The C-type Lectin, Mincle, Is A Macrophage Receptor For Candida Albicans.
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
The yeast Candida albicans is an important opportunistic infection that causes both mucosal and disseminated disease in patients whose innate or adaptive immune responses are impaired Infection and proliferation results in fungal colonisation of the tissues, and a variable degree of tissue damage. The latter is determined both by the virulence properties of the organism and by the genetic makeup of the host. This large, extracellular pathogen is eradicated from the body predominantly by acavenge ....The yeast Candida albicans is an important opportunistic infection that causes both mucosal and disseminated disease in patients whose innate or adaptive immune responses are impaired Infection and proliferation results in fungal colonisation of the tissues, and a variable degree of tissue damage. The latter is determined both by the virulence properties of the organism and by the genetic makeup of the host. This large, extracellular pathogen is eradicated from the body predominantly by acavenger (phagocytic) cells, which are also important in determining the severity of the associated tissue lesions. A phagocytic cell that is central to both innate and adaptive immune responses is the macrophage, which not only takes up and kills the yeast, but also is capable of of killing and digesting it, and presenting the components to cells of the adaptive immune system. This project is based on the postulate that the outcome and severity of infection is determined, at least in part, by the early functional response of the macrophage to the overall virulence properties of the yeast. The response is initiated by interactions with cell-surface receptors, and this study will show that a novel macrophage receptor, Mincle, is an important part of the innate immune response to fungal infections. We have shown that it is associated with differences in susceptibility to yeast infections in inbred mouse strains; it can discriminate between different isolates of the yeast; and it initiates the inflammatory signalling cascade. Our project will define the specific role of this receptor in fungal infection. The results will be important in understanding the basic biology of host resistance, and will offer new opportunities for therapeutic intervention by selectively blocking or modifying different activation pathways.Read moreRead less
What drives the pain associated with inflammation is unknown as is the relationship between pain and the extent of tissue damage associated with disease, for example, arthritis. Our laboratory has shown that a particular protein is a key mediator of inflammatory pain. The project is to understand how this particular protein promotes pain, including how it sensitzes neurons.
Proatherogenic CD4 NKT Cells And Atherosclerosis: Molecular Mechanisms And Therapeutic Strategies For Suppression
Funder
National Health and Medical Research Council
Funding Amount
$504,348.00
Summary
Immune cells called CD4+ iNKT cells are known to be activated by lipids which initiate development of atherosclerosis, a disorder of blood vessels which is responsible for most heart attacks and strokes. We aim to investigate how these cells contribute to the development of this important blood vessel disoder and examine potential ways of inhibiting their activation to prevent heart attacks and strokes.
Developmental-associated Dysregulation Of Innate Anti-microbial Immunity In Early Life As A Determinant Of Susceptibility To Atopic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Previous NHMRC-sponsored research from the applicants has demonstrated that one of the strongest risk factors for subsequent development of asthma is having chest infections during infancy that are so severe that they trigger symptoms of fever and wheeze. It is not known what predisposes susceptible infants to these severe infections, and this project will attempt to define the mechanisms of susceptibility.
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Athero-thrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$86,570.00
Summary
Vascular disease of the heart, brain and limbs affects many people in Australia and throughout the world. Current treatments assist in slowing the development and progression of established disease, but new developments are required. This project will investigate the role of C-reactive protein in vascular disease and evaluate its potential as a new therapeutic target in the future.
THE ROLE OF THE HEPATOCYTE HEDGEHOG PATHWAY IN PROGRESSIVE LIVER INJURY
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
This research plan investigates the role of a pathway, known as the Hedgehog pathway, in the development of liver disease which can result in end-stage scarring known as cirrhosis and even lead to liver cancer (known as Hepatocellular carcinoma). Hepatocellular carcinoma is the globally the third most common cause of cancer death and our research will help to better understand how liver injury develops and how this then leads to liver cancer.
Discovery And Characterisation Of Novel Tick Evasins As Inhibitors Of Chemokine-mediated Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$654,847.00
Summary
An important aspect of inflammatory diseases is the migration of white blood cells into the affected tissues. This is controlled by a group of proteins called chemokines. Ticks, which live on mammalian hosts, produce proteins called evasins, which interact with host chemokines and thereby prevent inflammatory responses. This project will discover new tick evasins, study their chemokine interactions and investigate their ability to block inflammation in allergic asthma.
Determining The Synergistic Effects Of Complementary Medicines On Pro-inflammatory Cytokines,
Funder
National Health and Medical Research Council
Funding Amount
$290,412.00
Summary
Diseases like influenza, commonly called ‘the flu’, produce symptoms such as fever, headaches, lethargy and lack of appetite. What most people don’t realise is that it is not the influenza virus that produces these symptoms, but the body’s immune response to the influenza virus. This immune response comes about because the influenza virus stimulates cells to produce molecules called cytokines, and cytokines have many effects in the body, including causing fever and a lack of appetite. In severe ....Diseases like influenza, commonly called ‘the flu’, produce symptoms such as fever, headaches, lethargy and lack of appetite. What most people don’t realise is that it is not the influenza virus that produces these symptoms, but the body’s immune response to the influenza virus. This immune response comes about because the influenza virus stimulates cells to produce molecules called cytokines, and cytokines have many effects in the body, including causing fever and a lack of appetite. In severe infections like those caused by the influenza virus responsible for the pandemic of 1918, and during “bird ‘flu” (H5N1) infections, people die because the immune response becomes overwhelming. Cytokines produced during these sorts of responses are actually very harmful, even though in small amounts they help to kill the virus and cure the infection. Researchers working in this field have likened these severe responses to a “cytokine storm”. This project focusses on finding alternative therapies such as those used in Chinese medicine to prevent a cytokine storm happening, so that if an influenza pandemic occurs these treatments could be quickly made available to everyone. Examples are the Chinese herbs Angelica sinensis and Salvia miltiorrhiza. Recent laboratory studies in New York have shown that both of these herbs have potent cytokine effects, decreasing levels of an inflammatory cytokine known to be associated with death in both malaria and sepsis. Our study aims to closely examine the effects of these Chinese herbs, as well as other commercially available herbal extracts, and traditional combinations of herbs, to find synergies between them that could be used to treat severe influenza infections.Read moreRead less