ROLE OF PROTEASE ACTIVATED RECEPTORS IN CYSTIC FIBROSIS LUNG PATHOLOGY
Funder
National Health and Medical Research Council
Funding Amount
$176,521.00
Summary
Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the ....Cystic fibrosis is a major debilitating disease which eventually kills those with the genetic defect. The lungs of patients become infected with the bacteria Pseudomonas aeruginosa or Burkolderia cepacia which initiate a chronic and vicious cycle of inflammation resulting in lung failure. Proteases released by the organisms as well as host cells (neutrophils) involved in clearing the infections play a major role in this cycle by causing the release of molecules (cytokines and mediators) from the respiratory epithelium. These, in turn, stimulate the movement of neutrophils from the blood to the lung where damage then ensues. How these proteases stimulate release is unclear but studies suggest other proteases involved in inflammation induce release through their interaction with a novel group of protease activated receptors (PAR). In this study, we wish to determine whether PAR are activated or inactivated by host and bacterial proteases commonly seen in the lungs of CF patients. If PAR are activated, it may be possible to develop antagonists which target specific PARS to modulate respiratory epithelial cell function. If inactivated, preservation by adjunct protease inhibitor treatment may be highly beneficial. We will use in vitro technology and cells derived from non-CF and CF patients. This study has great potential in the development of adjunct anti-inflammatory therapy for the treatment of both CF and other inflammatory lung diseases.Read moreRead less
Transport Pathways Of Host-derived Iron In Schistosomes Parasites
Funder
National Health and Medical Research Council
Funding Amount
$322,091.00
Summary
This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular resp ....This project will identify the diversity and biological roles of receptors for metabolic iron expressed on the body surface of the parasitic blood flukes (schistosomes) of humans. Schistosomes are a major health problem in many tropical countries and are responsible for significant human morbidity and lost productivity. Adult worms feed on human blood, from which derive amino acids for the production of many hundreds of eggs released per day into the human blood stream. The intense cellular response induced by parasite eggs trapped in body organs is the major cause of chronic human disease. We have discovered two intriguing phenomena of iron metabolism in schistosomes. Firstly, schistosomes have a greater reliance on iron than many other organisms, storing a surfeit in cells that produce the protein-rich egg shell. Secondly, a major transmembrane iron transporter of the parasites, thought to be involved in the uptake of iron, is found on the parasite external body surface and not in the parasite intestine. The extensive nutritional dependence of these worms on iron and the surface location of mediators of iron uptake raise the exciting possibility that we have uncovered a novel system that might be exploited for vaccine or drug-mediated control of these significant human parasites. If we can dissect the pathways schistosomes use to derive iron from their hosts, we may be able to generate vaccines to block this nutritional pathway, or use drugs to block embryogenesis. This project is a fact-finding mission that asks if the host-interactive tegument of these parasites is a major source of metabolic iron. Molecules we demonstrate to be present on the surface will be tested as vaccine candidates in mouse vaccine trialsRead moreRead less
A Five Year Follow-up Of People With Type 2 Diabetes & Other States Of Glucose Intolerance And Associated Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$2,677,855.00
Summary
The Australian Prospective Diabetes Study (APDS) is a 5 year follow-up study established to examine the natural history of diabetes and its complications, as well as heart disease and kidney disease. It is a follow-up to the recently completed AusDiab study and addresses some of the important gaps that exist nationally and internationally in the understanding of the burden of Type 2 diabetes and related problems. AusDiab found that 1 in 4 Australians aged 25 years and over has either diabetes or ....The Australian Prospective Diabetes Study (APDS) is a 5 year follow-up study established to examine the natural history of diabetes and its complications, as well as heart disease and kidney disease. It is a follow-up to the recently completed AusDiab study and addresses some of the important gaps that exist nationally and internationally in the understanding of the burden of Type 2 diabetes and related problems. AusDiab found that 1 in 4 Australians aged 25 years and over has either diabetes or a condition of impaired glucose metabolism (this condition is associated with substantially increased immediate risk of heart disease as well as increased risk of diabetes in the future). This new study-APDS, will be the first Australian and indeed international study of its type. We intend to invite 7000 out of the original 11,247 AusDiab sample to participate. Participants who agree to take part in the follow-up study will be involved in 2 ways: 1. A 6-12 monthly contact with participants by telephone or mail to allow reporting of changes in health and utilisation of health services. 2. A 5 year biomedical follow-up survey. This will involve a survey team travelling around Australia to test the participants for diabetes, heart and kidney disease and cardiovascular risk factors (e.g. blood pressure and cholesterol). It will accurately define how many Australians are likely to develop diabetes (as well as kidney and heart disease) in the future, and who is at highest risk. It is expected that outcomes from this study will provide crucial information for both planning and testing public health policy and for the appropriate allocation of resources including specific treatments of individuals and specific groups with or at risk of Type 2 diabetes and its complications within the Australian population.Read moreRead less
This study proposes to examine the quality of procedural medical care provided by rural doctors who are not specialists. The disciplines of Anaesthetics, Surgery and Obstetrics will be included. Most of these services in rural Australia are not provided by specialist medical practitioners, but rather by rural general practitioners who have obtained additional training, albeit shorter than that undertaken by specialist trainees, and who are supported by skilled nurses and other health professiona ....This study proposes to examine the quality of procedural medical care provided by rural doctors who are not specialists. The disciplines of Anaesthetics, Surgery and Obstetrics will be included. Most of these services in rural Australia are not provided by specialist medical practitioners, but rather by rural general practitioners who have obtained additional training, albeit shorter than that undertaken by specialist trainees, and who are supported by skilled nurses and other health professionals in relatively small rural hospitals. Patients and rural doctors often have little choice but to manage urgent cases locally and in some cases experienced and skilled local teams are able to offer a wider range of services, including a limited number of elective procedures. Despite underlying assumptions that the quality of the services cannot match that of specialist care in larger hospitals, there is no agreement on what constitutes quality of rural procedural care and little evidence that the quality is different. This issue is important as substantial government funds are spent on recruiting, training and retaining a qualified rural medical workforce, and yet fewer rural doctors are providing these services and fewer rural hospitals have the facilities to support those rural doctors still providing the services. Further, measuring the quality of care is a complex issue on which different stakeholders may have different views. This study proposes a multi-perspective approach to assessing the quality of care through a number of case studies provided by rural doctors.Read moreRead less
Validating And Optimising The Analysis Of Magnetic Resonance Physiology Data
Funder
National Health and Medical Research Council
Funding Amount
$91,725.00
Summary
Combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is used to detect the anatomical areas in the brain that show electrical activity. Several centres worldwide use this technique to localise the seizure focus in patients with epilepsy. However, there is a lack of validation of the currently applied techniques. Current analysis methods have been developed and validated for other fMRI paradigms, such as motor tasks. It is not known whether the same principles ar ....Combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is used to detect the anatomical areas in the brain that show electrical activity. Several centres worldwide use this technique to localise the seizure focus in patients with epilepsy. However, there is a lack of validation of the currently applied techniques. Current analysis methods have been developed and validated for other fMRI paradigms, such as motor tasks. It is not known whether the same principles are applicable and optimal for fMRI-EEG data. The proposed project aims at validating and optimising the analysis strategies for fMRI-EEG data.Read moreRead less