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
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.
Acute Respiratory Illness In Indigenous And Non-Indigenous Australian Children And The Pathways To Chronic Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Dr Kerry-Ann O'Grady aims to establish a comprehensive research program addressing acute and chronic respiratory infections in Australian children in urban, rural and remote areas. Drawing on national and international collaborations, Dr O'Grady will undertake a range of epidemiological and clinical studies that will address burden, risk, pathways to chronic lung disease and novel interventions aimed at improving lung health.
Breathe Well: A Centre For Research Excellence In Chronic Respiratory Diseases And Lung Ageing
Funder
National Health and Medical Research Council
Funding Amount
$2,527,082.00
Summary
Our CRE is based on common respiratory conditions covering wide spectrum of ages and severity. We will investigate how to maintain optimal respiratory health, through innovative approaches to early detection, improved therapy and adherence. We have a strong multi-disciplinary team of collaborators and we will build capacity through post-doctoral fellowships to improve our structural balance and optimise translational outputs. Tasmania is an ideal community to host a strong CCRE.
Reducing The Community Burden Of Respiratory Infections In Indigenous Children
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Lower respiratory infections are the leading cause of preventable mortality among Indigenous children in the Northern Territory. Streptococcus pneumoniae remain one of the major paediatric respiratory pathogens. In this proposal I will describe the impact of past and present pneumococcal vaccination strategies on the burden of infant respiratory infections in this region.
Perinatal Microbe-host Interactions Regulate Neonatal Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$1,293,576.00
Summary
Acute lower respiratory tract infections (ALRI) are the leading cause of childhood mortality globally, and increase the risk of chronic lung diseases in later-life. Diverse communities of microorganisms - the microbiome - assemble in infancy and support immune development. In this study, we will explore the relationship between the microbiome and its metabolites, and the expression of an important hormone that regulates the development of the immune system to confer protection against ALRI.
Otitis Media In Indigenous And Non-Indigenous Children: Microbiological And Immunological Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$534,400.00
Summary
Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. ....Otitis media (middle ear infections) is a major health problem in children. Many children suffer repeated attacks requiring frequent courses of antibiotics, some need surgery and some suffer serious consequences, particularly hearing loss. This can affect performance at school, hence employment and social circumstances in adulthood. Indigenous children suffer much higher rates of disease with more complications than non-Indigenous children. Many factors predispose to the heavy burden of disease. In the Kalgoorlie-Boulder area we are following Indigenous and non-Indigenous children from birth to 24 months to look at a broad range of factors in order to proceed as soon as possible to appropriate intervention programs. Samples from the back of the nose are collected to find out the relationship between carriage of a range of bacteria or viruses and risk of getting otitis media. Information on antibiotic resistance of the bacteria we isolate will assist in ensuring appropriate treatment of otitis media. We also collect a sample of breast milk from mothers and several samples of saliva to find out about the immune system of babies and how this relates to disease to assist in an ongoing program of vaccine development for prevention of otitis media. We will find out how environmental factors such as crowding or passive smoking relate to carriage of bacteria and whether a combination of different factors increase risk of disease. A new vaccine called pneumococcal conjugate vaccine, recently licensed in Australia, is highly effective in preventing severe diseases such as pneumonia and meningitis and affords some protection against ear infections. It is likely to be offered first to Indigenous children because they suffer very high rates of pneumococcal disease. The vaccine may alter the types of bacteria in the nose. This needs to be monitored carefully which will be possible during this study.Read moreRead less
Extending The MIS BAIR Randomised Trial Of BCG To Prevent Childhood Allergy And Infection
Funder
National Health and Medical Research Council
Funding Amount
$939,504.00
Summary
BCG (used till recently to prevent tuberculosis) is a potential low cost and readily available vaccine which could reduce the rates of allergy and infection in Australian children. We propose to extend our existing NHMRC-funded trial, which studies whether BCG vaccinatinon given at birth prevents the development food allergy, eczema and infection in the 1st year of life, to see if this effect continues until 5yrs of age. At this age, we can also see if BCG vaccination at birth prevents asthma.
How Anti-inflammatory Drugs Differentially Affect The Bronchoprotective Signalling Of Protease-Activated Receptor-2
Funder
National Health and Medical Research Council
Funding Amount
$421,690.00
Summary
Asthma contributes significantly to the burden of ill health and impaired quality of life in Australian communities, and for many measures of asthma, Australia has amongst the highest prevalence when compared with other countries. Furthermore, there is evidence that the prevalence of asthma has increased during the latter part of the 20th century. There is currently no cure for asthma, and the need for better asthma therapies through the discovery of novel targets for drug development has never ....Asthma contributes significantly to the burden of ill health and impaired quality of life in Australian communities, and for many measures of asthma, Australia has amongst the highest prevalence when compared with other countries. Furthermore, there is evidence that the prevalence of asthma has increased during the latter part of the 20th century. There is currently no cure for asthma, and the need for better asthma therapies through the discovery of novel targets for drug development has never been more acute. PAR2 is a receptor that is located on the surface of many cell types in the respiratory tract, including the epithelial cells that line the airway tubes. When PAR2 is stimulated it causes the epithelial cells to produce and release large amounts of PGE2 (prostaglandin E2). PGE2 released from epithelial cells then binds to other proteins such as the prostanoid EP2 receptor located on smooth muscle cells. This causes the airway smooth muscle cells to relax. Drugs that cause airway smooth muscle cells to relax - called bronchodilators - make breathing easier, and are often used during an asthma attack to relieve bronchoconstriction. It also appears that activation of the PPP axis inhibits airway wall swelling (that is, has anti-inflammatory actions). Thus, drugs that activate the PPP axis may be beneficial in the treatment of asthma by reducing airway sweeling and producing smooth muscle relaxation. Thus, we we are investigating ways of optimally stimulating the PAR2-PGE2-prostanoid EP2 receptor axis (the PPP axis), as a means of develeping novel treatments for asthma.Read moreRead less