New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. ....New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. Therefore many Australians will suffer from the combined impact of the AIDS illness itself, opportunistic infections, the side-effects of treatment and natural aging. We aim to develop new drugs to combat this disease to help people everywhere lead happier, healthier and more productive lives.Read moreRead less
Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential ....Second messenger-activated calcium channels in liver cells. This project concerns second messenger-activated calcium channels, part of the family of hormone-activated calcium channels which are essential to the functions of all animal cells. The aims are to elucidate the properties of a novel "large conductance" Ca2+ channel (using maitotoxin as an artificial activator), an inositol 1,4,5-trisphosphate-activated calcium channel, and the calcium channel formed by the transient receptor potential-1 (TRP-1) protein in hepatocytes. The electrophysiological properties, mechanisms of activation and intracellular trafficking of the channels will be investigated. It is anticipated the results will provide basic information on the physiological functions of second messenger-activated calcium channels. This will benefit the understanding of liver function, hepatotoxicity in animals, animal production and the development of pharmaceuticals in animal husbandary.Read moreRead less
Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechani ....Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechanisms will have a strong impact on many scientific fields from the control of pathogen growth to human blood pressure regulation. This collaboration will establish Australian scientists and as world-leading in the field of NO and redox signalling. This development will also be of substantial benefit for the training of the next generation of Australian students and scientists.Read moreRead less
Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competiti ....Cell biology of gastric acid secretion. This research will result in a better understanding of the membrane structures in cells. In turn, this information could be exploited to manipulate ion transport, uptake, secretion of biological molecules, signal transduction events and the delivery and uptake of drugs in a number of disease situations thus leading to more effective therapies.
Furthermore, this work will utilise and develop state-of-the-art technologies, contributing to national competitiveness in this area. A number of students and postdoctoral fellows will be trained as a consequence of working on this project
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The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic pote ....The development of tyrosine kinase inhibitors for the treatment of inflammation and malignant disease. Through the combination of expertise from the Industry partner and the Hume group this project aims to develop specific inhibitors of the CSF-1 receptor protein tyrosine kinase in order to demonstrate their efficacy as modulators of CSF-1 dependent macrophage and tumour cell function in vitro. The expected outcome will be a lead set of targets which can be further assessed for therapeutic potential in clinical trials.Read moreRead less
Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and ....Structure and Function of the AMP-activated protein kinase. The AMP-activated protein kinase (AMPK) is a member of the metabolic stress sensing protein kinase subfamily that is present in all eukaryotes, including the yeast homologue, snf1p protein kinase essential for adapting to growth without glucose. The AMPK plays an important role in matching metabolism to nutrient supply and energy demand of perhaps all physiological processes. The aim of this project is to understand the structure and function of the AMPK. This work may provide important opportunities for drug design, understanding the impact of metabolism and ageing as well as increasing our knowledge of signalling pathways that control cellular events.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882890
Funder
Australian Research Council
Funding Amount
$130,000.00
Summary
Investigating protein/protein interactions. To establish and maintain a prominent position in scientific research, Australian scientists must have access to state of the art technology. The Bio21 Institute is a multidisciplinary research centre specialising in medical agricultural and environmental science and is ideally suited to house an SPR facility. SPR provides unique functional, kinetic and thermodynamic information on molecular interactions which give rise to both physiological and path ....Investigating protein/protein interactions. To establish and maintain a prominent position in scientific research, Australian scientists must have access to state of the art technology. The Bio21 Institute is a multidisciplinary research centre specialising in medical agricultural and environmental science and is ideally suited to house an SPR facility. SPR provides unique functional, kinetic and thermodynamic information on molecular interactions which give rise to both physiological and pathological outcomes. A detailed knowledge of molecular interactions is fundamental to the understanding of all biological systems. When placed at the Bio21 Institute, the facility will foster the development of diversified collaborations between the applicants and the wider research community.Read moreRead less
The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of ....The control of elongation factor 2 and its role in the regulation of protein synthesis. Protein synthesis is a key process in living cells. The main stage, elongation, is regulated through phosphorylation of elongation factor eEF2 in response to hormones, amino acids and cellular energy status, via changes in the activity of eEF2 kinase. We will study how these conditions control eEF2 kinase by studying its phosphorylation and identifying new kinases that regulate it. We will explore the role of eEF2 in controlling protein synthesis, seek new substrates for eEF2 kinase and initiate work to elucidate the structure of this unusual enzyme. This will enhance, in a range of ways, fundamental understanding of cell physiology.Read moreRead less
Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the ....Biochemical, Genomic and Phenomic Analysis of Gastric Parietal Cells from Wildtype and Mutant Mice. The interface between the cell and its environment is the cell membrane. Signals, nutrients, and ions all have to cross this barrier. In addition, the cells contain many specialized intracellular membranous compartments. We know little about the signals that direct the synthesis of these structures and determine their final composition and shape. This grant will utilize acid secretory cells in the stomach to examine these questions because they contain a very extensive membrane system. We will use a state-of-the-art genetic and cell biological technologies to manipulate and analyse these cells in a whole animal setting.Read moreRead less
Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ....Coordinating energy metabolism to enhance exercise capacity. Diet and exercise contribute to health and ageing productively whereas high caloric diets and sedentary life styles are deleterious. The enzyme AMPK regulates energy metabolism in response to diet and exercise and by studying it we expect to learn why diet and exercise are beneficial at the molecular level. This may allow the development of nutritional, exercise and drug strategies to enhance exercise capacity and well being during ageing as well as suppress age onset diseases that include obesity diabetes cardiovascular disease hypertension and neurodegeneration.Read moreRead less