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
Array-based Comparative Genomic Hybridisation In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. In particular, we will whether there is an abnormal number of copies of genes in the lung cancer. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Molecular Characterisation And Diagnosis Of Malignant Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$421,250.00
Summary
Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in ....Malignant mesothelioma (MM) is an aggressive, asbestos-related tumour of increasing incidence throughout the world that is estimated to be cause approximately 20,000 deaths per annum . MM was rare until approximately 20-30 years ago but it is now more, or as, common a cause of death in Australia as cancers of the bone, liver, cervix, bladder and ovary. Although asbestos use has declined to virtually zero across most of the developed world, due to 30 to 40 year latency of the disease, the peak in cases of mesothelioma is not expected until 2010. MM is one of the most aggressive and debilitating tumours known, with a median survival of 7-10 months and a clinical pattern that usually involves substantial pain and dyspnea. Advances in therapy-prevention of mesothelioma will have not only have a major health impact, but potentially an extraordinary economic impact. MM is predicted to cost the Australian economy around $5 billion in compensation over the next 35-40 years. Government, insurance companies and industry will share that cost. The significance of this disease therefore extends beyond its actual incidence. There is growing evidence in many tumour types that the best diagnostics and treatments for cancer will come about as a result of understanding the molecular logic that underpins carcinogenesis, and designing therapies and diagnostics accordingly. We will carry out a project using the most comprehensive microarrays available to profile gene expression in malignant mesothelioma. We will use the expression data we obtain to fulfil three aims. Firstly, we will use patient outcome information to search for genes whose expression is indicative of response to therapy. Secondly, we will search the data to identify candidate secreted molecules which may be useful in the early detection of MM. Finally, we will develop a molecular assay to unequivocally diagnose MM from cells collected from pleural effusions.Read moreRead less
Genomic Profiling To Predict Lung Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$323,500.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Integrated Analysis And Functional Characterisation Of Gene Amplicons In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$453,068.00
Summary
In Australia in 2001 there were ~1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes have multiple copies in ovarian cancer cells and these may be good targets for therapy. We aim to find these genes and determine which ones have a functional effect in the tumour.
Analysis And Regulation Of Leptospiral Virulence Factors.
Funder
National Health and Medical Research Council
Funding Amount
$630,465.00
Summary
Leptospirosis is a globally important infectious disease caused by Leptospira spp. This project aims to identify and characterise factors which play a role in disease development by knocking out genes, then investigating the impact on overall gene-protein expression in the mutant strain and its ability to cause disease. This will allow us to gain insights on mechanisms by which Leptospira spp. cause disease, leading to development of better methods of disease control and prevention.
A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
Regulatory Networks Controlling Virulence In Neisseria Gonorrhoeae And Neisseria Meningitidis.
Funder
National Health and Medical Research Council
Funding Amount
$147,500.00
Summary
Bacteria that cause disease produce substances called virulence determinants, often on their cell surface. These virulence determinants are either directly involved in allowing infection to take place, or cause the damage that we recognize as an infectious disease. Some virulence determinants are produced all the time, while others are only made under particular conditions, that is, their expression is regulated. To target efforts in the development of new vaccines and treatments, it is importan ....Bacteria that cause disease produce substances called virulence determinants, often on their cell surface. These virulence determinants are either directly involved in allowing infection to take place, or cause the damage that we recognize as an infectious disease. Some virulence determinants are produced all the time, while others are only made under particular conditions, that is, their expression is regulated. To target efforts in the development of new vaccines and treatments, it is important to identify all the virulence determinants produced by a particular bacterial species, but also to know which are regulated, and the environmental signals that determine their expression. Neisseria gonorrhoeae and Neisseria meningitidis are two important disease-causing bacteria that exclusively infect humans and cause gonorrhoea, and meningitis. The complete DNA sequence of both of these bacteria is now known. From computer analysis of these data, it appears that these bacteria have few of the specific regulatory systems that are present in other bacteria. Because of the limited repertoire of regulatory systems still present in N. gonorrhoeae and N. meningitidis, it is feasible to mutate each one and determine which are involved in regulation of virulence determinants. We have made copies of every individual gene found in the DNA sequence of these bacteria and have attached each one individually to a glass slide to form a microarray measuring 18mm x 18mm. This microarray will allow us to monitor the expression of every gene in these bacteria in response to environmental signals. This information will be used to identify all the virulence genes controlled by each regulatory system. Such an analysis has never been previously achieved for any bacterial species, because of the number and complexity of the regulatory systems usually present.Read moreRead less
The Transcriptional Profile Of A Metastatic Circulating Melanoma Cell
Funder
National Health and Medical Research Council
Funding Amount
$273,630.00
Summary
Melanoma is an aggressive skin cancer, and the leading cause of skin cancer related deaths. Disease spread is difficult to detect and difficult to cure. We previously identified circulating melanoma cells in patient peripheral blood and showed that their presence is associated with disease stage and recurrence. We will now fully characterise the phenotype of actively metastatic circulating melanoma cells for better patient prognosis and routine monitoring.
Regulation Of Macrophage Function And Gene Expression By The Th2-Promoting Stimulus, ES-62
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to c ....White blood cells are responsible for co-ordinating the immune response against foreign micro-organisms. Macrophages are a particular type of white blood cell that attempt to destroy microbes during the initial stages of an infection, but also release toxic substances that are responsible for pathology and side effects during many immune responses. This project aims to address how macrophages are involved in a particular type of immune response that develops when individuals are susceptible to certain diseases including asthma and diseases associated with intracellular infections. We are identifying genes expressed in macrophages during these immune responses that are likely to be involved in susceptibility to such diseases.Read moreRead less