Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 ....Control of transcription by the cardiac homeodomain protein Nkx2-5. The transcriptional regulatory protein Nkx2-5, a member of the homeodomain superfamily, is essential for heart development and mutations in the human gene cause congenital heart disease. We seek to define the molecular mechanisms that regulate the transcriptional activity of Nkx2-5. We have previously identified a transcriptional activation domain in the C-terminal region that is bipartite in nature and conserved among Nkx2-5 proteins from diverse species. We will characterise the consequences of mutations in this domain in mouse models and search for interacting proteins. Results will advance our understanding of gene regulation in the context of heart disease.Read moreRead less
Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation tec ....Functional Genomics and Host Cell Specificity of Herpesviruses. Herpesviruses cause severe diseases in many species, but research on their large DNA genomes has been difficult due to the need to use animal cell cultures for the generation of virus mutants. The cloning of complete herpesvirus genomes as Bacterial Artificial Chromosomes (BACs) has revolutionized herpesvirus genomics, and it is now possible to examine herpesvirus gene functions in unprecedented detail using elegant new mutation techniques. The project, based on two related equine herpesviruses, will identify new targets for antiviral drugs or vaccines. These herpesvirus BAC systems represent frontier science that greatly facilitates the study of links between genome and phenome.Read moreRead less
Development Of A New High Throughput Screen For Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$351,320.00
Summary
Inadvertent drug block of hERG, a potassium channel in the heart, can cause cardiac arrhythmias and sudden cardiac death. Screening for hERG toxicity has become a major hurdle for development of new drugs. We will use a mutant hERG protein that has enhanced drug binding to develop a high throughput test for hERG toxicity. Identification of dangerous drugs early in the drug discovery process will save the pharmaceutical industry millions of dollars in the costs of brining new drugs to market.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Centre Of Research Excellence In Medicines Intelligence
Funder
National Health and Medical Research Council
Funding Amount
$2,500,000.00
Summary
The NHMRC Centre of Research Excellence in Medicines Intelligence is a co-ordinated research program that will accelerate the development and translation of evidence on prescribed medicines use and outcomes for regulators and payers. The CRE is perfectly placed to embrace the national ‘call to action’ from the Health Minister's recent announcement to establish Quality Use of Medicine Safety as a National Health Priority.
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882512
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefit ....Advanced high throughput functional genomics and gene mapping. Infrastructure requested will expand the capacity of researchers in NSW to undertake experiments using state-of-the-art technologies based on the recent advances in genomic and proteomic analysis. It will ensure the retention of leading researchers in the exciting areas of functional genomics and systems biology as contribute to biomolecular research in medicine, agriculture and environmental biology, thereby providing major benefits to the wider community. The application aims to enhance existing genomic technologies by adding platforms that will increase the scope of experiments that can be performed as well as providing automation and increased capacity to handle the increasing demand for these techniquesRead moreRead less