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.
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.
SULT4A1 is not a sulfotransferase, but a sulfotransferase inhibitor. It forms high affinity heterodimers with other sulfotransferases via a conserved dimerisation site in its carboxyl terminus attenuating catalytic activity. Consequently, it is important for the metabolism of numerous important molecules including estrogens, thyroid hormones, neurotransmitters and many therapeutic agents.
Dynamics And Mechanisms Of Immune Complex-mediated Skin Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,467.00
Summary
Type III hypersensitivity underlies a number of common autoimmune diseases, including rheumatoid arthritis and lupus erythematosus. These diseases are caused by the deposition of immune complexes (IC) and the accumulation of neutrophils within small blood vessels. We will use real time imaging to dissect in space and time the recruitment of neutrophils and IC deposition during type III hypersensitivity reactions in order to better understand the pathogenesis of these conditions.
Location, Location, Location: Sub-cellular Specific Targeting Of JNK As A Novel Therapy In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$633,755.00
Summary
The ‘triple negative’ breast cancer subtype is the most aggressive form of breast cancer, and unlike other subtypes, there are no drugs to specifically this subtype. While many potential drug targets have been identified, they cannot be utilised clinically because of other beneficial roles within the body. We are now deploying our innovative experimental platforms to specifically target the tumour promoting functions of a protein known as ‘JNK’, whilst retaining its beneficial functions.
Diabolic Regulation Of Macrophage Cell Death Pathways By Legionella
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
The bacterial pathogen Legionella causes fatal pneumonia in immuno-compromised humans. Infections depend on a sophisticated secretion machinery that translocates hundreds of proteins into host cells. These proteins subvert several essential defense pathways, including cell death signals. This project will highlight how Legionella interfere with cell death pathways and control the survival of its host cells. These findings will facilitate the development of promising new anti-bacterial agents.
Amyloid Precursor Protein Signalosome: Directing Abeta Production In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$681,459.00
Summary
Alzheimer's disease is the most common form of dementia and is the fourth biggest killer in developed countries. Amyloid precursor protein plays a central role in the development of the disease, through the generation of a toxic peptide called Abeta. In this project we will decipher the fine molecular details of what the protein looks like and how various molecules known to bind to it affect Abeta production. This knowledge is expected to lead to novel therapies to treat the disease.