Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardi ....Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardiac pathways for a better understanding of heart formation and disease, and to develop advanced techniques that will contribute to strengthen Australian basic and strategic research.Read moreRead less
YrdC translational control: physical and functional interactions, identification and influence of amino acid phosphorylation. This project will expand our basic understanding of the mechanisms with which a newly identified and highly conserved protein, YrdC203 regulates the process of protein synthesis from mRNA. This work will lead to basic insights into how gene expression is regulated at the level of translation, and generate valuable research tools, such as YrdC203 knockdown tools, peptide m ....YrdC translational control: physical and functional interactions, identification and influence of amino acid phosphorylation. This project will expand our basic understanding of the mechanisms with which a newly identified and highly conserved protein, YrdC203 regulates the process of protein synthesis from mRNA. This work will lead to basic insights into how gene expression is regulated at the level of translation, and generate valuable research tools, such as YrdC203 knockdown tools, peptide mimetics and decoys, phospho-specific and phospho-non specific antibodies. Exploitation of this breakthrough science will open up new avenues for therapeutic intervention in the future, while commercial exploitation of such reagents that recognise or interfere with YrdC203 will generate economic returns to Australia.Read moreRead less
New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-r ....New functions for bioactive flavonoids in plants and mammals. We have discovered natural products with biological activity in plants and mammals. These molecules affect plant shape and development and the process of mammalian blood vessel formation. We seek to understand how these molecules work. More understanding is required before one can begin to utilise these molecules for possible beneficial agriculture or human health outcomes. Plant shape influences such things as yield or more drought-resilient root systems. Importantly, we have discovered specific molecules that either promote or inhibit blood vessel formation. A better understanding of how these molecules work could lead to novel treatments for cancer or cardiovascular disease.Read moreRead less
Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preven ....Examination of the Calcium Signalling Dynamics Linked to Integrin Adhesion Utilising a Novel Micro-imaging System. This study aims at increasing our understanding of the fundamental cell processes that allow cells to adhere to surfaces. The proposed study will lead to a greater understanding of the calcium signalling mechanisms that are fundamental to diverse biological phenomena such as, tissue regeneration and repair, blood clotting, cancer metastasis, and neuronal cell function. From a preventative health perspective, the investigation of platelet calcium signalling will greatly accelerate the development of new pharmaceuticals to tackle acute and chronic cardiovascular diseases, such as stroke, heart attack and artherosclerosis. Read moreRead less
Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these response ....Studies of the pi3-kinase enzyme family using selective inhibitors. The objective of this project is to study the function of the PI3-kinase enzyme family in blood platelets. To do this, inhibitors which block the action of specific family members, will be evaluated for their effects in assays of platelet function. The results will enhance our understanding of the way in which platelets and other cells respond to stimuli, and lead new approaches to designing novel drugs that block these responses.Read moreRead less
Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality ....Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality of life. The proposal has focused on targeting the protective effects of 'good' heart growth by identifying genes elevated in the heart in response to exercise. Targeting genes elevated in the athlete's heart to improve function of the failing heart represents a new strategy for the treatment of heart failure.Read moreRead less
Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australia ....Development and Characterization of Chemokine Receptor Mimics. The proposed research will provide important fundamental insights into the molecular events underlying inflammatory diseases and cancer metastasis. The innovative nature of the research and the significance of the results will enhance Australia's international research standing. Moreover, the insights gained from this work will contribute to the development of therapies that will ultimately enhance the quality of life for Australians.Read moreRead less
A redox sensor and triple receptor function for guanylyl cyclase. Nitric oxide (NO) protects from blood vessel spasms and clot formation. Conversely, insufficient NO occurs in cardiovascular disease. Life-saving drugs like glycerol trinitrate supply more NO to blood vessels, however these drugs are limited in their action when their target protein (NOGC) is decreased or defective, eg. in hypertension or arteriosclerosis. We have elucidated the reason for this defect and simultaneously discovered ....A redox sensor and triple receptor function for guanylyl cyclase. Nitric oxide (NO) protects from blood vessel spasms and clot formation. Conversely, insufficient NO occurs in cardiovascular disease. Life-saving drugs like glycerol trinitrate supply more NO to blood vessels, however these drugs are limited in their action when their target protein (NOGC) is decreased or defective, eg. in hypertension or arteriosclerosis. We have elucidated the reason for this defect and simultaneously discovered an entirely novel group of drugs which activate NOGC without NO. Impressively, these drugs are most effective in diseased blood vessels. The aim is the development of novel blood pressure lowering/anti-anginal drugs with higher effectiveness and less side-effects because they work in an entirely new way.Read moreRead less
Biochemical properties of S-nitroso-myoglobin and its role in regulating nitric oxide bio-availability. Nitric oxide (NO) stimulates blood vessel dilation. Vessel dilation is essential to maintaining blood pressure. Altered NO-regulation leads to vessel dysfunction. Within blood vessels, myoglobin regulates NO concentrations through oxidation and binding reactions. In contrast, S-nitroso-myoglobin represents a novel source of NO in humans. The goal of this study is to expand the knowledge on ....Biochemical properties of S-nitroso-myoglobin and its role in regulating nitric oxide bio-availability. Nitric oxide (NO) stimulates blood vessel dilation. Vessel dilation is essential to maintaining blood pressure. Altered NO-regulation leads to vessel dysfunction. Within blood vessels, myoglobin regulates NO concentrations through oxidation and binding reactions. In contrast, S-nitroso-myoglobin represents a novel source of NO in humans. The goal of this study is to expand the knowledge on NO-regulation by myoglobin through determining S-nitroso-myoglobin's - chemical stability, rates of formation and decay, concentration in human vessels and whether it can cause blood vessel dilation similar to authentic NO. Such novel data represents a major fundamental advance in understanding the role of myoglobin in NO-homeostasis.Read moreRead less
Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carboh ....Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carbohydrate-containing structures. The importance of carbohydrates in the regulation of cellular and protein function is increasingly recognised and forms a foundation for the rapidly expanding discipline of glycobiology. This project will strengthen Australia's glycobiology research capacity.Read moreRead less