INSIDE THE SKIN: UNDERSTANDING DIFFERENT HOST RESPONSES IN SCABIES
Funder
National Health and Medical Research Council
Funding Amount
$499,095.00
Summary
Scabies is an underlying cause of poor health in indigenous communities worldwide. Crusted scabies is a poorly understood, life-threatening form of the disease compromising the success of community control strategies. This research compares the immune response in the skin of scabies patients, and in a world-first animal model of human scabies. This will reveal specific immune defects predisposing to disease, ultimately resulting in improved skin health for disadvantaged communities
A Cluster RCT Of The Impact Of A Community-based Hygiene And Sanitation Programme On Infection With Intestinal Parasites Following Mass Albendazole Chemotherapy In Timor-Leste
Funder
National Health and Medical Research Council
Funding Amount
$1,178,136.00
Summary
Intestinal parasites cause anaemia, stunting, wasting and poor mental development in childhood, and are related to poverty and poor hygiene. Treatment with antiparasitic drugs cures infections in human hosts, but does not prevent rapid re-infection when people contact a parasite-contaminated environment. We will quantify the impact of a hygiene and sanitation programme that reduces environmental contamination in communities that receive mass treatment with the antiparasitic drug albendazole.
Development Of Specific Inhibitors Of Parasitic Enzymes
Funder
National Health and Medical Research Council
Funding Amount
$199,413.00
Summary
Parasitic diseases such as malaria, schistosomiasis, filariasis, leishmaniasis, and american trypanosomiasis (Chaga?s disease) are a significant public health issue, especially in tropical and subtropical regions of the world. In children, they cause death or impaired growth and in adults debilitating chronic illness. These parasitic infections are increasingly being recognized as responsible for chronic illness in many industrialized countries as well. There are no vaccines currently available ....Parasitic diseases such as malaria, schistosomiasis, filariasis, leishmaniasis, and american trypanosomiasis (Chaga?s disease) are a significant public health issue, especially in tropical and subtropical regions of the world. In children, they cause death or impaired growth and in adults debilitating chronic illness. These parasitic infections are increasingly being recognized as responsible for chronic illness in many industrialized countries as well. There are no vaccines currently available for the treatment of any of the human parasitic infections. In addition, the drugs that are currently used are becoming less effective because of the spread of drug resistant strains. Schistosomiasis, is the second most prevalent parasitic disease, after malaria, and is a leading cause of severe morbidity and death in many parts of the world. The disease is caused by flatworms or blood flukes, the eggs of which indirectly cause damage to the liver and spleen of infected individuals. These parasites feed on human red blood cells and use hemoglobin as their major food source. Our collaborative team (Brindley, Abbenante, Fairlie) has identified two enzymes that these flatworms need to use to eat red blood cells. This project aims to develop compounds that will stop these enzymes from functioning. These compounds will be tested to see whether they can cause the parasites to die of starvation. If successful these new compounds can be used as drugs to treat the disease and the general strategy can be applied to other blood-feeding parasites.Read moreRead less
Understanding Interactions Between Eosinophils And Tissue-Invasive Parasitic Helminths
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Eosinophils are blood cells which contribute to our defences against parasitic worms. Given the right opportunity, eosinophils can cause damage to some parasites within just a few hours of contact. This is quite a feat because parasitic worms are multicellular organisms which are much larger than eosinophils and which have evolved to live in the presence of active immune responses. To do it's job properly an eosinophil probably makes use of small soluble molecules in the blood and others fixed t ....Eosinophils are blood cells which contribute to our defences against parasitic worms. Given the right opportunity, eosinophils can cause damage to some parasites within just a few hours of contact. This is quite a feat because parasitic worms are multicellular organisms which are much larger than eosinophils and which have evolved to live in the presence of active immune responses. To do it's job properly an eosinophil probably makes use of small soluble molecules in the blood and others fixed to it's own cell surface, to recognize the parasite and to promote adhesion to the target. You might like to consider these molecules as hands grabbing onto handles on the surface of the parasite. The more hands there are, the better the grip and some hands grip more strongly than others. We are investigating what these molecules are and how they work. By understanding how eosinophils operate, we may be able to devise ways in which we can make them more effective. We are also trying to understand why some species of parasite are resistant to attack by eosinophils. We think that resistant parasites secrete substances which either block the binding of eosinophils to the parasite surface, or prevent the functioning of eosinophils that do bind. It is possible that these inhibitory substances may even kill the eosinophils before they can do their job. Resistant parasites might induce eosinophils to commit suicide, a useful property for us when we no longer need these cells, but a definite drawback if they still have a job to do. Parasitic worms have evolved to avoid at least some of our defences and sometimes they do this by mimicing natural processes important for regulating immune responses. In some diseases like asthma and allergy eosinophils slip from normal controls which regulate them and then they can cause tissue damage. Inhibitors of eosinophils which are produced by parasites might form the basis of new drugs to control these cells in diseases like asthma.Read moreRead less
Mechanisms Of In Vivo Modulation Of Granulomatous Inflammation In Human Schistosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
Schistosomiasis is a serious parasitic disease responsible for up to 300,000 deaths annually. The cause are blood flukes that produce considerable disease severity, resulting from host inflammation against the parasite eggs lodging in the liver, giving rise to fibrosis, liver damage, enlarged spleen and death. The pathogenesis is regulated by molecules called cytokines and this project will unravel the mechanisms that regulate disease progression to the severe forms of chronic schistosomiasis.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Identification And Development Of Novel Vaccine Candidates For Malaria
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
The aim is to improve methods of preventing and treating malaria by understanding the basic biological mechanisms the pathogen that causes the most severe form of human malaria, uses to invade and survive in the host erythrocyte, and survives in the hostile environment of the blood, as this determines disease outcome. I have outlined an ambitious program for the next five years that will utilize our basic knowledge of how this parasite infects and causes disease to identify novel vaccine candida ....The aim is to improve methods of preventing and treating malaria by understanding the basic biological mechanisms the pathogen that causes the most severe form of human malaria, uses to invade and survive in the host erythrocyte, and survives in the hostile environment of the blood, as this determines disease outcome. I have outlined an ambitious program for the next five years that will utilize our basic knowledge of how this parasite infects and causes disease to identify novel vaccine candidates from the genome of P. falciparum. This represents a major task that will not only provide new information for the malaria field but also identify the most promising candidates that will be pursued into clinical development. I will use two strategies; firstly, a consortium will be formed that brings together expertise that will credential the P. falciparum genome. This provides our experience in functional genomics with EHIME University who have developed methods to express correctly folded P. falciparum proteins in a high throughput system using wheat germ in vitro translation and University of Pennsylvania who have expertise in bioinformatics of the malaria genome. It provides the critical mass and expertise required for a major project. We have developed novel methods for expression of protein domains on the surface of the P. falciparum-infected erythrocyte and this has important utility for analysis of function and immune responses to these proteins. To utilize and develop these tools I will build a critical mass of expertise by forming a consortium between Australian scientists together with Papua New Guinea Institute of Medical Research, KEMRI Institute for Geographic Medicine (Kenya), Harvard University and the Swiss Tropical Institute (Switzerland). This consortium will provide access to malaria endemic areas and the expertise in fieldwork and epidemiology to fully utilize the parasite lines we will construct. The formation of these consortia will greatly strengthen our ability to identify the most promising candidates for clinical development. This will also have great benefit to Australia by increasing the internationalization of our science and therefore access of our researchers to other expertise and also provides a means for networking outside of this country. To foster and increase our leadership in malaria I will develop a Functional Genomics facility that will provide the capacity to construct large panels of transgenic parasites and the ability to develop new genetic tools. Additionally, I will develop a specialized microscopy facility at WEHI to provide the advanced equipment required for visualizing molecular events in live cells. This facility will include a number of instruments including a Line scanner confocal that will be essential for following cellular events such as protein trafficking in live parasite lines.Read moreRead less
Immunomodulatory Molecules Of Parasitic Helminths As Novel Therapeutics For Allergic Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$321,532.00
Summary
Australia has one of the highest rates of asthma in the world with almost 3 million Australians are affected by this disease. Previous research has shown that infection with various types of parasitic worms lessens the severity of asthma. The aim of this research is to find out why this happens and to isolate the ingredients from the parasite that suppress asthma. Once found, these molecules can be used to create new drugs for the prevention of asthma and allergies in children and adults.
Schistosomiasis is one of the world's most serious and prevalent diseases affecting nearly 200 million people world-wide. It is currently treated with a single drug, though there is growing concern about the development of resistance to it. In this proposal we will explore whether a new cellular pathway involving the cell death machinery we have identified in the disease-causing parasites could provide a possible target for the development of new treatments against schistosomiasis.