Identification And Development Of Novel Vaccine Candidates For Malaria
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
The aim is to improve methods of preventing and treating malaria by understanding the basic biological mechanisms the pathogen that causes the most severe form of human malaria, uses to invade and survive in the host erythrocyte, and survives in the hostile environment of the blood, as this determines disease outcome. I have outlined an ambitious program for the next five years that will utilize our basic knowledge of how this parasite infects and causes disease to identify novel vaccine candida ....The aim is to improve methods of preventing and treating malaria by understanding the basic biological mechanisms the pathogen that causes the most severe form of human malaria, uses to invade and survive in the host erythrocyte, and survives in the hostile environment of the blood, as this determines disease outcome. I have outlined an ambitious program for the next five years that will utilize our basic knowledge of how this parasite infects and causes disease to identify novel vaccine candidates from the genome of P. falciparum. This represents a major task that will not only provide new information for the malaria field but also identify the most promising candidates that will be pursued into clinical development. I will use two strategies; firstly, a consortium will be formed that brings together expertise that will credential the P. falciparum genome. This provides our experience in functional genomics with EHIME University who have developed methods to express correctly folded P. falciparum proteins in a high throughput system using wheat germ in vitro translation and University of Pennsylvania who have expertise in bioinformatics of the malaria genome. It provides the critical mass and expertise required for a major project. We have developed novel methods for expression of protein domains on the surface of the P. falciparum-infected erythrocyte and this has important utility for analysis of function and immune responses to these proteins. To utilize and develop these tools I will build a critical mass of expertise by forming a consortium between Australian scientists together with Papua New Guinea Institute of Medical Research, KEMRI Institute for Geographic Medicine (Kenya), Harvard University and the Swiss Tropical Institute (Switzerland). This consortium will provide access to malaria endemic areas and the expertise in fieldwork and epidemiology to fully utilize the parasite lines we will construct. The formation of these consortia will greatly strengthen our ability to identify the most promising candidates for clinical development. This will also have great benefit to Australia by increasing the internationalization of our science and therefore access of our researchers to other expertise and also provides a means for networking outside of this country. To foster and increase our leadership in malaria I will develop a Functional Genomics facility that will provide the capacity to construct large panels of transgenic parasites and the ability to develop new genetic tools. Additionally, I will develop a specialized microscopy facility at WEHI to provide the advanced equipment required for visualizing molecular events in live cells. This facility will include a number of instruments including a Line scanner confocal that will be essential for following cellular events such as protein trafficking in live parasite lines.Read moreRead less
Genome-based Tools To Support Urogenital Schistosomiasis Control
Funder
National Health and Medical Research Council
Funding Amount
$429,644.00
Summary
More than 100 million sub-Saharan Africans have urogenital schistosomiasis, a disease that promotes malignant cancer and HIV/AIDS. Control depends on a single drug, making resistance an imminent threat. We will deliver new molecular tools to assess parasite genetic diversity and to prioritise a panel of anti-parasitic drug targets and vaccine candidates. These outcomes will deliver the next generation of interventions against urogenital schistosomiasis.
Does Mass Drug Administration For Scabies Result In Control Of Serious Bacterial Complications? A Proof Of Concept Towards Global Elimination.
Funder
National Health and Medical Research Council
Funding Amount
$883,760.00
Summary
Scabies is common skin disease in developing countries, in particular in the Pacific region. In Fiji, one in two children suffer from the infestation, which affects over 20% of the population. A recent study conducted in Fiji on 2000 people showed that mass drug administration (MDA) with oral ivermectin is a safe and effective way to reduce the burden of scabies in the community. We will expand the MDA program to 100,000 people, the largest study of MDA ivermectin for scabies ever undertaken.
Infection With The Human T Cell Lymphotropic Virus Type 1 Among Indigenous Australian Residents Of Remote Communities
Funder
National Health and Medical Research Council
Funding Amount
$902,865.00
Summary
The Human T Lymphotropic Virus type 1 is endemic to Aboriginal communities in WA, SA and the NT. HTLV-1 Infection is associated with life-threatening sequelae including leukaemia and chronic lung disease. This project will determine rates of HTLV-1 infection and of HTLV-1 associated conditions in a remote community setting.
Optimising Large-scale Public Health Interventions To Control Neglected Tropical Diseases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Neglected tropical diseases (NTD) are a group of health conditions that affect the poorest of the poor, particularly in remote and rural areas. They affect the most vulnerable communities and cause substantial, chronic health harms impairing personal and social development. Several debilitating NTD are common in remote indigenous communities and Pacific islands. I propose a series of studies to investigate new strategies to control NTD in large populations where these diseases are endemic.
I am an immunologist studying host immune responses during malaria and visceral leishmaniasis, two important human infectious diseases. I aim to identify immune responses that promote safe and effective control of parasite growth and distinguish them from
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
Mechanisms Of In Vivo Modulation Of Granulomatous Inflammation In Human Schistosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$276,598.00
Summary
Schistosomiasis is a serious parasitic disease responsible for up to 300,000 deaths annually. The cause are blood flukes that produce considerable disease severity, resulting from host inflammation against the parasite eggs lodging in the liver, giving rise to fibrosis, liver damage, enlarged spleen and death. The pathogenesis is regulated by molecules called cytokines and this project will unravel the mechanisms that regulate disease progression to the severe forms of chronic schistosomiasis.
Immunochemical And Functional Studies On A Novel Protein Of Plasmodium Falciparum Containing EGF-like Domains
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Malaria infection of humans is one of the most important and deadly infectious diseases in the world, killing more than two million people each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. Unfortunately, both of these have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed and this project focuses on developing a better understanding of how the malaria parasite fu ....Malaria infection of humans is one of the most important and deadly infectious diseases in the world, killing more than two million people each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. Unfortunately, both of these have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed and this project focuses on developing a better understanding of how the malaria parasite functions. If important processes such as red blood cell invasion can be understood in detail then it becomes possible to identify proteins essential for survival of the parasite. These could then be used as a vaccine against the disease. Current work suggests that the vaccine will be need more than one parasite protein and it becomes essential to identify the best combination of components. The parasite protein called MSP1 is thought to be a very promising candidate, but it is insufficiently active on its own. We have recently discovered a new protein in the human malaria parasite Plasmodium falciparum, that is similar to MSP1. We would like to know more about this protein and determine if it may be a useful addition to MSP1 for a vaccine. This project intends to further characterize the properties of this new protein including its role in red blood cell invasion and to examine whether immunization with the rodent malaria form of the protein is able to protect mice against malaria infection. The results of this project will be highly significant in the field of malaria vaccine development and will indicate whether this new protein will be a useful component of the eventual malaria vaccine.Read moreRead less