During the pathogenic blood phase of the complex life cycle Plasmodium spends >99.9% of its life cycle inside host cells. This obligate intracellular niche in an extreme environment (i.e. terminally differentiated erythrocytes) requires metabolic adaptations, which until to date form the basis for antimalarial chemotherapy. This is exemplified by the drug chloroquine that inhibits non-toxic (hostderived) hemoglobin degradation in the parasite food vacuole. In this research area four projects examine the strict dependence of the parasite on external nutrient supply, ranging from ions to complex lipids.
KAI MATUSCHEWSKI (HUB) in partnership with Alexander Maier (ANU), Kiaran Kirk (ANU), and Giel van Dooren (ANU)
In this project a systematic experimental genetics analysis of candidate membrane transport proteins that are shared amongst apicomplexan parasites or unique to distinct Plasmodium species will identify and prioritize candidate drug targets. Lipids are often overlooked as some of the most important and versatile principal cellular components.
EDDA KLIPP (HUB) in partnership with KIARAN KIRK (ANU) and Adele Lehane (ANU)
The project entails obtaining quantitative biochemical and physiological data and incorporating these into a quantitative description of ion homeostasis in the intracellular malaria parasit. The model will contribute to an understanding of the mechanism-of-action of ‘ion-disrupting’ antimalarials that are emerging as priority drug candidates in the malaria-medicine pipeline.
ALEXANDER MAIER (ANU) in partnership with Edda Klipp (HUB)
The project will combine state-of-the-art lipidomics analyses of synchronized and selected parasite stages with mathematical modelling of lipid fluxes in order to select key enzymes and transporters that can be validated experimentally. An integrated mathematical model for ion and cell volume homeostasis in the malaria parasite-infected human erythrocyte remains elusive.
NISHITH GUPTA (HUB) in partnership with Kiaran Kirk (ANU) and Alexander Maier (ANU)
The project will employ ultra-fast optogenetic regulation of ion channels to monitor the immediate cellular responses upon external stimuli and identify potential novel regulatory cascades that are unique to parasite stage conversion.
The Australian National University
Research School of Biology
134 Linnaeus Way
Canberra - Acton ACT 2601
Humboldt-Universität zu Berlin
Unter den Linden 6