Clinical Impact Of Clonal Pseudomonas Aeruginosa In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$547,238.00
Summary
In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on ....In patients with cystic fibrosis (CF), the normal defence mechanisms are compromised by an inherent genetic fault which results in an extremely sticky and dehydrated mucus. The respiratory system is unable to eradicate microbes (infection) from the lungs of patients with CF which begin to multiply and cause infection and inflammation. Recurring infections are treated with multiple courses of antibiotics and frequent hospitalisation and eventually result in premature death. This study focuses on the major bacterial problem, Pseudomonas aeruginosa. Several studies from Australia and the UK, including our own have shown that about 30% to 45% of patients share the same strain of Pseudomonas aeruginosa within a centre. We know that two dominant strains of Pseudomonas aeruginosa are found in CF centres on the eastern board of Australia. This is unexpected as this bacterium is usually acquired from the environment. The emergence of these clonal strains is causing increasing anxiety in the CF community. This study is designed to provide vitally needed information on the clinical implications of being infected by an clonal strain of Pseudomonas aeruginosa and the risk factors for the acquisition of an clonal strain. This new information will provide a rationale basis for the need for changes to infection control policies (including patient segregation), better outcome predictors for patients infected with clonal strain of Pseudomonas aeruginosa.Read moreRead less
Development Of New Therapies For Respiratory Diseases And Infection
Funder
National Health and Medical Research Council
Funding Amount
$847,490.00
Summary
Prof Hansbro’s group have developed world 1st experimental models of emphysema, severe asthma infection and lung cancer. He uses them to further our understanding of these untreatable diseases. This has led to the development of new potential therapeutic approaches. Now, in discovery programs he will expand studies of pathogenesis to identify new therapeutic targets these diseases. In development and translational programs he will progress new therapies towards clinical application.
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
Prevention Of Asthma In Young Children Via Immunostimulation
Funder
National Health and Medical Research Council
Funding Amount
$679,683.00
Summary
Persistent asthma is a major problem for Australia yet none of the current therapies do more that control the condition. The long-term solution is to prevent asthma from progressing to the persistent form. The major risk factors are: family history, early allergy and recurrent severe lower respiratory infections (sLRI) in the early life. We will conduct a randomized clinical trial to prevent sLRI using a novel bacterial-derived immunostimulant in infants at high risk of developing asthma.
In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an i ....In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an important process in both the development and progression of asthma. The reason why remodelling occurs in the lungs of people with asthma is not known. It is thought that persistent inflammation drives the remodelling process; however remodelling can perpetuate inflammation, thereby creating a cyclic series of events. Furthermore we have shown that cells from non-asthmatic volunteers which are grown on asthmatic ECM change to become more like cells from asthmatic subjects. Viruses which infect the lungs may play a role in the development of asthma, and in the increased remodelling which is observed. Many common respiratory viruses are capable of infecting lung cells, eg epithelial cells, which evokes an inflammatory response. I will investigate if viral infection can alter the remodelling process, using lung cells isolated from asthmatic and non-asthmatic volunteers. Furthermore, I will assess if current and novel treatments are effective in reducing the remodelling process. We have preliminary evidence that infection of lung epithelial cells with rhinovirus (the common cold virus) alters the amount of ECM deposited by these cells. I hypothesise that this process will be increased in cells from volunteers with asthma compared to non-asthma. As current therapeutics are unlikely to be able to reverse these remodelling events these experiments will enable the development of new therapeutics which can target this important aspect of airway disease.Read moreRead less
Use Of Advanced Bronchoscopic Techniques In The Diagnosis And Staging Of Suspected Primary Lung Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$118,796.00
Summary
Lung cancer is common in Australia. Multiple diagnostic procedures may be used, thought they have never been directly compared. Our study will determine the optimal path of investigation of patients with suspected lung cancer, examining safety, diagnostic accuracy, cost, and the ability to provide essential information required in lung cancer care. Work will focus on use of CT-guided tests, or bronchoscopy (examination of the inside of the airways), the two most commonly used diagnostic methods.
RNAi Therapeutic Intervention Of Human Viral Respiratory Disease
Funder
National Health and Medical Research Council
Funding Amount
$584,117.00
Summary
Human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. HMPV is emerging as a major cause of morbidity and life-threatening respiratory tract disease in infants, young children and the elderly worldwide. No treatment is currently available. The objectives of this proposal are to develop novel antiviral drugs that silence the expression of viral genes and to examine protection against the disease.
Cigaratte Smoke Exposure Suppresses Alveolar Macrophage Responses To Lipopolysaccharide By Modifying The TLR4 Pathway
Funder
National Health and Medical Research Council
Funding Amount
$506,283.00
Summary
Long term cigarette smoke exposure is a major risk factor for cancer, heart disease and emphysema. A less known fact about smoke exposure is that it also leaves people susceptible to respiratory infections by i) physically damaging the lung lining and ii) suppressing cells responsible for coordinating the lungs defence system. This project will identify how smoke exposure blocks the early response to infection by the immune system and discovery novel ways of restoring normal lung defences.