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
Molecular mechanisms of stem cell self-renewal. Muscle growth and regeneration is critically dependent on its stem cell compartment. We have discovered that the p38 MAPK pathway is essential for stem cell self-renewal in the C2C12 myogenic cell line. This proposal seeks to understand the molecular basis of stem cell self-renewal in skeletal muscles, data that may be applicable to many stem cell systems, and to the enormous promise of stem cell therapies for injury and diseases of the aged. We wi ....Molecular mechanisms of stem cell self-renewal. Muscle growth and regeneration is critically dependent on its stem cell compartment. We have discovered that the p38 MAPK pathway is essential for stem cell self-renewal in the C2C12 myogenic cell line. This proposal seeks to understand the molecular basis of stem cell self-renewal in skeletal muscles, data that may be applicable to many stem cell systems, and to the enormous promise of stem cell therapies for injury and diseases of the aged. We will attempt to alter the balance of stem cell production by enforced p38 expression, and take microarray and proteomics approaches to define stem cell pathways.Read moreRead less
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less
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
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.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
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