I am an epidemiologist working in the areas of public health and prevention, with a focus on HIV infection, viral hepatitis and sexually transmitted infections.
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
I am a microbiologist with expertise in virology and parasitology. My principal focus is understand the pathogenic processes adopted by the human malaria parasite Plasmodium falciparum
Development Of Improved Preventative Therapeutic Strategies For The Control Of Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bact ....A major objective of this Australia Fellowship application is to provide a mechanism whereby, for the first time in my career, I can devote myself full-time to my program of research. This program addresses an issue of global significance, namely the control of bacterial infectious diseases. These continue to cause massive global morbidity and mortality and constitute a profound threat to human health, in spite of the availability of antimicrobial drugs for over 60 years. WHO estimates that bacterial infections are responsible for >10 million deaths p.a., and the economic impact is inestimable. For most major pathogens, vaccines are either unavailable or have serious shortcomings. Resistance to commonly used antimicrobials is increasing at an alarming rate, and modern travel has assisted the rapid global dissemination of highly resistant and virulent clones. Morbidity and mortality are also predicted to increase as a consequence of human-induced environmental changes and the growing proportion of the population with increased susceptibility to infection. Effective management of bacterial infectious diseases in the 21st century will require a two-pronged approach involving the development of cheaper and more effective vaccines, as well as novel anti-infectives refractory to known resistance mechanisms. However, formulation of optimal therapeutic and preventative strategies demands a thorough understanding of the biology of disease, particularly the complex interactions between bacterial pathogens and their human hosts. I have also played a leadership role in establishing the Pneumococcal Vaccine Consortium, which has just submitted a co-ordinated suite of multicentre proposals to PATH Vaccine Solutions to fund final preclinical testing, GMP scale-up and Phase I-II-III trials of protein-based pneumococcal vaccines that we have developed. The PATH accelerated pneumococcal vaccine development program is of enormous potential significance, because there is now a very real probability of pneumococcal protein vaccines being fast-tracked into human trials. Our aim is to create a direct pipeline from antigen discovery in the collaborators’ laboratories into the clinic. If successful, these vaccines could save millions of lives. This will be of enormous satisfaction to me personally, as it was I who originally proposed and demonstrated “proof of principle” for the vaccine potential of pneumococcal proteins, and I have been advocating assessment of their protective efficacy in humans for over 20 years. Thus, receipt of an Australia Fellowship will undoubtedly further support the internationalisation of Australian medical research.Read moreRead less