The Effect Of Heterogeneity And Airway Closure On Distensibility Measurements In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$35,085.00
Summary
Long term asthma can result in stiffening of the airways, which cannot currently be measured with standard lung function tests. A new non-invasive technique, using sound, has been shown to measure airway stiffness, but this may be adversely influenced by other respiratory changes that occur with asthma (airway closure, heterogeneity). We are investigating the effects of these confounding factors to fully characterise this novel technique, so that it can be used in the clinical environment.
Correction And Measurement Of The Basic Defects In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$929,335.00
Summary
Airway disease caused by the genetic disease cystic fibrosis (CF) cannot currently be prevented or cured. Current treatments (other than lung transplant) can only slow the inevitable decline in lung health. Early death from lung failure occurs for many with CF. We have developed a gene transfer technique to introduce the corrective gene (CFTR) into CF-diseased airway cells. We have used airways in mice to test and develop this method, to determine if long-lasting genetic correction of the airway ....Airway disease caused by the genetic disease cystic fibrosis (CF) cannot currently be prevented or cured. Current treatments (other than lung transplant) can only slow the inevitable decline in lung health. Early death from lung failure occurs for many with CF. We have developed a gene transfer technique to introduce the corrective gene (CFTR) into CF-diseased airway cells. We have used airways in mice to test and develop this method, to determine if long-lasting genetic correction of the airway cells can be achieved. The gene is introduced into the airway as a single small dose of special delivery-particles (vector) that have been built using highly-modified components of the HIV-1 virus. If ultimately successful in humans with CF, the disease should be halted, or even cured. Our recent work indicates that we have been able to insert the gene into airway progenitor cells, confirming our hypothesis that long-lasting gene expression can be achieved this way. To know if the method would be safe and effective in humans, we must now test the technique in sheep (as a human-size lung) and in marmosets (as a human-like lung) before clinical trials could be considered. We will monitor animals for up to 3 years to be sure the effect of the gene is truly long-lasting, and we will document how the gene-transfer vector disappears from the body. We have also discovered a new way to examine the detail of the very thin fluid layer on the airway surface. This fluid is too shallow in CF airway (allowing bacteria to stick and start disease) and so a successful gene therapy should return the fluid to it's proper depth. This method uses X-ray light from a synchrotron, and we expect it will work without the need to sacrifice animals to measure the airway surface. If successful it also has potential to be used much like a normal X-ray in humans with CF, to test if a gene therapy has worked.Read moreRead less
Synchrotron X-ray Assessment Of Airway Surface Physiology For Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$778,228.00
Summary
We seek a cure or long-lasting therapy for the fatal airway disease in cystic fibrosis. Disease is caused by a shallow and dehydrated airway surface liquid (ASL), allowing bacteria to infect the lung. We can introduce a corrective gene into mouse airways where it can be effective for over 1 yr, but no fast, accurate and non-invasive measurement exists to test if treatments are successful. We will develop methods using synchrotron light to directly measure ASL depth changes in live mouse airways.
MPM Non-invasive Imaging Of Biological Interactions Following Drug Delivery With Micro-nanoprojection Patches.
Funder
National Health and Medical Research Council
Funding Amount
$403,612.00
Summary
The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery devi ....The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery device is a set of microscopic nanoneedles coated with drug substance and applied to the skin as a small patch. The device is practical, needle-free and pain-free. The aim of this current project is to use the micro-nanoprojection array patches-configured to uniquely deliver biomolecules to cells within given strata-to find: 1) what delivery sites of antigen-expression plasmid- toll like receptor (TLR) agonist lead to strong humoral immune responses in the intact animal. 2) whether delivery of different TLR agonists have different effects on the maturation and migration of the different professional antigen presenting cells (APCs) in the skin, as visualised locally by Multi-Photon Microscopy (MPM). 3) whether differences in APC maturation and migration are associated with different systemic antibody responses. We will identify optimal delivery sites of drugs-vaccines to the skin (layer, cells targeted, duration of delivery) with MPM for desired systemic immune responses. This will have important contributions towards improving immunotherapeutics of major diseases via skin targeting with micro-nanoprojection array patch technologies (and other methods).Read moreRead less
Use Of Molecular Tumour Markers To Improve Diagnostic Performance Of Bronchoscopy In Assessment Of Pulmonary Nodules And Early Diagnosis Of Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$303,014.00
Summary
Pulmonary nodules may represent early lung cancer though difficulty in accurate diagnosis means many patients experience delayed diagnosis, or unnecessary surgical biopsy or repeat CT imaging (& consequent radiation exposure). I will identify molecular (DNA, protein) markers in bronchoscopic & blood specimens to accurately characterize malignant & benign nodules. These biomarkers will also be investigated for their value as a non-invasive screening test for lung cancer
How Do Thick Airway Walls Affect Airway Hyperresponsiveness In Asthma?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Asthmatic airways narrow too easily, a characteristic called airway hyperresponsiveness (AHR). To understand the cause of asthma we need to understand the cause of AHR. Thickened airway walls could amplify airway narrowing and increase AHR. However, thick airway walls are also stiff, and stiff walls could reduce narrowing and AHR. This project will examine the relationships between AHR and airway wall thickness and stiffness during and after treatment that reduces airway wall thickness.
Mechanisms Of Immune-evasion By Group A Streptococcus During Skin Infection
Funder
National Health and Medical Research Council
Funding Amount
$602,609.00
Summary
Infections by Group A Streptococcus (GAS), or Streptococcus pyogenes, represent a global health concern. Currently no vaccine exists against GAS thereby mandating a better understanding of the immune response against the bacterium. Using in vivo microscopy, the aim of this proposal is to dissect in real time how neutrophils detect and destroy GAS following skin infection, and how the bacterium manages to circumvent the attack by innate immune cells.
Is Asthma In The Elderly A Disease Of The Peripheral Airways?
Funder
National Health and Medical Research Council
Funding Amount
$502,437.00
Summary
Elderly asthmatics have poorer clinical outcomes compared with younger asthmatics. The reasons for this are unclear but may involve age-related changes in the disease itself. In this project we aim to show that asthma in the elderly is dominated by abnormalities of very small peripheral airways, in contrast to younger patients where the abnormalities occur in larger airways. The results will provide the basis for new and better targeted treatment strategies for asthma in the elderly.