The Clag Gene Family Of P. Falciparum; Examining Roles In Cytoadherence, Rheological Properties Or Tissue Trophism.
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking 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 ....There are approximately 500 million of cases of malaria per year worldwide and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by the sticking of red blood cells which contain malaria parasites to the lining of microscopic veins and blocking 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, and our data provides evidence that it sticks the parasitised red cells to veins via a protein called CD36 on the internal surface of veins. Our evidence for this has been published in two prestigious international journals. We propose here to examine the same gene in a mouse malaria model as it should be highly informative to see what effect destoying clag has on the disease in a living animal. Obviously this cannot be tested in people. It has now become clear that there are a number of slightly different clag genes and we do not know what the others do. We propose here that they may enable the parasitised red cells to stick to targets other than CD36 on the surfaces of veins, or affect blood flow of infected cells, or direct the parasitised red cells to other organs. The experiments that we propose should reveal whether these ideas are true.Read moreRead less
Defining The Role Of Lymphotoxin Alpha In Experimental Cerebral Malaria
Funder
National Health and Medical Research Council
Funding Amount
$158,250.00
Summary
Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often deat ....Malaria kills millions of children every year. A major cause of death is cerebral malaria (CM) resulting from Plasmodium falciparum infection. At present, there is no effective vaccine available and drug-resistant parasites are widespread. CM is a serious neurological condition characterised by the sequestration of infected red blood cells (iRBC) in cerebral blood vessels. This event is thought to initiate a cascade of inflammatory reactions that ultimately lead to cerebral damage and often death. The factors that cause the sequestration of iRBC in the brain are poorly understood. In this project, we will use an experimental model to define the changes that occur in the cerebral vessels during malaria. The identity of the cells and molecules that mediate the binding of iRBC to the blood vessels of the brain will be identified. It is anticipated that results from this work will increase our understanding of the development of pathology in the brain, as well as identify potential targets for modulation to prevent disease.Read moreRead less
Disease Burden, Risk Factors And Treatment Of Knowlesi Malaria
Funder
National Health and Medical Research Council
Funding Amount
$95,564.00
Summary
Plasmodium knowlesi is a form of monkey malaria recently found to also cause increasing numbers of natural infections in humans in South-East Asia. This research will describe the burden of P. knowlesi malaria in an area of Malaysian Borneo. The risk factors for acquiring P. knowlesi malaria will be assessed. Finally the optimal treatment for non-severe cases of P. knowlesi and P. vivax malaria will also be evaluated by comparing the 2 currently recommended anti-malarial medications in Malaysia.
Functional Resolution Of PTEX, The Exporter Of Virulence Factors In Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$625,212.00
Summary
Almost half a million people die each year of malaria and nearly half the world’s population are at risk. To eliminate malaria this century we will need new drugs and vaccine to fight the disease. One potential drug target are the molecular gateways called PTEX, that are used by parasites to export virulence proteins into their human host cells. This grant aims to understand how the PTEX molecular machines work so we can develop new drugs to block them and kill the parasites.
The transmission of malaria is dependent on gametocytes, the sexual stages of parasite development that are taken up by mosquitoes when feeding on an infected person. While gametocytes are not responsible for disease symptoms, it is clear that malaria eradication is not be possible without an understanding of their biology and the tools to prevent transmission. My research focuses on understanding the biology of gametocytes and identifying new drug targets for transmission blocking strategies.
Griseofulvin, A Novel Host-directed Antimalarial Drug
Funder
National Health and Medical Research Council
Funding Amount
$461,551.00
Summary
This grant is for a Phase II clinical trial to test an FDA & TGA approved drug for a new use as an antimalarial drug. The parasite uses an enzyme from the human RBC to help it replicate & early trials show this drug appears to disrupt the life cycle of the parasite. This Phase II clinical trial will test the drug on human subjects, & if successful, the drug will be a new and novel way in which to treat and prevent malarial infections in humans.
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
Development Of Novel Anti-malaria Drugs That Block Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$1,035,623.00
Summary
Malaria is a devastating parasitic disease that kills over 400,000 people a year. Antimalarial drugs play a crucial role in helping eradicate malaria but of great concern is that parasites are becoming resistant to current drugs. We are developing drugs that prevent parasites from invading and proliferating in human blood which causes malaria. We are also discovering how the drugs work with the aim of greatly improving their performance towards clinical uptake.