Novel Vasoactive Pathways In Liver Disease; Experimental And Clinical Studies
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.
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.
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.
Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current ....Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current therapies do not reduce this progression. It is believed that one major cause of this permanent disability is permanent myelin loss. Interestingly, we have already shown that the growth factor LIF is made by the body during MS-like inflammation, and that it limits damage by directly protecting myelin-producing cells. However, the bodies own LIF production during inflammation is sub-maximal, because myelin protection can be enhanced by giving additional therapeutic LIF. This suggests that (1) The brain produces a defence response to harmful inflammation and that (2) This defence response can be enhanced therapeutically. We therefore want to define exactly how LIF enhances myelin survival. We have measured the response to LIF in myelin-producing cells, and have discovered that it strongly stimulates the production of the small protein galanin. We will now assess if galanin itself protects myelin and myelin-producing cells, and we will test this both in isolated cells and whole animal models. If galanin production is a major mechanism by which the body tries to limit the damage from abnormal inflammation during MS, then medications that mimic the action of galanin (which are already under development for different reasons) could become a major new therapy for Multiple Sclerosis.Read moreRead less
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
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.
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
Identification Of Novel Mechanisms Governing Stage-specific Regulation Of The Human Globin Genes
Funder
National Health and Medical Research Council
Funding Amount
$481,826.00
Summary
Hemoglobin is the major protein in red blood cells and is essential for the transport of oxygen from the lungs to the tissues. The disorders of hemoglobin production are the commonest genetic diseases worldwide. These diseases can be markedly improved with elevation of the form of hemoglobin produced by the developing embryo, fetal hemoglobin. We have identified key factors important for fetal gene expression. Our goal is to translate these findings into therapies for the hemoglobin disorders.