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
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
Changing Decision-making Behaviour In General Practice By Providing Access To Online Evidence.
Funder
National Health and Medical Research Council
Funding Amount
$206,375.00
Summary
The case for a shift to evidence-based practice, and the substantial economic and health outcome benefits of that shift, have been repeatedly made. Despite the vision, significant barriers to evidence-based practice remain, and the demonstration of a positive role for on-line systems would result in a significant change in strategies for clinician behaviour change. This study will make a specific and significant contribution to our understanding of the efficacy and effectiveness of online eviden ....The case for a shift to evidence-based practice, and the substantial economic and health outcome benefits of that shift, have been repeatedly made. Despite the vision, significant barriers to evidence-based practice remain, and the demonstration of a positive role for on-line systems would result in a significant change in strategies for clinician behaviour change. This study will make a specific and significant contribution to our understanding of the efficacy and effectiveness of online evidence retrieval systems as a component in any evidence-based strategy, through a rigorous and controlled approach to the study of clinical behaviour change. It will also provide a powerful test of the value of search filters as a specific technology in support of evidence retrieval. The focus on prescribing patterns in NHMRC priority areas as an outcome measure will also provide a significant data set reflecting current practice in primary care.Read moreRead less