Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this prop ....Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this proposal we aim to define a complex between two transcriptional regulators (HOP and SRF) involved in cardiac development and to begin to define other interactions that make up a transcriptional network essential for development of a normal heart.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989078
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Unique, state-of-the-art lipidomics infrastructure. The new technologies provided through this grant will significantly enhance our understanding of lipids and their role in normal cell biology and disease. These new insights will be vital in improving our understanding of lipid-related disorders such obesity, type 2 diabetes and cardiovascular disease and helping to improve their treatment and prevention.
Long Chain Omega-3 Polyunsaturated Fatty Acids and Heart Health in Humans. The primary aims of the project is to assess the effect of DHA rich tuna oil on cholesterol carrying lipoproteins and to determine a quicker method in assessing someone's omega-3 status. The expected outcomes include the determination of: 1) the most appropriate blood sample and a rapid test and for evaluating the omega-3 status; 2) the minimum dose of tuna oil required which will not only improve a person's omega-3 statu ....Long Chain Omega-3 Polyunsaturated Fatty Acids and Heart Health in Humans. The primary aims of the project is to assess the effect of DHA rich tuna oil on cholesterol carrying lipoproteins and to determine a quicker method in assessing someone's omega-3 status. The expected outcomes include the determination of: 1) the most appropriate blood sample and a rapid test and for evaluating the omega-3 status; 2) the minimum dose of tuna oil required which will not only improve a person's omega-3 status but also improve their plasma lipid profile and hence reduce their overall risk for cardiovascular disease (CVD); and 3) the use of the Omega-3 Index by medical practitioners. The significance is the increased knowledge of the health benefits of DHA rich tuna oil and that a new CVD risk marker will be generally accepted.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.
Activation of Tissue Factor by a Disulphide-Bond Switch. This project will define the molecular mechanism of activation of tissue factor, the initiator of blood coagulation, and design and test novel antibody therapeutics that block this activation. The applicant suggests that tissue factor is activated by a disulphide-bond switch. Should this hypothesis prove correct it would be the first example of activation of a mammalian protein by this means and, moreover, would be very amenable to therape ....Activation of Tissue Factor by a Disulphide-Bond Switch. This project will define the molecular mechanism of activation of tissue factor, the initiator of blood coagulation, and design and test novel antibody therapeutics that block this activation. The applicant suggests that tissue factor is activated by a disulphide-bond switch. Should this hypothesis prove correct it would be the first example of activation of a mammalian protein by this means and, moreover, would be very amenable to therapeutic intervention because activation occurs on the membrane surface inside blood vessels. Tissue factor activation and thrombus formation is the precipitating event in acute myocardial infarction, unstable angina and ischemic stroke, which are responsible for the majority of deaths in Australia.Read moreRead less
Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's diseas ....Defining the Regulatory Pool of Cholesterol in the Mammalian Cell. Heart disease remains the greatest killer of Australians and Alzheimer's disease represents a growing burden in our aging population. The information gained in this project will be invaluable in advancing our understanding of how cholesterol levels are controlled within the cell and will provide the groundwork for further research that can help to identify novel targets for new drugs to fight heart disease and Alzheimer's disease.Read moreRead less
The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between ....The ApoE Interactome in Human Plasma. In this, the post-genome era, the emphasis has switched from the delineation of genome structure to the tremendous task of characterizing the gene products. One of the important aspects evolving in this new era is the design of strategies that enable identification of global protein-protein interactions, defined by the Human Proteome Organisation as the interactome. This, the apoE interactome in human plasma project, will identify novel interactions between plasma proteins and apoE, which is a lipid-binding protein genetically linked to age-related diseases affecting more than 500,000 Australians. This project will therefore provide scope for novel treatments and early detection of disease, namely cardiovascular and Alzheimer's disease.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
Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve f ....Cellular response to pro-oxidative myoglobin. The heart is vulnerable to oxidative damage as specialised muscle cells termed myocytes are unable to regenerate. Oxidative damage to myocytes decreases cell viability and in turn heart muscle function. Pro-oxidative forms of the protein myoglobin are present in the heart and may play a role in damaging myocytes. This study will determine whether a series of novel synthetic antioxidants inhibit myoglobin-mediated damage to heart muscle and preserve function. This may lead to new therapies to combat cardiovascular disease and enable ageing Australians to maintain productive and independent lifestyles.Read moreRead less
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. Read moreRead less