Dissecting the molecular basis of protective immunity to malaria using interdisciplinary approaches

Malaria remains a leading public health threat with approximately 40% of the world’s population at risk. The Plasmodium spp. parasite which causes malaria has a complex life cycle and has co-evolved with the human host over thousands of years. Protective immunity against malaria can be induced in experimental systems by immunization with the intact parasite, suggesting that a malaria vaccine is feasible. However the development of an effective vaccine has been hindered by the complexities of the parasite and the host, and by our poor understanding of the mechanisms of protective immunity. Animals or humans exposed to Plasmodium typically develop a multi-faceted immune response including antibodies and CD8+ and CD4+ T cell components directed against multiple antigens, but little is known about the fine specificities of protective immunity and how to induce the correct specificities by vaccination. To address this, we are investigating the molecular basis of immunity to malaria, taking advantage of well established rodent models of lethal and non-lethal malaria, a unique controlled human-experimental blood-stage infection system, and cross-sectional and longitudinal field studies in malaria-endemic areas. In the rodent models, we employ gene deficient and transgenic mice, including cytokine- and cell-deficient lines, reporter lines, and transgenic lines that allow depletion of specific cellular subsets of interest. We have access to state-of-the-art flow cytometry, microscopy and immunohistochemistry facilities as well as cutting-edge molecular based technologies including protein microarrays, gene expression platforms, high throughput sequencing, and bioinformatics. A specific interest is in the field of systems immunology, which differs from reductionist approaches that analyse isolated components of the immune system, by studying the integration of the various components using high throughput molecular techniques combined with mathematical and computational tools. The focus of this project will be to employ cutting-edge molecular technologies to define the critical cells and signalling pathways required for long-term protective immunity against malaria, with an emphasis on the interface between innate and adaptive immunity.

http://www.qimr.edu.au/page/Lab/Mol_Vaccinology/
http://www.qimrberghofer.edu.au/page/Lab/Mol_Vaccinology/Mol_Vaccinology_student_projects/
Please email Prof Denise Doolan with your academic CV