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.
Modification Of Dendritic Cell Function And Priming Of Protective Immunity By Malaria Blood-stage Parasites
Funder
National Health and Medical Research Council
Funding Amount
$316,500.00
Summary
Approximately 2 billion individuals live in areas where malaria is a risk. Children and naive individuals who get infected for the first time, usually travellers, are most at risk of dying from a Plasmodium falciparum infection, with an estimated 2 million children under 3 years of age killed each year. Surviving adults living in malarial areas have partial immunity after a series of infections. It is unclear how this protective immunity, particularly cellular immunity is acquired, and also uncl ....Approximately 2 billion individuals live in areas where malaria is a risk. Children and naive individuals who get infected for the first time, usually travellers, are most at risk of dying from a Plasmodium falciparum infection, with an estimated 2 million children under 3 years of age killed each year. Surviving adults living in malarial areas have partial immunity after a series of infections. It is unclear how this protective immunity, particularly cellular immunity is acquired, and also unclear why it takes so long to develop. Recent advances in immunology have indicated that Dendritic Cells (DCs) are necesssary to induce effectively cellular immunity and prime memory responses. DCs take up foreign proteins and show them to T cells resulting in their activation. T cells are critical for the establishment of long-term protective immunity to malaria. However, it has not been known if DC can take up malaria parasites or malaria infected red-blood cells and process them to activate protective T cell responses. Our preliminary data shows that both human and mouse DC can take up parasitised red-cells, but that the interaction of parasite derived proteins on the surface of the red cell with DC receptors causes a defect in DC maturation. This defect may prevent effective priming of T cells during natural malaria infection, contributing to the poor development of immunity in malaria endemic areas. Given these novel fundamental findings, it is now important to elucidate: 1) The nature of the DC defect induced by the parasites 2) Assess whether this is a common feature of all Plasmodia, or whether it may relate to strain virulence 3) Determine the nature and extent of the malaria specific response induced by the defective DC. Understanding how parasites may be able to sabotage a critical inducing component of the immune system has wide implications for the use of any immuno-therapies in malaria endemic regions.Read moreRead less
Identification Of Novel Strategies To Mediate Immunity Against Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$325,084.00
Summary
The immune system consists of two arms - innate and adaptive. Current vaccine strategies rely mainly on adaptive features of the immune system to mediate immunity against pathogens. Many pathogens have evolved sophisticated strategies to manipulate the adaptive immune system to render it ineffective. This project will investigate microbial detection by the innate immune system, and aims to discover novel, more effective strategies to mediate immunity against intracellular pathogens.
Exported Malaria Kinases And Red Blood Cell Remodeling
Funder
National Health and Medical Research Council
Funding Amount
$408,710.00
Summary
Malaria is a serious disease affecting half the world's population and every year, more than a million people (mostly children) die as a result of the infection. Our work will help us to understand how malaria parasites alter human red blood cells and make them stick in organs such as the brain. Preventing infected red cells from becoming stiff and sticky by developing new drugs will open up new lines of attack to combat this devastating disease.
The Mechanism Of Action Of New 5-nitroimidazole Drugs Which Are Effective Against Metronidazole-resistant Giardia
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
We have discovered new 5-nitroimidazole drugs which can overcome giardial resistance to metronidazole, the most prescribed 5-nitroimidazole drug to treat giardiasis. We will focus on defining mechanisms of action of these new 5-nitroimidazole drugs in the anaerobic gut protozoan parasite Giardia. Using biochemical techniques, we will determine whether our potent new drugs are activated more efficiently by the same mechanisms as metronidazole or by novel enzyme pathways in the parasite.