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Physiological Function Of Nedd4-2 In Regulating The Epithelial Sodium Channel And Cystic Fibrosis Transmembrane Conductance Regulator
Funder
National Health and Medical Research Council
Funding Amount
$949,572.00
Summary
Optimal transport of sodium and chloride ions is essential for the maintenance of electrolyte balance, blood volume, blood pressure and lung function. We are studying the control of a key sodium channel (the epithelial sodium channel) and a key chloride channel (cystic fibrosis transmembrane conductance regulator) by an enzyme called Nedd4-2. This project will enable us to understand how Nedd4-2 regulates these two ion channels and to study the pathological consequences of the loss of Nedd4-2.
Identification Of The Mechanisms Of Hepatic Fibrogenesis Aid In The Detection And Prediction Of Clinical Outcomes In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in ....Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in both diagnosis and predicting clinical outcome.Read moreRead less
A Randomized Controlled Trial Of Effects Of Early Life Exposure To General Anaesthesia On Neurobehavioural Outcomes In Children With Cystic Fibrosis (CF)
Funder
National Health and Medical Research Council
Funding Amount
$587,240.00
Summary
Anaesthesia permits surgeries and other interventional procedures that benefit the health of children to be performed painlessly and non-traumatically. This study will provide critical information about whether the drugs used commonly for general anaesthesia represents a risk to very young children in terms of their neurobehavioural development.
Identifying And Preventing The Epithelial Triggers Of Neutrophilic Inflammation In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$961,124.00
Summary
We have identified aberrant immune responses to viruses and bacteria as potential triggers of damaging airway inflammation soon after children are diagnosed with cystic fibrosis after newborn screening. We will investigate the mechanisms underlying these responses and develop therapies with the potential to reduce inflammation and prevent lung disease.
Clinical And Psychosocial Changes Over Late Childhood And Adolescence And Early Life Determinants Of Long Term Clinical Outcomes In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,135,570.00
Summary
Cystic fibrosis is the most common life shortening inherited disease in Caucasians. Lung damage starts in infancy and lung function falls most rapidly in adolescence although why and how this happens and early life determinants are not known. This study takes advantage of a previous study that monitored young children from 3 months to 5 years of life and follows them closely through early adolescence to investigate the protective and risk factors for falling lung function.
Biomarkers To Define The Treatment End-point For Pulmonary Exacerbations In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,031,371.00
Summary
Sensitive and reliable tests are required to monitor lung disease severity in cystic fibrosis. A number of potential methods have emerged in recent years. We will investigate how these tests track an acute episode of lung disease and determine whether, following a typical course of treatment, there is evidence of residual damage that contributes to overall progression of lung disease.
The Emerging Problem Of Non-tuberculous Mycobacteria Infection: Understanding Aetiology, Geospatial Epidemiology And Developing Interventions
Funder
National Health and Medical Research Council
Funding Amount
$988,791.00
Summary
This project will be largest study of non-tuberculous mycobacterial (NTM) infection in cystic fibrosis. By combining growing the bacteria with detailed information from the CF patient data registry, geographical location and environmental conditions, this study will provide novel insights into factors associated with NTM. Gene sequencing and airway infection profiling will extend understanding and has the potential to identify novel risk factors and biomarkers for NTM-related airways disease.
Epithelial Drivers Of Neutrophil Plasticity In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$849,462.00
Summary
Why airway inflammation becomes chronic so early in life for people with cystic fibrosis (CF) is unclear. This project will use the latest techniques to characterise immune cells found in airways of infants with CF and model in the laboratory how immune cells react to the CF airway. We will challenge CF airway cells with different bugs that can infect the lung, then see if the responses by CF airway cells can change the normal response of immune cells, triggering chronic disease.
Extracellular Acidification And Its Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$371,529.00
Summary
This proposal focuses on the diseases cystic fibrosis and acute pancreatitis for which there are currently no treatments. In both diseases the affected organs become strongly acidic. Furthermore, these acid changes can be causal in disease progression. However, the source of this acidification is remains unknown. We will identify the routes of acid secretion, the causal role of acidification in disease progression and the effectiveness of treatments aimed at restoring acid-base balance.
Revolutionising The Diagnosis And Monitoring Of CF Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$818,391.00
Summary
Cystic fibrosis (CF) lung disease starts early in childhood and relentlessly progresses, with early death a common outcome. There is currently no method capable of detecting very early disease onset nor directly assessing the effectiveness of putative treatments. This project will apply our globally unique X-ray imaging tools, which are capable of imaging lung function at any point across the entire lung, for the very early detection of CF and assessment of clinically applicable treatments.