Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches ....Investigating the actions of anti-inflammatory pathways in chronic lung disease. There is an urgent need to develop better drugs for Chronic Obstructive Pulmonary Disease (COPD) as patients become resistant to currently used anti-inflammatory drugs with disease progression. This research will uncover fundamental biology into an important class of anti-inflammatory receptor termed ALX/FPR2. This receptor normally coordinates the clearance of infection and injured tissue and subsequently switches off inflammation. Essential knowledge into why this receptor pathway fails to switch off inflammation will be determined. Furthermore, the development of targeting strategies to this receptor represents an innovative approach to blocking damaging and chronic airway inflammation.Read moreRead less
Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-tr ....Elucidating the post-transcriptional regulation of mast cell proteases. Mast cells (MCs) are immune cells that protect against pathogens but may induce deleterious inflammation. MC function is mediated by specific proteases that are pre-formed and stored in granules. These proteases have unique yet poorly understood mechanisms of regulation. The aim of the project is to use a novel suite of molecular tools and genetically modified mice to identify the critical regions of transcripts that post-transcriptionally regulate the production and storage of these proteins. The project aims to identify the RNA binding proteins, microRNAs and other novel factors that also regulate them. This is expected to elucidate the post-transcriptional mechanisms of regulation of MC proteases.Read moreRead less
Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, an ....Novel human tryptases: their potential role in inflammatory diseases of the young and old. We have discovered a number of novel human tryptases, and while other members of this enzyme family have been implicated in the development of inflammatory diseases (including rheumatoid arthritis), little is known about these new molecules. We aim to characterise these new enzymes by determining what part of the body they are produced in, whether they are associated with specific inflammatory diseases, and what target molecules they act on. A better understanding of these factors will increase the chances of finding cures and developing better treatments for important inflammatory diseases of the ageing population.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.
Discovery Early Career Researcher Award - Grant ID: DE170100226
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affec ....How innate lymphoid cells regulate mammalian lung development. This project aims to determine the ability of a subset of lung resident immune cells to promote normal lung development through the regulation of stem cells. The lung is constantly exposed to countless environmental challenges including microbes. Mammals’ local immune systems protect the lung from these challenges. This is particularly important in early-life when the lung is still developing. However, impaired lung development affects humans and livestock, costing >$3 billion p.a. The intended outcome is to identify basic biological processes involved in normal mammalian lung development, which may lead to strategies to prevent chronic lung diseases in humans and animals.Read moreRead less
Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new pro ....Elucidating the roles of steroid receptors in mitochondria. This project aims to elucidate the roles of newly discovered steroid receptors in the functions of mitochondria. The project will characterise their impact on cellular respiration, oxidative stress, and the induction of inflammation. By defining these processes in the healthy state and in response to common environmental challenges of infection and smoke exposure, the project will characterise the fundamental biology of entirely new processes of how normal body hormones and administered steroids may function. This may eventually lead to new and more effective ways to control inflammation that will have significant benefits to mammalian health and improve health care and agriculture outcomes.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.