Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less
CHARACTERISATION OF NOVEL PICORNAVIRUS-LIKE VIRUSES IDENTIFIED FROM PATIENTS WITH ACUTE RESPIRATORY INFECTIONS.
Funder
National Health and Medical Research Council
Funding Amount
$366,998.00
Summary
The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common ....The common cold and serious chest colds are usually due to viral infections, and mostly occur in children. Unfortunately we can only be certain of the virus causing this illness in as little as 15% of cases. We intend to address this lack of research by examining, in detail, a new virus we recently identified in a child with serious respiratory illness that required admission to hospital. Testing by our laboratory suggests that the new virus is related to picornaviruses (which cause some common colds) but seems to be present in children with far more serious illness. Our study plans to more completely identify the new picornavirus-like virus (PLV) using the tools of molecular biology and the expertise of a senior team of Australian scientists and clinicians who have recently made several virus discoveries in Australia, demonstrating that Australian virus research is capable of achieving highly competitive results that benefit our hospitals and especially their young patients. Our studies will develop extremely sensitive tests which rely on the detection of very small amounts of the viral genome. We can use these tests to determine what the whole virus looks like, when it might occur during the year and whether the PLV are found worldwide. Our studies will also produce viral proteins in the laboratory and use these to make new tests for stored blood samples. If a blood sample comes from a patient who has previously been infected by PLV, their blood will contain specific antibodies which we will then be able to detect. We also intend to determine whether some strains of PLV are more or less likely to cause serious illness than others. Improved understanding of these and other viruses minimises the chance of illness spreading within a hospital, helps scientists to decide against which viruses to design vaccines and drugs and aids medical doctors to better identify what once went undiagnosed.Read moreRead less
Regulation Of Subcellular Localisation Of Respiratory Syncytial Virus M Protein: Implications For Pathology
Funder
National Health and Medical Research Council
Funding Amount
$580,195.00
Summary
Respiratory syncytial virus (RSV) is the major cause of viral pneumonia in infants and the elderly, causing more deaths in winter than influenza. We have observed RSV M protein in the nucleus of infected host cells where it inhibits host cell transcription. We propose to investigate the regulation of nuclear localisation of M by phosphorylation and binding to cellular factors and its importance to RSV pathogenesis. The results will relate strongly to future drug and vaccine development.
Mechanism/s Of Disease Caused By Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$479,517.00
Summary
A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract ill ....A newly discovered respiratory virus, human metapneumovirus (HMPV), causes clinical disease that is very similar to human respiratory syncytial virus (RSV) and co-circulates with RSV. Human RSV is a major cause of morbidity and life-threatening respiratory tract disease in infants and young children worldwide, and is recognised as an important respiratory pathogen in elderly adults and immune compromised patients. The recent isolation of HMPV from children hospitalised with respiratory tract illness similar to RSV, but with an unknown etiology, suggests that HMPV may mediate similar clinical pathology. Nothing is currently known about the immune response to HMPV, or the association of these responses with lung disease. The objectives of this proposal are to elucidate the mechanisms of immunity and disease pathogenesis associated with human metapneumovirus (HMPV) and to investigate the use of a novel vaccine to protect against HMPV infection. Once this data is obtained, the study will provide the foundation for further research in the development of vaccines or therapeutic protocols to treat HMPV. It will also provide valuable information for understanding the disease in humans. Also,it is likely that HMPV, like hRSV, may prove to be an agent associated with long-term decreased pulmonary function and airflow limitation perhaps developing to asthma.Read moreRead less
Immunity To Colonising Bacteria Of The Respiratory Tract In Atopic And Non-atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$246,478.00
Summary
Evidence that seemingly harmless and common bacterial infections have a role, in the development of allergic disease has been uncovered. The development of immune responses to these microbes will be studied in children with and without allergy to inhalant allergens.
Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variab ....Chronic obstructive pulmonary disease (COPD) is a chronic lung condition caused by cigarette smoking. COPD consists of emphysema and chronic bronchitis, which lead to worsening breathlessness, cough and sputum production and need for oxygen. COPD is the third highest cause of burden of disease to the community in Australia and the fourth leading cause of death. People with COPD suffer many chest infections, which need antibiotics and offer need admission to hospital. However there is much variability in the pattern of COPD related to infections. Natural chemicals produced by the body that fight infection are likely to be involved in this variability. Recently it has been discovered that there are variations in the genetic sequence of the genes that code for these chemicals. These genetic variations change the structure of the chemicals or the rate at which they are produced. Therefore it is highly likely that these genetic variations may influence the risk of developing COPD, and the risk of getting infections. In this study, we aim to systematically examine how these genetic variations alter the development of COPD and the risk of infections. At the start, we will collect a blood sample and phlegm (sputum) specimen from each person. The results of the genetic tests will then be compared to the risk of developing COPD, the chemicals produced and the risk of infection. We believe this study will improve our understanding of how COPD and its complications develop, leading to better treatment for this condition in the future.Read moreRead less
Invasive Assessment Of Pulmonary Vascular Physiology - Novel Methods For Early Detection Of Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$274,352.00
Summary
Pulmonary vascular disease (PVD) is a lethal condition characterised by progressive destruction of the lung blood vessels. One major problem with PVD is that diagnosis is often made very late in the illness, when the pulmonary blood pressure rises. This project aims to develop a novel method to detect the early and clinically silent phase of PVD, by assessing the lung's blood vessel reserves. Early diagnosis of PVD will enable earlier treatment thereby improving prospects for treatment.
Health, Economic, Psychological And Social Impact Of Educating Carers Of Patients With Advanced Pulmonary Disease (APD)
Funder
National Health and Medical Research Council
Funding Amount
$605,452.00
Summary
Our study aims to understand the health, economic and social costs associated with caring for patients with advanced pulmonary disease (APD) and to determine health, economic and social impact of improving the skills of caregivers of patients with APD has on patients and their carers. Patients with APD are a large population at high risk of health resource use, unnecessary medication use and emergency admission to hospital or residential care facilities. Although previous research has identified ....Our study aims to understand the health, economic and social costs associated with caring for patients with advanced pulmonary disease (APD) and to determine health, economic and social impact of improving the skills of caregivers of patients with APD has on patients and their carers. Patients with APD are a large population at high risk of health resource use, unnecessary medication use and emergency admission to hospital or residential care facilities. Although previous research has identified difficulties experienced by caregivers of the elderly in general, very little research has been undertaken with carers of patients with APD. The study will compare the usual practice of educating patients with APD who commence home oxygen therapy (HOT), and their carers, against a more detailed and individually targeted education program that increases the skills of patients and carers. This study has the potential to reduce hospital-residential care readmission, reduce carer distress, improve patient outcomes, reduce adverse effects of oxygen therapy and medication use, and minimize inappropriate presentation to tertiary care emergency departments.Read moreRead less
The Role Of Protein Oxidation And Isomerization Pathways In The Pathogenesis Of Neisseria Meningitidis
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
Neisseria meningitidis causes meningococcal disease. It lives on the surface of the nasopharynx and in certain circumstances, can invade into the bloodstream causing sepsis. This is a complicated process, which involves many proteins produced by the bacteria. Many of these proteins contain a special covalent bond, the disulphide bond, which allows them to function properly. We are investigating how these disulphide bonds are put into proteins.
Use Of Mouse Models To Study Mechanisms Of Pathology In Viral Exacerbations Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$411,960.00
Summary
We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our re ....We want to understand why cigarette smoke exposure worsens respiratory virus infections. People who smoke, or who have smoked in the past, or who are exposed to environmental (passive) smoke, get sicker than nonsmokers when they get a respiratory virus infection, such as a common cold or the flu. This is true for people of all age groups, but we don't know why smoke has this effect. We think it may be because smoke interferes with some aspects of the immune response. A particular focus of our research is chronic obstructive pulmonary disease. COPD is a serious lung disease which generally occurs in people who have smoked for many years. However, many COPD patients stopped smoking many years ago. COPD patients are especialy at risk of serious outcomes if they get a respiratory infection (known as an acute COPD exacerbation) and patients with COPD exacerbations use a lot of health care resources. There are no effective drugs to prevent or treat COPD exacerbations. We are currently using a mouse model of smoke exposure and virus infection to do this research, which is a much faster and more ethical approach than using humans in research. We believe that we will get a better understanding of how smoke affects the immune response to infection. This is likely to contribute to the development of better drugs for COPD exacerbations and other types of smoking related lung disease.Read moreRead less