Signalling During Red Blood Cell Invasion By Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$357,414.00
Summary
Malaria is one of the world's most devastating infectious diseases and is caused by a parasite called Plasmodium falciparum. AMA1 is a parasite surface protein crucial for blood cell invasion but how it works is not understood. We are investigating if AMA1 plays a role in helping the parasite sense when it has contacted a blood cell and should invade. Discovering how parasites attach to and invade bloods cells is a priority for the development of anti-parasite drugs and vaccines
Cytoskeletal Remodeling Of The Erythrocyte During Malaria Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$559,807.00
Summary
Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease ....Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease establishment.Read moreRead less
Elucidating The Mechanisms Of Action Of And Resistance To Endoperoxide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$716,755.00
Summary
Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targe ....Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targetted treatments.Read moreRead less
Effector Export In P. Falciparum Infected Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$1,066,920.00
Summary
We will investigate malaria, a parasitic disease that kills over 450,000 people a year. We will explore how the parasite identifies, invades and remodels the host cells in which it lives, scavenging nutrients and hiding from the immune system. We will characterize the proteins involved in these critical events, as they are potential targets for drugs. We will study how parasites cause disease and how the host responds to infection.
The Structural Resolution Of PTEX, The Translocon Of Virulence Proteins And Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
The extraordinary virulence of malaria parasites is in part due to their ability to export hundreds of proteins into their red blood cell hosts that help them obtain nutrients and avoid the immune system. Recently we discovered the molecular machine that exports proteins into the host cell and we now wish to establish how it works so drugs can be tailored to block the machine and kill the parasites.
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 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.