The Role Of Parasite Adhesins In Plasmodium Falciparum Invasion Of Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$385,434.00
Summary
Invasion of red blood cells is essential for the survival of malaria parasite within the human host. Red blood cell invasion is mediated by recognition of parasite proteins to specific blood surface receptors. My research focuses on understanding these parasite protein-host receptor interactions with emphasis on translating these findings as novel approaches for the prevention and treatment of malaria.
The Role Of Phosphorylation And Signalling For Invasion Of Plasmodium Falciparum Into Human Erythrocytes.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
The intracellular signals that govern Plasmodium falciparum malaria invasion of the red blood cell are poorly understood. It is likely calcium dependent phosphorylation leads to recruitment and activation of a cascade of proteins. This study combines a break-through in purification of viable P. falciparum merozoites with proteomic analysis of phosphorylation states to assess intracellular signalling. It is expected the processes identified will be unique to P. falciparum and targetable by drugs.
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
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.