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
Metabolomic Analysis Of Plasmodum Falciparum And Mode Of Action Of Antimalarial Compounds
Funder
National Health and Medical Research Council
Funding Amount
$917,196.00
Summary
There is an urgent need to develop new drugs to treat malaria, one of the most important diseases to afflict humanity. We have developed new analytical approaches for measuring parasite metabolism while they live inside host cells. These approaches will be used to identify metabolic pathways that are essential for parasite infectivity and to understand the mode of action of new classes of antimalarial compounds
There is an urgent need to develop new drugs to treat human leishmaniasis, a disease that causes debilitating and life-threatening diseases in millions of people worldwide. This project will investigate whether it is possible to develop a new generation of drugs that target a novel metabolic pathway in these parasites that we have shown to be essential for virulence.
One third of the world's population is infected with the protozoan parasite, Toxoplasma gondii, which can cause life-threatening infections. This proposal will utilize new analytical technologies to understand how these parasites are able to survive in a wide variety of different host cells, how they manage to persist within brain and muscle tissue for the life of the patient and how infection may be linked to mental health disorders, such as schizopohrenia.
Understanding And Targeting Coenzyme A Biosynthesis And Utilisation In Plasmodium Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$556,114.00
Summary
This grant describes a series of studies designed to understand how the human malaria parasite P. falciparum metabolises vitamin B5, an essential molecule for the parasite. We will also carry out experiments to determine how a new series of vitamin B5 analogues we have developed kill the parasite and aim to start developing these compounds into new and much needed antimalarial medications.
Targeting Toxoplasma Gondii Latent Stages Responsible For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,107.00
Summary
Many microbial pathogens become resistant to host immune response and drugs by entering a slow-growing, dormant state. These stages are commonly responsible for long term, chronic infections. We will investigate the molecular basis of dormancy in Toxoplasma gondii, which infects one in three people. These studies will identify metabolic pathways that are essential for dormancy with the view of developing new therapies for treating long term, recurrent infections.
Identifying Metabolic Pathways In Leishmania Parasites And Their Host Cells Required For Virulence
Funder
National Health and Medical Research Council
Funding Amount
$989,110.00
Summary
Our lack of understanding of microbial metabolism in infected animal tissues has hindered the development of effective therapies. This is particularly true for many parasitic diseases, including Leishmania spp that cause devastating disease throughout the tropics. We will utilize a range of innovative analytical and genetic approaches to identify metabolic pathway in Leishmania parasites and infected host cells that are required for virulence and are potential drug targets.
Mechanism Of Neurological Complications In Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$53,609.00
Summary
Malaria kills 1 million young children every year. About the same number are saved by treatment with anti-malarial drugs but have brain damage, leading to problems of understanding, learning or memory. The processes in the brain that lead to these changes are unknown. I will investigate a biochemical pathway that is activated during malaria infection, because I propose that this may cause the brain damage that leads to the long-term cognitive problems in survivors.
Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking ....Transfer ribonucleic acid (tRNA) synthetases as drug targets in Plasmodium falciparum. Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. The Fellow will study a new class of parasite drug targets, the transfer ribonucleic acid (tRNA) synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.Read moreRead less