We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
Dynamic Trafficking Of Amino Acid Transporters At Synapses And Their Role In Regulating Neurotransmission
Funder
National Health and Medical Research Council
Funding Amount
$421,219.00
Summary
Brain cells release chemical neurotransmitters to activate their neighbours. The most abundant neurotransmitter is glutamate, which mediates most of the communication in the brain. Following release, this neurotransmitter must be rapidly recycled to prevent levels being depleted and neurotransmission failing. The subject of this grant is to understand what molecules and pathways are used to recycle glutamate in the brain, and how its supply is controlled to sustain continual brain activation.
Thermo-electro-chemo-mechanical properties of biological systems. The proposal is aimed at developing a new theoretical framework for piezoelectric biological materials and structures, through theoretical analysis, computation and numerical simulations, as well as experimental investigations, to produce high-reliability, high-performance hydrogel components and smart soft tissue structures. It is envisaged that successful outcomes of this program will give the Australian biological industry a te ....Thermo-electro-chemo-mechanical properties of biological systems. The proposal is aimed at developing a new theoretical framework for piezoelectric biological materials and structures, through theoretical analysis, computation and numerical simulations, as well as experimental investigations, to produce high-reliability, high-performance hydrogel components and smart soft tissue structures. It is envisaged that successful outcomes of this program will give the Australian biological industry a technology edge over their competitors and provide easy-to-use guidelines for the design of smart biological systems.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Structures and properties of tissue engineering matrices for cartilage and bone: Imaging, visualising and modelling tissue/scaffold constructs in 3D. Tissue engineering of bone and cartilage has the potential to lower costs and improve outcomes. The first stage requires the design of porous 3D scaffolds. To date they have been found less than ideal for clinical applications. Our ability to design and optimise scaffolds has been ad hoc, as local structure and properties have not been measurable ....Structures and properties of tissue engineering matrices for cartilage and bone: Imaging, visualising and modelling tissue/scaffold constructs in 3D. Tissue engineering of bone and cartilage has the potential to lower costs and improve outcomes. The first stage requires the design of porous 3D scaffolds. To date they have been found less than ideal for clinical applications. Our ability to design and optimise scaffolds has been ad hoc, as local structure and properties have not been measurable during tissue growth and repair. In this proposal, an interdisciplinary group from three universities will utilise microCT imaging, visualisation and numerical modelling to determine these structures and properties. This will provide an invaluable understanding for the further development of tissue engineering scaffolds.Read moreRead less
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucida ....Ross River virus - identification of virulence determinants in clinical isolates from across Australia. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. The project has several national benefits. It will elucidate whether there is any association between RRV strain and the severity of human disease. It will also identify viral markers that could assist public health officials in determining likely disease outcomes of outbreaks and could provide new avenues for the design of antiviral strategies.Read moreRead less
Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is ....Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is an association between RRV strain and the severity of disease and if there are human factors that affect the seriousness of symptoms. Knowledge of both of these could provide new avenues for the design of prevention and treatment strategies.Read moreRead less
Development and characterization of a technology platform to study the mechanisms of scaffold/Bone Morphogenic Proteins (BMP) augmented large segmental bone healing. This project will increase understanding of bone engineering and in doing so will lead to superior treatments for bone defects. Such a treatment would be valuable in addressing the ever-increasing problems of diminished productivity and reduced quality of life associated with bone disorders as the population ages. The multidisciplin ....Development and characterization of a technology platform to study the mechanisms of scaffold/Bone Morphogenic Proteins (BMP) augmented large segmental bone healing. This project will increase understanding of bone engineering and in doing so will lead to superior treatments for bone defects. Such a treatment would be valuable in addressing the ever-increasing problems of diminished productivity and reduced quality of life associated with bone disorders as the population ages. The multidisciplinary and international team will be valuable in establishing Australia's prominence in this field and training the next generation of young scientists and engineers. The technologies developed will be of great interest to a large number of research groups and companies worldwide and will assist with fostering international collaboration and placing Australia at the forefront of this emerging field.Read moreRead less