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
Malaria In Pregnancy: Exposure, Immunity And Complications
Funder
National Health and Medical Research Council
Funding Amount
$549,723.00
Summary
Increasing malaria control efforts may lead to lack of exposure needed to develop immunity. We will use plasma samples from Africa, PNG and Asia, and measures of immunity we have developed, to discover (1) which are the most important protective immune responses and (2) how are these affected by changing exposure or new drugs. Overall, we hope to identify markers of protective immunity that can be used to identify women at most risk of malaria in pregnancy and its complications
Australia-Europe Malaria Research Cooperation - OzEMalaR
Funder
National Health and Medical Research Council
Funding Amount
$859,731.00
Summary
EVIMalaR is a European Virtual Institute for Malaria Research that combines 42 of the European Union’s leading malaria research groups plus 4 Africans, 1 Indian institution, and 1 Australian. EVIMalaR faculty will combine expertise to produce a Network of Excellence that enhances and harmonises experimental approaches through shared technological platforms, exchange visits, shared PhD students, shared resources such as databases, reagent banks and protocols across pathology, infection, immunolog ....EVIMalaR is a European Virtual Institute for Malaria Research that combines 42 of the European Union’s leading malaria research groups plus 4 Africans, 1 Indian institution, and 1 Australian. EVIMalaR faculty will combine expertise to produce a Network of Excellence that enhances and harmonises experimental approaches through shared technological platforms, exchange visits, shared PhD students, shared resources such as databases, reagent banks and protocols across pathology, infection, immunology and biochemistry. Malaria is a global problem with no single solution. A large, but sometimes disjointed, research community is addressing the problem, but more collaboration is vital. OzEMalaR will link 34 Australian labs with 47 European, African and Indian malaria researchers. Funding will enable exchange of modern technologies by supporting early career researchers (PhD and postdocs) from Australia to work and be trained in top European labs. European trainees will work and be trained by Australian malariologists using reciprocal EU supportRead moreRead less
The Structural Resolution Of PTEX, The Translocon Of Virulence Proteins And Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
The extraordinary virulence of malaria parasites is in part due to their ability to export hundreds of proteins into their red blood cell hosts that help them obtain nutrients and avoid the immune system. Recently we discovered the molecular machine that exports proteins into the host cell and we now wish to establish how it works so drugs can be tailored to block the machine and kill the parasites.
The major objective of this research is to advance the development of highly effective malaria vaccines through i) defining mechanisms and targets of human immunity to malaria to establish a rational basis for vaccine design; ii) advancing the development of lead candidates and promising new candidates and combinations; iii) advancing vaccine platforms that induce potent protective immune responses; iv) develop and validate urgently-needed immunological assays for vaccine development and testing
The growing momentum towards elimination of malaria and the need to control of drug-resistant parasites means that new drugs and vaccines are needed. In this Fellowship I will use the human malaria challenge system that I have developed to test whether new drugs and vaccines for malaria are working sufficiently well to justify their full development. In this system healthy volunteers are deliberately infected with malaria and then cured before they become unwell.
Improving Malaria Elimination Strategies With Genomics: Tackling The Unique Problems Posed By Plasmodium Vivax, And P. Falciparum Drug Resistance
Funder
National Health and Medical Research Council
Funding Amount
$327,193.00
Summary
Malaria parasites are becoming resistant to drugs, and some types can avoid treatment by hiding in the liver and recurring months later. Variation in human genes can also mean that some drugs are dangerous to certain people, or won’t work. DNA sequencing will allow us to understand the interplay between parasite and host genetics and the efficacy of drugs in the population, allowing us to provide ‘personalised’ treatments in that region.