Interactions Between The Malaria Parasite's Chloroquine Resistance Transporter And Antimalarial Drugs
Funder
National Health and Medical Research Council
Funding Amount
$485,641.00
Summary
The malaria parasite is a single-celled organism which invades the red blood cells of its host. The aim of this project is to characterize the parasite protein responsible for conferring resistance to chloroquine, and to study its interaction with other antimalarial drugs. The parasite's susceptibility to chloroquine, and other drugs, is altered by small changes in this protein. This work will advance our understanding of the increasingly widespread phenomenon of antimalarial drug resistance.
Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their s ....Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their structure and properties so that we can employ rational approaches to develop new drugs that can combat these diseases and ailments. Read moreRead less
Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project bring ....Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project brings national and international expertise together to define the structure and biological properties of these essential enzymes so that in the future we can employ rational approaches to develop new drugs that can combat these diseases and ailments.Read moreRead less
Proteasome Inhibitors As Reversers Of Resistance To Artemisinin-based Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$473,534.00
Summary
Current antimalarial control is highly dependent on Artemisinin Combination Therapy (ACTs), which makes recent reports of decreased clinical efficacy of artemisinins extremely concerning. This project will develop proteasome inhibitors to synergise the activity of artemisinins - effectively reversing resistance. We will confirm that the selected compounds have good bioavailability, low cytotoxicity in human cell lines and efficacy in mouse models of malaria.
Activation of invasion in Toxoplasma. Host cell invasion is critical for the establishment and maintenance of infection by the single-celled parasite Toxoplasma gondii, the causative agent of Toxoplasmosis. This project will use the latest molecular techniques to understand how invasion is activated and will define a new set of drug targets to treat Toxoplasmosis and related diseases.
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 proteomics of Giardia. This project will use the latest tools for dissecting and comparing genes and their protein products from one of the most common parasites infecting people, their pets, livestock and wildlife. This protozoan parasite Giardia is also of evolutionary and biological significance in terms of understanding the origin of higher animals from bacteria as well as fundamental questions about the parasitic way of life. Giardia proteins will be identified and characterised ....Functional proteomics of Giardia. This project will use the latest tools for dissecting and comparing genes and their protein products from one of the most common parasites infecting people, their pets, livestock and wildlife. This protozoan parasite Giardia is also of evolutionary and biological significance in terms of understanding the origin of higher animals from bacteria as well as fundamental questions about the parasitic way of life. Giardia proteins will be identified and characterised on the basis of their value in understanding disease processes and treatment, and by working with appropriate industry partners, proteins of commercial value will be exploited.Read moreRead less