Dissecting The Molecular Basis Of Actin Filament Disassembly In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$576,716.00
Summary
Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug targe ....Cell movement by the malaria parasites is fundamental to parasite infection and disease. However, whilst core components of the parasite motor driving movement are known, little is understood about their regulation, in particular actin – the dynamic force behind all parasite motility. Here by dissecting the role of actin-depolymerizing-factor-1, an essential parasite actin regulator, we hope to reveal one of the central processes that underlies motility and develop it into a potential drug target.Read moreRead less
The Role Of Exosome-like Vesicles In Cell-cell Communication Between P. Falciparum-infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$629,058.00
Summary
Cell-cell communication is a critically important mechanism for information exchange promoting cell survival by control of features such as population density and differentiation state. Malaria is caused by the parasite Plasmodium falciparum. We have shown that P. falciparum-infected red blood cells directly communicate between parasites within a population using small vesicles that are capable of delivering genes and signals. Our work aims to understand this process.
A New Animal Model For Genitourinary Schistosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$395,711.00
Summary
Schistosoma haematobium causes genitourinary schistosomiasis, a serious disease that affects reproductive health, urinary system health and potentially bladder cancer. This species is the most pathogenic species of all schistosomes, but comparatively less is know about it than other species because of a lack of a suitable model. We need a suitable model host for this important parasite. This project will test whether newborn pigs can be used as laboratory models.
Compounded by massive global food and water shortages, neglected tropical disease (NTD) pathogens have a devastating and long-term impact on billions of humans worldwide. Unlocking the fundamental molecular biology of these pathogens, particularly carcinogens, employing a raft of Frontier Technologies, will lead to new ways of controlling NTDs and will have substantial outcomes through the development of new drugs, vaccines and/or diagnostic tests. We will use cutting-edge molecular technologies ....Compounded by massive global food and water shortages, neglected tropical disease (NTD) pathogens have a devastating and long-term impact on billions of humans worldwide. Unlocking the fundamental molecular biology of these pathogens, particularly carcinogens, employing a raft of Frontier Technologies, will lead to new ways of controlling NTDs and will have substantial outcomes through the development of new drugs, vaccines and/or diagnostic tests. We will use cutting-edge molecular technologies to tackle this area head-on.Read moreRead less
Targeting Commitment To Sexual Differentiation In Plasmodium
Funder
National Health and Medical Research Council
Funding Amount
$688,954.00
Summary
Efforts to control malaria in endemic areas are very often thwarted by "carriers", who have transmissible parasites in their bloodstream (called gametocytes), but who suffer no symptoms. These gametocytes serve as a reservoir ready to reinitiate disease transmission when mosquito numbers increase. This project will develop urgently needed strategies to target gametocytes, and thus block malaria transmission.
Functional Dissection Of The Malaria RhopH Complex And Its Contribution To New Permeation Pathways
Funder
National Health and Medical Research Council
Funding Amount
$604,718.00
Summary
The ability of Plasmodium to invade and remodel its host erythrocyte are the most significant contributors to its ability to cause the disease malaria. This project aims to understand how proteins secreted from a specialized rhoptry organelle during erythrocyte invasion help Plasmodium to remodel the erythrocyte so that the parasite can gain access to the vital nutrients it requires for survival. This research will validate whether drugs targeting the rhoptry proteins are viable drug targets.
Retargeting The Antibiotic Azithromycin As An Antimalarial With Dual Modality.
Funder
National Health and Medical Research Council
Funding Amount
$773,613.00
Summary
Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensure alternative treatment strategies are available. We will retarget the safe and widely used antibiotic azithromycin as an antimalarial with dual modalities against parasite invasion and growth inside the host red blood cell. This strategy has significant potential to increase drug efficacy while reducing the chances for the development of resistance.
Targeting An Ion Pump In The Malaria Parasite With Multiple Compound Classes
Funder
National Health and Medical Research Council
Funding Amount
$384,686.00
Summary
Large-scale antimalarial drug screening projects have identified three different classes of compound that kill the malaria parasite at extremely low doses and which hold real promise as next-generation antimalarials. Genetic evidence, as well as preliminary data from our own lab, has led us to the hypothesis that all three compound classes exert their antimalarial effect by blocking a molecular ion pump on the parasite surface. The aim of this study is to test this.
Plasmodium vivax is a parasite that invades the youngest of human red blood cells. Our work will reveal how this malaria parasite enters our blood cells and the molecular mechanisms that allows successful invasion. This proposal will redefine our understanding of P. vivax invasion and explore novel ways to block its entry into red blood cells and therefore prevent malaria infection.
The Control And Regulatory Mechanisms Of Artemisinin Induced Dormancy In P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$495,552.00
Summary
Malaria is a major global health problem and can only be reliably treated with artemisinin combinations in many areas due to widespread of drug resistance. However a proportion of parasites appear to be able to avoid the lethal effects of the drug by becoming “dormant” following exposure. They resume growth after the drug is wanned, a feature which is reminisent to cell cycle arrest. This study investigates the role of cell cycle machinery in dormancy following arteminsinin treatment.