In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of ....In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of these antibodies. They might block adhesion to placental receptors, decreasing parasite numbers in the placenta. Or they might coat infected red cells, making them targets for phagocytosis (eating) by macrophages (white blood cells). We will examine the effects of HIV on each process, to find out how reduced antibody might affect the pregnant woman. HIV also affects macrophages and related immune cells, monocytes and dendritic cells. We will study how HIV infection in these cells impairs the way they eat malaria cells, and whether it alters the way they become activated and produce infection-fighting proteins when they encounter malaria. Without these proteins, malaria may grow unchallenged. Using our new assays we will study these responses in African women. We will discover whether HIV also affects antibodies to proteins expressed by parasites infecting children, who are at highest risk of malaria. HIV particularly decreases development of antibody to new targets, so children with little malaria experience may lack antibodies to many different proteins. We will find out whether low levels of malaria antibody in children may be the reason why the get more severe malaria. By understanding how HIV affects malaria immunity, we can develop better ways to protect people at risk from malaria. These findings will also be important to work on malaria vaccines. If HIV infected people respond poorly to natural infection, they may also fail to respond to vaccines.Read moreRead less
Helminth Secretomes: From Vaccines To Novel Anti-inflammatory Biologics
Funder
National Health and Medical Research Council
Funding Amount
$938,910.00
Summary
Billions of people in developing countries are infected with parasitic worms, but they have been eradicated from industrialised nations. Humans co-evolved with worms, so their recent removal has deprived us of signals required to keep inflammation in check. My research focuses on worm molecules that can be used to (1) develop vaccines to combat these parasitic infections in developing countries, and (2) as a novel platform of anti-inflammatory therapeutics for use in industrialised nations.
Genomic-based Tools To Support The Control Of Urogenital Schistosomiasis And Hepatic Opisthorchiasis
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Over 100 million people are affected by parasitic flukes that promote malignant tumours. Parasite control depends on a single drug, making resistance an imminent threat. I will deliver new genomic tools to unravel the complex interactions between parasites and humans, and explore parasite population diversity on a continental scale. I will then prioritise a panel of anti-parasitic drug targets and vaccine candidates to deliver the next generation of interventions against parasitic diseases.
Secreted Exosome-like Vesicles From The Carcinogenic Liver Fluke
Funder
National Health and Medical Research Council
Funding Amount
$771,543.00
Summary
Parasitic liver flukes secrete microscopic cell-like vesicles into the bile ducts when feeding on infected humans. These vesicles, called exosomes, are taken up by the cells lining the bile ducts and promote them to become pre-cancerous. We will characterise the contents of these fluke exosomes and identify the key molecules on their surfaces that can be used to prevent exosome uptake by cells and ultimately form the basis of a vaccine that prevents fluke infection and subsequent liver cancer.
Targeting Schistosome Calcium Signalling To Improve And Broaden Praziquantel Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$481,661.00
Summary
Schistosomiasis is caused by parasitic worms, treatment relies solely on praziquantel (PZQ). Schistosomes respond and recover from PZQ exposure through modulation of the gene CamKII. We will target this gene to both increase and extend the efficacy of PZQ in both adult parasites and in refractory juvenile parasites. Research will expand into assaying CamKII inhibitors to maximise effectiveness and take this work into animal models of this disease.
Tropical Diseases: Translating Discoveries Into Better Health
Funder
National Health and Medical Research Council
Funding Amount
$19,803,660.00
Summary
Major progress being made in control of many infectious diseases occurring in tropical areas, including malaria worms and the bacteria that causes strep throat. However, currently available tools will not permit their full control or elimination. This program is aimed to improve understanding of these diseases and to develop the much needed tools that will be required for their elimination.
Understanding How A Parasite-derived Peptide Prevents Immune Mediated Demyelination
Funder
National Health and Medical Research Council
Funding Amount
$496,978.00
Summary
Over millennia of co-evolution with humans, parasitic worms have developed the capacity to modulate the human immune system. We have characterised and identified novel molecules secreted by these worms. In this project we will assess the therapeutic potential of the parasite molecules using animal models of relapsing remitting multiple sclerosis.
Cytoskeletal Remodeling Of The Erythrocyte During Malaria Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$559,807.00
Summary
Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease ....Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease establishment.Read moreRead less
A Transmission-Blocking Vaccine To Prevent Toxoplasmosis
Funder
National Health and Medical Research Council
Funding Amount
$850,225.00
Summary
Toxoplasma gondii causes a globally important zoonotic disease. It is transmitted by cats, and finds its way into our food chain via infected meat and contaminated water. We have used a unique functional genomics pipeline to discover proteins crucial for reproduction of Toxoplasma in the cat. We will now test combinations of these proteins to immunise cats and prove that we can develop a vaccine that blocks transmission of this highly significant parasitic disease.
My research team is focused on human parasites of major relevance to the Australian water industry and/or global public health. Our primary focus is the use of advanced technologies to improve understanding of these parasites and to utilize this information to underpin development of new drugs to treat them and novel diagnostic tests to improve their control.