Specialised immune cells, called cytotoxic T cells, circulate through the body, and kill infected cells to protect us from disease. We discovered that a protein, DOCK8, is important for the regulation of T cell function. Importantly, humans with mutations in the DOCK8 gene suffer from a debilitating, and potentially lethal, immunodeficiency disease. This project will therefore elucidate the role of DOCK8 in immune cells, to better understand the consequences of DOCK8 deficiency for immunity.
Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value ....Tendon injury is one of the most common health problems worldwide and affects almost everyone at some point in particular the aging populaiton. However, the current treatments are not well defined. We identifed an extracellular molecules SPARC that potentially plays an important role in tendon function. The aim of this study is to examine the role of SPARC in tendon development, homestasis and degenerative using transgenic mice and gene therapy. We predict that SPARC will have therapeutic value for the treatment of tendinopathy.Read moreRead less
Modelling TRPV4 Skeletal Disorders Using Human IPSCs
Funder
National Health and Medical Research Council
Funding Amount
$1,171,187.00
Summary
Inherited skeletal disorders are a significant disease burden. Many gene mutations have been defined but we only have limited understanding about how they cause the disease. We will use patient skin cells and new in vitro re-programing technology to induce them to form cartilage cells to produce “disease in a dish” models of human skeletal disorders. These models will allow us to answer questions about how specific mutations cause disease and identify potential therapies
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
Modulating Cellular Copper Levels To Prevent The Effects Of Excitotoxicity In Neurodegenerative Diseases
Funder
National Health and Medical Research Council
Funding Amount
$434,652.00
Summary
Exitotoxicity has been implicated in many neurological disorders incluing Alzheimer's and Huntington's disesaes. This toxicity can be inhibited by modulated intracellular copper levels. Here we will ascertain the therapeutic potential of strategies designed to increase cellular copper levels.
The Microenvironmental Niche In Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
It is well accepted that the cells in the local environment of cancers can help to promote the growth and spread of tumour cells. We have shown that a cell type known as the pericyte previously thought to be involved in controlling tumour expansion by affecting new blood vessel formation, may directly influence tumour growth, a notion that will be tested in human skin and ovarian cancer models. We will also test if pericyte markers can predict those cancer patients at greater risk of relapse.
Regulation And Function Of The Zinc-finger Protein ASCIZ In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$640,101.00
Summary
Each human cell is exposed to more than 10,000 spontaneous DNA damage events per day. Inaccurate repair of this is damage is believed to be one of the key events in the onset of cancer. We have discovered a protein called ASCIZ that contributes to the repair of DNA base damage, and also has a separate function in the onset of lung development. Here we want to study in detail the mechanism of how it functions in DNA repair and thereby keeps mutation rates low and prevents the onset of cancer.
Defective Cell Migration As A Mechanism Of Dysregulated Asthmatic Airway Repair
Funder
National Health and Medical Research Council
Funding Amount
$616,712.00
Summary
Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specificall ....Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specifically through their ability to migrate.Read moreRead less
Bridging The Gap Between Cartilage Biology And Osteoarthritis Risk Prediction
Funder
National Health and Medical Research Council
Funding Amount
$512,256.00
Summary
Osteoarthritis is a painful and debilitating cartilage disease affecting just under 1 in 10 Australians and costs the Australian economy roughly $12 billion per year. This project will develop computational models of cartilage with the ability to incorporate genetic and environmental risk factors into a predictive model of cartilage disease.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.