Antibodies That Inhibit Erythrocyte Invasion By Plasmodium Falciparum And Their Role In Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$389,250.00
Summary
Malaria continues to be a leading cause of death and disease globally, resulting in up to 3 million deaths annually, mainly among children. After repeated episodes of malaria, children that survive develop immune responses that protect them against further episodes. Currently, it is not well understood how these protective immune responses work. Malaria parasites infect red blood cells and multiply inside them, leading to the symptoms and serious complications of malaria. Antibodies that block t ....Malaria continues to be a leading cause of death and disease globally, resulting in up to 3 million deaths annually, mainly among children. After repeated episodes of malaria, children that survive develop immune responses that protect them against further episodes. Currently, it is not well understood how these protective immune responses work. Malaria parasites infect red blood cells and multiply inside them, leading to the symptoms and serious complications of malaria. Antibodies that block the entry of parasites into red blood cells have been found in adults who are immune to malaria, and can be stimulated by certain vaccines, but little is known about this immune response and whether it is effective in protecting against malaria. Many investigators have focussed on the detection of antibodies, but we will focus on the function of antibodies in blocking parasite entry into red blood cells, thereby blocking parasite growth. We will examine how these antibodies develop among children at risk of malaria living in a region of Kenya where malaria is a major cause of death, and whether these antibodies protect children against malarial illness. Malaria parasites produce a variety of different proteins that enable them to stick and then enter red blood cells. We will identify the main proteins that antibodies target to block malaria growth. We will also determine whether variations in the proteins produced by malaria are used to avoid immune responses. Results from these studies will advance our understanding of how the immune system protects against malaria. With this knowledge, vaccines can be designed that will target essential malaria proteins, and reduce or prevent malaria infection and illness.Read moreRead less
Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology t ....Functional Genomic Analysis of Exported DNAJ Molecules in the Malaria Parasite Plasmodium falciparum. Malaria is not only a global health problem, but also affects countries surrounding Australia like PNG and Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (eg. aid and security personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for P. falciparum infection. Developing novel targets is mandated by humanity, and also to safeguard Australia's region against the social and economical implication of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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Molecular dissection of malaria parasite motility and host-cell invasion across the lifecycle. Malaria parasites move in a unique way, gliding across cell surfaces and infecting host cells using a unique molecular motor. This research aims to understand the molecular mechanics behind parasite movement and use this to develop novel drugs that might throw a spanner in the parasite motor, blocking movement and thereby preventing malaria disease.
Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identi ....Biogenesis of red blood cell membrane modifications by the malaria parasite Plasmodium falciparum. Malaria is not only a major global health problem, but also affects countries neighbouring Australia like Indonesia, reducing the region's stability and prosperity. Environmental changes and increased mobility of people (aid and military personnel) make Australia itself more prone to malaria. The project will translate recent genomic data into functional insights using frontier technology to identify new intervention targets for Plasmodium falciparum infection. Developing novel targets is mandated by humanity, but also to safeguard Australia's region against the social and economic implications of this disease. An Australian developed intervention would increase the global visibility of its science, leading to increased investments.Read moreRead less
Unlocking malaria invasion by ultraresolution microscopy. This project describes the microscopic analysis of malaria-causing parasites invading human blood cells. The project aims to better understand how this invasion works and to understand how it might be inhibited.