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
Development And Application Of Theoretical Models Of Plasmodium Transmission To Guide Malaria Elimination Efforts
Funder
National Health and Medical Research Council
Funding Amount
$315,401.00
Summary
There is currently a worldwide endeavour to eliminate malaria but there are few tools available to evaluate the impact of intervention strategies in the Asia-Pacific region. This project aims to address this deficiency by developing simulation models of Plasmodium vivax and mixed species infections, and using these new tools to investigate the likely impact of a variety of intervention strategies including bed nets, improved access to treatment and mass drug administration.
Functional Genomic Analysis Of Exported DNA J Molecules In The Malaria Parasite Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$529,698.00
Summary
Every day 3500 people die of malaria and more than 40% of the world s population is at risk. Malaria is one of the biggest scourges of mankind. This project aims to translate the available genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets against malaria is important from a humanitarian point of view, and also to safeguard Australia and its neighbouring regions against the social and economic ....Every day 3500 people die of malaria and more than 40% of the world s population is at risk. Malaria is one of the biggest scourges of mankind. This project aims to translate the available genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets against malaria is important from a humanitarian point of view, and also to safeguard Australia and its neighbouring regions against the social and economical implication of this disease. The malaria parasite seeks shelter from the host immune system by hiding in red blood cells, but at the same time it has to stay in contact with the blood environment. This is achieved by export of virulence factors onto the surface of malaria parasite-infected red blood cells, which are essential for the maintenance of malaria infection. Without these virulence factors the body's immune system can get rid of the malaria parasites by itself. For display on the surface the proteins have to pass several membranes and are transferred through the red blood cell. The whole transport and assembly process of the virulence factors into functional units is very complex and requires several helper and co-helper molecules. With the deciphering of the malarial genetic code it became obvious that the parasite displays an unusual large number of co-helper molecules, which are putatively exported into the red blood cell. We will generate transgenic parasites deficient in the expression of these exported co-helper proteins and assess their role on the pathogenesis of this debilitating infectious disease.Read moreRead less
Dissecting The Molecular Basis Of The Malaria Parasite-Erythrocyte Tight Junction Complex
Funder
National Health and Medical Research Council
Funding Amount
$547,356.00
Summary
The parasites that cause malaria disease must invade the human red blood cell to complete their lifecycle. Invasion requires the formation of a complex interface between parasite and red cell called the Tight Junction. However, this structure's molecular makeup is entirely unknown. Our research will use a combination of state-of-the-art microscopy and genetics to define, for the first time, the junction's organization, providing a critical platform for the development of a malaria vaccine.
Functional Studies On Two Essential Rhoptry Proteins Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$470,894.00
Summary
Malaria is one of the most important and deadly infectious diseases in the world, causing 250 million cases and nearly one million deaths each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. They have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed. An understanding of how proteins essential to parasite survival operate may identify novel targets for therapeutic i ....Malaria is one of the most important and deadly infectious diseases in the world, causing 250 million cases and nearly one million deaths each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. They have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed. An understanding of how proteins essential to parasite survival operate may identify novel targets for therapeutic intervention against this devastating disease.Read moreRead less
Functional Analyses Of The Major Merozoite Surface Protein Of Malaria Parasites
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to sp ....In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to specifically alter its genetic code. We have pioneered this technology and have developed many of the most effective tools for the process. Insight gained from these studies is likely to influence significantly the design and potential uses of MSP-1 as a vaccine to control malaria.Read moreRead less
Use Of Peptides From Phage Display Libraries To Probe The Function Of AMA-1 And Other Malaria Surface Proteins
Funder
National Health and Medical Research Council
Funding Amount
$316,650.00
Summary
Malaria remains a major cause of mortality and morbidity worldwide. Much current research is aimed at exploring the molecular interactions between malarial proteins and host components in order to gain a deeper understanding of parasite virulence mechanisms, design alternative anti-malarial approaches and improve vaccine design. The apical membrane antigen-1( AMA-1) is a surface exposed protein which is thought to play a crucial role in invasion of red blood cells by malaria parasites, and is cu ....Malaria remains a major cause of mortality and morbidity worldwide. Much current research is aimed at exploring the molecular interactions between malarial proteins and host components in order to gain a deeper understanding of parasite virulence mechanisms, design alternative anti-malarial approaches and improve vaccine design. The apical membrane antigen-1( AMA-1) is a surface exposed protein which is thought to play a crucial role in invasion of red blood cells by malaria parasites, and is currently one of the leading asexual stage vaccine candidates. While antibodies to AMA-1 prevents malaria invasion, little is known about the role of the antigen in the invasion process. The aim of this proposal is to investigate the molecular interactions that makes AMA-1 an important player in the invasion process. We propose to map the regions of AMA-1 responsible for binding a set of peptides which we have isolated from random peptide libraries. Since these peptides inhibit the invasion of parasites into red blood cells, regions of AMA1- that bind these peptides will be of functional significance. A further outcome will be the identification of peptide residues essential for the inhibition of invasion followed by in vitro evolution of these peptides to improve their binding and inhibitory properties. A molecular description of how AMA1 binding peptides prevent parasite invasion of host erythrocytes will improve our understanding of the invasion process, and aid in improving vaccines based on AMA-1. Furthermore, this peptide-AMA-1 interaction will be assessed as a possible target for the development of novel anti-malarial therapies. Using random peptide libraries we have selected peptides that specifically bind to other merozoite surface proteins thought to be involved in merozoite invasion of erythrocytes. The ability of these peptides to inhibit merozoite invasion will be examined and characterised as described above.Read moreRead less
Trafficking And Expression Of PfEMP1 On The Surface Of P.falciparum-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Malaria causes over 2 million deaths each year. The parasite infects human red blood cells and expresses a virulence protein on the erythrocyte surface allowing it to adhere to the microcapillaries preventing clearance through the spleen. We aim to understand how the parasite is able to express this virulence protein on the parasite-infected red blood cell surface. Identification of the proteins involved will provide potential drug targets to develop novel antimalarial compounds and strategies.