Ventilation Heterogeneity And Airway Remodelling In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$522,586.00
Summary
Asthma is a common and important as a cause of significant symptoms and even death. Associated with asthma is narrowing and stiffening of the arways which causes uneven ventilation of the lungs and reduced lung function. We have developed a new technique of imaging the lungs, as well as new lung function tests which measure uneven ventilation and stiffening of airways. This will help us design better medications, and help predict those who are at risk or severe asthma and death.
Respiratory failure at birth is a major cause of death and disease in newborn infants. At birth the airways must be cleared of liquid to allow the inhalation of air, but, little is known about the process of lung aeration, because it has not been possible to observe or measure it. We have developed imaging and analytical techniques to observed and measure lung aeration. We will determine ventilation procedures that promote uniform lung aeration and minimise lung injury in ventilated infants.
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
UTILITY OF NOVEL BIOMARKERS IN THE PREDICTION OF MAJOR COMPLICATIONS OF TYPE II DIABETES MELLITUS
Funder
National Health and Medical Research Council
Funding Amount
$510,639.00
Summary
Diabetes is increasingly common. It can cause a variety of complications, the most serious being heart and kidney disease. The reasons why some patients develop such complications are not fully understood so it is difficult to predict who will be affected. The current project will use samples from a large international study of patients with diabetes to assess whether levels of specific markers in the blood help to predict major complications and clarify why they occur.
An Examination Of Motor Functioning In Autism And Asperger's Disorder: An Analysis Of Gait & Cortical Brain Activity.
Funder
National Health and Medical Research Council
Funding Amount
$120,220.00
Summary
Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poo ....Autism is a developmental disorder characterised by a triad of deficits: delayed and atypical language development, impaired development of social skills, and ritualistic and stereotypic behaviour. Although not part of the standard diagnosis, movement disorders and gait abnormalities have been clinically observed in autism similar to those seen in Parkinson's disease. In addition, individuals with Asperger's disorder may appear more clumsy, have a stiff or awkward way of walking, and exhibit poor coordination in posture and gesture. It has been suggested that there is disruption within the basal-ganglia-thalamocortical circuitry (the region connecting the frontal and sub-cortical structures), which may cause the motor dysfunction seen in autism and Asperger's disorder. Few studies have attempted to isolate particular stages of motor functioning which may account for the coordination and motor delay observed clinically in autism and Asperger's disorder. A recent study of ours found evidence to suggest that motor planning deficiencies may account for the 'clumsy' movement patterns frequently reported in the autism - Asperger's disorder literature. Therefore, the aim of this research is to provide a comprehensive neurobehavioural and neurophysiological analysis of motor functioning in young people with autism and Asperger's disorder to further examine the exact stages of motor processing which are deficient in these disorder groups. Recent retrospective studies have shown that even as infants children with autism exhibit clear features of motor disturbance, which, if detected and clearly defined, could advance early diagnosis. In addition to advancing the clinical definition of autism and Asperger's disorder, a careful examination of motor disturbance may also illuminate the neurobiological underpinnings of these disorders.Read moreRead less
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
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.
Biology Of EGFR Mutations In Glioblastoma Multiforme
Funder
National Health and Medical Research Council
Funding Amount
$287,445.00
Summary
The epidermal growth factor receptor (EGFR) is a protein that has a critical role in the development of normal cells. In glioma, the most lethal of the brain cancers, the EGFR is altered. These alterations result in uncontrolled activation of the EGFR, causing signals that promote the growth and survival of brain cancer. This grant seeks to understand the nature of the signals mediated by the altered EGFR, in turn helping us develop better therapeutics for the treatment of this deadly cancer.
Functions Of FZD7 In The Intestine And Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,761.00
Summary
Wnt proteins are a family of signaling molecules that are critical for the function of normal and cancerous epithelial cells in the gut. However, the cell surface receptor that transmits Wnt signals is not known. Our research strongly implicates one Wnt receptor (FZD7). Here we test this using innovative mouse and cell line models. We wish to understand how Wnt-driven processes are activated. This knowledge will lead to novel avenues to block aberrant activation of Wnt signalling in cancer cells
Antigen Selection In The MHC-restricted Cellular Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$175,570.00
Summary
The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally appare ....The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.Read moreRead less