Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.
Molecular Analysis Of The Peroxisome Biogenesis Disorders
Funder
National Health and Medical Research Council
Funding Amount
$185,135.00
Summary
A group of human disorders arise from abnormal metabolic function of peroxisomes, small organelles found in the cells of most tissues. These abnormalities are caused by defects in the processes by which peroxisomes are formed in cells, and now known to be due to mutations in peroxisome biogenesis, or PEX, genes. In this project we will identify and assess PEX gene mutations in Australasian patients with these disorders to assist with future clinical diagnosis. In addition, because the mechanisms ....A group of human disorders arise from abnormal metabolic function of peroxisomes, small organelles found in the cells of most tissues. These abnormalities are caused by defects in the processes by which peroxisomes are formed in cells, and now known to be due to mutations in peroxisome biogenesis, or PEX, genes. In this project we will identify and assess PEX gene mutations in Australasian patients with these disorders to assist with future clinical diagnosis. In addition, because the mechanisms of disease formation, or pathogenesis, are poorly understood, we will develop animal models of the PBDs that may provide more detailed information about these corresponding processes in humans.Read moreRead less
Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not ju ....Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not just in Australia, but globally to inform pandemic planning and disease control policy around emerging infections and bioterrorism.Read moreRead less
THE EFFECT OF LONG ACTING BRONCHODILATORS ON VENTILATION IN COPD
Funder
National Health and Medical Research Council
Funding Amount
$143,676.00
Summary
COPD is a common and important smoking-related lung disease. Well-established treatments with inhaled medications including long-acting bronchodilators have a proven clinical track record. However the physiological basis for their effects is still under investigation. This research examines some of the physiological changes in lung function and the response to long-acting bronchodilators in patients with COPD, and may help explain why some patients respond to therapy while others do not, leading ....COPD is a common and important smoking-related lung disease. Well-established treatments with inhaled medications including long-acting bronchodilators have a proven clinical track record. However the physiological basis for their effects is still under investigation. This research examines some of the physiological changes in lung function and the response to long-acting bronchodilators in patients with COPD, and may help explain why some patients respond to therapy while others do not, leading to more targeted therapeuticsRead moreRead less
Resolving Eosinophil And Inflammatory Heterogeneity In Chronic Allergic Airway Disease For Safer, Effective And Lasting Precision Therapies
Funder
National Health and Medical Research Council
Funding Amount
$1,166,165.00
Summary
Many patients with upper airway inflammation and asthma have poorly controlled disease and are in need of new effective therapies. We have discovered new cell subsets in the airways of these patients. We will use cutting edge single cell and spatial analysis of human tissues to define human allergic disease and inflammatory cells at unprecedented resolution. This will identify new targets for treatment and match patients with effective therapies to facilitate precision therapy.
Making Signalling Through The Tumour Necrosis Factor Receptors Selective For Promoting Neutrophil Antimicrobial Activity
Funder
National Health and Medical Research Council
Funding Amount
$196,312.00
Summary
It is evident to the professional and general community that antibiotic and drug resistance displayed by bacteria is a continuing and growing problem in the treatment of infection with potentially casastrophic effect on the health of our community. This concern is only partly reduced by our potential to develop new antimicrobial agents and vaccines. If we were able to use immunomodulators in a relatively safe and appropriate manner to target and enhance the antimicrobial power of specific compon ....It is evident to the professional and general community that antibiotic and drug resistance displayed by bacteria is a continuing and growing problem in the treatment of infection with potentially casastrophic effect on the health of our community. This concern is only partly reduced by our potential to develop new antimicrobial agents and vaccines. If we were able to use immunomodulators in a relatively safe and appropriate manner to target and enhance the antimicrobial power of specific components of the immune system then this could be exploited in the treatment of infection. While body proteins formed (cytokines) which modify the behaviour of the immune system are being used as pharmaceuticals, their toxic side effects are problematic to the patient. Our project focusses on one of the cytokines, tumor necrosis factor (TNF), which increases the antimicrobial activity of phagocytic cells but in addition can have quite devastating effects on other tissues in the body. This is because when TNF binds to its receptor on cells and tissues it elicits a multitude of signals inside the cell which can also precipitate illness. The purpose of our investigations is to identify which signals are responsible for increasing resistance against infection and which are not. With this information we will then see if it is feasible to selectively stimulate this signal from outside the cell since this has a better chance of succeeding as a pharmaceutical. This task is likely to be achievable since our research team has made some unique observations about TNF signalling characteristics and we have developed a peptide TNF mimetic which shows only the characteristics of increasing antimicrobial activity.Read moreRead less
Comparative Pathophysiology And Clinical Epidemiology Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$267,172.00
Summary
The simian parasite P. knowlesi is the most common cause of malaria in Malaysia and can cause severe and fatal disease. We are currently conducting a study of all malaria patients admitted to a tertiary referral hospital in Sabah, Malaysia. This will allow us to describe the epidemiological and clinical features of the hospitalised patients, including changes over time. We are also conducting novel pathophysiological studies which will allow us to understand how P. knowlesi causes sever disease.