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I am a structural biologist investigating the structure and function of malaria surface proteins as vaccine candidates, regulators of cytokine signalling and pharmacologically active toxins.
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
The Australia Fellowship will enable Prof Good to pursue the development of vaccines for two major pathogens – malaria and group A streptococcus (GAS). Both research programs are entering exciting phases as we move into Phase I clinical trials. At the same time, the Fellowship will enable us to explore the development of the next generation vaccine candidates for these diseases. Malaria is responsible for approximately 1 million deaths per year, mainly of children under 5 years of age, while dis ....The Australia Fellowship will enable Prof Good to pursue the development of vaccines for two major pathogens – malaria and group A streptococcus (GAS). Both research programs are entering exciting phases as we move into Phase I clinical trials. At the same time, the Fellowship will enable us to explore the development of the next generation vaccine candidates for these diseases. Malaria is responsible for approximately 1 million deaths per year, mainly of children under 5 years of age, while diseases caused by group A streptococcus (such as rheumatic heart disease [RHD] and RHD-related stroke) are responsible for at least 500,000 deaths per year. Australia’s Indigenous population suffer the highest documented rate of RHD in the world. We have strong international support and collaboration for these vaccine research programs and have approached the US FDA for a license to conduct the trial for a GAS vaccine and will soon approach them for a licence to undertake the malaria vaccine trial.Read moreRead less
I am a clinician-scientist in infectious and tropical diseases, working towards the better understanding of the pathophysiology of malaria and other tropical diseases of public health importance in our region, and new ways of prevention and treatment.