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.
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
Genome-based Tools To Support Urogenital Schistosomiasis Control
Funder
National Health and Medical Research Council
Funding Amount
$429,644.00
Summary
More than 100 million sub-Saharan Africans have urogenital schistosomiasis, a disease that promotes malignant cancer and HIV/AIDS. Control depends on a single drug, making resistance an imminent threat. We will deliver new molecular tools to assess parasite genetic diversity and to prioritise a panel of anti-parasitic drug targets and vaccine candidates. These outcomes will deliver the next generation of interventions against urogenital schistosomiasis.
Hookworm Therapy In Coeliac Disease (CeD), Phase 1b
Funder
National Health and Medical Research Council
Funding Amount
$865,002.00
Summary
Parasitic worms have an amazing ability to manipulate the immune system, and our research group recently discovered how they may hold the key for treating inflammatory diseases such as Coeliac Disease. The aim of my research is to further develop this novel therapy in a clinical trial and study the mechanism of how worms control the immune response, including identifying the molecules that the worm produces that could be produced as a pill-based medication for treating coeliac disease.
Targeting Phosphoinositide Metabolism In Leishmania
Funder
National Health and Medical Research Council
Funding Amount
$990,904.00
Summary
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 an important signaling pathway in these parasites that we have shown to be essential for virulence
Somatic Gene Trapping In Schistosoma Mansoni _ The Key To Functional Analysis
Funder
National Health and Medical Research Council
Funding Amount
$623,270.00
Summary
Blood flukes are endemic in 76 countries and infect 300 million people worldwide. Control largely relies on the drug praziquantel. However, its wide scale use has led to concerns that drug resistance will develop. In this study we will use ñgene trap vectorsî to introduce insertional mutations into the schistosome genome. This will help to understand the function and importance of genes in biochemical pathways used by the parasite and to define effective targets for drug and vaccine development.
Discovery Of New And Better Treatments For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$837,615.00
Summary
Sleeping sickness, or human African trypanosomiasis, is present in 36 countries where there are 60 million people at risk of infection, with 50,000-70,000 new cases and 48,000 deaths per annum. Transmitted by the bite of the tsetse fly, this disease is caused by the protozoan parasite Trypanosoma brucei, and without treatment, death is inevitable. We have discovered some compounds that weakly inhibit T.brucei and the aim of this project is to make them potent enough to become drug candidates.
Functional Dissection Of Invasion Motor Regulation In Toxoplasma Gondii
Funder
National Health and Medical Research Council
Funding Amount
$500,396.00
Summary
The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds ....The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds to develop new treatments for Toxoplasmosis.Read moreRead less
Cluster Randomised Trial Comparing One Versus Two Doses Of Ivermectin For Mass Drug Administration To Control Scabies
Funder
National Health and Medical Research Council
Funding Amount
$540,512.00
Summary
Scabies is a common skin disease in developing countries, in particular in the Pacific region. In the Western Province of Solomon Islands, one in two children suffer from the infestation, and 20% of the population. We know that mass drug administration with two doses of oral ivermectin is effective to reduce the burden of scabies in the community. We now propose a study to determine whether one single dose is as effective. This would have major public health benefits.
Does Mass Drug Administration For Scabies Result In Control Of Serious Bacterial Complications? A Proof Of Concept Towards Global Elimination.
Funder
National Health and Medical Research Council
Funding Amount
$883,760.00
Summary
Scabies is common skin disease in developing countries, in particular in the Pacific region. In Fiji, one in two children suffer from the infestation, which affects over 20% of the population. A recent study conducted in Fiji on 2000 people showed that mass drug administration (MDA) with oral ivermectin is a safe and effective way to reduce the burden of scabies in the community. We will expand the MDA program to 100,000 people, the largest study of MDA ivermectin for scabies ever undertaken.