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Investigation Of A Virulence Locus On Chromosome 9 Of Plasmodium Falciparum Utilising Improved Transfection Technology
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Worldwide, there are approximately 500 million cases of malaria per year with over 1 million deaths, predominately in children under 5 years of age in Africa. We have identified a region of the malaria parasites' genome that we believe is responsible for two aspects of the parasites life cycle. Firstly, there is a gene responsible for the development of the sexual stage of the parasite that allows transmission from humans to mosquitoes and secondly there are two other genes that allow the parasi ....Worldwide, there are approximately 500 million cases of malaria per year with over 1 million deaths, predominately in children under 5 years of age in Africa. We have identified a region of the malaria parasites' genome that we believe is responsible for two aspects of the parasites life cycle. Firstly, there is a gene responsible for the development of the sexual stage of the parasite that allows transmission from humans to mosquitoes and secondly there are two other genes that allow the parasite to evade the human hosts immune system. We intend to investigate these genes using newly developed genetic engineering tools with the ultimate aim of finding agents or vaccines that can block their action, thus preventing either transmission of the parasite or the severe effects of infection.Read moreRead less
Novel Use Of Fungal Entomopathogens For Sustainable Control Of Mosquito-borne Viruses
Funder
National Health and Medical Research Council
Funding Amount
$605,993.00
Summary
Mosquito-born viruses such as Dengue, Ross River and Barmah Forest are increasing in regional significance. At a broader scale, an estimated 2.5 billion people live in areas at risk of epidemic Dengue transmission. Chemical insecticides are the mainstay of current mosquito control throughout many parts of the world. However, problems of insecticide resistance, environmental contamination and risks to human health, mean that chemical pesticides have not provided a universal solution, either as ou ....Mosquito-born viruses such as Dengue, Ross River and Barmah Forest are increasing in regional significance. At a broader scale, an estimated 2.5 billion people live in areas at risk of epidemic Dengue transmission. Chemical insecticides are the mainstay of current mosquito control throughout many parts of the world. However, problems of insecticide resistance, environmental contamination and risks to human health, mean that chemical pesticides have not provided a universal solution, either as outdoor sprays, residual house sprays or as insecticide treated nets. This creates a pressing need for practical alternatives. Building on approaches and technologies developed for control of locusts in Australia and Africa, we have recently discovered that the ability of mosquitoes to transmit malaria can be substantially reduced with insect fungal pathogens used as biological pesticides. We found that exposure to biopesticide-treated surfaces reduced the number of mosquitoes able to transmit malaria 80-fold. Other supporting data from semi-field trials confirm the feasibility of infecting mosquitoes under real field conditions. Together, these results represent a significant advance in the development of a cheap and sustainable biological alternative to chemical insecticides for disease control. We now wish to extend this research to explore the potential for use of fungal pathogens in control of mosquito-borne viruses. Preliminary studies already confirm that we can infect the key mosquito species responsible for transmitting Dengue. The aim of the current project is to conduct a more comprehensive evaluation of a wider range of fungal isolates to identify strains with the greatest potential to stop transmission of mosquito-borne viruses. The longer term goal is to translate this research into a practical product. Such a product would offer a cheap, environmentally friendly disease control measure, with reduced potential for resistance evolution.Read moreRead less
The Clag Gene Family Of P. Falciparum; Examining Roles In Cytoadherence, Rheological Properties Or Tissue Trophism.
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the ....There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene. Most Australians know of clag as a glue, and our data provides evidence that it sticks the parasitised red cells to veins via a protein called CD36 on the internal surface of veins. Our evidence for this has been published in two prestigious international journals. We propose here to examine the same gene in a mouse malaria model as it should be highly informative to see what effect destoying clag has on the disease in a living animal. Obviously this cannot be tested in people. It has now become clear that there are a number of slightly different clag genes and we do not know what the others do. We propose here that they may enable the parasitised red cells to stick to targets other than CD36 on the surfaces of veins, or affect blood flow of infected cells, or direct the parasitised red cells to other organs. The experiments that we propose should reveal whether these ideas are true.Read moreRead less
Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate t ....Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate the mechanism by which the parasite kill these cells, so that novel therapies can be designed.Read moreRead less
Placental Malaria, Placental Function, Nutrient Transport And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$483,517.00
Summary
Malaria infection in the placenta impairs the baby's growth, probably by causing placental inflammation. We believe this inflammation interferes with the ability of placental cells to transport nutrients such as amino acids and glucose from mother to baby. We will test this by examining the expression of genes and proteins involved in nutrient transport in placental samples from pregnant women, and in cell lines, and will examine how malaria affects growth factors that control this process.
Spatial Analysis Of The An. Punctulatus Group Of Malaria Vectors In Australia And Papua New Guinea.
Funder
National Health and Medical Research Council
Funding Amount
$66,430.00
Summary
Malaria has been eradicated from Australia but the country remains receptive to its reintroduction as the mosquitoes which transmit the disease are still present in the tropical north of the country. These are the Anopheles punctulatus group which are the major malaria vectors in the south west Pacific region. The Australian Army Malaria Institute conducted Operation Anopheles to collect these mosquitoes in northern Australia and Papua New Guinea by detailed surveys with the aid of helicopters a ....Malaria has been eradicated from Australia but the country remains receptive to its reintroduction as the mosquitoes which transmit the disease are still present in the tropical north of the country. These are the Anopheles punctulatus group which are the major malaria vectors in the south west Pacific region. The Australian Army Malaria Institute conducted Operation Anopheles to collect these mosquitoes in northern Australia and Papua New Guinea by detailed surveys with the aid of helicopters and 4-wheel-drive vehicles. These surveys, which were made for a month each year between 1984-1998, represent the most detailed dataset of mosquito locality records that have ever been produced. This project will utilise the computing power of modern Geographical Information Systems (GIS) software and computer induction techniques to spatially map the range of the different mosquitoes collected during Operation Anopheles to highlight environmental characteristics which limit their distribution and to permit control activities to accurately target the species which actually transmit malaria.Read moreRead less
Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by ....Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene; most Australians know of Clag as a glue. Our evidence for this has been accepted for publication by the prestigious USA journal Proceedings of the National Academy of Sciences of the USA. Recent work overseas aimed at determining the entire DNA sequence of the malaria parasite has shown that clag is not alone; there are at least 9 slightly different clag genes in the malaria parasite. What do the others do? We propose two possibilities. The first is that all of them act in cytoadherence but that different clags enable the parasitised cells to stick to different things on the lining of veins. The second is that they enable the parasitised cells, or perhaps the parasites alone, to stick to other things at different stages of the complex life cycle of the parasite. The experiments that we propose should show whether either of these proposals is true.Read moreRead less
Dissecting The Molecular Basis Of The Malaria Parasite-Erythrocyte Tight Junction Complex
Funder
National Health and Medical Research Council
Funding Amount
$547,356.00
Summary
The parasites that cause malaria disease must invade the human red blood cell to complete their lifecycle. Invasion requires the formation of a complex interface between parasite and red cell called the Tight Junction. However, this structure's molecular makeup is entirely unknown. Our research will use a combination of state-of-the-art microscopy and genetics to define, for the first time, the junction's organization, providing a critical platform for the development of a malaria vaccine.
Role Of NK Receptors In Susceptibility And Resistance To Human Malaria
Funder
National Health and Medical Research Council
Funding Amount
$546,588.00
Summary
Malaria kills 2 million children every year. However, many eventually become resistant to the disease. What causes some kids to die, and how others become resistant, is unknown. We believe that genes for Natural Killer molecules in the immune system can protect people against malaria, but can also over-react in the wrong way and make things worse. We plan to investigate the role of Natural Killer genes in causing disease and also protecting in young children in Papua New Guinea against malaria.
Phagocytic Clearance And Immune Activation In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Macrophage white blood cells clear malaria infected cells by eating them, by three routes- by recognising ANTIBODIES or COMPLEMENT on the cell surface, or by the cell BINDING directly to the macrophage. Each has different results, such as amounts of cytokines produced. Cytokines clear malaria; in excess they can cause fatal immune pathology. We will investigate how variations in amount of antibody and complement and route of uptake of malaria infected cells might determine malaria outcome.