Polysaccharide Biosynthesis As A New Drug Target In Leishmania Parasites
Funder
National Health and Medical Research Council
Funding Amount
$422,517.00
Summary
Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involv ....Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involved in its synthesis and develop new chemical tools for generating highly specific inhibitors of Leishmania sugar biosynthesis. This project will provide new insights into processes that are essential for the survival and infectivity of an improtant group of human pathogens, and lead to the development of new classes of enzyme inhibitors with anti-parasite activity.Read moreRead less
Tissue Specific Antigen Presenting Cell Functions During Infection.
Funder
National Health and Medical Research Council
Funding Amount
$555,325.00
Summary
T cell activation is often inefficient following infection or vaccination, resulting in poor control of pathogens. In this grant, we propose to investigate the cellular basis for sub-optimal CD4+ T cell activation following infection. Specifically, we will study the roles of antigen presenting cells in CD4+ T cell activation in an experimental model of visceral leishmaniasis caused by the human protozoan parasite Leishmania donovani.
Metabolomic Analysis Of Leishmania Parasites; Identifying Metabolic Pathways Required For Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Leishmania are single-celled parasites that target a major class of immune cell, affecting millions and killing thousands of people worldwide. We have developed new approaches for investigating how these parasites survive in the immune cells, and why different species of Leishmania cause markedly different pathologies. This information will be used to identify and validate new drug targets in these parasites.
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.
Immunological Prevention Of Cysticercosis And Hydatid Disease
Funder
National Health and Medical Research Council
Funding Amount
$510,000.00
Summary
Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, there ....Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, thereby breaking the parasite life-cycle and preventing the diseases being passed to humans. Substantial preliminary research has been undertaken by the applicant, including completion of successful preliminary vaccine trials. This project will optimise the vaccines and complete initial field trials in countries with high rates of disease transmission.Read moreRead less
From Maps To Efficient Multi-parasite Control In The Philippines
Funder
National Health and Medical Research Council
Funding Amount
$358,121.00
Summary
Schistosomiasis and soil-transmitted helminths are major parasitic infections in Asia, causing anaemia, poor growth and poor school performance and death in some chronic schistosomiasis cases. We will use maps to demonstrate the geographic distribution of these parasites in the Philippines. We will estimate the impact and costs and benefits of parasite control programmes. This research will help plan more efficient parasite control and reduce the impact of these infections in the Philippines.
Impact Of The Three Gorges Dam On Transmission And Future Control Of Human Schistosomiasis In China
Funder
National Health and Medical Research Council
Funding Amount
$1,420,135.00
Summary
A million Chinese have schistosomiasis or snail fever. When the Three Gorges Dam on the Yangtze River is fully operational, considerable environmental-ecological changes will result, increasing spread of this parasitic disease. In a unique study we will assess the impact of the Dam on schistosomiasis, and test and model a series of options for its control. The findings will be important for China and other areas where schistosomiasis occurs and where similar dams are planned or are under way.
Development Of Purine Nucleoside Phosphonates As Anti-malarial Drugs Targeting Nuceloside Synthesis In Plasmodium
Funder
National Health and Medical Research Council
Funding Amount
$428,917.00
Summary
Malaria is one of the most serious infectious diseases today. Because of its location in a malaria endemic region, the tropical regions (above 19 S in latitude) of Australia face an emerging threat. The causative agent of the disease is the parasite, Plasmodium. Because of increasing resistance to existing medicines, new drugs are now needed. The drugs we will develop target the parasites replication cycle and are related in structure to those in use to treat viral infections including AIDS.
Defining The Roles Of TNF, Lymphotoxin Alpha And LIGHT In Experimental Visceral Leishmaniasis
Funder
National Health and Medical Research Council
Funding Amount
$410,148.00
Summary
Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate sig ....Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate significant tissue pathology, particularly in the spleen, following L. donovani infection. In this grant, we will define the roles of several key members of the TNF family in the generation of immunity and pathology during experimental VL. We will also test if the activity of these molecules can be modulated to control disease without detrimental side effects. Results from this research have implication for the design of new vaccines and therapeutics to control VL. In addition, given the important role of TNF family members in cancers and autoimmune diseases, the work in this grant will have advance our understanding of pathogenic processes that are common to many important human diseases.Read moreRead less
Functional Characterisation Of A Maurer's Cleft Protein Involved In Adhesion Of Malaria-infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$160,500.00
Summary
Malaria is a serious disease that affects half of the world's population and frequently kills humans after a bout of high fever and coma. Many of those who die are young children who live in areas of the world where health care is very poor. The effectiveness of drugs that we currently have available to prevent or treat malaria is rapidly reducing and there is no vaccine available to prevent people from catching the disease. Our research is important because in order to make better medicines for ....Malaria is a serious disease that affects half of the world's population and frequently kills humans after a bout of high fever and coma. Many of those who die are young children who live in areas of the world where health care is very poor. The effectiveness of drugs that we currently have available to prevent or treat malaria is rapidly reducing and there is no vaccine available to prevent people from catching the disease. Our research is important because in order to make better medicines for malaria we have to get to know more about how the malaria parasite makes people sick. The most vicious form of malaria is caused by a tiny parasite called Plasmodium falciparum that lives inside the red blood cells in our bodies. As these minute parasites grow, they make a lot of major changes to the red blood cells and as a result they become very stiff and sticky. This is very bad for the infected person because instead of flowing around the body like normal red blood cells, the infected cells become trapped in small veins and can no longer do their normal job. The ability of the parasite to redecorate red blood cells and make them stiff and sticky is what makes this type of malaria so dangerous, particularly when red cells get stuck in the brain. The research that we will do here will help us to understand the ways in which the malaria parasite sends out these sticky substances to the walls of red blood cells. Eventually, this will help us to find ways to stop the red blood cells from becoming sticky and prevent so many people from becoming very sick and dying with malaria.Read moreRead less