Molecular Dissection Of Proteins That Regulate The Invasion Of Toxoplasma Gondii Into Human Cells
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Toxoplasma gondii is an obligate intracellular parasite responsible for congenital birth defects and disease of immuno-compromised individuals. I propose to identify and characterize molecules essential for T. gondii invasion into human cells. These represent novel targets for therapeutic intervention for disease caused by this important organism.
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
One third of the world's population is infected with the protozoan parasite, Toxoplasma gondii, which can cause life-threatening infections. This proposal will utilize new analytical technologies to understand how these parasites are able to survive in a wide variety of different host cells, how they manage to persist within brain and muscle tissue for the life of the patient and how infection may be linked to mental health disorders, such as schizopohrenia.
A Transmission-Blocking Vaccine To Prevent Toxoplasmosis
Funder
National Health and Medical Research Council
Funding Amount
$850,225.00
Summary
Toxoplasma gondii causes a globally important zoonotic disease. It is transmitted by cats, and finds its way into our food chain via infected meat and contaminated water. We have used a unique functional genomics pipeline to discover proteins crucial for reproduction of Toxoplasma in the cat. We will now test combinations of these proteins to immunise cats and prove that we can develop a vaccine that blocks transmission of this highly significant parasitic disease.
Regulation Of Toxoplasma By The NLRP1 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$623,070.00
Summary
Toxoplasmosa is an endemic pathogen worldwide, approaching 80% of the population in some areas, with a large burden of disease, particularly of immunocompromised and pregnant individuals. Our preliminary data identifies a receptor protein in immune cells that detects Toxoplasma. This can defeat the parasite, but also causes pathology for the host. The outcome of our project will work out what part of Toxoplasma is recognized by this receptor, with significance for the treatment of Toxoplasmosis.
Targeting Toxoplasma Gondii Latent Stages Responsible For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,107.00
Summary
Many microbial pathogens become resistant to host immune response and drugs by entering a slow-growing, dormant state. These stages are commonly responsible for long term, chronic infections. We will investigate the molecular basis of dormancy in Toxoplasma gondii, which infects one in three people. These studies will identify metabolic pathways that are essential for dormancy with the view of developing new therapies for treating long term, recurrent infections.
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
Toxoplasma Gondii Infection Of Human Retinal Pigment Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$460,668.00
Summary
Ocular toxoplasmosis is a vision-threatening parasitic eye infection that is common in Australia and worldwide. No treatment cures the disease. This work will characterize cellular and molecular events occuring in the eye during an infection, which is an important first step toward the development of more effective treatments for patients with the condition.
Regulation Of Actin Polymerization During Malaria Parasite Invasion Of The Human Erythrocyte
Funder
National Health and Medical Research Council
Funding Amount
$318,147.00
Summary
Malaria parasites depend on successful invasion of red blood cells for their survival. Invasion is powered by a molecular motor based on two key proteins: actin and myosin. Non-specific drugs that inhibit parasite actin block invasion, demonstrating how important its regulation is to parasite success. This project will study several newly identified malaria actin-regulators, aiming to identify new drug targets that will block malaria actin function, stop motility and as such prevent disease.