Cytosolic And Organellar TRNA Synthetases In Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$424,262.00
Summary
Malaria is a major worldwide infectious disease. The disease kills around 2 million people every year, and current drugs are increasingly failing due to parasite drug resistance, creating an urgent demand for new drugs, that inhibit different targets. I will study a new class of parasite drug targets, the tRNA synthetase enzymes to find novel inhibitors. Compounds blocking these enzymes may lead to new drugs to combat malaria.
Transcriptome Profiling Of The Human Pathogen Schistosoma Japonicum
Funder
National Health and Medical Research Council
Funding Amount
$257,560.00
Summary
The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different g ....The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different genes, and to determine where and when they are active, thus placing the mass of data generated by genome sequencing programs into a biological and functional context. Microarrays provide a unique, cutting-edge, tool for investigating schistosome biology. We have fabricated a microarray representing some 20,000 schistosome genes. We will use this resource to perform large scale monitoring of schistosome gene expression during the parasite's complex life cycle, targetting the regionally important Asian schistosome, Schistosoma japonicum, for study. This will provide the single largest insight into the genetic changes that occur during schistosome development, will greatly further our understanding of the adaptations needed for the growth, development and survival of the parasite, and will identify genes involved in key biological processes, all of which may be exploitable for future interventions and treatments.Read moreRead less
Interactions Between The Malaria Parasite's Chloroquine Resistance Transporter And Antimalarial Drugs
Funder
National Health and Medical Research Council
Funding Amount
$485,641.00
Summary
The malaria parasite is a single-celled organism which invades the red blood cells of its host. The aim of this project is to characterize the parasite protein responsible for conferring resistance to chloroquine, and to study its interaction with other antimalarial drugs. The parasite's susceptibility to chloroquine, and other drugs, is altered by small changes in this protein. This work will advance our understanding of the increasingly widespread phenomenon of antimalarial drug resistance.
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
Exported Malaria Kinases And Red Blood Cell Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$408,710.00
Summary
Malaria is a serious disease affecting half the world's population and every year, more than a million people (mostly children) die as a result of the infection. Our work will help us to understand how malaria parasites alter human red blood cells and make them stick in organs such as the brain. Preventing infected red cells from becoming stiff and sticky by developing new drugs will open up new lines of attack to combat this devastating disease.
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
Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate t ....Malaria infects millions of people worldwide causing serious morbidity and mortality. However, individuals do not develop natural immunity to malaria even after years of exposure to the parasite. There have be a multitude of attempts to make a vaccine , with products going to clinical trials, but no vaccine is able to provide adequate protection for the long term. We recently showed that Plasmodium had evolved a mechanism to kill cells that protect in the long-term. This study will investigate the mechanism by which the parasite kill these cells, so that novel therapies can be designed.Read moreRead less
Unravelling The Tetraspanin Web In The Schistosome Tegument.
Funder
National Health and Medical Research Council
Funding Amount
$309,537.00
Summary
Infection with the human blood fluke, Schistosoma mansoni, is a major human ailment affecting almost 200 million people world wide and causing approximately 200 000 deaths per year. Current control efforts rely on anthelminthic drugs but, to sustain their effects, they must be applied for an indefinite period of time due to reinfection. This project will extend recent efforts to develop a vaccine for this organism and decrease the public health burden and mortality associated with infection.
Immunological Prevention Of Cysticercosis And Hydatid Disease
Funder
National Health and Medical Research Council
Funding Amount
$510,000.00
Summary
Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, there ....Cysticercosis and hydatid disease are caused by infections with the larval stages of tapeworm parasites. These infections cause substantial morbidity and mortality throughout the world, but particularly in developing countries. They are zoonotic diseases, being transmitted to humans from animals. This project aims to develop practical vaccines to assist with the prevention of both cysticercosis and hydatid disease in humans. The vaccines will be used in the parasites' natural animal hosts, thereby breaking the parasite life-cycle and preventing the diseases being passed to humans. Substantial preliminary research has been undertaken by the applicant, including completion of successful preliminary vaccine trials. This project will optimise the vaccines and complete initial field trials in countries with high rates of disease transmission.Read moreRead less