High Resolution Genome-wide Genomic Analysis Of DCIS To Identify Genes Involved In Disease Initiation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$543,370.00
Summary
DCIS is the most common type of noninvasive breast cancer and in some women may progress to malignant disease but little in know about how it develops. We will bring to bear our experience with cutting edge technology and access to extensive clinical resources to the analysis of a large series of pure DCIS with the aim of identifying previously unknown cancer causing genes. This data will lead to the identification of novel breast cancer genes that will assist clinical management.
Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, ....Growth hormone is responsible for normal postnatal growth, is an important metabolic regulator in starvation, and has many useful therapeutic applications, including forms of cardiac insufficiency, Crohns disease and, it is thought, amelioration of ageing. The means whereby GH brings about these changes are not known, although we do know a considerable amount about how the individual domains within the GH receptor signal. What we do not know is which genes are regulated by GH in these processes, and how this will change the state of the cell. We propose here to use the new technique of gene arrays to uncover the programs, or groups of genes, which GH regulates to change important cellular processes. When used in conjunction with cells expressing GH receptor mutants which are unable to signal to defined pathways, we will be able to know which functional families genes are regulated, and how they are regulated. This information will enable us to know how GH regulates cell growth and metabolism, and therfore to understand what goes wrong when GH or its mediator, IGF-1 , are abnormal. We can also use this information to validate small molecules designed to mimic GH through activating its receptor, to be certain that they are acting in the same way as GH.Read moreRead less
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.
Development And Validation Of A Finite Element Model For Orthopaedic Screw Insertion Into Trabecular Bone
Funder
National Health and Medical Research Council
Funding Amount
$420,454.00
Summary
Osteoporosis is a disease of the bones that results in reduced bone strength and susceptibility to fragility fractures. Due to the spongy nature of osteoporotic bone, surgeons face major difficulties in obtaining secure fixation of bone screws. Our aim is to develop and validate a computer model of orthopaedic screw insertion into trabecular bone based on micro-computed tomography image data. This will allow an assessment of the most appropriate screw designs for stable fixation of implants.
Cystic fibrosis is a life-threatening disease of the lungs and digestive system. It is the most common single gene disorder of Caucasian populations and most of the moratility is caused by the presence of chronic lung infections, most notably with the bacterial pathogen, Pseudomonas aeruginosa. Despite the cystic fibrosis gene being discovered over 10 years ago we still have no clear indication as to how defects in the CF gene cause susceptibility to bacterial infections, and result in the infla ....Cystic fibrosis is a life-threatening disease of the lungs and digestive system. It is the most common single gene disorder of Caucasian populations and most of the moratility is caused by the presence of chronic lung infections, most notably with the bacterial pathogen, Pseudomonas aeruginosa. Despite the cystic fibrosis gene being discovered over 10 years ago we still have no clear indication as to how defects in the CF gene cause susceptibility to bacterial infections, and result in the inflammation of the lung. Our studies address this issue by examining thechanges of gene expression in response to infection with Pseudomonas aeruginosa and therefore provide us with routes to therapies which are targetted against CF gene mediated inflammation.Read moreRead less
Induction Of Reactive Oxygen Species By Hepatitis C Virus And Its Role In Liver Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that vira ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that viral proteins and viral replication play in the development of liver disease are not well characterized. Previous experiments in the laboratory have shown that one of the hepatitis C virus proteins results in the formation of toxic oxygen molecules known as a reactive oxygen species. This toxic oxygen molecules can have an effect on liver cells that may enhance the progression of the liver disease process in hepatitis C virus infected individuals. The role that these molecules play in liver cells is unknown but experiments are planned in laboratory model systems and in specimens obtained from hepatitis C virus infected individuals to further examine potential mechanisms. This will hopefully lead to the identification of new treatments for hepatitis C virus liver disease. Some patients with hepatitis C will develop liver cancer, however, all the reasons are not known. Using new technology known as microarray, a consequence of the human genome project, we have been able to look at the expression levels of thousands of genes in liver cancer. Experiments are planned to determine if these genes are important in liver cancer and if they can be used as targets for therapy or to more easily diagnose liver cancer.Read moreRead less
Mechanisms Of Induction And Progression Of Childhood Asthma: Investigations In A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$517,586.00
Summary
This project investigates how certain respiratory viral infections in very young children might predispose to developing asthma, and how inflammation in the airways in asthma might then worsen. The experimental work, which will use unique mouse models developed in the laboratories of the chief investigators, will focus on changes in genes that control the pattern of immune response to allergens and that regulate the progression of inflammation.
The Role Of MicroRNAs In The Regulation Of Antiviral And Inflammatory Responses During Experimental Rhinovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Asthma exacerbations due to viral infections are a major health and economic burden to our society. Treatment of asthma exacerbations focuses on reducing the symptoms rather than the cause of the disease. Virus-induced asthma exacerbation are widely thought to be due to an abnormal influx of white blood cells into the lungs (inflammation) and an altered anti-viral responses. In this project we will explore novel strategies to inhibit inflammation and to promote the anti-viral response.