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.
Ion Transport In The Malaria Parasite, Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$225,721.00
Summary
Malaria is an infectious disease caused by single-cell protozoan parasites which, during the course of their complex lifecycle, invade the red blood cells of their human hosts. In recent years the emergence and spread of malaria parasites with high levels of antimalarial drug resistance has given rise to the very real possibility that within a few years, there will be large parts of the world in which malaria is an untreatable disease. There is therefore an urgent need for new antimalarial drugs ....Malaria is an infectious disease caused by single-cell protozoan parasites which, during the course of their complex lifecycle, invade the red blood cells of their human hosts. In recent years the emergence and spread of malaria parasites with high levels of antimalarial drug resistance has given rise to the very real possibility that within a few years, there will be large parts of the world in which malaria is an untreatable disease. There is therefore an urgent need for new antimalarial drugs. Despite the enormous clinical significance of the malaria parasite, the basic physiology of this organism is not understood. Pathways involved in ion balance, in the uptake of essential nutrients and in the release of potentially toxic waste products all play a crucial role in the survival of the parasite and are potential chemotherapeutic targets. However the properties of these pathways are, as yet, largely unknown. This work will provide fundamental (and pharmacological) information about these pathways. It will thereby open up exciting new possibilities with regard to the chemotherapy of malaria and will provide a rational basis for a strategy in which these pathways might be exploited as antimalarial drug targets.Read moreRead less
Chloroquine Resistance And The Physiology Of The Malaria Parasite S Digestive Vacuole
Funder
National Health and Medical Research Council
Funding Amount
$287,921.00
Summary
Malaria is an infectious disease, caused by a single-celled parasite which invades the red blood cells of its human host. Each year, malaria causes the death of up to 3 million people, mostly children under the age of 5 The parasite has become resistant to most, if not all, of the antimalarial drugs presently available, and there is no vaccine. There is therefore an urgent need to develop new antimalarial drugs, and-or to devise strategies for overcoming the parasite s drug resistance mechanisms ....Malaria is an infectious disease, caused by a single-celled parasite which invades the red blood cells of its human host. Each year, malaria causes the death of up to 3 million people, mostly children under the age of 5 The parasite has become resistant to most, if not all, of the antimalarial drugs presently available, and there is no vaccine. There is therefore an urgent need to develop new antimalarial drugs, and-or to devise strategies for overcoming the parasite s drug resistance mechanisms. Chloroquine was, for many years, the mainstay of antimalarial chemotherapy and was, in many senses, a 'wonder-drug' cheap, safe and effective. However the emergence and spread of parasites that are resistant to chloroquine has meant that the drug is now largely useless as an antimalarial. Chloroquine kills (sensitive) parasite through an effect on the parasite s digestive vacuole an internal acidic compartment in which the parasite breaks down protein taken up from its host red blood cell. This compartment plays a crucial role in the growth and proliferation of the parasite. Yet we understand very little about its basic physiology, and nor do we understand the mechanism by which chloroquine-resistant parasites are able to survive exposure to the drug. The aim of the work proposed here is to gain an increased understanding of some of the mechanisms underlying the physiology of the parasite s digestive vacuole, as well as some of the factors influencing the accumulation of chloroquine within this compartment. The former part of the work may well reveal new antimalarial drug targets. The latter part of the work will increase our understanding of the mechanism of chloroquine resistance, thereby laying the groundwork for strategies by which these mechanisms might be circumvented and chloroquine-related drugs thereby restored to the front-line of our ongoing and increasingly desperate fight against malaria.Read moreRead less
Functional Characterisation Of Pendrin: The Anion Transporter Causing Pendred Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Mutations in the human pendrin protein cause progressive hearing loss from an early age in Pendred syndrome. Using techniques of molecular and cellular biology, we intend to test the effects of Pendred-causing mutations on the function of pendrin expressed in frog and cultured mammalian cells. Our approach will enable us to determine how pendrin functions in both the normal and diseased states, which is currently unknown. This will allow us to consider ways of correcting the ion channel defect a ....Mutations in the human pendrin protein cause progressive hearing loss from an early age in Pendred syndrome. Using techniques of molecular and cellular biology, we intend to test the effects of Pendred-causing mutations on the function of pendrin expressed in frog and cultured mammalian cells. Our approach will enable us to determine how pendrin functions in both the normal and diseased states, which is currently unknown. This will allow us to consider ways of correcting the ion channel defect associated with the Pendred syndrome.Read moreRead less