Understanding The Mechanisms Of Nanomedicine Absorption From The Lungs And The Application Of This Knowledge To Improving The Delivery Of Chemotherapeutic Nanomedicines Towards Primary And Secondary Lung Cancers
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
The administration of chemotherapeutic 'nanomedicines' via the lungs has the capacity to improve the specific delivery of toxic anti-cancer drugs specifically towards primary and metastatic lung cancers. This project aims to evaluate how nanomedicines are absorbed from the lungs after an inhaled dose, and how they can be best developed as inhaled chemotherapeutics for the treatment of lung cancers.
Lung Injury: Influence Of Sodium, Water, Albumin, Gravity And Body Position
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Although patients with poor oxygenation often require mechanical ventilation, only therapies that reduce lung damage improve outcome whereas therapies that improve oxygenation have not been shown to improve outcome. This project will examine the role of two common interventions in critically ill patients, fluid resuscitation and posture change, on lung injury. It is anticipated this will lead to clinical trials that will further improve survival in ventilated patients with respiratory failure.
Determinants Of Circulating Surfactant Protein Levels In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$276,221.00
Summary
The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term ....The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term Olung healthO to encompass the broad spectrum. Generally speaking, lung health can be compromised by lifestyle or disease. Whereas lifestyle changes are typically progressive and chronic, those associated with disease tend to be severe and acute. Monitoring lung health clearly has important implications in terms of occupational health and lifestyle issues, including smoking. The need for a marker of lung permeability is also regarded as the Oholy grailO in the intensive care setting. Currently, there is no way of doing so. The alveolus is lined with a liquid layer into which is secreted a complex mixture of lipids and specific proteins known as alveolar surfactant. Surfactant reduces the work of breathing. Recently, we fortuitously discovered that surfactant proteins leak into the circulation and that changes in their levels are a sensitive and early generic index of the lung?s integrity. We discovered that lung damage from conditions as diverse as smoking to the acute respiratory distress syndrome elevate circulating surfactant proteins levels. To refine our discovery we aim to: Improve the techniques used to measure the proteins Study the rate at which they enter and clear the circulation Study the influence of storage, gender, age, circadian rhythm, and smoking on the levels Study the levels in acute lung injury and in radiotherapy and cytotoxic drug treatment where the ability to monitor lung damage has immediate benefit for the patients.Read moreRead less
Identifying How The Enteric Nervous System Regulates Gut Permeability In Autism
Funder
National Health and Medical Research Council
Funding Amount
$448,643.00
Summary
This project aims to investigate causes of increased gut permeability in neurological disorders including autism and will apply neuroscience, immunological and microbiology techniques to clarify the causes of increased gut permeability in a well-characterised genetic mouse model of autism.
Modulating Inflammation As A Therapy For Harlequin Ichthyosis
Funder
National Health and Medical Research Council
Funding Amount
$718,739.00
Summary
Harlequin Ichthyosis is a severe inherited skin disease caused by mutations in a protein which regulates how skin cells control their levels of lipids. Treatments for this disease are limited and do little to improve patients condition. We believe we have found a new way to treat this condition by altering tissue inflammation. This grant will undertake important experiments aimed at developing new therapies for this currently incurable disease.
Understanding How Bcl-2 Proteins Form The Apoptotic Pores That Kill Cells
Funder
National Health and Medical Research Council
Funding Amount
$893,614.00
Summary
Programmed cell death termed apoptosis is a process our bodies use to remove cells that are a threat to our health, e.g. cancer cells. The proteins that regulate cell death are attractive targets for therapeutics that have become resistant to this defence mechanism. This study will reveal how proteins from the Bcl-2 family regulate cell death at the molecular level. Understanding this process will inform the development of drugs aimed at regulating cell death in cancer and other diseases.