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
Use Of Snake Venom Prothrombin Activators In Blood Collection Tubes To Produce High Quality Serum To Improve Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$284,706.00
Summary
The timely availability of high quality serum and plasma samples are of the utmost importance for accurate biochemical analysis in a clinical setting. This requirement is particularly true for patients on anti-clotting therapeutic agents such as warfarin and heparin. In this study we will employ potent prothrombin activators purified from snake venom to enhance the clotting efficiency of blood for serum preparation for biochemical analysis.
CHARACTERIZATION AND PURIFICATION OF A NOVEL ANTI-HIV FACTOR
Funder
National Health and Medical Research Council
Funding Amount
$170,810.00
Summary
We have identified biological evidence for a novel anti-HIV factor in a patient who has not progressed to HIV disease in 22 years. We have identified active forms in a solution, which confer potent activity against HIV. This factor helps in creating the pool of specialized antigen presenting cells, which are vital to combating with HIV in vivo. We propose to characterize this factor biologically, proteomically and genomically.
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.
Stage II In The Development Of Eph/ephrin Based Tumor Targeting Reagents: Optimisation Of Drug Efficacy And Delivery
Funder
National Health and Medical Research Council
Funding Amount
$204,125.00
Summary
In the final stage of cancer, including melanoma, tumor cells gain the ability to spread, a process called metastasis. Altered communication between cancer and normal cells is one of the causes of this invasive characteristic. We have started the development of novel agents that target and modulate proteins on the cell surface that control these properties and are found in metastatic tumors. We propose to refine the targeting and killing properties of these agents for early clinical testing.
Control Of Refractive Error Through Ionically Driven Fluid Movements
Funder
National Health and Medical Research Council
Funding Amount
$208,600.00
Summary
Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oede ....Myopia affects about half the world's population with recent studies suggesting epidemic proportions among some Asian schoolchildren though we are not seeing this in Australia. Costs associated with detection, monitoring and optical correction of low and high myopia are huge. High myopes (15% with > 6D) also have a greatly increased risk of blindness between the ages of 30 and 50 years due to secondary disorders associated with impaired fluid balance (retinal and choroidal oedema, macula oedema, retinal detachment and glaucoma). Currently there is no accepted pharmaceutical treatment for myopia though our studies in chick have provided the theoretical rationale and experimental data for a potential therapy and patent. This patent is now at the PCT stage and attests that changes in the abundance of the ions of the subretinal space control fluid movements across the retina to choroid and can be modulated therapeutically by diuretics to control fluid flow and hence axial growth and myopia. This application aims to take our current knowledge about fluid control in myopic chick into a mammalian model prior to preclinical trials in monkey. We anticipate it will take 1 year to establish the feasibility of diuretic control of experimentally induced myopic refractive errors in guinea pigs and the best drug and best the dosage range. These studies will contribute to the scientific understanding and bring the proposed pharmaceutical therapy for myopia in adults and children to a point of full commercialization. We believe that the results found in chick will have significance for early and late-onset myopia in humans as it is highly likely that the same mechanisms of ocular growth regulation operate throughout life.Read moreRead less
Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models ....Chronic infections and cancers are major causes of global disease burden. Harnessing the immune system to combat these diseases has proven difficult and cumbersome to date. We invented a new technology to boost the ability of the immune system to fight chronic infections such as AIDS and Hepatitis C. This involves using someone�s own blood treated with sets of short proteins. We term this therapy Overlapping Peptide Pulsed Autologous CelLs (OPAL). This shows great promise in robust animal models. We now propose to refine this technique in animals in preparation for human clinical trials.Read moreRead less
The DietAdvice Website A New Innovation For Dietitians In Clinical Practice.
Funder
National Health and Medical Research Council
Funding Amount
$140,975.00
Summary
Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food int ....Due to the growing incidence of obesity within Australia, use of computer technology may be a method of targeting these people by increasing access to dietary services. Currently available dietary software in the Australian context only allows analysis of nutrient information. Thus when a dietitian sees a patient they must manually translate food intake to nutrient information, a largely time consuming exercise. DietAdvice is a website that was developed for people to enter in their own food intakes. The food information is sent to a dietitian who develops individualised dietary advice for them. A pilot study of the website has already found it to be feasible in the primary healthcare setting. Tested for 12 months the website was used by 224 patients from GP practices in the Illawarra region of NSW. Approximately 73% of patients were overweight and patients with a high BMI were 1.88 times more likely to use the website in the comfort of their home. Further research about the website however was needed. The research to follow on from the pilot study will aim to refine the DietAdvice website, leading towards its commercialisation for dietitians in clinical practice. The research will be broken into 3 phases. Phase 1 will involve a usability test of the website, assessing the underlying algorithms and testing it with dietitians in private practice. Phase 2 will see volunteers using the website on multiple occasions after being given pre-weighed amounts of food to eat. This will determine how reliable and accurate the information is; and phase 3 will evaluate whether the website is cost effective and if it increases accessibility of health services especially in rural areas. By confirming these attributes there will be a sound basis to commercialise the product.Read moreRead less
Application Of Follistatin To The Resolution Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$330,990.00
Summary
Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing li ....Liver fibrosis or scarring is a consequence of a number of diseases, leading eventually to extensive damage known as cirrhosis. It is a significant health problem both here in Australia and overseas with around 180,000 patients diagnosed each year in the Western world. Cirrhosis arises from many causes, two major groups being patients who contract hepatitis and alcoholics. People with cirrhosis have a much increased risk of liver failure, which requires liver transplantation, or of developing liver cancer, for which current treatments have limited success. We have been studying two proteins, activin and follistatin, both of which are made in the liver. We are interested in activin because it is one of the body's mechanisms to control cell growth, and also seems to stimulate the development of scar tissue. Follistatin is the natural inhibitory substance for activin. It blocks the effects of activin and helps promote cell growth in the liver. We believe that follistatin may also be useful in controlling liver scarring. This process will be studied in animal models of cirrhosis, in the hope that follistatin treatment will reduce the level of liver damage. If successful, this would be important information that would enable us to design treatments applicable to human sufferers of these liver diseases. In another part of the project, we will assess whether activin and follistatin might be useful markers of liver disease. Most patients require a liver biopsy to assess the amount of liver damage, and a simple blood test would be a far easier, less traumatic and cheaper alternative.Read moreRead less