the cell surface called receptor. In one class of such receptors called G protein-coupled recept ....The maintenance of optimum health and function living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific reciever protein at the cell surface called receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works, and in particular to know how they work in living cells. This project utilizes state-of-the-art methodologies to examine interactions between receptors and their cognate G proteins, in living cells and in real-time. The work will answer fundamental questions about the nature of G protein-coupled receptor signaling, in particular whether new classes of drugs can be identified that more selectively activate signaling pathways or factors that attenuate signaling. This work has potential for future development of more effective therapeutic agents.Read moreRead less
Molecular Mechanisms Underlying G Protein Coupled Receptor Signaling
Funder
National Health and Medical Research Council
Funding Amount
$596,956.00
Summary
The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled r ....The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works, and in particular to know how they work in living cells. This project utilizes state-of-the-art methodologies to examine interactions between receptors and their cognate G proteins, in living cells and in real-time. The work will answer fundamental questions about the nature of G protein-coupled receptor signaling and will aid in the future development of more effective therapeutic agents.Read moreRead less
On the mechanism of boiling instability in microchannels. This project will enable designers to create highly efficient miniaturised devices based on the boiling of fluids such as water or organics. These devices include micro-power generation systems, coolers for computer chips and solar collectors, and micro-chemical process systems. Such devices provide environmental, safety and economic benefits.
High Energy Density - High Delivery Rate Thermal Energy Storage. This project aims to address the intermittency of renewable energy sources using novel thermal storage media. Advanced heat transfer modelling and in situ neutron diffraction and imaging are intended to be used to optimise the microstructure of newly developed miscibility gap thermal storage systems. The new media store energy as the latent heat of fusion of one phase in a stable, high thermal conductivity inverted microstructure. ....High Energy Density - High Delivery Rate Thermal Energy Storage. This project aims to address the intermittency of renewable energy sources using novel thermal storage media. Advanced heat transfer modelling and in situ neutron diffraction and imaging are intended to be used to optimise the microstructure of newly developed miscibility gap thermal storage systems. The new media store energy as the latent heat of fusion of one phase in a stable, high thermal conductivity inverted microstructure. The high energy density of the latent heat (0.5-4.5 Mega Joules/Litre) requires storage volumes as little as five per cent of those relying upon heat capacity and the metal matrix has a hundred-fold greater thermal conductivity than current systems. It is proposed that a range of such materials will be engineered for concentrated solar thermal and space heating applications.Read moreRead less