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.
Host Metabolism And Responses Contributing To Flavivirus Replication And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$592,772.00
Summary
We aim to determine how viruses affect the cells they infect, In particular how they can alter the metabolism and balance of lipids in cells and how this impacts the bodies capability to respond immunologically. We believe that by understanding these basic principles we can target ares fr antiviral therapeutic potential.
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.
Molecular Mechanisms Underlying Induction Of Haematopoietic Stem Cells In The Embryo
Funder
National Health and Medical Research Council
Funding Amount
$577,573.00
Summary
Hematopoiesis, the processes of making blood cells, represents one of the best-defined paradigms for studying stem cell biology, but our understanding of how theses cells form in the embryo is incomplete.Our preliminary studies have revealed the existence of a novel "buddy cell" that directly regulates the induction of blood stem cells. This grant seeks to further these observations, and its general aim is to identify the molecular signals that the buddy cell uses to make blood stem cells
Role Of Hepatic Stellate Cell And Liver Progenitor Cell Interactions In The Regulation Of Wound Healing And Liver Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
The liver has a remarkable capacity for regeneration following acute and chronic liver injury, however, the mechanisms which facilitate this wound healing are not understood. This project will examine the interactions between different liver cell populations, including hepatic stellate cells (liver fibroblasts) and liver progenitor cells (stem cells of the liver) and will determine which factors regulate inflammation, liver scarring and restitution of liver mass following chronic liver injury.
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.
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.
Applying Quantitative Immunology To The Analysis Of Complex Genetic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$864,596.00
Summary
The immune response of each individual varies. For some, the response invoked by foreign challenge is weak, leading to a lifetime of difficulty with infection. For others, the response is stronger, yielding excellent immunity, but opening the potential for overactive responses to self-material and autoimmune disease. We have a new theory for how the health of our immune system can be measured and we aim to apply it to understand the genesis of the many different forms of human immune diseases.
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.