Host Parasite Interactions: Disease, Pathogenesis And Control
Funder
National Health and Medical Research Council
Funding Amount
$13,738,897.00
Summary
Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic p ....Our program will investigate two major global parasitic diseases: malaria and leishmaniasis. We will explore how the parasites identify and invade the host. This is a critical stage of the infection and we will characterise proteins involved as they are potential targets for drugs and vaccines against the parasites. Many of these recognition and interaction components are excellent candidates for the development of vaccines to interrupt the cycle of infection. We are also unravelling metabolic pathways unique to the parasites using a mixture of genetic and computational tools complemented with sophisticated instrumentation to chemically identify the parasite�s entire repertoire of metabolic compounds. These pathways, absent from human hosts, are also highly vulnerable and we will feed the key steps into the drug development facet of the program. Our program also looks at how the parasites cause disease and how the host responds to the disease. We will explore the reactions of the immune system to infection and consequences of the body�s (often only partially successful) attempts to fight off the disease.Read moreRead less
Structural Diversity And Evolution Of Variant-specific Surface Proteins In The Protozoan Parasite, Giardia
Funder
National Health and Medical Research Council
Funding Amount
$436,417.00
Summary
Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect ....Giardia are well-known as a cause of travellers' diarrhoea, but our knowledge about these parasites remains rudimentary. Infections are common in Australia, especially in day-care centres and outback Aboriginal communities. The 1998 Sydney water crisis highlighted the necessity of monitoring reservoirs and reticulated water for contamination by faecal cysts of both human and animal origin. The aim of this project is to learn more about the 'coat' proteins which cover the organisms. These protect the parasites against digestion, enabling them to reside indefinitely within the intestine. However, the proteins are also the principal target of host immunity. Analysis of Giardia populations has shown that as many as 150-200 different coat proteins can be made. Although individual cells have coats comprised of only a single protein type, these can 'switch' spontaneously to production of another type - a phenomenon known as 'antigenic variation'. This process occurs slowly but continuously, giving rise to 'variants' which survive successive host responses (directed against each predominant coat type) and occupy the vacancies left by the destruction of their immediate forebears. It is important to gain information about the structural diversity of these variant-specific proteins (VSP), as any 'Giardia' vaccine is likely to require inclusion of each major type. It is also important to elucidate how the 'switching' process occurs, as this may provide clues as to how it might be interrupted. The project addresses both aspects.Read moreRead less
Structure And Biosynthesis Of Entamoeba Histolytica Proteophosphoglycans
Funder
National Health and Medical Research Council
Funding Amount
$85,380.00
Summary
The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar m ....The intestinal parasite, Entamoeba histolytica is the cause of amoebic dysentry and liver abscess. It is the second most important parasitic disease after malaria, infecting 50 million people and causing 110 000 deaths annually. We have recently shown that the cell surface of infective stages of this parasite are coated by an unusual class of macromolecules called proteophosphoglycans (PPGs). These molecules appear to be major virulence factors, and the expression of PPGs with particular sugar modifications is associated with highly pathogenic strains. This proposal aims to determine the precise structure of the PPGs and to define functionally important domains in these molecules. We will also investigate how these molecules are assembled and processed in the parasite. In particular, we aim to characterize enzymes that generate PPG structures only found in virulent strains of Entamoeba histolytica. Assays will be established for these enzymes which will allow us to screen for inhibitors that may be used as potential anti-amoebic drugs. These studies will provide insights into the surface chemistry of these important human parasites and identify new drug targets.Read moreRead less
Quantifying The Microbial Health Risks Of Expanded Alternative Water Use
Funder
National Health and Medical Research Council
Funding Amount
$305,496.00
Summary
Addressing current and future water shortages requires substitution of high quality drinking water with alternative water sources for an expanded range of purposes. However, potential adverse health effects must be avoided. This project measures health risks associated with a variety of alternative water sources and water use combinations. Project outputs will help determine appropriate requirements for water treatment and help refine guidelines to ensure that water use is safe.