Structural Analysis Of Poxvirus Immature Particles And Spheroids
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Despite the eradication of smallpox by vaccination, poxviruses remain a threat to public health because of bioterrorist scares from kept variola stocks and because of the possible emergence of other poxvirus pathogens from the extensive animal reservoir. The structural analysis of the assembly of poxvirus will not only improve our knowledge of fundamental processes, highly conserved in DNA viruses, but could also provide valuable targets for the rational design of antiviral drugs.
Novel Actions Of Leptin In Implantation And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of f ....The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of fetal growth. In human pregnancy, the placenta becomes an additional major source of leptin, and this is secreted into the mother and the fetus. Recent work in animal models also indicates that the process of implantation, whereby the embryo embeds itself in the lining of the uterus and establishes a placenta, cannot proceed in the absence of leptin. But how leptin exerts these critical effects on the implantation process and placental function is not known. In this study we will explore several potential actions of leptin in the uterus and placenta, and examine whether the leptin signaling system is aberrant in cases where the fetus does not grow normally. Of particular interest is the possible interaction of leptin with another group of important signaling molecules called the peroxisome proliferator-activated receptors, or PPARs. One of these, PPAR-gamma, plays an indispensable role in the establishment of the placenta, particularly in relation to the formation of blood vessels, a process that is also a target for leptin action. Several lines of evidence, most notably in fat cells, suggest that both PPAR-gamma and leptin regulate common aspects of cell function. Such interactions provide us with important clues as to how leptin and the PPARs could work together to promote the optimal establishment, growth and function of the placenta, and these will be explored in this project.Read moreRead less
Peroxisome Proliferator Activated Receptor Gamma Is A Novel Therapeutic Target For Inflammation And Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$307,436.00
Summary
Asthma affects over 2 million Australians with 300 deaths each year. Current drugs are not always effective. A new approach is to reduce the thickening and stiffening of the airway muscle found in asthma. Rosiglitazone, an antidiabetic drug in current use, inhibits growth of airway muscle in the test tube and chest tightening in a mouse model of asthma. Cells from asthmatics will be used to confirm these positive findings, and to support rapid clinical evaluation of this drug to benefit patients ....Asthma affects over 2 million Australians with 300 deaths each year. Current drugs are not always effective. A new approach is to reduce the thickening and stiffening of the airway muscle found in asthma. Rosiglitazone, an antidiabetic drug in current use, inhibits growth of airway muscle in the test tube and chest tightening in a mouse model of asthma. Cells from asthmatics will be used to confirm these positive findings, and to support rapid clinical evaluation of this drug to benefit patients.Read moreRead less
Molecular Analysis Of The Peroxisome Biogenesis Disorders
Funder
National Health and Medical Research Council
Funding Amount
$185,135.00
Summary
A group of human disorders arise from abnormal metabolic function of peroxisomes, small organelles found in the cells of most tissues. These abnormalities are caused by defects in the processes by which peroxisomes are formed in cells, and now known to be due to mutations in peroxisome biogenesis, or PEX, genes. In this project we will identify and assess PEX gene mutations in Australasian patients with these disorders to assist with future clinical diagnosis. In addition, because the mechanisms ....A group of human disorders arise from abnormal metabolic function of peroxisomes, small organelles found in the cells of most tissues. These abnormalities are caused by defects in the processes by which peroxisomes are formed in cells, and now known to be due to mutations in peroxisome biogenesis, or PEX, genes. In this project we will identify and assess PEX gene mutations in Australasian patients with these disorders to assist with future clinical diagnosis. In addition, because the mechanisms of disease formation, or pathogenesis, are poorly understood, we will develop animal models of the PBDs that may provide more detailed information about these corresponding processes in humans.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100121
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Three-dimensional super-resolution nanophotonic fabrication facility. This stimulated emission depletion microscopy nanophotonic fabrication facility will be the first nanophotonic fabrication facility that is able to achieve optical resolution far beyond the diffraction limit, which will facilitate breakthroughs in cutting-edge nanotechnology research areas.
Assembly Of Mitochondrial Respiratory Chain Complexes And Their Defects Associated With Disease.
Funder
National Health and Medical Research Council
Funding Amount
$413,431.00
Summary
Mitochondrial “respiratory chain complexes are multi-subunit assemblies that function to produce most of our cellular energy. Defects in the assembly of these complexes can result in mitochondrial disease, including infant death. The assembly of the respiratory complexes is a complicated procedure and the mechanisms involved in disease remain elusive. This work will aid in our understanding of how these protein complexes are built and how defects in their assembly can cause disease.
Understanding The Role Of The Scaffolding Protein D13 In Poxvirus Assembly And Its Inhibition By Rifampicin
Funder
National Health and Medical Research Council
Funding Amount
$371,275.00
Summary
Smallpox is one the most notorious diseases in human history. Despite its eradication in the 1970s, human cases of animal poxviruses such as monkeypox virus and the potential use of smallpox as a bioterrorism weapon have called for an improved preparedness of Australia against (re)-emerging poxviruses. This project combines structural biology approaches to understand the complex assembly of poxviruses and provide the basis for the development of broad-spectrum antiviral drugs.