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Role Of NK Receptors In Susceptibility And Resistance To Human Malaria
Funder
National Health and Medical Research Council
Funding Amount
$546,588.00
Summary
Malaria kills 2 million children every year. However, many eventually become resistant to the disease. What causes some kids to die, and how others become resistant, is unknown. We believe that genes for Natural Killer molecules in the immune system can protect people against malaria, but can also over-react in the wrong way and make things worse. We plan to investigate the role of Natural Killer genes in causing disease and also protecting in young children in Papua New Guinea against malaria.
Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by ....Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene; most Australians know of Clag as a glue. Our evidence for this has been accepted for publication by the prestigious USA journal Proceedings of the National Academy of Sciences of the USA. Recent work overseas aimed at determining the entire DNA sequence of the malaria parasite has shown that clag is not alone; there are at least 9 slightly different clag genes in the malaria parasite. What do the others do? We propose two possibilities. The first is that all of them act in cytoadherence but that different clags enable the parasitised cells to stick to different things on the lining of veins. The second is that they enable the parasitised cells, or perhaps the parasites alone, to stick to other things at different stages of the complex life cycle of the parasite. The experiments that we propose should show whether either of these proposals is true.Read moreRead less
Mechanisms Underlying Brain Metabolic Changes In Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$334,061.00
Summary
About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early symptoms are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection die and the remainder recover, sometimes with slight neurological impairment. During the cerebral malaria attack, the way that the brain ha ....About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early symptoms are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection die and the remainder recover, sometimes with slight neurological impairment. During the cerebral malaria attack, the way that the brain handles sugar, in order to make the energy needed for brain function, is changed. It adopts a pattern rather like a brain that has been starved of oxygen, though whether this actually occurs is not clear. An alternative idea is that this change in brain biochemistry is caused by cytokines. These are protein molecules produced by the immune system as part of the attack on the malaria parasite. Unfortunately, in excess it is known that some of them, particularly the one called tumour necrosis factor, can have deleterious effects on the host (in this case, human beings). Using an experimental model in mice, we will find out which of the two possibilities (lack of oxygen, over-stimulation by cytokines) is responsible for the biochemical changes in the brain in cerebral malaria. This is important because the brain is very susceptible to changes in the pathways that produce the energy needed for it to function properly. From this work we hope to find out better ways of treating cerebral malaria.Read moreRead less
Microparticles Are Pathogenic Elements In The Pathophysiology Of Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$605,205.00
Summary
Cerebral malaria (CM) is still a world health problem. We aim to better understand its mechanisms by deciphering the role of small blood elements called microparticles (MP). We discovered elevated numbers of MP in CM patients and demonstrated that preventing MP overproduction in mice protects against this fatal disease. Our research will investigate the mechanisms of action and the fate of MP in the blood vessels during CM and allow us to identify strategies for patientÍs treatment and care.
Functional Characterisation Of A Maurer's Cleft Protein Involved In Adhesion Of Malaria-infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$160,500.00
Summary
Malaria is a serious disease that affects half of the world's population and frequently kills humans after a bout of high fever and coma. Many of those who die are young children who live in areas of the world where health care is very poor. The effectiveness of drugs that we currently have available to prevent or treat malaria is rapidly reducing and there is no vaccine available to prevent people from catching the disease. Our research is important because in order to make better medicines for ....Malaria is a serious disease that affects half of the world's population and frequently kills humans after a bout of high fever and coma. Many of those who die are young children who live in areas of the world where health care is very poor. The effectiveness of drugs that we currently have available to prevent or treat malaria is rapidly reducing and there is no vaccine available to prevent people from catching the disease. Our research is important because in order to make better medicines for malaria we have to get to know more about how the malaria parasite makes people sick. The most vicious form of malaria is caused by a tiny parasite called Plasmodium falciparum that lives inside the red blood cells in our bodies. As these minute parasites grow, they make a lot of major changes to the red blood cells and as a result they become very stiff and sticky. This is very bad for the infected person because instead of flowing around the body like normal red blood cells, the infected cells become trapped in small veins and can no longer do their normal job. The ability of the parasite to redecorate red blood cells and make them stiff and sticky is what makes this type of malaria so dangerous, particularly when red cells get stuck in the brain. The research that we will do here will help us to understand the ways in which the malaria parasite sends out these sticky substances to the walls of red blood cells. Eventually, this will help us to find ways to stop the red blood cells from becoming sticky and prevent so many people from becoming very sick and dying with malaria.Read moreRead less
Roles Of CD8-positive T Cells And Chemokines In Cerebral Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$392,545.00
Summary
About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early after infection there are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection, and are treated with anti-malarial drugs, die and the remainder recover, sometimes with slight neurological impairment. One t ....About 2 million people die each year from complications of malaria infection. The most common form of these fatal complications is called cerebral malaria. For reasons that are not fully understood, the brain of the patient becomes affected. Early after infection there are behavioural changes, progressing to coma. About 20% of people who enter coma with malaria infection, and are treated with anti-malarial drugs, die and the remainder recover, sometimes with slight neurological impairment. One theory to explain cerebral malaria is that is caused by the body's own immunological response against the parasite. Using an experimental model in mice, we will find out whether the immune system cells called CD8-positive T lymphocytes are important in causing the brain complications. We also will find out whether messenger molecules called chemokines are important. From this work we hope to discover better ways of treating cerebral malaria.Read moreRead less