The Impact Of Influenza A Virus PB1-F2 Protein On Host Immunity And The Potential For Therapeutic Targeting
Funder
National Health and Medical Research Council
Funding Amount
$317,076.00
Summary
The 1918 influenza virus pandemic resulted in 50 million deaths globally and there is potential for new pandemics, such as the predicted H5N1 Bird Flu . Exact causes of such devastating lethality are not fully identified. Newly discovered influenza A virus (IAV) PB1-F2 protein is present in nearly all highly pathogenic IAVs and promotes virus virulence. This study will further examine the way in which PB1-F2 impacts the host, revealing potential therapeutic targets to lessen disease burden.
Enhancement Of Mucosal Immunity And CTL Avidity Against HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$553,070.00
Summary
Production of strong antiviral immunity at the local mucosa (genito-rectal track) is essential for protection against HIV-AIDS. We believe that expression of small hormone-like molecules known as Th2 cytokines IL-4-IL-13 negatively influence the generation of protective immunity against HIV. Thus we aim to counteract these effects by co-expressing proteins known as chemokines together with vaccine antigens to improve the quality of mucosal vaccine immunity.
Characteristics And Mechanisms Of Persistent Asthma After Common Cold Virus Infection
Funder
National Health and Medical Research Council
Funding Amount
$407,750.00
Summary
Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma, and despite a fall in asthma deaths, large number of people continue to have severe attacks requiring hospitalisation. In most cases the deterioration in asthma symptoms is related to a cold or flu like illness. Viruses are the leading cause of these infections and are known to make asthma symptoms worse. We have identified how viruses do this b ....Asthma is a major health problem for the Australian community. Recent studies have shown increasing numbers of people of all ages are developing asthma, and despite a fall in asthma deaths, large number of people continue to have severe attacks requiring hospitalisation. In most cases the deterioration in asthma symptoms is related to a cold or flu like illness. Viruses are the leading cause of these infections and are known to make asthma symptoms worse. We have identified how viruses do this by triggering a type of inflammation in the airways. We have also found that after a severe attack of asthma some people do not recover completely. They appear to have persistent problems, and in some cases the virus can still be isolated from the airways. How and why this occurs is not known. We are seeking to understand this problem and describe how it affects people with asthma. We plan to investigate what effect certain viruses have on the lungs of people with asthma by measuring cells and chemicals that are present in sputum. We will use recently developed technologies to accurately see what viruses are infecting these people, and how the immune system is working. This study will shed important light on potential causes of unstable asthma and the role that viral infection plays in this. It may also lead to new opportunities to develop treatments that are more effective in preventing and controlling asthma.Read moreRead less
Investigations Into The Mechanism Of Vaccine- Induced Protection Against The Gastric Pathogen Helicobacter Pylori.
Funder
National Health and Medical Research Council
Funding Amount
$276,000.00
Summary
Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this ....Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this disease. Vaccination against H. pylori is effective in laboratory animal models. A few vaccines have entered the early phases of clinical trials in human volunteers, however the results have been disappointing. We still do not understand how vaccination leads to killing of bacteria in the stomach, although it is known that antibodies are not responsible. A better understanding of how vaccination works in mice will help the design of vaccines for humans. In a novel approach to study vaccination, the gene expression pattern in the stomachs of immunized mice was analyzed using DNA micro-array technology. In this way we identified several novel genes, and as a result we have developed a new theory for how vaccination might lead to killing H. pylori. We propose that a combination of factors, act together to control H. pylori in the stomach: Leptin, known chiefly as the Obese gene, is a hormone produced by fat cells and controls appetite. Recently leptin has also been shown to influence immune cells (T- cells) in the stomach mucosa. These T-cells in turn send signals to the (epithelial) cells on the surface of the stomach which induces them to produce other proteins; some of which we believe may slow the fast-swimming H. pylori bacteria, and some small anti-microbial proteins (defensins), which are able to kill the bacteria directly by making holes in their membranes. The results of this research will be used to help design better H. pylori vaccines for humans.Read moreRead less
Interaction Of Anti-viral IDO And NOS2 In Vivo In A Novel Murine STD Model.
Funder
National Health and Medical Research Council
Funding Amount
$573,629.00
Summary
Sexually transmitted viral diseases (STD) are increasing globally, but we know little of how virus is controlled early in infection. We have shown for the first time in vivo, in our STD model, that during an antiviral immune response, soluble factors turn on an enzyme, indoleamine 2,3-dioxygenase (IDO), to break down and deplete the amino acid, L-tryptophan, starving virus to reduce growth early in STDs. Our project will further define the action and control of IDO in STD.
Finding Therapeutic Targets For An Opportunistic Human Fungal Pathogen
Funder
National Health and Medical Research Council
Funding Amount
$404,068.00
Summary
Penicillium marneffei is a fungus that causes disease in patients with depressed immunity. This project models this infection in zebrafish, which have advantages for modelling infectious disease. It uses fluorescent fungi and fish with fluorescent immune cells to study the way white blood cells fight this infection, and mutant zebrafish and mutant fungi to find new therapeutic targets in the host-pathogen interaction.
Fine Positioning And Effector Function Of T Cells Recruited To The HCV Infected Liver
Funder
National Health and Medical Research Council
Funding Amount
$321,973.00
Summary
The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue in ....The majority of patients who become infected with hepatitis C virus (HCV) are unable to mount an effective immune response and clear the virus and therefore develop lifelong (chronic) infection. The persistence of virus in the liver of patients with chronic infection results in the recruitment of significant numbers of immune cells, notably T cells, from the bloodstream into the liver where they are involved in both viral control (but not viral clearance) and liver injury. The level of tissue injury observed and the speed of disease progression may be linked to the type of T cells recruited, their function, and their position in the liver. The aims of this project are to determine the factors involved in the fine positioning of T cells in the liver and establish a relationship between T cell recruitment, function, and progression of HCV disease in the liver.Read moreRead less
Suppression Of Immune Toll-like Receptor (TLR) Signaling By Hepatitis B E Antigen (HBeAg)
Funder
National Health and Medical Research Council
Funding Amount
$542,320.00
Summary
Hepatitis B virus (HBV) infection is a major world-wide health problem, which the current treatment strategies are not ideal. Therefore understanding how HBV inteacts with the immune system is of critical importance to developing intervention strategies to promote better health outcomes. This grant will develop our novel findings that a protein produced by HBV 'blinds' the host immune system by producing a protein that blocks the innate immune response to allow HBV to replicate unchallenged.
Understanding, Detecting, Monitoring And Treating Brain Dysfunctions Due To Chronic Immune Diseases
Funder
National Health and Medical Research Council
Funding Amount
$415,219.00
Summary
The role of immune burdens on the brain of middle-aged persons is not well understood. For example the combined brain effects of HIV and cardio-vascular diseases are unknown. Our research is about better understanding those processes using advanced neuropsychology and brain imaging methods. It is also about developing new instruments to detect problems as early as possible, to monitor them accurately and to better treat them in Australia and the Asia-Pacific region.
Visualisation Of Gamma-delta T Cell Responses In Cutaneous Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$570,876.00
Summary
Mycobacterial infections remain a major burden of modern society. This proposal aims to define the role of an understudied immune cell subset, gamma-delta T cells, in the response against mycobacteria. We will use cutting-edge multi-photon imaging to track these cells in real-time directly within infected tissues. This will facilitate generating a new vista of anti-mycobacterial immune responses and may aid the development of improved vaccines.