Lipid Trafficking At Membrane Contact Sites: The Role Of Oxysterol-Binding Protein-Related Protein 5 And 8 (ORP5 And ORP8)
Funder
National Health and Medical Research Council
Funding Amount
$466,400.00
Summary
Abnormal subcellular lipid distribution is associated with a number of common diseases including cancer, cardiovascular disease, and Alzheimer’s disease. The overall aim of this proposal is to identify and characterize new molecules that regulate the transport of lipids between different cell membranes. Results from the proposed studies will help developing novel therapeutic agents against common human diseases.
The cell is the building block of life. This proposal focusses on the surface of the cell, the plasma membrane, and specialised structures called caveolae that are an abundant feature of animal cells. Altered caveolae are a feature of many human disease conditions. In this proposal we will address the function of caveolae. We will test the idea that proteins are released from caveolae into the cell when cells are stressed forming a novel signalling pathway disrupted in disease.
Function And Molecular Mechanism Of Histidine-rich Glycoprotein In Necrotic Cell And Pathogen Clearance
Funder
National Health and Medical Research Council
Funding Amount
$525,957.00
Summary
This research proposal is to investigate the molecular mechanism and function of a blood serum protein, histidine-rich glycoprotein (HRG), in protecting against tissue injury caused by inflammation and infection. HRG has been implicated in controlling important aspects of tissue injury by aiding removal of dead cells and pathogens. Understanding the role of HRG in these disease settings may allow the development of approaches for the treatment of inflammatory, autoimmune and infectious disease.
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
VITAL: Vaccine Immunomodulation Throughout The Aging Lifespan
Funder
National Health and Medical Research Council
Funding Amount
$795,117.00
Summary
The elderly respond less well to vaccines than their younger counterparts. Flu is particularly dangerous to the elderly. In this proposal we will determine the likely immune mechanism undelying this difference, as well as specifically address the urgent issue of whether prior injection with a whooping cough vaccine makes Flu vaccines less likely to be effective.
Microenvironmental Regulation Of Blood Cells By Retinoic Acid Receptor Gamma.
Funder
National Health and Medical Research Council
Funding Amount
$958,428.00
Summary
Vitamin A deficiency causes profound effects in humans, with anaemia and an inability to fight infection being consequences of vitamin A deficiency on blood cells. We have evidence that these effects of vitamin A deficiency occur via one of the receptors for vitamin A. Furthermore, these effects are due to changes in the non-blood cells that help to make blood cells. By understanding how this occurs we may identify better treatments for patients with impaired immune systems.
Regulation Of The Signalling Efficiency Of The T Cell Antigen Receptor
Funder
National Health and Medical Research Council
Funding Amount
$456,557.00
Summary
An immune response starts with activation of the T cell antigen receptor (TCR). How T cell receptor signalling begins, however, is not well understood. We have developed a novel imaging approach that allows us to directly observe what happens after an antigen binds to the receptor. The research will provide mechanistic insights into how T cells sense and discriminate antigens. This knowledge will aid the development of cancer immunotherapies and vaccines.
Delineating The Mechanism Of Amyloid Beta Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$565,242.00
Summary
Alzheimer’s disease and beta amyloid toxicity: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by progressive memory loss, confusion, and cognitive deficits. In 2011, an estimated 269,000 Australians are currently living with dementia and without a significant medical breakthrough soon, it is anticipated that this will rise to about 981,000 by 2050
The Impact Of Obesity On Immunological Tolerance Of The Fetus
Funder
National Health and Medical Research Council
Funding Amount
$378,366.00
Summary
Obesity increases the risk of miscarriage during pregnancy. The reasons for this are not known, although it is thought that abnormal levels of hormones and metabolic parameters are a contributing factor. We hypothesise that the immune system plays a role. In this project we will determine if obesity upsets the fine-tuning of the immune system that is crucial for successful pregnancy. Understanding the reason behind adverse pregnancy outcome will allow appropriate management of maternal obesity.
The Role Of EphrinB1 Reverse Signalling In Osteogenic Differentiation During Skeletal Development And Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$567,292.00
Summary
The present proposal will identify the importance of ephrinB1 during the deregulation of bone remodelling that occurs in osteoporosis, by deleting ephrinB1 in committed osteoblast precursor cells in a mouse model of osteoporosis. Knowledge gained from this proposal could potentially translate into alternative therapeutic treatment strategies for patients with osteoporosis with the use of Eph/ephrin targeted drugs currently being developed for cancer treatment.