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.
Cell-specific Regulation Of The MicroRNA/RNAi Pathway
Funder
National Health and Medical Research Council
Funding Amount
$659,390.00
Summary
MicroRNAs are a group of molecules that are critical for controlling the activity of genes. They function in a diverse range of biological systems, such the brain and immune system. Although we know that these molecules are important, how they are made in cells is still poorly understood. Because these molecules have potential therapeutic applications, it is essential that we gain a precise understanding of their biology before we will be able to apply these to medicine.
Intrinsic Hearing Protection Mechanisms: A Pathway To Prevention Of Noise-induced Hearing Loss
Funder
National Health and Medical Research Council
Funding Amount
$625,900.00
Summary
Noise-induced hearing loss (NIHL) is a significant contributor to the total burden of disease. We recently determined that when the ear is exposed to sustained noise, the cochlea is protected from damage by activation of a specific (P2X2) receptor, evident as reversible hearing adaptation. This study will determine the downstream signalling from this receptor. This will support assessment of vulnerability to NIHL and contribute to development of hearing therapeutics.
Mechanisms Of Antibiotic-induced Persistent Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$632,048.00
Summary
Golden staph still causes significant human infections and resistance to antibiotics is an ever growing problem with this bacteria. This project will determine how resistance to some antibiotics is also changing the bacteria to promote persistent, difficult to treat infections. The insights from this study will help understand evolution of this bacteria, and help design new strategies for management.
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.
Colorectal Cancer Membrane Protein Interactomics [A Major Discriminator Of Clinical Outcome]
Funder
National Health and Medical Research Council
Funding Amount
$643,778.00
Summary
This project studies the molecular causes of colorectal cancer (CRC) malignancy because CRC is the 2nd most common malignancy by incidence and cause of death in the Western world. It currently results in 13.1% of Australian cancer deaths. The aim of this NHMRC project is to gain a detailed understanding of how particular cell membrane proteins interact with each to give cancer cells the ability to invade and spread.
Defining Ubiquitin Ligase Substrates: New Therapeutic Strategies In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Current cancer therapies use drugs that target both tumor cells and rapidly growing normal cells – causing side effects and limiting effectiveness. Newer treatments aim to target molecules that are unique to tumor cells, leaving normal cells unharmed. This project will study a process that tags proteins for destruction by a cellular recycling system, which is often disrupted in cancer. This research will not only help us understand how cancer develops, but also identify new targets for therapy.
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
Understanding The Molecular Basis Of Epididymal Maturation: How Does The Epididymis Modify Spermatozoa, Allowing Them To Recognise The Egg ?
Funder
National Health and Medical Research Council
Funding Amount
$585,898.00
Summary
Male infertility is a significant clinical problem affecting one in twenty Australian men. A common feature of this condition is the sperm’s inability to recognize the egg. Sperm gain this property as they transit an organ known as the epididymis. We have produced genetically modified mice with a specific epididymal defect that prevents sperm-egg recognition. This study will examine the structure of these defective sperm to generate new insights into the molecular basis of sperm-egg interaction.