Phagocytic Clearance And Immune Activation In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
Macrophage white blood cells clear malaria infected cells by eating them, by three routes- by recognising ANTIBODIES or COMPLEMENT on the cell surface, or by the cell BINDING directly to the macrophage. Each has different results, such as amounts of cytokines produced. Cytokines clear malaria; in excess they can cause fatal immune pathology. We will investigate how variations in amount of antibody and complement and route of uptake of malaria infected cells might determine malaria outcome.
Understanding Immune Regulation During Parasitic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Chronic infectious diseases such as HIV/AIDS, tuberculosis, malaria and leishmaniasis are responsible for significant morbidity and mortality. They are all characterised by severe immune dysfunction. We will study a parasitic infection to identify important immune cell populations and molecules that promote chronic infectious disease. This knowledge will enable the development of better treatments and vaccines for range of infectious diseases that affect people in many parts of the world.
Effector Export In P. Falciparum Infected Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$1,066,920.00
Summary
We will investigate malaria, a parasitic disease that kills over 450,000 people a year. We will explore how the parasite identifies, invades and remodels the host cells in which it lives, scavenging nutrients and hiding from the immune system. We will characterize the proteins involved in these critical events, as they are potential targets for drugs. We will study how parasites cause disease and how the host responds to infection.
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.
Functional Dissection Of The Malaria RhopH Complex And Its Contribution To New Permeation Pathways
Funder
National Health and Medical Research Council
Funding Amount
$604,718.00
Summary
The ability of Plasmodium to invade and remodel its host erythrocyte are the most significant contributors to its ability to cause the disease malaria. This project aims to understand how proteins secreted from a specialized rhoptry organelle during erythrocyte invasion help Plasmodium to remodel the erythrocyte so that the parasite can gain access to the vital nutrients it requires for survival. This research will validate whether drugs targeting the rhoptry proteins are viable drug targets.
Determining The Mechanistic Basis Of The Patterns Of Inverse Drug Susceptibility Induced By Two Key Drug Resistance Proteins Of The Malaria Parasite.
Funder
National Health and Medical Research Council
Funding Amount
$567,273.00
Summary
The inexhaustible capacity of many pathogens and cancers to develop resistance to new drugs is a serious threat to world health. Yet in acquiring resistance to one drug, many pathogens and cancer cells become hypersensitive to one or more other drugs. We seek to elucidate several of the molecular mechanisms underpinning this phenomenon in the malaria parasite. Insights gained from this work will contribute to the formulation of new therapeutic strategies that overcome or retard drug resistance.
Malaria is a devastating disease of global significance. With mounting resistance to current drugs and no licensed malaria vaccine, there is a pressing need to search for new strategies to reduce the global burden of malaria. My research program aims to understand how the parasites that cause malaria extensively renovate the cells in which they reside and subvert their host so that they can thrive and survive, with a view to identifying new pathways that can be targeted by drugs or vaccines.
Functional Characterisation Of The Malaria Protein Export Machinery
Funder
National Health and Medical Research Council
Funding Amount
$556,104.00
Summary
The ability of malaria parasites to cause one of the most devastating infectious diseases of humans is in part due to their ability to export hundreds of proteins into their host red blood cells to obtain nutrients, evade the immune system and contribute to associated pathologies. Recently, we discovered the molecular machine that exports proteins into the host cell and so now we wish to establish how it works so that drugs can be tailored to block it to kill these parasites.