The Role Of Protein Glycosylation In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$644,428.00
Summary
The parasites that cause malaria have unique proteins on their surface that are essential for infection of humans. These proteins are useful for making vaccines to train our immune system to recognize and block infection by the malaria parasite. Our latest research has shown that these proteins are modified with sugars that enhance parasite virulence. We are studying these modifications more closely to facilitate the development of improved malaria vaccines.
Role Of Exported Proteins In Malaria Parasite Development In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$520,613.00
Summary
Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasi ....Each year over 250 million people contract malaria and over 1 million die. The key to the malaria parasite’s success is the ability to live inside host cells, including hepatocytes and erythrocytes. Here, we aim to determine how the malaria parasite lives within hepatocytes, to engineer mutant parasites that can no longer do so and to assess whether mutant parasites confer protection against future malaria. Our program will use the most virulent human parasite P. falciparum and the rodent parasite P. berghei.Read moreRead less
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Autophagy: A New Pathway For Presenting Antigen In Dendritic Cells.
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Microbes are chopped up and digested before being displayed to the immune system. Here we will investigate a new pathway termed _autophagy� that helps cells to digest material for immune display.
I am a cell biologist investigating the means by which intracellular compartmentalization of signalling proteins determines signalling outcomes and cell fate. I focus particularly on signals that regulate immune function and cancer progression.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Subcellular Trafficking Of P Proteins Of Human Pathogenic Viruses: Roles In Viral Pathogenicity And Targeting For Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$578,352.00
Summary
In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destructi ....In order to infect humans, pathogenic viruses such as rabies, Nipah, Hendra and Australian bat lyssavirus must be able to evade the immune response. To do this, viruses produce "interferon antagonists" that interfere with specific immune processes by mechanisms that are not fully understood. Our study will characterise the mechanisms used by rabies and other viruses to block immunity, and identify strategies to disable viral immune evasion, rendering these lethal viruses susceptible to destruction by the human immune system.Read moreRead less
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.Read moreRead less