The Role Of Chemokine Networks In Severe Malaria And The Control Of Parasite Density
Funder
National Health and Medical Research Council
Funding Amount
$620,731.00
Summary
Two contributing factors have been identified as the main determinants of severe malaria: high parasite densities and host inflammatory responses. To date it is not clear whether inflammation is a cause or a consequence of high parasite densities. We have identified a new biomarker (IP-10) of disease severity in a malaria-endemic area of Papua New Guinea that is associated with high parasite densities. Here we will decipher the mechanisms by which IP-10 contributes to the development of high par ....Two contributing factors have been identified as the main determinants of severe malaria: high parasite densities and host inflammatory responses. To date it is not clear whether inflammation is a cause or a consequence of high parasite densities. We have identified a new biomarker (IP-10) of disease severity in a malaria-endemic area of Papua New Guinea that is associated with high parasite densities. Here we will decipher the mechanisms by which IP-10 contributes to the development of high parasite burden and severe malaria.Read moreRead less
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.
Malaria infection affects many millions around the world each year. This project brings together scientists working on mouse models of malaria and on clinical studies of malaria in Africa and Asia, with mathematicians and physicists who will analyse and model their experimental data. The project involves 'data mining' to apply novel statistical and mathematical modelling approaches to understand how the immune system controls malaria infection.
Genome-based Tools To Support Urogenital Schistosomiasis Control
Funder
National Health and Medical Research Council
Funding Amount
$429,644.00
Summary
More than 100 million sub-Saharan Africans have urogenital schistosomiasis, a disease that promotes malignant cancer and HIV/AIDS. Control depends on a single drug, making resistance an imminent threat. We will deliver new molecular tools to assess parasite genetic diversity and to prioritise a panel of anti-parasitic drug targets and vaccine candidates. These outcomes will deliver the next generation of interventions against urogenital schistosomiasis.
Functional Analysis Of The Toxoplasma Myosin Driving Tissue Dissemination And Host Cell Invasion
Funder
National Health and Medical Research Council
Funding Amount
$763,241.00
Summary
The single-celled parasite Toxoplasma gondii is the cause of Toxoplasmosis and is an important basis of eye disease, congenital birth defects and illness in immunocompromised individuals. To perpetuate infection T. gondii moves through tissue and invades host cells using a molecular motor, termed the 'glideosome'. We will reveal how the glideosome produces the force required for movement and characterise its critical features. Our work will provide a foundation in which to model novel drugs that ....The single-celled parasite Toxoplasma gondii is the cause of Toxoplasmosis and is an important basis of eye disease, congenital birth defects and illness in immunocompromised individuals. To perpetuate infection T. gondii moves through tissue and invades host cells using a molecular motor, termed the 'glideosome'. We will reveal how the glideosome produces the force required for movement and characterise its critical features. Our work will provide a foundation in which to model novel drugs that could be designed to treat Toxoplasmosis.Read moreRead less
The Role Of Exosome-like Vesicles In Cell-cell Communication Between P. Falciparum-infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$629,058.00
Summary
Cell-cell communication is a critically important mechanism for information exchange promoting cell survival by control of features such as population density and differentiation state. Malaria is caused by the parasite Plasmodium falciparum. We have shown that P. falciparum-infected red blood cells directly communicate between parasites within a population using small vesicles that are capable of delivering genes and signals. Our work aims to understand this process.
Export Of PfEMP1, The Major Virulence Protein Of P. Falciparum, To The Parasite-infected Erythrocyte Surface
Funder
National Health and Medical Research Council
Funding Amount
$588,532.00
Summary
The malaria parasite infects red blood cells in the human host and initiates major remodelling. This involves export of a major virulence protein to the surface of the red blood cell. This research seeks to understand how the parasite exports this protein, a key determinant of disease.
Functional Assays Of Immunity To Malaria In Pregnant Women
Funder
National Health and Medical Research Council
Funding Amount
$578,905.00
Summary
Pregnant women are highly susceptible to malaria due to the adhesion of infected erythrocytes to the placenta. Antibodies to these infected erythrocytes can block their placental adhesion and/or facilitate their clearance by immune cells, improving pregnancy outcomes. We aim at informing vaccine design by better understanding the placental adhesion mechanisms and identifying targets of protective immunity as well as antibody correlates of protection from placental malaria and its consequences.
Functional Dissection Of Invasion Motor Regulation In Toxoplasma Gondii
Funder
National Health and Medical Research Council
Funding Amount
$500,396.00
Summary
The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds ....The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds to develop new treatments for Toxoplasmosis.Read moreRead less
Population Genomics Of Plasmodium Vivax In Papua New Guinea
Funder
National Health and Medical Research Council
Funding Amount
$597,238.00
Summary
Plasmodium vivax malaria is a serious global public health problem that has not received the attention it deserves, despite having serious clinical implications and presenting a major problem for regional malaria control programmes. In a study of people living in a malarious area of PNG, we aim to investigate the diversity of natural parasite populations, to better understand the possible effects of malaria control interventions on transmission and human immunity.