Developmental And Cellular Mechanisms Involved In The Pathological Changes To The Epithelium In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$263,500.00
Summary
A consensus has developed in recent years that asthma involves chronic airway inflammation superimposed upon a background of airway remodelling. If untreated, these processes result in increased airway responsiveness, variable airflow obstruction and ultimately a progressive decline in lung function). Recently the role of the epithelium in the pathogenesis of asthma has been emphasised based upon observations indicating that the epithelium can play an important role in airway inflammation and re ....A consensus has developed in recent years that asthma involves chronic airway inflammation superimposed upon a background of airway remodelling. If untreated, these processes result in increased airway responsiveness, variable airflow obstruction and ultimately a progressive decline in lung function). Recently the role of the epithelium in the pathogenesis of asthma has been emphasised based upon observations indicating that the epithelium can play an important role in airway inflammation and remodelling. However, this paradigm has been developed using data accumulated almost exclusively from studies in adults. Epidemiological studies suggest that airway remodelling might play a less significant role in the majority of childhood asthma since most children with asthma have relatively minor symptoms, minimal disruption of lung function and tend not to have symptoms that persist into adulthood. Clearly the relative importance of inflammation and remodelling and the regulatory mechanisms involved are important factors to understand particularly if new, effective prevention and therapeutic strategies are to be developed. For the first time in children, the proposed project will allow the study of asthma mechanisms using target organ tissue (airway epithelium) from a large unselected population. Primary cell samples recovered by bronchial brushing will be analysed separately and also cultured in order to investigate critical elements of the pathogenesis of asthma. Data collected from symptomatic children can be easily compared with that from healthy controls and also with data from adults to determine age related factors that contribute to asthma. Furthermore, the establishment of a repository of cultured epithelial cells from these children will provide a unique resource that will allow future collaborations with scientists studying a variety of mechanisms in asthma and with the pharmaceutical industry.Read moreRead less
The Molecular Basis To The Development And Function Of The Thymic Microenvironment.
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The ability of the body to defend itself against infection is dependent on white cells in the blood called T lymphocytes, so-named because they are produced in the thymus gland. In the absence of these T cells, there is severe immunodeficiency. On other hand if the T cells are hyperactive, they can confuse their role and destroy normal tissues (autoimmunity). Imbalances in the types of T cells can also predispose patients to allergies and failures in responses to tumours. This project seeks to i ....The ability of the body to defend itself against infection is dependent on white cells in the blood called T lymphocytes, so-named because they are produced in the thymus gland. In the absence of these T cells, there is severe immunodeficiency. On other hand if the T cells are hyperactive, they can confuse their role and destroy normal tissues (autoimmunity). Imbalances in the types of T cells can also predispose patients to allergies and failures in responses to tumours. This project seeks to identify the genes required to create T cells in the thymus. Specifically it addresses the structural cells of the thymus which provide the unique environment for converting bone marrow precursors exclusively into T lymphocytes. Understanding the genetic and thus molecular basis to this will be very important biologically but may also provide more sophisticated stratgies for treating diseases on T cell origin.Read moreRead less