Functional Effects Of Polymorphic Variation Of The Aromatase (CYP19) Gene On Enzyme Activity:relationship To Disease
Funder
National Health and Medical Research Council
Funding Amount
$237,708.00
Summary
After menopause, oestrogen synthesis changes from an ovarian to an adipose source by concersion of androgens to estrogens, a process catalyzed by aromatase, the product of the CYP19 gene. We will generate mutants of the CYP19 gene that we have previously found in humans by site-directed mutagenesis and observe the effects of these mutants on aromatase function. This research will help with diagnosis and treatment of breast and other cancers and osteoporosis in humans .
A Case-control Study Of Environment And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$808,948.00
Summary
Breast cancer is the most common cancer in Australian women and there have been a number of recent events which have raised public concern that occupational exposures are contributing to the increasing occurrence of this cancer. In this study, we will investigate occupational causes of breast cancer, particularly shift work, industrial solvent use and combustion products. We will compare occupations of 1000 women with breast cancer and 2000 women without cancer.
Postviral Wheezing In Childhood: Disregulation Of Airway Tone?
Funder
National Health and Medical Research Council
Funding Amount
$577,040.00
Summary
Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. Ho ....Asthma is a very common childhood condition that is becoming increasingly more common. Wheezing is common in infants and young children following viral infections and is often thought of as the first manifestation of asthma. However, many children and infants who wheeze with viral infections appear to grow out of asthma in their teenage years. Asthma that persists into adult life is usually associated with allergies to common environmental allergens, such as house dust mite and grass pollens. However, many infants who wheeze with viral infections, especially in the first year of life, do not develop allergies in later life, raising the possibility that they did not have the same type of asthma as those whose symptoms persist. This project will study the effects of viral infections on lung function to determine whether particular types of virus can have detrimental effects of lung function lasting for years. We will also examine whether the age at which the infection occurs and the severity of the infection influence the long-term outcome. The project involves studying infants during the recovery phase of respiratory viral infections, older children years after documented infections and experimental animal models that have been infected under controlled conditions. By determining whether respiratory viral infections can have long-term effects on lung function that can mimic asthma, we will advance our understanding of how asthma develops. In addition, specific treatment and preventative strategies could then be developed to prevent these long-term abnormalities, instead of relying on asthma medication (especially inhaled corticosteroids) as is the current practice. Preventative strategies could include encouraging the development of specific vaccines.Read moreRead less
Leukaemia-cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of these is augmented activity of enzymes called tyrosine kinases including members of the Src family. One called Lyn has been implicated in several leukaemias as well as cancer. We have identified a novel mechanism of down-regulating this family of enzymes mediated by small proteins. These may allow us to develop novel therapeutics for cancer-leukaemia treatment.
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