Plasmodium vivax is a parasite that invades the youngest of human red blood cells. Our work will reveal how this malaria parasite enters our blood cells and the molecular mechanisms that allows successful invasion. This proposal will redefine our understanding of P. vivax invasion and explore novel ways to block its entry into red blood cells and therefore prevent malaria infection.
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 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
We will investigate malaria, a parasitic disease that kills over 600,000 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 and vaccines. We will study how parasites cause disease and how the host responds to infection.
Retargeting The Antibiotic Azithromycin As An Antimalarial With Dual Modality.
Funder
National Health and Medical Research Council
Funding Amount
$773,613.00
Summary
Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensure alternative treatment strategies are available. We will retarget the safe and widely used antibiotic azithromycin as an antimalarial with dual modalities against parasite invasion and growth inside the host red blood cell. This strategy has significant potential to increase drug efficacy while reducing the chances for the development of resistance.
Role Of Plasmepsin V And PTEX Complex In Plasmodium Liver Infection
Funder
National Health and Medical Research Council
Funding Amount
$848,408.00
Summary
Plasmepsin V and PTEX are essential proteins for malaria parasites to grow inside red blood cells. These proteins control the export of parasite proteins into red cells, causing disease. Before red blood cells are infected, parasites invade liver cells. Plasmepsin V and PTEX are expressed during liver infection but their function is currently unknown. We hypothesise that they allow parasites to export proteins into liver cells in order to survive and, thus, are antimalarial drug targets.
Identifying Metabolic Pathways In Leishmania Parasites And Their Host Cells Required For Virulence
Funder
National Health and Medical Research Council
Funding Amount
$989,110.00
Summary
Our lack of understanding of microbial metabolism in infected animal tissues has hindered the development of effective therapies. This is particularly true for many parasitic diseases, including Leishmania spp that cause devastating disease throughout the tropics. We will utilize a range of innovative analytical and genetic approaches to identify metabolic pathway in Leishmania parasites and infected host cells that are required for virulence and are potential drug targets.
Interdisciplinary Insights Into The Rational Design Of Malaria Therapy And Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Malaria is a global health concern with almost half a million deaths annually. There is an urgent need for a highly effective malaria vaccine and new antimalarials. However, despite decades of research into this pathogen, our understanding of what causes illness in a person and how immunity operates is limited. This project will use a mathematical modelling approach to provide a new way to understand infection, as a rapidly changing and intricate process.
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