Asthma Prevention And Treatment Using UVB Radiation-induced Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radia ....The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radiation have been previously described but have not been scientifically linked with asthma development. This is a very new and novel research area which supports century-old anecdotal reports that holidays at beach and mountain resorts associated with increased UVB exposure are beneficial in asthma treatment. This is a proof of principle study. If we can confirm that UVB is immunomodulatory and better understand the mechanisms by which UVB suppresses inflammation in the airways, we will investigate the potential of non-carcinogenic, UVB-induced, skin-derived intermediary molecules to have the same regulatory effects.Read moreRead less
A Novel Strategy Targeting Quorum Sensing Molecules And Catalase Function To Block Pseudomonas Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$451,118.00
Summary
Pseudomonas aeruginosa causes serious infections, particularly in those with Cystic Fibrosis, immunocompromise, serious burns or long term catheters. We will use a unique strategy to target virulence factors that will assist in clearing acute infection, prevent establishment of new chronic infections, and potentially reduce severity of established chronic infections. It has the potential to make antibiotic therapy more effective and lessen the extent of antibiotic therapy required.
Quorum Sensing Signal Molecule Modulation Of Immunity: Role In Host Responses To P. Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$251,014.00
Summary
Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune sy ....Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune system. We will be investigating how this QSSM may suppress immunity and what influence this has on both the severity of infection and the potential for development of chronic infection. The study will first of all determine where the QSSM exerts its effects (that is, can it escape from the site of infection to affect other host sites) and this will direct us in how we may learn more about the way it can affect the host during an infection. We will investigate the direct affects of QSSM on acute and chronic types of P. aeruginosa lung infection and then from this, determine if the outcome exacerbates a subsequent infection. The work is significant in that a knowledge and understanding of these virulence factors will assist in the design of better therapeutic and prophylactic strategies for both prevention of infection in susceptible individuals and treatment of those that suffer from chronic infection.Read moreRead less
Understanding The Mechanisms Of Respiratory Viral Infection- And COPD-induced Predisposition To Secondary Bacterial Pneumonia
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Bacterial pneumonia is a major health problem particularly for children and the elderly. Bacteria are resistant to antibiotics and new treatments are urgently required. Viral infection and emphysema lead to increased risk of pneumonia. We will investigate the mechanisms of how viral infections and emphysema lead to pneumonia. We will then use new treatments to stop these mechanisms from occurring to prevent and treat pneumonia. This project may produce new treatments and cures for pneumonia.
Immune Recognition Of Upper Airway Microbiota In Early Life As A Determinant Of Respiratory Health In Children
Funder
National Health and Medical Research Council
Funding Amount
$1,135,837.00
Summary
The study will investigate the impact of respiratory infections during infancy on lung & immune function & respiratory health between 3-7 years of age. Children were previously enrolled in a population based birth cohort study (ORChID study) which collected detailed information about the respiratory health during the first 2 years of life with daily respiratory diary & weekly nasal swab collection. In this study lung function & immune function will be assessed annually in the same children (3-7)
Anti-viral Immune Dysfunction In Severe Asthma Varies Across Inflammatory Phenotypes.
Funder
National Health and Medical Research Council
Funding Amount
$997,153.00
Summary
Common cold viruses often trigger asthma flare-ups , but have relatively minor effects on healthy people. Why this happens is not clear. We have identified two different ways in which the immune system can react badly to a common cold virus in people with asthma. In this study we will find out more about why the immune system does not react normally in a large group of people with severe asthma. This study will help us discover improved treatments that can be targeted to people with asthma.
Developmental Aspects Of Respiratory Inflammation, Allergy And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$7,169,609.00
Summary
Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longit ....Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longitudinal studies in cohorts of children recruited before birth. Having the ability to study children as they grow and develop conditions such as allergies and asthma allows us to understand why these conditions occur and allow us to predict which children are likely to develop them. Our research Program also has a solid focus on Translational Research, in which we will use the findings from our basic science studies to develop and test new methods of preventing and of treating asthma. These studies will include new methods for preventing the development of allergies, preventing the damage done to the lungs by severe viral respiratory infections in early life and better methods of treating established allergic asthma by improving immunotherapy techniques. By its very nature, primary prevention of disease in young children is controversial and raises some interesting questions. As part of this Program we intend to initiate consultation and debate in public, academic, regulatory and industry circles. An important role for our Program is shifting the current emphasis away from treatment of established disease towards preventing disease occurring. This is the best way to decrease the health, social and economic burden of chronic diseases such as asthma.Read moreRead less
The Mechanisms Of Infection Of Bronchial Epithelial Cells By Human And Avian Influenza Viruses In Chronic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$395,559.00
Summary
Influenza is an important infection that causes disease every year in the Australian population. People with lung disease are at particular risk to its effects. The ability of the virus to grow in birds and change its appearance to our immune system allows this virus to cause severe disease every year. We will examine the immune response to this virus in human cells, comparing this response to human and bird strains of the virus and see why subjects with lung disease are more susceptible.
Exposure Of Bronchial Epithelial Cells To Inflammatory Stimuli Impairs Their Innate Immune Response To Rhinovirus.
Funder
National Health and Medical Research Council
Funding Amount
$325,966.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhi ....Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhinovirus and fail to react to this infection effectively. We propose to further elucidate this defect and for the first time determine if it is also present in subjects with COPD. We will examine the airway cells of subjects with asthma and COPD and look for evidence of a defective immune response, relating this to the presence of persistent bacterial infection. We will then grow these and infect them with rhinovirus, carefully examining the mechanisms behind this impaired response to infection and then see if we can induce such impairment in these cells with chronic exposure to infection and inflammatory stimuli. Our laboratory is well placed to investigate these problems with an established track record in investigating patients with inflammatory airways disease and virus infection, unparalleled access to sufficient well characterised clinical samples and have demonstrated the ability to study virus epithelial cell interactions. This work will highlight those at risk of developing frequent debilitating exacerbations along with the reasons for this and identify areas to target novel therapeutic interventions.Read moreRead less
Innate Immune Factors Regulate Steroid-resistant Airways Hyperreactivity And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$524,456.00
Summary
Infection induced asthma is often difficult to manage because of lack of efficacy of steroid treatment. The innate immune system plays an important role in inflammation associated with infection. I have shown that two innate immune factors, IFN-gamma and lipopolysaccharide (LPS), induce airways hyperreactivity that is resistant to steroid therapy in a mouse model. Identification of how this pathway works may help in the treatment of infection induced steroid-resistant difficult to manage asthma.